CHAPTER XVII

SUMMARY

Means of defence of the animal against infective agents.—Absorption of micro-organisms.—Phagocytes, and their function in inflammation.—The action of phagocytes in the absorption of micro-organisms.—The cytases, phagocytic ferments.—The cytases are closely bound up with the phagocytes.—The fixatives and their function in acquired immunity.—The fixatives are excreted by the phagocytes and pass readily into the fluids of the body.—Essential mechanism of the action of the fixatives.—Adaptation of phagocytes to destroy micro-organisms in acquired immunity.—Difference between the fixatives and the agglutinins.—Antitoxins and their analogy with the fixatives.—Hypotheses as to the origin of antitoxins.—Cellular immunity is a fact of general import.—Susceptibility and its rôle in immunity.—Applications of the theory of immunity to medical practice.

[Sidenote: [568]]

When an animal remains unharmed in spite of the penetration of infective agents it is said to be immune to the diseases usually set up by these agents. This idea embraces a very great number of phenomena which cannot always be sharply separated from allied phenomena. On the one hand, immunity is closely connected with the process of cure, on the other, it is related to the disease. An animal may be regarded as unharmed if the penetration of a very dangerous virus sets up merely an insignificant discomfort. Nevertheless, this discomfort is accompanied by morbid symptoms, though they may be very slight. It is useless and impossible to set up any precise limits between immunity and allied states.

Immunity presents great variability. Sometimes it is very stable and durable; in other cases it is very feeble and transient. Immunity may be individual or it may be generic. It may be the privilege of a race, of a species.

Immunity is often innate, as is the case of the immunity which is called natural. But it may also be acquired. This last category of immunity may be developed either by natural means, after an attack of an infective disease, or as a result of human intervention. The principal means of obtaining artificial acquired immunity consists in the inoculation of viruses and of vaccines.

[Sidenote: [569]]

Immunity is a phenomenon which has existed on this globe from time immemorial. Immunity must be of as ancient date as is disease. The most simple and the most primitive organisms have constantly to struggle for their existence; they give chase to living organisms in order to obtain food, and they defend themselves against other organisms in order that they may not become their prey. When the aggressor in this struggle is much smaller than its adversary the result is that the former introduces itself into the body of the latter and destroys it by means of infection. In this case it takes up its abode in its adversary in order to absorb the contents of its host and to produce within it one or more generations. The natural history of unicellular organisms, both vegetable and animal, often presents to us these examples of primitive infection.

But infection also has its counter. The attacked organism defends itself against the little aggressor. It protects itself by interposing a resistant membrane, or it uses all the means at its disposal to destroy the invader. As a very large number of organisms, in order to obtain nourishment, are obliged to submit their food to digestion by various chemical substances, they utilise these substances in the struggle against the infective agents. They digest them whenever they are able to do so.

One of the most primitive of organisms, the plasmodium of the Myxomycetes, which is composed of formless protoplasmic masses intermediate between lower animals and plants, ingests foreign bodies of various kinds. It often happens that it incorporates numerous bacteria which are growing alongside it on rotten wood or elsewhere. The plasmodium allows them to live for some time within its digestive vacuoles. But in the end it digests them by means of its soluble ferments, substances intermediate between pepsin and trypsin. Owing to this digestive power the plasmodia are not attacked by bacterial infections.

[Sidenote: [570]]

This example, taken from amongst the most simple organisms, may serve as a prototype for the phenomena of immunity in general. At the commencement of the study of this remarkable property of so many living organisms it was thought that the pathogenic micro-organisms encountered, within the refractory organism, a medium which did not allow them to live, either because of the absence of certain nutritive substances indispensable for their existence or because it contained some substance injurious to micro-organisms. Very numerous and detailed researches have demonstrated the incorrectness of these hypotheses. There are, of course, certain pathogenic micro-organisms which are very exacting as regards the medium in which they will grow. Some will develop only in the presence of particular substances, whilst others are extremely sensitive to the slightest traces of poisons. These, however, are quite the exception. The great majority of pathogenic micro-organisms belonging to the group of bacteria readily adapt themselves to all kinds of culture media, and most of them live and develop freely in the blood or other fluids of refractory organisms. This, therefore, is not the cause of the immunity in such organisms. The cause must be sought for amongst factors more closely connected with life.

Wishing to penetrate more deeply into these phenomena the hypothesis was put forward that the unharmed organism got rid of the infective micro-organisms by expelling them to the outside along with the excreta. It was maintained for a considerable time that the animal organism possessed the means of causing pathogenic bacteria to pass into the kidneys, whence they were eliminated by the urine. It had to be acknowledged, however, that this elimination never takes place in cases of immunity, and only comes into operation when the animal is ill and the integrity of the renal filter is impaired.

The infective micro-organisms, after they have entered into the unharmed organism, remain there for a longer or shorter period, and perish without being expelled. This disappearance of the micro-organisms takes place by the same mechanism that rids the plasmodium of those bacteria which it has managed to ingest during its slow peregrinations over dead leaves or rotten wood. The micro-organisms are absorbed into the refractory organisms as the result of a true act of digestion. It is very remarkable that the gastro-intestinal ingestion, so well provided with means of rendering the most varied aliments soluble, is generally incapable of digesting pathogenic or other micro-organisms. It is very rare to meet with soluble ferments of the intestinal canal which are capable of digesting microscopic organisms, especially bacteria. Consequently this organ, so rich in digestive diastases, is generally inhabited by a large number of bacteria and other micro-organisms.

[Sidenote: [571]]

Even in animals whose food contains large numbers of microorganisms, _e.g._ the larvae of flies, the digestive juices are powerless to destroy them. Nevertheless, there are organisms which feed exclusively, or almost exclusively, on bacteria and which are quite capable of digesting them. These are the Protozoa, such as the _Amoebae_ and certain Infusoria, which, without any trace of a digestive tube, easily bring about this result. _Amoebae_ can be grown on the surface of agar by taking care to sow along with them bacteria for their nourishment. It is only necessary to give them a single species of micro-organism, and this may be selected from the pathogenic forms, such as the cholera vibrio or the _Bacillus coli_. The _Amoebae_ ingest a number of these bacteria in the living state. They then kill them and digest them in their digestive vacuoles which contain, along with a little acid, a ferment belonging to the trypsin group, the amoebodiastase.

The bodies of lower and higher animals, alike, are very rich in elements which closely resemble the _Amoebae_. Sometimes these are to be found in the epithelial cells of the digestive canal which put out protoplasmic processes for the purpose of seizing food and transferring it to their interior, where it is submitted to the action of digestive ferments. Sometimes they are the cells disposed between the body wall and that of the intestinal canal, which float freely in the fluids of the body or are more or less fixed in the interstitial tissue. The animal kingdom presents a great variety of these amoeboid elements, known under the general name of phagocytes (cells capable of devouring solid bodies). One of the most primitive arrangements of phagocytes is met with in _Ascaris_ and its allies belonging to the group of the Nematoda. All the organisation that these round worms possess consists merely of four, or a few more, enormous cells attached to the body wall. These are phagocytes which push out processes of enormous length, capable of exploring the whole of the internal cavity of the body.

[Sidenote: [572]]

The majority of phagocytes circulate in the lymph and blood and pass into the exudations. These white corpuscles have a comparatively uniform structure in the Invertebrata and present themselves as small cells with a nucleus and a protoplasm capable of amoeboid movements. In the Vertebrata we meet with two great categories of white corpuscles, of which one group resembles those of the Invertebrata in that they also possess a single large nucleus and an amoeboid protoplasm. These are the macrophages of the blood and of the lymph, and are intimately connected with the macrophages of such organs as the spleen, lymphatic glands, and bone marrow. Another group of white corpuscles in the Vertebrata is made up of small amoeboid cells which are distinguished by having a nucleus which, although single, is divided into several lobes. These are the microphages whose chief peculiarity, the multi-lobed form of the nucleus, must be regarded as an adaptation for the purpose of passing as rapidly as possible through the walls of capillaries and small veins.

The diapedesis of the white corpuscles, their migration through the vessel wall into the cavities and tissues, is one of the principal means of defence possessed by an animal. As soon as the infective agents have penetrated into the body, a whole army of white corpuscles proceed towards the menaced spot, there entering into a struggle with the micro-organisms. Aided by the special form of their nucleus the microphages are the first to pass through the walls of the vessels. Each of the several small lobes, into which the nucleus and its protoplasm is divided, passes readily through the minute orifices between the endothelial cells of the vessels. The macrophages follow the microphages and become mixed in greater or less numbers with the exudations. But it is not micro-organisms only which set up this inflammatory reaction accompanied by the emigration and the accumulation of leucocytes. The introduction of inert bodies and of aseptic fluids brings about the same result. The phagocytes are, as a matter of fact, endowed with a special susceptibility, which enables them to perceive exceedingly small changes in the chemical or physical composition of the medium that surrounds them.

The leucocytes, having arrived at the spot where the intruders are found, seize them after the manner of the _Amoebae_ and within their bodies subject them to intracellular digestion. This digestion takes place in the vacuoles in which usually is a weakly acid fluid which contains digestive ferments; of these a very considerable number are now recognised.

Just as the _Amoebae_ and the Infusoria make a choice from amongst the small organisms that surround them, so the leucocytes choose bodies which are best suited to their use. The macrophages seize by preference animal cells such as the blood corpuscles, the spermatozoa, and other elements which are derived from animals. Among the infective micro-organisms the macrophages have a predilection for those that set up chronic diseases such as leprosy, tuberculosis, and actinomycosis and also for those which are of animal nature. Into this last category come the amoeboid parasites of malaria, Texas fever and the _Trypanosomata_. The macrophages can also ingest the bacteria of acute diseases, but, save in exceptional cases, their intervention is of little moment.

[Sidenote: [573]]

The microphages, on the other hand, appear to play their part specially in acute infections. Their intervention against animal cells is _nil_, or almost so. Thus they rarely seize the red corpuscles of the same or of a foreign species of animal. They also appear to be repelled by parasites of animal origin and by certain bacteria which set up chronic diseases. Whilst the macrophages seize the bacilli of leprosy with great avidity, the microphages ingest them only exceptionally.

The morphological and physiological differences between the two great categories of mobile phagocytes (leucocytes), correspond to differences in the composition of their soluble ferments. Just as the _Amoebae_ digest their prey by means of their amoebodiastase, a soluble ferment of the group of trypsins, so the white corpuscles submit the foreign bodies ingested by them to the action of what are now known as cytases. These cytases (alexins or complements of other writers) are soluble ferments which also belong to the trypsin group. They act in a medium which is feebly acid, neutral, or feebly alkaline, and, like the amoebodiastase, they are distinguished by a great sensitiveness to heat. When the cytases are contained in fluids, a temperature of 55°–56° C. destroys them rapidly and completely. When they are found in organs reduced to the state of an emulsion, their sensitiveness diminishes and it is necessary to raise the temperature to 58°–62° C. in order to destroy their activity.

[Sidenote: [574]]

Bordet maintains that the cytases are very different in the various species of animals, but that in the same species only one cytase exists. Ehrlich and Morgenroth, on the other hand, hold that the same serum contains several, sometimes many, different cytases. This question is too difficult to be definitely solved at present. It appears to me very probable that there exist, in the same species of animal, two different cytases. One of these, the macrocytase which is found in the lymphoid organs and in the serum of the blood, acts more particularly on animal cells. Thanks to this substance an extract or maceration of the spleen, omentum or lymphatic glands dissolves the red blood corpuscles more or less readily; these extracts and macerations, however, are incapable of destroying bacteria. When the macrophages seize the nucleated blood corpuscles they digest them completely, not sparing even the nucleus, so resistant to attack, but when the same phagocytes ingest such micro-organisms as are most easily digested, such as the cholera vibrio, their action is feeble. The vibrios, without any transformation into granules, remain alive for some time and are destroyed and digested with very great difficulty. The cytase of the microphages, or microcytase, is distinguished by other properties. It destroys and digests easily many micro-organisms, but has little or no action upon the red blood corpuscles and other animal cells. The exudations which are rich in macrophages, such as those of the lymphoid organs, are not at all or only slightly bactericidal, but exhibit a solvent action on red blood corpuscles. On the other hand, the exudations, which are composed in great part of microphages, leave red blood corpuscles intact, but readily destroy micro-organisms. Similar properties distinguish the bone marrow, extracts and suspensions of which do not dissolve red corpuscles, but attack micro-organisms. Now, we know that the bone marrow is the principal seat of origin of the microphages.

Even after the addition of some of the specific fixative to the microphagic exudations no solution of the red corpuscles is produced, which demonstrates most clearly that the microcytase is really incapable of attacking these animal cells.

We are, therefore, compelled to accept the existence of two different cytases, of which one (the macrocytase) acts specially upon elements of animal origin, and the other (the microcytase) acts principally on micro-organisms. The indication of any more detailed differentiations is impossible in the present state of our knowledge.

[Sidenote: [575]]

There are certain ferments which, during the life of the cells which produce them, pass readily into the surrounding fluids. For instance, sucrase can be recovered without difficulty from the culture fluid of moulds and yeasts. The ferments of the intestinal digestion also pass with great facility into the secreted fluids. Other soluble ferments, on the other hand, remain very closely bound up with the cells which manufacture them. Thus the zymase of the yeasts can only be freed from the cells of these fungi with great difficulty, under the influence of great pressure and under conditions which profoundly alter the cell. The proteolytic ferment of the yeast is also very adherent to the cells of these organisms. The fibrin-ferment, or plasmase of the white corpuscles, is not secreted by these cells so long as they are quite intact. But it is sufficient to subject them to unfavourable conditions of existence to cause them to throw it out from their bodies. The leucocytes, when removed from the animal, undergo a deterioration which soon leads to the deposition around them of filaments of fibrin.

The cytases must also be grouped with the soluble ferments which are not thrown off by the phagocytes so long as these remain intact. Immediately these cells are injured, however, they allow a part of their cytases to escape. In the blood, withdrawn from the animal, the white corpuscles allow the plasmase to pass into the fluid, where it sets up the coagulation of the fibrin and the formation of a clot. At the same time these cells give up some of their cytases which communicate to the serum its haemolytic and bactericidal properties. This fact is of the highest importance in connection with the question of immunity. The best demonstration of this has been furnished by a comparison of the bactericidal power in the different parts of the body and in the body fluids extracted from the animal.

When micro-organisms are introduced into those situations in the refractory animal which contain pre-existent leucocytes, the leucocytes, under the influence of the shock, undergo serious lesions, accompanied by the throwing out of the cytases. Under these conditions the least resistant micro-organisms (such as the cholera vibrio) exhibit undeniable signs of deterioration: they become transformed into granules and may even die in greater or less numbers. When, however, the leucocytes are well protected and withstand the injection of the micro-organisms without being profoundly altered, the extracellular destruction of the micro-organisms does not take place. On the contrary, a very rapid phagocytosis is produced which brings about the death and intracellular digestion of these micro-organisms. Under these conditions vibrios are also transformed into granules and perish, but only within the leucocytes. The phenomena I have just mentioned are brought about in the peritoneal cavity and in the blood vessels of refractory animals, that is to say, in situations rich in leucocytes.

[Sidenote: [576]]

In the subcutaneous tissue, in the fluids of oedemas and in the anterior chamber of the eye of these same refractory animals, the phenomena are very different. As in these situations there are no pre-existing leucocytes or their number is insignificant, the micro-organisms introduced do not suffer serious injury; they continue to live up to the moment when the leucocytes, having come up as the result of the inflammatory reaction, seize them alive, kill them, and digest them within their substance. Just as it is easy, in situations populated by pre-existing leucocytes, to suppress the extracellular destruction of the micro-organisms by preserving the phagocytes against injury or phagolysis, so this same extracellular destruction is easily set up in situations where leucocytes are absent. When, after exudations rich in leucocytes have been injected into the subcutaneous tissue, we introduce micro-organisms which are not very resistant, such as the cholera vibrio, it is observed that these vibrios are destroyed outside the cells, having first been transformed into granules.

There can be no doubt as to the conclusion to be drawn from these various experiments. The microcytase is the substance which transforms the vibrios into granules. It is within the microphages, when they remain intact, that the vibrios undergo transformation. When, on the other hand, the microphages are injured and allow the microcytase to escape, the transformation of the vibrios into granules and their partial destruction take place in the plasmas outside the phagocytes.

This conclusion is supported by comparative researches on the bactericidal power of the serum and of the blood plasma outside the animal. It is true that it is impossible to prepare a fluid which shall in all respects be comparable to the plasma of the circulating blood. There is, however, always a means of obtaining outside the animal a fluid which approaches much more closely to blood plasma than does serum. Gengou succeeded in preparing in tubes coated internally with paraffin a fluid which coagulates very tardily, and which contains very little fibrin-ferment. This fluid is found to be much less bactericidal than is the blood serum of the same animal. It is, indeed, often found to be entirely without bactericidal power, whilst the corresponding serum is capable of destroying a large number of micro-organisms.

[Sidenote: [577]]

In the phenomena of the absorption of cells also a great number of facts are met with which demonstrate that the macrocytase escapes from the macrophages at the moment of their phagolysis only. For example, the extracellular solution of the red corpuscles takes place easily in the peritoneal fluid of animals prepared by a previous injection of the same corpuscles. When the leucocytes of the peritoneal cavity are abandoned to their fate, a marked phagolysis is produced and consequently a solution of the red corpuscles in the fluid itself. When, on the other hand, phagolysis is prevented, the macrophages remaining intact do not allow their macrocytase to escape and the solution of the red corpuscles takes place almost exclusively inside the phagocytes.

In certain animals the blood serum arrests the movements of their own spermatozoa at once, whilst these remain quite motile in the animal itself. This is due to the fact that the immobilising macrocytase is contained within the macrophages and does not escape from them so long as these cells remain intact. When, in such animals, their own spermatozoa are introduced into the subcutaneous tissue, they remain motile for a long time; when, on the contrary, the spermatozoa are injected into the peritoneal cavity, where the leucocytes have not been prepared, phagolysis is produced at once and the spermatozoa become motionless immediately.

As all these data agree in demonstrating that the uninjured phagocytes retain the cytases—which remain within them, and are not found in the surrounding fluids,—we can readily understand the reason for the differences between the phenomena of immunity and the bactericidal power of the body fluids. The rat’s serum is capable of destroying a large number of anthrax bacilli, although these rodents are certainly susceptible to anthrax. The reason for this is that in the serum of the rat the bacilli are destroyed by the microcytase which is set at liberty, whilst in the body of the animal it remains enclosed within the bodies of the living microphages. So long as these cells exhibit a negative chemiotaxis against the anthrax bacillus, the micro-organism remains in the plasma, where it is not interfered with. Thanks to this, multiplication of the bacilli goes on in the body of the animal, the micro-organism killing it after becoming generalised in the blood and in the organs. The susceptibility of the leucocytes is, then, the cause of the death of the rats from anthrax, the organism of these rodents being unable to take advantage of its richness in bactericidal microcytase.

Another paradoxical fact is met with in guinea-pigs immunised against Gamaleia’s vibrio (_Vibrio metchnikovi_). As demonstrated by von Behring and Nissen, the blood serum of these guinea-pigs is very bactericidal for the vibrio in question. A contact of less than an hour is quite sufficient to destroy large numbers of the micro-organisms. Nevertheless, when a small dose of a culture is injected subcutaneously into these hypervaccinated guinea-pigs, the vibrios remain alive for several days, up—indeed, to the moment when they are ingested and destroyed by the leucocytes which come up in large numbers to the menaced spot. This apparent contradiction is easily explained by the fact that it is in the serum only that the vibrios encounter the microcytase, which has escaped from the microphages at the time of the formation of the clot and the separation of the serum.

[Sidenote: [578]]

Alongside those cases in which the serum of susceptible animals is found to be very bactericidal, examples are not wanting where the blood and the serum of refractory animals are entirely without this power. For instance, the pigeon is refractory to Pfeiffer’s influenza bacillus, but the blood of the pigeon forms the best culture medium for this micro-organism. The dog is refractory to the anthrax bacillus, against which the blood serum of the same animal is not at all bactericidal. The cause of this absence of parallelism between immunity and the bactericidal power of the serums must be sought in the difficulty with which the cytases escape from the leucocytes, and also in the modifications which they may undergo, once they are distributed in the fluids.

[Sidenote: [579]]

In cases of natural immunity, the cytases rid the animal of the micro-organisms without the slightest observable co-operation on the part of other soluble ferments. It is impossible to settle definitely even the question whether, in animals which enjoy this innate immunity, there exists, alongside the microcytase, any ferments which come to its aid. The conditions are quite otherwise in a very large number of cases of acquired immunity. Here it is found, as a fairly general rule, that in addition to the microcytases there exist other substances whose rôle in the defensive action offered by the animal against micro-organisms is very important. These substances are fixatives which co-operate in a remarkable fashion with the bactericidal action of the cytases; but whilst these latter injure the bacterial cell directly, the fixatives do not interfere with its life. The bacteria, permeated by fixatives, may even continue to reproduce themselves and, under certain conditions, to invade the animal. The fixatives, then, are not bactericidal, but by fixing themselves upon the micro-organisms they render them much more susceptible to the bactericidal action of the microcytases. These latter are further distinguished, in several other respects, from the cytases. The fixatives must also be classed with the group of soluble ferments, but they resist much higher temperatures than those which destroy the cytases. Whilst the latter are quite destroyed at 55° C., the fixatives, to be completely altered, must be heated to beyond 60° C. and even 65° C. On the other hand, the fixatives are distinguished by a high specificity which is never observed in the cytases. The majority of the fixatives are incapable of fixing themselves upon more than a single species of bacteria or upon a single class of animal cells, and only certain of them can fix themselves upon allied species or cells, such as the red corpuscles of several species of animals. In these cases, too, there exists a sharp quantitative difference between the fixation on the different formed elements. The same microcytases are, on the other hand, able to attack all kinds of micro-organisms, and the same macrocytases attack all kinds of animal cells.

We have seen that the cytases correspond to the zymase and to the proteolytic diastase of the yeasts in the sense that all these soluble ferments adhere with tenacity to the cells which produce them and contain them. The fixatives, in this respect, approach sucrase (invertin): these various soluble ferments pass readily into the fluids which bathe the cells that produce them. The fixatives are found not only in the blood serums, prepared outside the body, but also in the blood plasma, whence they pass into the fluids of the exudations and transudations. Whilst no cytases are found in the subcutaneous tissue, or in the clear fluids of oedemas containing no, or almost no, cells, fixatives are not absent from these various situations just indicated. For this reason, when micro-organisms are introduced subcutaneously, they are not found to be altered by the cytases, but it is easily seen that they are permeated with fixatives. The same rule applies to the fixatives of the animal cells. In the example we have cited, the spermatozoa, in an animal whose serum renders these cells motionless, remain quite motile in the epididymis and below the skin. From this fact it may be concluded that these situations contain no free macrocytase. It is sufficient, however, to add to these motile spermatozoa a drop of normal serum containing macrocytase to stop their movements at once, the fixative being well distributed in the plasma of the living animal. The spermatozoa, then, were sensibilised by the fixative which was found in both the epididymis and in the subcutaneous tissue.

[Sidenote: [580]]

The cytases are soluble ferments which are essentially intracellular: the fixatives are, on the other hand, soluble ferments which are humoral. These fixatives, however, although circulating in the plasmas, are undoubtedly of cellular origin. This fact was first demonstrated by Pfeiffer and Marx, who found the specific fixative of cholera vibrios in the “haematopoietic organs,” that is to say, in the spleen, lymphatic glands, and bone marrow, at a period when there was, as yet, none in the blood. This fact has been extended to other examples of fixatives of micro-organisms, and it cannot be questioned that the phagocytes produce these soluble ferments. Under the influence of the introduction of micro-organisms into the body, a phagocytic reaction is produced which has, as a consequence, the digestion of these micro-organisms and the production of corresponding fixatives. There is every reason to believe that, in these cases, it is the microphages which, seizing and digesting the micro-organisms, produce the fixatives.

But the macrophages are also capable of producing these adjuvant ferments. Even in normal animals the macrophagic organs, such as the spleen, and especially the mesenteric glands, contain fixatives which help in the solution of the red blood corpuscles. Into this group of facts we must also place the production by the mesenteric glands, as well as by certain other lymphoid organs, and the leucocytes of exudations and the blood, of enterokynase,—the soluble ferment which aids the digestive action of trypsin. This enterokynase is also a species of fixative; it permeates the flakes of fibrin and renders them much more accessible to the influence of the trypsins.

The fact that the enterokynase of the intestinal digestion corresponds in so many respects to the fixatives which act in the absorption of formed elements in general and of micro-organisms in particular, furnishes a further proof that the destruction of micro-organisms in the animal is an act similar to true digestion.

[Sidenote: [581]]

Phagocytes, those elements which accomplish the absorption of micro-organisms and of animal cells, those holders of digestive cytases, are also the manufacturers of fixatives. Having brought about this absorption, the phagocytes set to work to elaborate large quantities of fixatives, although they are unable to increase the amount of cytases in any marked degree. The fixatives, produced in abundance, can be excreted outside the phagocytes and pass into the blood plasma, and, with it, into the fluids of exudations and transudations. But this excretion is not an indispensable act for the functioning of the fixatives. As these ferments prepare the way for the digestive action of the cytases, it is necessary only that they should be able to fix themselves on the formed elements before the latter. It is, therefore, easy to explain cases of acquired immunity in which no fixatives are found in the body fluids. Such examples are not rare, and are characterised by the absence of any protective action on the part of the blood serum. In these cases, the fixatives, whose existence is very probable, remain lodged within the phagocytes, just as are the cytases. Within these digestive cells the fixatives may quite well fulfil their preparatory rôle, this being followed immediately by the action of the cytase. The same rule may apply also to the cases of absorption in the unprepared animal, where fixatives are not found in the blood serum, but where they are able to act within phagocytes.

The excretion of fixatives into the plasmas, which constitutes the rule in cases of acquired immunity, presents an analogy with the excretion of pepsin into the blood. This soluble ferment can and does pass habitually from the stomach into the blood and thence into the urine, where it is often met with. As the pepsin, which only acts in an acid medium, cannot be utilised in the alkaline blood plasma, it is evident that its excretion is only the consequence of a too abundant over-production.

In recent years great attention has been paid to the essential mechanism of the action of fixatives on the formed elements on the one hand, and on the cytases on the other. According to Ehrlich, the fixatives are bodies intermediate between the two. In possession of two haptophore molecular groups, they are capable of entering into chemical combination with the micro-organisms or the animal cells on the one hand, and with the cytases on the other. It is for this reason that Ehrlich applies to them the name of “amboceptors” or “intermediary substances.” Based on analogous examples in organic chemistry, Ehrlich thinks that the fixatives serve to introduce the cytases into the cells upon which they have to act. Bordet does not share this view and maintains that the action of the fixatives is not a chemical action in the proper sense of the word, but is a kind of mordanting which sensibilises the formed elements to the fermentative action of the cytases. According to him, the fixatives have no affinity for the cytases and in no way serve them as intermediaries, for which reason he gives to them the name of sensibilising substances. The question is still under discussion, but we may hope that it will soon enter into its final phase.

[Sidenote: [582]]

According to Ehrlich’s theory, the fixatives contain no product coming from the micro-organisms or from the animal cells upon which they are fixed. The fixatives are, according to him, side-chains or receptors, produced in excess and expelled into the blood plasma by the cells which produce them. Ehrlich does not tell us to what category these cells belong; he maintains only that these cells must be in possession of receptors endowed with a specific affinity for certain molecular groups of micro-organisms and of animal cells. As soon as the receptors are saturated by these molecular groups, the cells which make use of the former for their nutrition produce them in superabundant quantity. The cells of animals, treated with micro-organisms and their soluble products, or with red blood corpuscles or any other kind of element of animal origin, acquire the property of elaborating more and more of the corresponding receptors, a large proportion of which are expelled into the blood plasma.

The common point between Ehrlich’s theory and the view maintained in this work consists in the admission of a cellular property which develops more and more in proportion to the treatment of the animal by formed elements of all kinds. As, in acquired immunity against micro-organisms, the fixatives are most frequently found in the body fluids, it must be concluded that, in all these cases, the cells which produce them have become adapted by a kind of education to manufacture increasing quantities of fixatives. But even in those examples of acquired immunity where fixatives are not found in the plasmas, we must accept a modification of the cells which resist the invasion of micro-organisms. These changes in the cellular properties constitute, therefore, the most general, and consequently the most important, element in acquired immunity against micro-organisms.

As already mentioned Ehrlich does not assign any position to the cells which exhibit these modifications. It must, however, be accepted that they belong to the category of phagocytes. Indeed, the phagocytes put themselves into most intimate contact with the micro-organisms and foreign animal cells, and it is in the phagocytic organs that the fixatives are found before they are met with in the blood plasma. It may then be concluded that, in acquired immunity against micro-organisms, the phagocytes become adapted to elaborate the fixatives in large quantities, of which a portion is excreted into the body fluids, as has been shown in many examples of such immunity.

[Sidenote: [583]]

The progressive adaptation of the phagocytes in intracellular digestion can be demonstrated by the fact that in an immunised animal the fixatives are found more especially in the phagocytic organs. The leucocytes which digest gelatine exhibit in an even more distinct fashion the modification of these cells in animals which have received several injections of gelatine. The leucocytes of exudations, when the fluid is removed, become much more fitted to digest the gelatine than they were at first.

A similar adaptation is also observed in intestinal digestion, which may serve as a fresh point of comparison between the intracellular digestion of the phagocytes and the extracellular digestion in the intestines. The pancreas, in order to secrete its soluble ferments, adapts itself to the nature of the food which passes into the digestive canal.

The fixatives are not the only soluble ferments which appear in large quantities in the fluids of the immunised animal. Very often there are found along with them substances which agglutinate the micro-organisms in animals which have received several injections of micro-organisms of the same or an allied species. The same fact is observed in animals treated with animal cells. Thus the fluids of animals injected with blood corpuscles become agglutinative for these corpuscles.

[Sidenote: [584]]

The analogy between the agglutinins and the fixatives is so great that for some time several observers assumed them to be one and the same substance. This can no longer be upheld, for it is clearly demonstrated that the property of the body fluids to agglutinate micro-organisms and animal cells is different from that which brings about their permeation by fixatives. The agglutinins resist the same temperatures as the fixatives; both are specific to the same degree and pass equally from the cells which produce them into the plasmas of the blood, lymph, exudations, and transudations. The agglutinins capable of clumping the formed elements into masses may, under certain conditions, render their ingestion by the phagocytes more easy. In general, however, the part played by the agglutinins in acquired immunity must be regarded as of little importance, and for that reason we abstain from basing any theory of this immunity on the agglutinative property of the body fluids. Besides fixatives and agglutinins, the fluids of an animal which has acquired immunity very probably possess other properties which must have a greater or less function in acquired immunity. Thus, we are often struck by the stimulating action of these fluids on the normal animal into which they are introduced. This stimulation is especially manifested against the phagocytic reaction.

As, in the majority of cases of acquired immunity, the blood serum contains fixatives in considerable proportion, and as these fixatives aid the action of the cytases in a remarkable fashion, we can readily understand that the introduction of such a blood serum into a normal animal, unprepared by any vaccination, may bring about a great resistance against the corresponding pathogenic micro-organisms. The fixatives, injected with the serum, fix themselves with avidity upon the micro-organisms. These organisms may become a more ready prey to the phagocytes and be destroyed very rapidly. In particular cases, where the injection of microbial cultures sets up a phagolysis, enough cytases are thrown out to affect the microbes already sensibilised by the fixative. This is followed by a refractory condition of the animal proportionate, in general, to the amount of fixative serum that is injected. This kind of acquired immunity, conferred by serums or certain other body fluids rich in fixative substances, has often received the name of passive immunity. This term is only justified in those rare cases where the introduced serum itself contains a sufficient amount of cytases to destroy all the micro-organisms. Most often it is the normal animal which has to furnish this bacteriolytic ferment. Now, as in phagolysis the quantity given off is too small, it is to the co-operation of the holders of cytases, that is to say, to the phagocytes, that the animal must have recourse. The phagocytes, being susceptible cells, their co-operation can only be counted upon in cases where they exhibit a sufficient activity. When these elements are weakened by narcotics or by any other cause, they become incapable of intervening with efficacy and the animal falls a victim to the pathogenic micro-organisms, in spite of the more than sufficient amount of fixatives that was introduced.

[Sidenote: [585]]

In natural or acquired immunity, it is the resistance of the animal against the micro-organisms which plays the principal part. The introduction of toxins ready prepared is only done under artificial conditions, as in laboratory experiments. Hence we see that, under natural conditions, it is against the penetration of the micro-organisms that the animal must be protected. So soon as these producers of poisons can no longer maintain themselves in the immunised animal their toxic secretions do not come into play. It is for this reason that animals vaccinated against pathogenic micro-organisms do not suffer from intoxication, although they are by no means insusceptible to the microbial poisons. It is a fact of the highest importance from the point of view of immunity in general, that the resistance offered to micro-organisms in no way implies insusceptibility to their poisons. The view has frequently been expressed that, in acquired immunity at least, the animal must first acquire immunity against the microbial toxins, after which the micro-organisms, deprived of their principal weapon, descend to the rank of inoffensive saprophytes. Such cases may be found, but it is none the less true that immunity against micro-organisms may be acquired independently of that against the toxins, and that this constitutes the general rule.

Immunity is much more readily acquired against micro-organisms than against their toxins. Hence, antimicrobial vaccination was accomplished by science before that against their toxins. In the early researches on this subject antitoxic immunity appeared to be very difficult of attainment, and it was only after the discovery made by von Behring, who inaugurated a new path in microbiology, that better results were obtained. Von Behring not only succeeded in immunising animals against some of the principal microbial toxins, he demonstrated the existence of specific antitoxins in their body fluids.

This very unexpected conception of antitoxins at once took root in science, for it has been possible, thanks especially to the remarkable works of Ehrlich, to extend it to toxins of non-microbial origin. We are already acquainted with a certain number of antitoxins which, however, are not comparable in number to the other antibodies. Amongst these, the fixatives have many points of analogy with the antitoxins. Like them, they are resistant to heat: they exhibit also a fairly marked specificity, and, like the fixatives, they are distributed in the plasmas.

[Sidenote: [586]]

In the presence of so many points of similarity with the fixatives, one is tempted to attribute to the two categories of antibodies the same origin. The elaboration of antitoxins by the phagocytic elements, accumulated in the blood and disseminated in the organs, appears, in fact, to be very probable. Certain facts bearing on the absorption of various toxins by the leucocytes, as well as the distribution of antitoxins in the animal body, speak in favour of this view. On the other hand, the impossibility of attributing the elaboration of antitoxins to cells attacked by the corresponding toxins is quite in harmony with the same hypothesis. This hypothesis is especially supported by the numerous facts which prove the readiness with which the leucocytes react against all kinds of poisons, microbial or other toxins, as well as against organic and mineral poisons, such as the alkaloids and the arsenical combinations. However, in spite of so many data which speak in favour of the phagocytic origin of antitoxins, it has been impossible to support this view by rigorous facts easy of interpretation, such as those which science possesses in support of the phagocytic origin of fixatives.

The antitoxins have acquired a very great importance in the artificial cure of toxo-infective diseases, the aim in these cases being to paralyse the action of the toxins already produced by the micro-organisms and absorbed by the diseased animal. But their function is less in the protection against diseases where the object to be obtained is a reaction against the micro-organisms before these are able to inundate the animal with their toxic secretions. It is for this reason that the immunity against toxins must, in the study of immunity, occupy a less preponderant place than does the immunity against micro-organisms.

As the micro-organisms placed in the refractory animal ultimately undergo a digestion by chemical substances elaborated by the phagocytes, so also the toxins undergo a chemical modification due to the presence of substances in the production of which the living elements of the animal play a large part. The direct action of antitoxins on the toxins, so well demonstrated, especially by Ehrlich’s investigations, does not, however, exclude the intervention of living cells, which, though sometimes not very manifest, is in other cases very marked.

[Sidenote: [587]]

The reaction of the living elements against the microbial toxins and their allies leads to the production, and even the over-production of antitoxins. According to Ehrlich, these elements are the receptors, or side-chains, which, to a certain extent, pre-exist in the cells which are capable of elaborating the antitoxins. On entering into combination with the toxin molecules, the side-chains, which are indispensable for the nutrition of the cells, are reproduced in very large numbers. After having saturated, so to speak, the productive elements of the antitoxin, the superfluous side-chains escape from the cell and pass into the plasmas of the body fluids. This theory may be brought into harmony with the other theory, which maintains that certain elements of the animal, capable of acting on the complex molecules of microbial toxins and their allies, produce special soluble ferments, which digest the toxins whose introduction frequently excites the hypersecretion of the ferments. Here we have something similar to the hypersecretion, by the glands of the stomach, of pepsin, a part of which passes into the blood in order to escape with the urine.

According to Ehrlich’s theory, the antitoxins are only capable of neutralising the injurious action of toxins when the former are found dissolved in the body fluids. The same receptors which fix the toxins in the plasmas and thus prevent them from reaching the susceptible elements, bring about an opposite result when they are found inside the cells. In this latter case, the receptors, owing to their great affinity for the toxins, attract them and allow them to pass into the cells, in this way aiding the dangerous function of the toxophore group.

This is an ingenious idea, conceived to bring into harmony a certain number of observed facts. In the present state of our knowledge it cannot be subjected to rigorous experimental test. Many well-established facts, however, are not in complete accord with this hypothesis. According to it the antitoxic immunity resides exclusively in the body fluids; the living cells, instead of acquiring immunity, become more and more susceptible. Under these conditions it is difficult to conceive of an immunity against poisons of the simplest organisms; nevertheless, this certainly exists. A plasmodium, which becomes adapted to all kinds of toxic substances, acquires an immunity against them, and this is due to changes taking place in the living elements; it is not the result of modifications in the toxic fluids which bathe them. This biological adaptation is observed in the case of physical factors which may interfere with the life of these primitive organisms.

On the other hand, it must be accepted that the living cells of a complicated and higher organism may also acquire immunity against toxins. The first example of this kind was shown in relation to the red blood corpuscles of mammals vaccinated against the toxic serum of the eel. Whilst the body fluids of immunised rabbits become antitoxic, their red blood corpuscles, when completely freed from the serum, in certain cases resist the action of the eel’s serum. It must be admitted that in this example we have an acquired immunity of the cells similar to that met with in lower organisms.

[Sidenote: [588]]

A second example of the immunity of the red corpuscles was observed by Ehrlich and Morgenroth in goats prepared by injections of the blood of other individuals of the same species. In this case, according to these writers, no co-operation by antitoxin is met with. The body fluids of the goats do not become capable of neutralising the toxin of the haemolytic serum, whilst the red corpuscles themselves acquire an immunity against this toxin, an immunity entirely cellular. Ehrlich attempted to penetrate into the essential mechanism of the resistance of the red blood corpuscles on the supposition that these corpuscles, instead of reproducing their receptors, as when there is production of antitoxin, get rid of them entirely. Deprived of receptors, they can no longer be affected by the haemolytic cytase which, as Ehrlich maintains, only penetrates into the red corpuscles owing to the affinity of the intermediate substance (fixative) for the receptor. This hypothesis of the mechanism of acquired cellular immunity scarcely accords with the hypothesis of the special function attributed to the receptors in the nutrition of the living elements.

Cellular immunity can be most easily demonstrated in relation to the red corpuscles of the blood, as these elements are very numerous and are capable of being isolated and freed from the fluid in which they are bathed. For this reason, science does not as yet possess sufficiently exact data on the immunity of other cells in higher animals. Many facts, however, indicate that such immunity does exist. There are, indeed, living elements which only acquire immunity with great difficulty and very slowly. Such are the nerve cells, elements which are specially susceptible. Von Behring has strongly insisted on the fact that in animals subjected to repeated injections of bacterial toxins, the nerve centres not only do not become accustomed to their injurious action, but even acquire a hypersusceptibility which is often very great. The observation is perfectly accurate, but it is none the less true that this period of exaggerated susceptibility is followed by another, during which the susceptibility becomes less marked and ends by giving place to a true adaptation. We are, therefore, compelled to accept the fact that even the nerve cells are no exception to the general rule, but are able to acquire a diminished susceptibility to a poison.

[Sidenote: [589]]

Several facts of another series confirm this conclusion. In the study of the action of the nervous system one frequently has occasion to observe instances of adaptation. I will cite as an example the adaptation of animals to spinal concussion studied by Lépine[922]. By percussing the lumbar region of rabbits and guinea-pigs we may induce in them an immediate paraplegia. This is transitory, and lasts at most for a few hours. The phenomenon may be reproduced several times in the same animal. “But,” remarks Lépine, “when these experiments are continued for several days or several weeks, striking always at the same level, we soon observe that the resistance of the animals to the blows increases very rapidly, and that excitations which, in normal animals, produce paraplegias of several hours’ duration, produce no effect upon those which have been under experiment for several days.” We have in this example a real adaptation of the spinal region when subjected to concussion.

Similar facts are known to everyone as an experience of daily life. We can become habituated more or less easily to all kinds of violent sensations. Light and very intense noises which, at first, excite exaggerated reflex actions are ultimately perceived without setting up the least movement. Even in the psychical sphere habit dulls painful feelings, and it is very probable that a whole gamut of adaptation, starting from unicellular organisms which accustom themselves to live in an unsuitable medium, up to cultured human beings who habituate themselves to a disbelief in human justice, will be found to rest upon one and the same fundamental property of living matter.

[Sidenote: [590]]

Regarded from this point of view, immunity becomes a very general phenomenon, passing far beyond the resistance offered by the animal to infective diseases. After all is said and done, it invariably reduces itself to that cellular susceptibility [irritability] which governs so many of the vital phenomena in plants and in animals. It is this susceptibility which impels the branch towards the light and the root towards the ground, and which guides the spermatozoon towards the ovum. From the very commencement of embryonic life the cells derived from the segmentation of the egg exhibit a marked susceptibility. Wilhelm Roux[923] observed that the earliest cells of the frog embryo, if they are separated by artificial intervention, guided by their positive chemiotaxis again come together. In the formation of the tissues cellular susceptibility plays an important undoubted rôle. The prolongations of the nerve cells direct themselves towards the organs of sense or towards the muscular fibres, according to their specific susceptibility[924]. The mother-cells of the capillary vessels are also guided by susceptibility, when they go towards a new-formed tissue, or when they approach one another and come together in order to form a vascular loop.

The phenomena of the organism which bear the sharpest impress of their physical and chemical nature, also come under the influence of cellular “sensations.” Thus, in gastro-intestinal digestion, the secretion of the active juice is subordinated to the control of the nerve centres and even of the psychic centres. The sight of various kinds of food stimulates, unconsciously, by reflex action the activity of different digestive glands. In the same way the contraction of the contents of the cells of a plant subjected to plasmolysis, brings about the secretion of acid in order to augment the osmotic pressure.

Susceptibility, whose part is so great in the phenomena of immunity, taken as a whole, is a general property of living beings, regulated by a common law. Thus, in the chemiotaxis of the lowest unicellular organisms, as in the movements and the osmotic reaction of plants, there is manifested the same psycho-physical law of Weber-Fechner which regulates our own sensations.

[Sidenote: [591]]

All cells are able, by modifying their function under the direction of susceptibility, to adapt themselves to changes in the surrounding conditions. All living elements are able, therefore, to acquire a certain degree of immunity. But, amongst all the cells of the animal body, the elements which have retained most independence—the phagocytes—most easily and first acquire immunity to infective diseases. These are the cells which betake themselves to situations where micro-organisms and their poisons make their appearance, and which manifest a reaction against them. The phagocytes of the immune organism ingest and destroy micro-organisms and absorb toxins and other poisons. The final act of the reaction of the phagocytes is constituted by the chemical or chemico-physical processes concerned in the digestion of the micro-organisms, with the help of cytases, assisted by the fixatives; in the defence offered against poisons the phagocytes must also exert a chemical action. Before these phenomena come into play, however, the phagocytes manifest phenomena which are purely biological, such as the perception of chemiotactic and other sensations, the migration towards menaced situations, the ingestion of micro-organisms and the absorption of toxins, and finally the secretion of substances to be utilised in intracellular digestion.

The immunity in infective diseases presents itself, therefore, as a section of cellular physiology, and especially as a phenomenon concerned in the absorption of micro-organisms. This absorption being carried out by an act of intracellular digestion, the study of immunity comes into the chapter on digestion regarded from the general point of view.

As in the struggle of the body of the animal against infective agents the phagocytes play the principal part, it happens that in certain diseases the micro-organisms in order to manifest their morbific effect must be protected from the attacks of these defensive cells. It is for this reason that the cholera vibrio, which is not very injurious when introduced below the skin of the human subject, becomes very formidable when it succeeds in gaining access to the digestive canal. Incapable of maintaining a struggle against the phagocytes, the vibrio is able to overcome in the stomach and in the intestines without difficulty the obstacles which it here meets with. It is for this reason that the channel of entrance of the micro-organisms at times plays such a prominent rôle in immunity against infective diseases.

The question is often asked whether a theoretical study of immunity is capable of rendering service in the search for means of conferring immunity on the animal. It must not be forgotten that theory and practice frequently march side by side, but that sometimes they advance without very much regard for each other. Thus the first preventive inoculations against snake-bite, small-pox, and pleuropneumonia, attempted by laymen were evidently made independently of any theoretical ideas of any kind, but were guided by the purest empiricism. On the other hand, the theoretical researches on the nature and origin of ferments led to the discovery of vaccinations by means of micro-organisms and microbic products which have rendered immense services to practical medicine.

[Sidenote: [592]]

[Sidenote: [593]]

The discovery of antitoxins, so rich in practical applications, was influenced by theoretical researches on the mechanism of immunity. Von Behring began his important series of investigations on this subject with the study of the immunity of rats against the anthrax bacillus. It did not suggest itself to anyone to suppose that this question could have the slightest immediate practical interest; nevertheless, starting from this investigation, von Behring, after giving up the theory of the bactericidal property of the body fluids as a cause of immunity, advanced, step by step, to the discovery of the antitoxic power of the serums. When a study of the properties of the blood of animals treated with the red corpuscles of another species was commenced, no one would have suspected that these researches would end in the discovery of new methods for the recognition of human blood in medico-legal researches, or in the interests of hygiene for the determination of the source of a milk. The cellular theory of immunity is, as yet, of too recent date for us to claim the right to expect it to have amongst its assets methods for purely practical application. Nevertheless, it has already been found to be of service in the investigation of problems very closely affecting medical practice. Lord Lister, the greatest surgeon of the nineteenth century[925], asked himself how it was that wounds could heal “by first intention under circumstances before incomprehensible. Complete primary union was sometimes seen to take place in wounds treated with water-dressing, that is to say, a piece of wet lint covered with a layer of oiled silk to keep it moist. This, though cleanly when applied, was invariably putrid within twenty-four hours. The layer of blood between the cut surfaces was thus exposed at the outlet of the wound to a most potent septic focus. How was it prevented from putrefying as it would have done under such influence if, instead of being between divided living tissues, it had been between plates of glass or other indifferent material?” “How were the bacteria of putrefaction kept from propagating in the decomposable film? Metchnikoff’s phagocytosis supplied the answer. The blood between the lips of the wound became rapidly peopled with phagocytes which kept guard against the putrefactive microbes and seized them as they endeavoured to enter. If phagocytosis was ever able to cope with septic microbes in so concentrated and intense a form, it could hardly fail to deal effectually with them in the very mitigated condition in which they are present in the air. We are thus strongly confirmed in our conclusion that the atmospheric dust may safely be disregarded in our operations; and Metchnikoff’s researches, while they have illumined the whole pathology of infective diseases, have beautifully completed the theory of antiseptic treatment in surgery.” (_Rep. Brit. Ass._, p. 27.)

We may even attempt to increase phagocytosis in surgical operations, especially in those on the peritoneal cavity, by there setting up an artificial aseptic inflammation, by means of various substances, innocuous in themselves, which attract a large number of leucocytes. In laboratory practice this method is in daily use for the purpose of increasing the resistance of an animal against intraperitoneal injections of various micro-organisms, and Durham has suggested the extension of the same method to human medicine. Certain surgeons have already made attempts in this direction.

The application of the cellular theory of immunity to researches on new micro-organisms of infective diseases has already been crowned with success. Nocard and Roux have attempted to cultivate in the animal body the virus of the pleuropneumonia of cattle. They selected the rabbit, an animal naturally refractory against this infection. On the supposition that, in this immunity, the phagocytes must play an important part as destroyers of the presumed micro-organisms, the idea suggested itself to them to withhold the virus from their voracity. With this object they filled sacs of collodion or of reed pith with pleuropneumonia virus, and introduced these sacs into the peritoneal cavity of rabbits. Some time after this operation these investigators were able to demonstrate in the contents of the sacs impregnated by the blood fluid of rabbits, immune animals, the development of specific micro-organisms, the smallest discovered up to the present. By means of cultivations of this micro-organism, obtained in suitable media, they worked out a method of vaccinating animals which, as mentioned in Chapter xv., has already begun to give good results in veterinary practice. This method has thus contributed to the prevention of diseases, a branch of knowledge which has made such great advances since medicine became an exact science under the inspiration of the discoveries and ideas of Pasteur.

[Sidenote: [594]]

Within a very short period immunity has been placed in possession not only of a host of medical ideas of the highest importance, but also of effective means of combating a whole series of maladies of the most formidable nature in man and the domestic animals. Science is far from having said its last word, but the advances already made are amply sufficient to dispel pessimism in so far as this has been suggested by the fear of diseases, and the feeling that we are powerless to struggle against them.

LIST OF AUTHORITIES QUOTED.

Abel, 443, 444, 445, 536

Abel. _See_ Loeffler

Achalme, 96

Achard and Bensaude, 264, 451

Adil Bey. _See_ Nicolle

Almquist, 178

Arloing, 264, 452

Arloing, Cornevin and Thomas, 471

Arnold, 411

Arthus, 95

Babes, 75, 348

Bach, 408, 410

Bail, 151, 185, 359

Balbiani, 13, 23, 133

Bardach, 150

Barthels, 507

Bary (de), 31, 32

Batzaroff, 411

Baumgarten, 138, 193, 521, 522, 524

Bayeux. _See_ Roger

Behring, 20, 152, 153, 205, 242, 290, 334, 335, 348, 350, 352, 367, 369, 374, 375, 378, 417, 526, 540, 561, 564, 567

Behring and Kitasato, 266, 344, 347, 354, 357, 493, 495

Behring and Kitashima, 42, 290, 368, 370, 373

Behring and Knorr, 355

Behring and Nissen, 211, 226, 526, 531

Bensaude, 439

Bensaude. _See_ Achard

Bernard, 59

Bernheim, 408

Bertrand. _See_ Phisalix

Besredka, 111, 191, 231, 263, 273, 318, 353, 390, 396

Besson, 170

Beumer and Peiper, 230

Biedl and Kraus, 44

Birch-Hirschfeld, 514

Bitter, 525

Bizzozero, 48, 177, 418, 428

Bjelooussoff, 55

Blagovestchensky, 323

Bolton, 205

Bordet, 22, 68, 79, 87, 90, 94, 95, 105, 107, 111, 112, 115, 123, 166, 179, 185, 193, 194, 196, 199, 215, 217, 223, 244, 251, 256, 257, 258, 282, 298, 302, 313, 320, 321, 535, 537

Bordet. _See_ Gengou

Bordet and Danysz, 467

Borrel, 478

Borrel. _See_ Roux, Yersin

Bouchard, 184, 232, 286, 323, 343, 427, 529

Bouchard and Charrin, 42, 528

Bourne, 327

Braun, 12

Brieger, 369

Brieger and Fränkel, 344

Briot, 109

Brücke, 66

Brunner, 45

Buchner, 87, 95, 184, 185, 188, 193, 255, 357, 362, 377, 412, 512, 527, 528, 530, 539, 540

Cahanescu, 430

Calmette, 334, 339, 345, 346, 347, 348, 358, 365, 386, 389, 395, 425, 489

Calmette. _See_ Yersin

Calmette and Deléarde, 365

Calmette and Salimbeni, 491

Camus and Gley, 110, 121, 360

Cantacuzène, 224, 225, 306

Castle. _See_ Davenport

Cattani, 446

Cayley, 484

Celakovsky, 30

Celli, 278

Centanni, 446

Chamberland, 470

Chamberland. _See_ Pasteur, Roux

Chantemesse, 259

Chantemesse and Widal, 230, 267, 319, 437

Chapeaux, 55, 56

Charrin, 232, 286, 287, 427, 428, 541

Charrin. _See_ Bouchard

Charrin and Gamaleia, 290, 343

Charrin and Gley, 446

Charrin and Lefèvre, 419

Charrin and Magnin, 427

Charrin and Roger, 232, 256

Chatenay, 393

Chauveau, 289, 446, 455, 511, 512

Chépowalnikoff, 59

Cherry. _See_ Martin

Cienkowski, 446

Cobbett, 205

Cohn, 23

Colombot. _See_ Sabrazès

Cornevin, 452

Cornevin. _See_ Arloing

Couch, 53

Courmont, 400

Courmont. _See_ Nicolas

Courmont and Doyon, 330, 386, 394

Curtis, 172

Czaplewski, 146, 147

Dallinger, 26

Danysz, 21, 25

Danysz. _See_ Bordet

Daremberg, 87

Darwin, 8

Davenport and Castle, 27

Davenport and Neal, 24

Decroly and Rousse, 396

Deléarde. _See_ Calmette

Delezenne, 61, 96, 98, 107, 116

Delezenne and Froin, 66

Delius and Kolle, 277

Dembinski, 147

Denys, 533

Denys and Havet, 151, 185

Denys and Kaisin, 151

Denys and Leclef, 243, 246, 283, 312

Denys and Marchand, 313

Denys and van de Velde, 359

Deutsch, 107, 293, 294, 537

Dienert, 26

Dieudonné, 139, 143, 147

Dinkelspiel. _See_ Nuttall

Doederlein, 429

Dönitz, 391

Dominici, 78

Dominici. _See_ Gilbert

Doyon. _See_ Courmont

Dreyer, 350

Duclaux, 26

Dujardin-Beaumetz, 478

Dungern (von), 91, 109, 123, 324

Durham, 256, 261, 569

Dzierzgowsky, 448, 449

Effront, 26

Ehrlich, 114, 115, 344, 346, 349, 356, 360, 361, 365, 378, 391, 392, 420, 449, 562, 563

Ehrlich and Hübener, 446, 452

Ehrlich and Lazarus, 76

Ehrlich and Morgenroth, 88, 89, 92, 95, 104, 114, 116, 124, 193, 194, 199, 268, 537, 538, 563

Ehrlich, Kossel and Wassermann, 496

Ehrlich and Wassermann, 356

Elmassian. _See_ Morax

Emden (van), 264

Emmerich, 237, 322, 527

Emmerich and di Mattei, 236, 527

Emmerich and Löw, 254

Emmerich and Mastbaum, 475

Ermengem, 420, 491

Errera, 39

Escherich. _See_ Klemensiewicz

Faber (Knud), 344

Fahrenholtz, 138

Fehleisen, 434

Fermi and Pernossi, 109

Ferran, 480

Fischer, 193, 213, 253

Fischl and Wunschheim, 445

Fleck, 413

Flügge, 43, 184, 525, 540

Fodor, 184, 525

Foerster, 380

Fontana, 333

Forssmann, 565

Frank, 35, 154, 542

Fränkel, 344, 347, 499, 534

Fränkel. _See_ Brieger

Fränkel and Sobernheim, 268

Frantzius, 425

Fraser, 345, 425

Frédéricq, 55, 57

Freudenreich, 323

Freund, Grosz and Jelinek, 365

Froin. _See_ Delezenne

Funck, 267, 319, 320, 456

Galeotti. _See_ Lustig

Gamaleia, 419

Gamaleia. _See_ Charrin

Garnier, 220, 304

Gaule, 515

Gautier, 400

Gengou, 19, 20, 146, 151, 157, 185, 190, 203, 242, 252, 255, 260, 264, 308, 543

Gengou and Bordet, 190

Geret. _See_ Hahn

Gheorghiewsky, 210, 234, 236, 261, 269, 301, 307, 359

Gibier, 137

Giessler, 37

Gilbert and Dominici, 424

Gilkinet, 172

Gley. _See_ Camus, Charrin

Glogner, 434

Goldschmidt, 411

Gottstein, 499

Gramatschikoff, 412

Grancher. _See_ Pasteur

Grawitz, 513, 515

Griffon. _See_ Landouzy

Grosz. _See_ Freund

Gruber, 224, 256, 262, 542

Gscheidlen. _See_ Traube

Guarnieri, 455

Guinon. _See_ Voisin

Günther, 541

Haeckel, 517

Haffkine, 480, 486–488

Hafkine, 17

Hahn, 188, 190

Hahn and Geret, 197

Hankin, 156, 187

Hardy. _See_ Kanthack

Harnack, 337

Häser, 507

Havet. _See_ Denys

Hayem, 47, 514

Hegeler, 196

Herbst, 565

Héricourt. _See_ Richet

Herzen, 62

Hess, 144, 149, 524

Hewlett. _See_ Thomson

Heymans. _See_ Lang

Heymans and Masoin, 396

Hildebrandt, 109, 119, 412

Himmel, 182

Hippocrates, 342

Hirsch and Mehring, 64

Hoffmann and Recklinghausen, 46

Horvath, 337

Hübener. _See_ Ehrlich

Hudalo, 436

Hueppe, 254

Hugenschmidt, 415

Issaeff, 219, 262, 287, 318, 320, 441

Issaeff. _See_ Pfeiffer

Jakowski, 42

Jeanselme, 411

Jelinek. _See_ Freund

Jenner, 507

Jetter, 193

Jona, 172

Joubert. _See_ Pasteur

Kaisin. _See_ Denys

Kanthack, 360, 542

Kanthack and Hardy, 185

Karlinsky, 134, 260

Kempner and Schepilewsky, 387

Kempner. _See_ Rabinowitsch

Kilborne. _See_ Smith

Kitasato. _See_ Behring

Kitashima. _See_ Behring

Klebs, 514

Klecki (von), 44

Klein, 324

Klemensiewicz and Escherich, 443

Klemperer, 271, 356, 411, 441, 449

Klipstein, 170

Knorr, 361, 362, 370, 375, 378, 383, 392, 443

Knorr. _See_ Behring

Koch, 137, 247, 278, 279, 283, 419, 425, 434, 436, 466, 514, 529

Kolle and Turner, 466, 467

Kolle. _See_ Delius, Pfeiffer

Kondratieff, 365

Kossel, 110, 121, 183

Kossel. _See_ Ehrlich

Kossiakoff, 25

Kovalevsky, 41, 133, 134, 209

Krafft-Ebing, 436

Krajouchkine, 465

Kraus and Seng, 258

Kraus. _See_ Biedl

Kretz, 371

Krikliwy, 46

Krompecher, 83

Krönig. _See_ Menge

Krukenberg, 30, 49, 55

Kübler, 458

Kupffer, 75

Kuprianow, 204, 340

Kurt, 499

Laehr, 413

Landouzy and Griffon, 451

Landsteiner, 100

Lang, Heymans and Masoin, 363

Langhans, 73, 84

Laschtschenko, 188

Laurent, 33, 35, 86

Laveran and Mesnil, 173, 248, 316

Lazarus, 272, 441

Lazarus. _See_ Ehrlich

Leber, 79, 96

Leclainche, 475, 476

Leclainche. _See_ Nocard

Leclainche and Vallée, 107, 171, 472, 523

Leclef. _See_ Denys

Le Dantec, 13

Lefèvre. _See_ Charrin

Leishman. _See_ Wright

Leo and Senator, 66

Lépine, 564

Lermoyez. _See_ Wurtz

Lesage, 47

Le Sourd. _See_ Widal

Leube, 67

Levaditi, 223

Levin, 159

Lewes, 53

Lewin, 337, 338

Lignières, 247, 279

Lindemann, 68

Lingelsheim, 193, 244, 312

Lister, 521, 530, 568

Loeffler, 7, 283, 513

Loeffler and Abel, 267

Löhr, 500

Lombard, 396

London, 94

Lorenz, 475

Löw. _See_ Emmerich

Lubarsch, 141, 151, 184, 529

Lustig and Galeotti, 490

Madsen, 349, 350

Madsen. _See_ Salomonsen

Magnin. _See_ Charrin

Maksutow. _See_ Pawlowsky

Malm, 149

Manfredi, 428

Mankowski. _See_ Podwyssozki

Marchand, 167

Marchand. _See_ Denys

Marchoux, 240, 276, 309, 311

Marie, 331, 382, 465

Marinesco, 75

Marmorek, 243, 312

Martel, 150, 159

Martin and Cherry, 361

Marx, 465, 476, 497

Marx. _See_ Pfeiffer

Masoin. _See_ Heymans, Lang

Massart, 34, 38, 39, 79, 281

Mastbaum. _See_ Emmerich

Mattei (di). _See_ Emmerich

Maupas, 16

Mehring. _See_ Hirsch

Melkich. _See_ Sawtchenko

Mendez, 470

Menge and Krönig, 429, 430

Mesnil, 55, 75, 78, 135, 139, 141, 143, 188, 209, 221, 238, 262, 270, 305, 307, 527

Mesnil. _See_ Laveran

Metchnikoff, 31, 55, 69, 70, 73, 100, 101, 116, 131, 137, 138, 146, 149, 151, 153, 154, 156, 160, 163, 180, 181, 185, 214, 221, 227, 237, 239, 241, 256, 259, 266, 271, 275, 286, 287, 290, 302, 304, 311, 377, 382, 385, 393, 396, 405, 426, 441, 520, 521, 522, 531, 532, 534

Metchnikoff (Mme), 20, 159, 193

Métin, 44

Miller, 414, 415, 418

Mitchell, 423

Morax and Elmassian, 409

Morgenroth, 109, 119, 331

Morgenroth. _See_ Ehrlich

Morishima, 390

Morse, 412

Mouton, 15

Moxter, 101, 185, 199

Müller, 17, 89, 114, 233

Myers, 68, 107

Myers. _See_ Stephens

Neal. _See_ Davenport

Néfédieff, 68

Neisser, 194, 196

Neisser and Wechsberg, 205, 298, 349, 359

Nencki, 419, 424, 427

Nencki and Sieber, 109, 355

Nencki, Sieber and Wyznikiewicz, 468

Netter, 503

Nicolas and Courmont, 353

Nicolas, Courmont and Prat, 353

Nicolle and Adil Bey, 279, 468

Nikanoroff, 348

Nissen. _See_ Behring

Nittis (de), 277, 288

Nocard, 148, 279, 494

Nocard and Leclainche, 461

Nocard and Roux, 130, 466, 478, 479, 569

Nolf, 94, 96

Nowakowski, 12

Nuttall, 107, 138, 150, 184, 192, 525, 527

Nuttall and Dinkelspiel, 107

Oken, 337

Opitz, 43, 44

Oppel, 231

Orlowski, 443, 444

Pagel, 507

Panum, 514

Pasteur, 2, 181, 208, 288, 322, 477, 508, 510, 511, 569

Pasteur, Chamberland and Roux, 469

Pasteur and Joubert, 144

Pasteur, Roux and Grancher, 208

Pasteur and Thuillier, 283, 473

Patella, 97

Pawloff, 59, 62, 65, 427

Pawlowsky, 44, 323

Pawlowsky and Maksutow, 348

Peiper. _See_ Beumer

Péré, 26

Pernossi. _See_ Fermi

Petruschky, 138

Pfaundler, 259

Pfeffer, 27, 38, 79

Pfeiffer, 130, 165, 185, 219, 221, 267, 269, 271, 277, 290, 301, 303, 320, 365, 438, 455, 532, 533, 534

Pfeiffer and Issaeff, 212, 533

Pfeiffer and Kolle, 230, 267, 274, 302, 319, 481

Pfeiffer and Marx, 185, 264, 291, 442

Pfeiffer and Proskauer, 253

Phisalix, 387, 425

Phisalix and Bertrand, 333, 337, 338, 345, 347

Pierallini, 218, 219

Plato, 181

Podwyssozki, 77

Podwyssozki and Mankowski, 456

Pollender, 11

Ponfick, 46

Portier, 96

Prat. _See_ Nicolas

Preobrajensky, 431

Prevôt, 374

Proskauer. _See_ Pfeiffer

Rabinowitsch and Kempner, 248, 316

Ransom, 351, 379, 382, 389

Ranvier, 409

Rauchfuss, 501

Recklinghausen (von), 514

Recklinghausen. _See_ Hoffmann

Remlinger, 447, 450

Répin, 420

Rhumbler, 15

Ribbert, 413, 428, 524

Richet and Héricourt, 266, 532

Rindfleisch, 514

Rochebrune (de), 506

Röden, 109

Roger, 243, 257, 287

Roger. _See_ Charrin

Roger and Bayeux, 414

Rogers, 468

Römer, 401

Roncali, 170

Roser, 515, 516

Ross, 129

Rossbach, 95

Rouget. _See_ Vaillard

Rousse. _See_ Decroly

Roux, 156, 347, 358, 497, 498, 530

Roux. _See_ Nocard, Pasteur

Roux (W.), 565

Roux and Borrel, 340, 383, 386, 391

Roux and Chamberland, 530

Roux and Vaillard, 347, 355, 356, 357, 367, 379, 432, 493

Roux and Yersin, 343

Ruffer, 427, 428, 523

Rysselberghe (van), 37, 39

Sabouraud, 406

Sabrazès and Colombot, 135

Sakharoff, 160, 177

Salimbeni, 222, 245, 261, 478

Salimbeni. _See_ Calmette

Salmon, 455

Salomon, 418

Salomonsen, 19

Salomonsen and Madsen, 346, 356, 370, 379, 380

Saltykoff, 272

Samoïloff, 63

Sanarelli, 262, 287, 415

Sanchez-Toledo, 170

Sarassewitch, 195

Sawtchenko, 21, 99, 156, 162, 227, 240, 260, 270

Sawtchenko and Melkich, 162, 227

Schattenfroh, 172, 188, 196

Schepilewsky. _See_ Kempner

Schiff, 62

Schimmelbusch, 42

Schoumow-Simanowski. _See_ Sieber

Schumacher, 451

Schütz, 283, 422

Schütz. _See_ Voges

Schütze, 107, 114

Schütze. _See_ Wassermann

Sclavo, 276, 310

Selander, 290

Senator. _See_ Leo

Seng. _See_ Kraus

Serpa Pinto, 506

Shaffer, 42

Sicard. _See_ Widal

Sieber. _See_ Nencki

Sieber and Schoumow-Simanowski, 419, 424

Skchiwan, 172

Slateano, 277

Slawyk, 501

Smith, 259

Smith and Kilborne, 247, 279

Sobernheim, 242, 276, 310, 441

Sobernheim. _See_ Fränkel

Soudakewitch, 75

Soulié, 460

Stadelmann, 97

Stahl, 30, 31

Stein, 12

Stephens and Myers, 360

Stern, 419, 542

Sticker, 411

Stöhr, 428

Stoudensky, 388, 394

Strassman, 499

Straus and Wurz, 417, 418

Stroganoff, 429

Takaki. _See_ Wassermann

Talma, 424

Tarassewitch, 86, 87, 98, 99

Tchistovitch, 68, 75, 106, 110, 120, 121, 122, 283, 413

Thiltges, 145, 147

Thomas, 452

Thomas. _See_ Arloing

Thomson and Hewlett, 410

Thuillier. _See_ Pasteur

Tizzoni, 357, 446

Tooth, 484

Torday, 498

Toussaint, 509

Trapeznikoff, 139, 145

Traube and Gscheidlen, 184

Trommsdorff, 23, 189

Trumpp, 261

Turner. _See_ Kolle

Uhlenhuth, 68, 107

Vaillard, 204, 335, 347, 356, 372, 447

Vaillard. _See_ Roux

Vaillard and Rouget, 169, 170

Vaillard and Vincent, 169, 394

Vallée, 289, 425

Vallée. _See_ Leclainche

Velde (van de). _See_ Denys

Viala, 465

Vincent. _See_ Vaillard

Vincenzi, 443

Virchow, 48, 519, 524

Voges, 238, 272

Voges and Schütz, 475

Voisin and Guinon, 502

Vries (de), 35

Wagner, 144

Waldeyer, 514

Wallgren, 168

Walter, 64

Walz, 193

Warlomont, 456

Washbourn, 485

Wassermann, 115, 191, 205, 231, 234, 273, 317, 318, 319, 322, 351, 358, 371, 441

Wassermann. _See_ Ehrlich

Wassermann and Schütze, 107

Wassermann and Takaki, 292, 382, 394

Wassilieff, 65

Watson-Cheyne, 323

Weber-Fechner, 27, 38, 566

Wechsberg. _See_ Neisser

Wecker, 502

Wehrmann, 417, 419, 424

Weichhardt, 118, 124

Weigert, 363, 379, 399, 424, 523

Werigo, 281

Wernicke, 276, 446, 447

Widal, 257

Widal. _See_ Chantemesse

Widal and Le Sourd, 439

Widal and Sicard, 260, 261, 264, 439, 440, 450

Wood. _See_ Woodhead

Woodhead and Wood, 323

Wright, 482

Wright and Leishman, 482

Wunschheim. _See_ Fischl

Wurtz and Lermoyez, 410

Wurz. _See_ Straus

Wyssokowitch, 43, 412, 485

Wyznikiewicz. _See_ Nencki

Yersin, 468

Yersin. _See_ Roux

Yersin, Borrel and Calmette, 487

Zabolotny, 95

Zeliony. _See_ Zilberberg

Ziegler, 519, 522

Zilberberg and Zeliony, 282

INDEX.

Abrin, 344, 345, 346, 401

Abrin intoxication, action of body fluids on, 365, 420; leucocytic reaction against, 393, 401

Absorption. _See_ Resorption

Acari, mechanical action of, 3

Acclimatisation. _See_ Adaptation

Acid reaction inside phagocytes, 83, 182

Acid, secretion of, in osmosis, 37, 566

Acidophile microbian flora of stomach, 418

Actinians, digestion in, 53, 82, 85

Actinodiastase, 57, 197

_Actinophrys_, 14, 18

Adaptation. _See also_ Immunity

Adaptation to toxic substances, 21–27, 30, 342, 390; to saline solutions, 23, 30, 515; to physical conditions, 26, 30–31; of plasmodia to arsenious acid, 31; of pancreatic secretion to kind of food, 64, 65; of phagocytes to destroy micro-organisms, 281, 558, 566; of animals to spinal concussion, etc., 564; of cells, 513

Addiment (syn. Complement), 95

Agglutination in natural immunity, 202, 206; and phagocytosis, 202, 242, 245; in the diagnosis of typhoid, 256, 257, 261, 439; its mechanism, 257; of red blood corpuscles by serums, 258; of red blood corpuscles by ricin, 360; does not prevent growth of micro-organisms, 262

Agglutinative power, transmission by heredity or suckling, 450; not developed parallel with bactericidal power, 483

Agglutinins in immunity, 242, 245, 256–265, 295, 542, 559; characters of, 255, 559; origin of, in immunised animal, 263–265, 294; difference between fixatives and, 255, 265, 559; not the same as protective substances, 268, 269, 294

Albuminoid substances, resorption of, 106–127

Alexins. _See also_ Cytases

Alexins, 87–95, 96, 98, 184, 193, 255, 528, 533, 535, 539

Alimentary canal. _See_ Intestine

Alizarin sulpho-acid, 13, 83, 183

Alligator, 77, 143, 332, 401

Amboceptors (syn. fixatives), 91, 93, 297, 557

_Ammocoetes_, 77, 78

_Amoeba_, 14, 18, 23, 547, 549

Amoebo-diastase, 16, 197, 549

Amoeboid cells. _See_ Leucocytes and Phagocytes

Amphibia. _See_ Frog, Axolotl

Amylase, 95; in the urine, 65

_Androctonus._ _See_ Scorpion

_Anopheles_ and malaria, 129

Antagonism between certain bacteria, 323

Anthrax, 11, 20, 21, 25, 41, 46, 180; immunity of dog against, 149–151, 242; acquired immunity of _Scolopendra_ against, 209; natural immunity of white rat against, 526; protective serums against, 20, 276, 309–311; phagolysis in acquired immunity against, 280; immunisation against, by means of other bacteria, 323; infection by inhalation, 412; by ingestion, 423; immunity against, transmitted to offspring, 445, 447; vaccinations against, 208, 241, 468–471; method, 470; statistics, 471; vaccination against, by heated anthrax blood, 507; vaccines against, 208, 470, 509; phagocytosis in, 521, 523

Anthrax bacillus, action on rabies, 150; bactericidal action of blood serums on, 20, 146, 150, 151, 156, 157, 240; increasing the virulence of, 150; attenuation of, 208, 288; eosinophile transformation in, 198; protective thickening of bacterial membrane in, 242; agglutination of, 203, 242, 260, 264; natural immunity against, 132–140, 143, 147, 149–159, 511, 512; acquired immunity against, 239–242, 276, 277; antagonism between, and certain bacteria, 323; fate of, in Algerian sheep, 512; destruction of, by defibrinated blood, 525

Anthrax, symptomatic: immunity against bacilli of, 171; heredity of immunity against, 452; vaccinations against, 471–473; phagocytosis in, 523

Antiabrin, 401

Anti-arsenic serum, 390

Anticytases, 112

Anticytase serum, 115, 371

Anticytotoxins, 110, 118, 122, 127, 360

Antidiastase, 109

Antidiastatic serums, 361

Anti-enzymes, 109

Antifixative, 112

Antihaemolysins, 111

Antihaemotoxins, 111, 119, 122

Anti-infective. _See_ Protective

Antileucocidin, 359

Antineurotoxin, 116

Antirennet, 109

Antiricin, 360

Antisepsis, Nature replaces by asepsis, 432

Antiseptics. _See also_ Toxins and Adaptation

Antiseptics and foods, 26

Antiseptic action of the gastric juice, 417

Antispermofixative, 124

Antispermotoxins, 116, 122–126

Antistreptococcic serum, 243–245

Antitetanin, nervous origin of, 390

Antitoxic. _See also_ Protective

Antitoxic unit of Ehrlich, 373, 496; action of non-specific and normal serums and of broth, 365; function of the saliva, 417; function of pepsin and other digestive ferments, 419, 424; action of intestinal flora, 427; property of the body fluids, 531 (_see_ Body fluids, Serums); power of the blood of new-born children, 445

Antitoxins, natural, in normal blood, 111, 204, 444; rarity in body fluids in natural immunity, 204, 532, 533; development of, during immunisation, 354; properties of, 354; present in various fluids of immunised animal, 355, 531; mode of action of, on toxins, 356–362, 371; conditions acting in mixtures of, with toxins, 362; immunity against toxins not in direct constant ratio to amount of, 367–376; effect of using serum from same species, 379; hypothesis as to nature and origin of, 377–402, 562; probable part played by phagocytes in production of, 400–402; rapid regeneration of, after bleeding, 379; augmentation in production of, by pilocarpin, 380; transmission of, by milk to offspring, 449; analogy of, with fixatives, 561; hypersecretion of, 563

Antivenomous property of blood of scorpion, 328; action of serums, 334, 338; serum, action of, 334, 338, 358, 360

Aqueous humour, bactericidal action of, 184, 192; in immunised animals contains no fixative, 217, 222; in immunised animals contains antitoxin, 355

Arsenic; adaptation to, 31, 343, 390; protective serum against, 390; leucocytic reaction against, 396–399; as a remedy against microbial disease, 513

Arsenic acid, action of, on anthrax bacillus, 25

Arsenious acid, adaptation of plasmodia to, 31

Arthropoda. _See_ Clothes-moth, Crayfish, Crustacea, _Daphnia_, _Scolopendra_, Scorpion, Spider, Tick

Arthrospores of Hueppe, 254

_Ascaris_, poor microbian flora in intestine of, 421; phagocytic organs of, 547

Asepsis is Nature’s method, 432

Aspergillosis, 2, 4. _See also_ Mycoses

Atrophic diseases, probably due to a parasite, 3

Atropin, reaction of rabbit and guinea-pig to, 395, 396

Attenuation. _See also_ Vaccination, Vaccines

Attenuation of micro-organisms and viruses, discovery and application of, 208, 247, 288, 508; of micro-organisms by the fluids of immunised animals, 286–289; of toxins, 344

Autodigestion in yeast, 197

Autospermotoxins, 101

Autotoxins, 104

Axolotl, susceptible to tetanus toxin, 330

Bacilli, anaerobic, natural immunity against, 169, 170

_Bacillus aërogenes_, agglutination in, 264

_Bacillus chauraei._ _See_ Anthrax symptomatic

_Bacillus coli_ attacks potato, 35; vaccination against, 267; transformation of, into granules, 198; modified growth on certain serums, 259

Bacillus of Doederlein, 429; of Kiel water, 408

_Bacillus pyocyaneus_, 42, 180, 254, 528; acquired immunity against, 210, 232–236, 301; Pfeiffer’s phenomenon in, 234, 307; special forms of growth in serums from vaccinated animals, 256; agglutination of, 261, 307; susceptibility to the toxins of, 290, 351; action of specific serum on, 307, 358; antagonistic to anthrax bacillus, 323; immunisation against toxin of, 351; a leucocidin from, 359; action of liver on toxin of, 427; heredity of immunity against toxin of, 446

_Bacillus ranicida_, 140

Bacteria. _See_ Micro-organisms

Bactericidal action of serum, influence of alkalinity or acidity on, 196; function of the tears, 408

Bactericidal property. _See also_ Body fluids, Humoral theory, Serums

Bactericidal property: in blood and other fluids, 20, 146, 150, 151, 156, 157, 184–193, 211, 226, 233, 238, 240, 241, 243, 244, 512, 525–531, 542, 554; of body fluids, theory of osmotic pressure, 193, 213; of extracts of glands and exudations, 195; of the saliva, 415; absence of, from the intestinal ferments, 424, 567; of serums, Wright’s method of testing, 483; does not develop parallel with agglutinative, 483; and immunity, absence of parallelism, 554

Bactericidal substance (alexin, complement, cytase): in blood and other fluids, 184–193, 534; source of, in body fluids, 185–193; theory of leucocytic secretions, 187–191; presence in body fluids due to phagolysis, 191; is of phagocytic origin, 185, 192; in body fluids, microphages source of, 187; not resistant to heat, 268; and so distinguished from protective substance, 268; Pfeiffer’s theory of, 534

Bacteriolysis. _See_ Micro-organisms, destruction of

Bacteriolysis, analogy between haemolysis and, 537

Bat, immunity against tetanus of hibernating, 339

Baumès-Colles’ law in syphilis, 436

Behring’s “normal serum,” 496

Bile, function of, 60; salts protective against snake venom, 388; protective function of, 424

_Bipinnaria_, 70, 518

Blastomycetes. _See also_ Yeast-cells

Blastomycetes, resistance of _Daphnia_ to, 131, 404, 520; fate of, in refractory organism, 172; acidophile, 418

Blood, pepsin in the, 66, 563; precipitins in the, 68, 106, 107, 568; fate of effusions of, 73; bactericidal power of, 184 (_see also_ Bactericidal, Serums); natural antitoxins in normal, 111, 204, 444; stimulant (protective) action of human, 271, 318; immunity conferred by maternal, 447; recognition of, in medico-legal research, 107, 568; from convalescents, protective power of, 437, 441, 443; agglutination of (_see_ Agglutination)

Blood corpuscles, resorption of red, 47, 50, 56, 57, 70, 72, 79–100, 537 (_see also_ Haemolysis); fixation of cytase by red, 194; agglutination of red, by serums, 258; agglutination of red, by ricin, 360

Body fluids. _See also_ Bactericidal, Blood, Humoral theory, Serums

Body fluids, natural immunity and the composition of, 128–131, 146; in natural immunity, absence of antitoxic property in, 204; bactericidal power of, 184–193, 512, 525–531, 542 (_see also_ Body fluids, Serums); antitoxic power of the, 204, 531, 533, 543; protective properties of, 266–280

_Boophilus bovis_, 247

Bordet’s sensibilising substance, 91, 199, 298, 535, 537, 557

Botulism, protective action of fats against toxin of, 387; action of digestive diastases on toxin of, 420

Bouchard’s theory of acquired immunity, 232, 286; of attenuating power of serums, 286–289

Bouillon de panse, 473

Bovidae, acquired immunity of, against Texas fever, 247, 279; protection of, against tetanus, 494; vaccination of, against rinderpest, 425, 466–468; against rabies, 466; against anthrax, 470; against symptomatic anthrax, 471; against pleuropneumonia, 477–479; ancient methods against pleuropneumonia in, 506

Broth as a protective fluid, 320, 321, 365

Buccal cavity, microbial products in the protection of the, 416; flora of, 414

Buchner’s theory of immunity, 512, 527

Calf lymph vaccine, method of preparation, 456

_Carassius._ _See_ Goldfish

Carmine, fixation of tetanus toxin by, 388, 394

Cattle. _See_ Bovidae

Cattle plague. _See_ Rinderpest

Cayman. _See_ Alligator

Cellular or histogenic immunity, 335, 336, 340, 563–565

Cellulosase, 86

Cerebral substance, action of emulsions of, on toxins, 386

Cerebral tetanus, 383, 391

Chemiotaxis. _See also_ Hyperleucocytosis, Susceptibility

Chemiotaxis in Infusoria, 19; in plasmodia of the Myxomycetes, 30; of duodenal mucous membrane, 64; of phagocytes, 79, 108, 133, 167, 177, 280; of leucocytes for rennet, &c., 119; positive, in segmentation-cells of frog embryo, 565

Cholera antibody (fixative), 253, 267, 292

Cholera, Asiatic, protective power of blood of convalescents from, 441; vaccinations against, 480–481

Cholera peritonitis, heredity of immunity against, 447, 448; immunity of guinea-pig against, 533

Cholera toxin, alligator resistant to, 333; immunisation against, 350; action of normal serum of goat on, 365

Cholera vibrio. _See also_ Pfeiffer’s phenomenon, Vibrios

Cholera vibrio, adaptation of, to bactericidal substance, 23; susceptibility of larva of Rhinoceros beetle to, 40, 133; immunity of frog against, 142; of guinea-pig against, 163, 533; extracellular destruction of, 165, 212 (_see also_ Pfeiffer’s phenomenon); eosinophile transformation in, 198; arthrospores of, 254; agglutination of, 261, 264; protective action of serums against, 268, 271, 318; of human blood against, 271, 318; immunity to, is not insusceptibility to its toxin, 290; origin of protective property against, 291; protective action of various fluids against, 320; antagonism between certain bacteria and, 324; in stomach, 419, 567; susceptible to acids _in vitro_, 419; in intestine, 423, 567; serum from animals immunised against, 532

Cholesterin. _See also_ Fats

Cholesterin, fixation of toxins by, 387; fixation of saponin by, 389

_Chytridium_, 12

Cicatrisation of plants, 34

Clasmatocytes, 78

Clavelée (la). _See_ Sheep-pox

Clavelisation against Sheep-pox, 460

Clothes-moths, micro-organisms absent from digestive canal of larvae of certain, 420

_Coccobacillus prodigiosus._ _See under Micrococcus_

Cockchafer larva, 70, 326

Complement of Ehrlich, 88, 91, 193, 251, 297

Complementoids of Ehrlich, 115

Concussion, spinal, adaptation to, 564

Conjunctiva, elimination of micro-organisms by the, 408; absorption of toxins by the, 409

Copula of P. Müller, 91

Cornea, protective resistance by the, 409

Crayfish, susceptible to certain toxins, 345; blood of, antitoxic against scorpion venom, 366; poor intestinal flora of, 421

Crickets and micro-organisms, 41, 133; natural immunity against toxins in, 329

Crustacea. _See_ Crayfish, _Daphnia_

Crustacea, protective function of integument of, 404

_Cyprinus._ _See_ Goldfish

Cytase of Laurent, 86

Cytases (syn. alexins, complements), 93, 98, 123; elaborated by phagocytes, 197, 252, 539, 549–556; thrown out into plasmas during phagolysis, 95, 99, 102, 197, 252, 551–554; bactericidal power of, 183, 184, 191, 193–198, 217 (_see also_ Bactericidal, Body fluids, Serums); unity or plurality of, in same serum, 193, 197; absorption of, 194, 200; two kinds of, macrocytase and microcytase, 195, 296, 549; characters of the, 197, 549; enzymes other than, in phagocytes, 197; in the immunised organism, 250–255, 296, 317, 554; presence or absence of, how determined, 253; Ehrlich’s and author’s views on, contrasted, 297; compared with fixatives, 555

Cytotoxins, 105 (note), 110, 116

_Daphnia_, resistance of, to Blastomycetes, 131, 404, 520

Darwin on the extinction of the elephant, 8

Dermis, arrest of micro-organisms in the, 406

Desmon (of London), 91

Diastases. _See_ Digestive ferments, Ferments

Digestion in the higher animals, 49, 59–65; psychical and nervous elements in, 62, 566; extracellular, by secreted juices, 49, 58, 62; the liver of the Mollusca as second organ of, 59; in the tissues, 67; and resorption closely related, 69, 85; by macrophagic organs, 85, 150

Digestion, intracellular. _See also_ Phagocytes, Phagocytosis, Resorption

Digestion, intracellular, 48, 85, 517, 518, 520; in the Protozoa, 13, 30, 49; in Planarians, 49, 71, 82; in Actinians, 53, 82, 85; in Sponges, 69, 517; transition from, to digestion by secreted juices, 49, 58

Digestive ferments, antitoxic function of, 424; action of, on toxin of botulism, 420

Diphtheria, 7, 41, 132, 204; antitoxic power of blood of convalescents from, 443; antitoxic power against, in blood of healthy persons, 444; and in blood of new-born children, 445; heredity of immunity against, 445, 447, 448; influence of anticytase serum on, 371; vaccinations against, 495–503; serum against, 495; standardisation and testing of this serum, 496–498; its protective and antitoxic powers do not develop in equal ratio, 497; its prophylactic use, 498–503; accidents during treatment, 499, 502; statistics, 500–503

Diphtheria toxin, increased susceptibility of immunised guinea-pig to, 290; natural immunity of rat and mouse against, 204, 339; natural immunity of frog against, 330; immunisation against, 344, 347, 349, 353; attenuation of, 344; preventive action of nucleohiston on, 365; action of, on brain of laboratory animals, 386; sets up local lesions in the conjunctiva, 409; pepsin destroys, 419

_Diplococcus pneumoniae._ _See_ Pneumococcus

Diseases, fear of, and pessimism, 1, 569; atrophic, probably due to a parasite, 3; mechanical element as etiological factor, 3; toxic element as etiological factor, 4; developed on the earth at a very early epoch, 8; and extinction of species, 8; infective, in multicellular plants, 29–39; set up by Fungi. _See_ Fungi

Dog, immunity of, against anthrax, 149–151, 242; action of anthrax bacillus on rabid, 150; immunity of, against streptococci, 167; naturally refractory against a staphylococcus, 266; bactericidal action of blood of, on anthrax bacillus, 150, 151, 156; digestion of gelatine by leucocytes of, 108; enterokynase in lymphoid organs of, 61; digestive fluids of, 62–65; disinfecting power of small intestine of, 422; phagocytosis in, 149, 151; haematozoon in, 279

Domestic animals, immunisation of, against disease. _See_ Bovidae, Dog, Goat, Horse, Pig, Sheep, Swine, Vaccines, Vaccinations

Dourine, 2, 247

_Drepanidium_, 515

Drugs, absorption of, by leucocytes, 400

Duodenum, chemiotaxis of mucous membrane of, 64

“Dust” cells, 75, 411–414

Eel’s serum. _See also_ Ichthyotoxin

Eel’s serum, toxic action of, 20, 111, 563; and precipitins, 68, 106

Effusions of blood, fate of, 73

Ehrlich’s neutral red reaction, 13, 83, 181; classification of leucocytes, 74, 76–78; theory of side-chains or receptors, 120, 381–384, 538, 557, 562–563; compared with theory of phagocytes, 296–299, 538, 558; “immunising unit,” 373, 496

Elephant, extinction of, 8

Elimination of micro-organisms from the body, 43, 46; by the epidermis, 406; by the conjunctiva, 408; by the nasal mucosa, 410

_Emys._ _See_ Turtle

Endo-enzymes, 197

Endotrypsin of yeast, 197

Enterokynase, 59, 98

Enzymes. _See_ Ferments

Eosinophile leucocytes, secretion by, in bacteriolysis, 187, 542

Eosinophile staining reaction, 198

Epidermis, exfoliation of the, 406

Ernst’s bacillus, immunity of frog against, 140

Erysipelas. _See_ Swine erysipelas

Erysipelas, immunity in, 434

Erysipelas streptococcus, protective action of, against anthrax, 323; its use in malignant tumours, 434

Excretion. _See also_ Elimination

Excretion in relation to micro-organisms, 43, 432; of pepsin in the urine, 65; of pepsin in the blood, 66, 563

Exfoliation of the epidermis, 406

Exudations, bactericidal power of, 185, 193, 195

Farcy, slow evolution of, 406

Fats, protective action of, against toxins, 387

Ferments. _See also_ Intestinal, Digestive, Fibrin-ferment, Gastric juice, Saliva, Trypsin

Ferments, Pasteur on the organised nature of, 2; soluble (diastases or enzymes), in digestion, 49, 55, 57, 108, 109, 197; antitoxic function of digestive, 424; phagocytic, 197, 549–559; hypersecretion of, 563

Fibrin ferment (plasmase), 95, 197, 550

Fishes. _See_ Goldfish

Fishes, phagocytosis in, 135

Fixatives (immunising body, or amboceptor, or sensibilising substance), 88, 92–95, 97, 98, 103–105, 199–202, 296; synonyms of, 91; analogy of, with enterokynase, 98; presence of, in plasmas, 103, 112–114, 217; in protective serums, 269, 438; in mesenteric glands, 98; in spermotoxins, 101; origin of, 103, 294, 537, 556–559; specificity of, 88, 105, 216, 251, 253, 296; rarity of, in normal fluids, 199–201, 250; method of determining whether present in a serum, 199; absent from aqueous humour of immunised animals, 217, 222, 251; in the immunised organism, 250–255; properties of, 251, 253, 255, 554; differ from agglutinative substances, 255, 265, 559; relation of, to phagocytosis, 291, 295; part played by, in Pfeiffer’s phenomenon, 251, 295; and protective substances closely connected, 269, 294, 295, 561; compared with cytases, 555; mechanism of action of, 557

Food substances, absorption of, by other channel than alimentary canal, 67

Foods and antiseptics, 26

Foreign bodies, fate of, in organism, 46, 52, 55, 56, 517

Formed elements, resorption of the, 47, 67–105

Fowl, immunity of, against anthrax, 144, 159; phagocytosis in, 144, 282; bactericidal action of plasma of, on anthrax, 146; blood serum of, and tetanus, 204; immunity of, against tetanus, 204; natural immunity of, against tetanus toxin, 335; influence of removal of parts of brain and cord on tetanus in, 384

Fowl cholera, infection of laboratory animals with, 181; vaccine against, 208; phagocytosis in, 282; action of exudations of fowls vaccinated against, 288; acquired immunity against, 288, 508; failure of bacillus of, to grow in certain media, 510

Friedländer’s bacillus prevents infection by anthrax, 323

Frog, phagocytosis in, 137, 142; immunity of, against anthrax, 137; against Ernst’s bacillus, 140; against bacillus of mouse septicaemia, 141; against cholera vibrio, 142; acquired immunity of, against pyocyanic disease, 210, 301; natural immunity of, against tetanus toxin, 330; against diphtheria toxin, 330; immunisation of, against abrin, 345; absorption of tetanus toxin by brain of, 386

Frog embryo, positive chemiotaxis in segmentation-cells of, 565

Fungi, diseases set up by, 2, 4, 18, 32, 131, 135, 404 (_see also_ Aspergillosis, Mycoses)

Galactose. _See_ Milk-sugar

Gamaleia’s vibrio. _See Vibrio metchnikovi_

Gastric juice, antiseptic action of, 417; psychic influence on, 63, 566. _See_ Pepsin

Gelatine, resorption of, 107

Gentilly bacillus. _See_ Pneumo-enteritis

Gerbil, tubercle in, 22, 183

Goat, action of normal serum of, on cholera toxin, 365; vaccination of, against rabies, 466; acquired immunity in, 563

Goldfish, 72, 135

Goose septicaemia. _See Spirochaete anserina_

“Greek method” of variolisation against small-pox, 507

Gruber’s theory of immunity, 256, 262

Guinea-pig, immunity of, against spirilla, 160, 162; against vibrios, 163, 211–227, 275, 287, 531, 533; against streptococci, 165; against tetanus bacillus, 169; against symptomatic anthrax, 171; against _Trypanosomata_, 173; acquired immunity against spirilla of recurrent fever, 227–230; against typhoid, 191, 230; against _Bacillus pyocyaneus_, 234–236; against anthrax, 276, 277; phagocytosis in, 162, 163, 166, 170, 223; hypersusceptibility of immunised, to diphtheria toxin, 290; protective power of serum of immunised, 293; effect of removal of spleen of, 293; antivenomous action of serum of, 338; immunisation of, against cholera toxin, 351; increasing natural susceptibility of, to toxins, 369, 370; reaction of, to atropin, 396

Haematopoietic organs. _See also_ Lymphoid organs

Haematopoietic organs as source of protective substance, 292–294

Haematozoa. _See_ _Piroplasma_, _Trypanosoma_

Haematozoon in dog closely allied to that of Texas fever, 279

Haemolysis. _See also_ Blood corpuscles, resorption of

Haemolysis, 79–100, 111, 112, 537; the two substances which act in, 88, 98, 538; analogy between bacteriolysis and, 537

Haemomacrophages, 76, 136

Haptophore atomic group in a toxin, 120, 350, 384

Hedgehog, natural immunity of, against poisons and venoms, 337

_Helix pomatia_, 70, 134

Heredity of immunity, 445–453, 513

_Herpestes._ _See_ Mongoose

Hibernation, effects on resistance to toxins, 339

_Hippocampus_, 135

Histogenic immunity, 336 (_see_ Immunity, cellular)

Hog cholera, resemblance of bacillus of, to that of pneumo-enteritis, 259; serum of animals vaccinated against, 260; agglutination in, 260; protective action of serums against, 272; susceptibility of vaccinated animals to the toxin, 290

Horse. _See also_ Diphtheria

Horse, acquired immunity against cholera vibrio, 222; against streptococci, 244, 245, 313; local reaction to tetanus toxin in, 352; immunised, with poor yield in antitoxin, 373, 375; reaction of, to one unit of toxin, 378; antitoxic power of serum of normal, 380; phagocytosis in, 245, 313; antivenomous action of serum of, 338; vaccination of, against rabies, 466; vaccination of, against anthrax, 470; protective serum against tetanus in, 493

Humoral phenomena in immunity, 184, 250, 290, 437–440, 525–531, 542, 543

Humoral theories of immunity, 184, 525–531, 542, 543; attempts to reconcile with theory of phagocytes, 539

Humours. _See_ Body fluids, Serums

Hyperleucocytosis. _See also_ Chemiotaxis

Hyperleucocytosis during immunisation, 352, 393

Hypersecretion, 563 (_see_ Receptors)

Hypersusceptibility to toxins in immunised animals, 290, 368–374, 564

Hyphomycetes, diseases caused by, 2

Hypopyon, pus of, 96

Ichthyotoxin, 110, 120, 121, 122, 326, 360 (_see also_ Eel’s serum)

Immunisation. _See_ Immunity, acquired, artificial and temporary, Vaccination

Immunisation against toxins, principal methods of, 345–350; by unmodified toxins, 345–346; by modified toxins, 347; by mixtures of toxin and antitoxin, 348; by toxones and toxoids, 349; phenomena produced during, 352–354

Immunising body of Ehrlich, 91, 251; unit of Ehrlich, 373, 496

Immunity, historical sketch, 505–543; summary, 544–569; by attenuated micro-organisms, 2; predisposition or absence of, 7; against infective diseases, 9; definition of, 10; against micro-organisms, 10, 41, 42, 128–206, 207–324; against toxins, 10, 41, 42, 325–341, 342–402; not same as against micro-organisms, 290, 351; in unicellular organisms, 11–28; in multicellular plants, 29–39; in plants, action of manures on, 36; in the animal kingdom, 40–66; cellular or histogenic, 335, 336, 340, 563–565; active (Ehrlich), 378 = isopathic immunity (von Behring); passive (Ehrlich), 378, 453 = antitoxic immunity (von Behring); passive against micro-organisms, 300–324, 560; isopathic (von Behring), 378; antitoxic (von Behring), 378; of the skin, 403–407; of the mucous membranes, 407–432; susceptibility in, 565 (_see also_ Hypersusceptibility, Susceptibility); channel of entrance in, 567; applications of theory of, to medical practice and to the research of new organisms, 567–569

Immunity, natural: 10, 17, 18, 30; amongst Invertebrates, 40, 131–135; amongst Vertebrata, 41, 135–174; against micro-organisms, 128–174, 175–206; and composition of body fluids, 128–131; against anaerobic bacteria, 169, 170; part played by inflammation in, 176; importance of microphages in, 177; humoral theory of, 184; agglutination in, 202, 206; against toxins, 325–341

Immunity, acquired: 10, 19, 31; against micro-organisms, 207–249, 250–299; against vibrios, 211–227; against pyocyanic disease, 210, 232–236, 301; against spirilla of recurrent fever, 227–230; against typhoid bacillus, 230; against swine erysipelas, 236–239; against anthrax, 239–242; against streptococcus, 243–247; against _Trypanosomata_, 247–249, 316; against staphylococcus, 266

Immunity, rapid and temporary: against micro-organisms, 300–324; conferred by specific serums, 301–317; conferred by normal serums, 317–320; conferred by fluids other than serums, 320–322; conferred by non-specific micro-organisms, 322–324

Immunity, artificial, against toxins, 342–402; against bacterial toxins, 343; against vegetable toxins, 344, 365; against snake venom, 345; not in direct ratio to amount of antitoxin in body fluids, 367–376

Immunity acquired by natural means, 433–453; acquired after recovery from infective diseases, 433–444; acquired by heredity, 445–453; conferred by maternal blood, 447; by the yolk, 449; by the milk of the mother, 449

Immunity, acquired: amongst Invertebrata, 209–210; amongst Vertebrata, 210–249; relation of Pfeiffer’s phenomenon to, 224; Bouchard’s theory of, 232, 286; double action of cytases and fixatives in, 250–255, 296, 554; agglutinative substances in, 242, 245, 256–265, 295, 542, 559; protective properties of body fluids in, 266–280; phagocytosis in, 220, 223–226, 245, 280–286, 295; origin of fixative properties in body fluids in, 294; relation between fixatives and phagocytosis in, 291, 295; humoral phenomena in, 184, 250, 290, 525–531, 542, 543; bactericidal power of fluids in, 250; Gruber’s theory of, 256, 262; against micro-organisms, susceptibility to the specific toxin in, 289; principal phenomena associated with, 295–296; against micro-organisms in no ratio to protective power of blood, 372–374; by suckling, mouse the only animal in which, 450, 452; theory of exhaustion of nutrient medium as cause of, 510–512; theory of presence of inhibitory substance, 511, 512; theory of local inflammatory reaction, 512; theory of adaptation of cells in, 513; theory of phagocytes in, 514–525, 539–543; theory of bactericidal power of body fluids, 525–531, 542, 543; theory of antitoxic power of body fluids, 531; theory of extracellular destruction of micro-organisms by leucocytic secretions, 187–191, 533–537, 542; theory of side-chains, 120, 381–384, 538, 557, 562–563; present phase of the question of, 540–543

Immunproteidin of Emmerich and Löw, 254

Infection, agents, mechanical and other, that prevent or aid, 3–5, 170–173, 426 (_see also_ Diseases, Elimination, Micro-organisms)

Inflammation in immunity, 176, 512; Cohnheim on, 518; and phagocytosis, 516, 519–520, 547, 568

Influenza bacillus, cultivation of, in body fluids, 130, 554; vaccination against, 277

Infusoria. _See also Trypanosoma_

Infusoria, 12–20, 23, 26, 326

Inoculation. _See_ Immunisation, Vaccination

Insects, natural immunity in, 132, 326, 329; acquired immunity in, 209; protective lining of digestive canal of, 421

Insusceptibility of cells of refractory animals, 341

Integument of Invertebrata, protective function of, 404

Intermediary body, 88, 91, 296, 557

Intestine, protective function of the, 422; microbian flora of, 420; antitoxic action of this flora, 427

Intestinal ferments, absence of microbicidal power from, 424, 567; intestinal micro-organisms, favouring and retarding functions of, 426; destruction of toxins by, 427

Invertebrata, natural immunity in the, 40, 131–135, 326–329; acquired immunity in the, 209–210, 301; immunisation of, by specific serums, 301; protective function of integument of, 404

Iodine trichloride in immunisation, 347

Iron, absorption of, by leucocytes, 399

Irritability, part played by, 18, 27 (_see also_ Susceptibility); in plants, 38

_Isaria_, resistance to infection by, 329

Koch’s phenomenon in tuberculosis, 437

Kupffer’s cells, 75

Leprosy, etiological factors in, 4

Leprosy bacillus, 75, 411

Leucocidin, and its neutralisation, 359

Leucocytes. _See also_ Phagocytes

Leucocytes (amoeboid cells) in resorption, 47, 73, 175, 514, 515; adaptation of, to virulent bacteria, an education, 281; various categories of, 74–79; soluble ferments of, 95; chemiotaxis of, 119, 177; theory of bactericidal secretions by, 187–191, 533–537, 539, 540, 542; action of leucocidin on, 359; absorption of poisons by, 393–400; situations where there are no pre-existing, 551

Lily of the valley, acquired immunity in, 513, 515

Liver, serum against cytotoxin acting on, 116; protective function of the, 427; of Mollusca an organ of second digestion, 59

Lizard, resistance of, to tetanus toxin, 332

Lugol’s solution in immunisation, 347

Lupus, slow growth of, 406

Lymphocytes. _See also_ Leucocytes, Phagocytes

Lymphocytes, 76, 78

Lymphoid organs. _See also_ Haematopoietic organs, Phagocytic organs

Lymphoid organs, protective function of the, 428; as source of sensibilising substance (fixative), 537

Lymphomacrophages, 76

Macrocytase (alexin, complement), 86, 98, 105, 112, 196, 549; analogy of, with actinodiastase, 86; escape of, during phagolysis, 95, 99, 102, 552; presence of, in spermotoxin, 101; origin of, 103; active for resorption of animal cells, 196, 197, 296; in extracellular solution of red corpuscles, 552

Macrophages, 76, 77, 79, 547; the part they play in resorption, 80–100, 176; staining reactions of, 77; in phagocytosis, 144, 148, 154, 157, 161, 162, 164, 173, 184, 228, 245, 321, 548; act more especially in resorption of animal cells, 176, 196, 548; but intervene specially against human tubercle bacillus in pigeon, 148; against spirilla, 162, 177, 228; and against streptococci, 245; not source of bactericidal substance in body fluids, 187; part played by, in arsenic poisoning, 397; the principal source of antitoxin, 401; of skin, reaction of, against micro-organisms, 407

Macrophagic organs, digestive property of, 85, 150

Malaria, immunity against, 129, 278; protective action of serum in, 278; immunity acquired after, 434

Manures, influence on plant diseases, 36

Marmot, immunity of hibernating, against tetanus, 339

Martin’s broth (bouillon de panse), 473

Massowah vibrio, acquired immunity against, 221; action of specific serum on, 305

Mastzellen, 77

Membranes, protective secretion of, by bacteria, 21, 242

_Meriones shawii_, 22, 183

Mesenteric glands, 62, 85, 98, 195

Mesoderm, function of amoeboid cells of, 518

Microbicidal. _See_ Bactericidal

_Micrococcus prodigiosus_, 42, 45; antagonistic to anthrax bacillus, 323; action of vaginal mucus on, 430

Microcytase digests bacteria, 196, 197, 296, 550; in immunity, 218; escape of, during phagolysis, 218, 222, 230, 295, 554; transforms vibrios into granules, 552; action of, on _Vibrio metchnikovi_, 553

Micro-organisms, minuteness of certain pathogenic, 3; variability in action of, 5; staining reactions of, 13, 83, 181, 183, 198, 213; immunity by attenuated, 2, 509; pathogenic, in healthy persons, 7; adaptation of, to toxic substances, 21, 25; protective secretion of membranes by, 21, 242; defence in plants against, 35; defences of animals against, 545; elimination of, from the body, 43, 46 (_see also_ Elimination); resorption of, 46, 175, 546; antidiastase against enzymes of, 109; natural immunity against pathogenic, 128–174, 175–206; acquired immunity against pathogenic, 207–249, 250–299, 300–324; anaerobic, immunity against, 169, 170; pathogenic animal, 2, 173, 247–249, 277–279, 316; destruction of, an act of resorption, 175, 206 (_see_ Bacteriolysis); presence of, in white corpuscles, 514; adaptation of phagocytes to destroy, 558, 566; mode of entry into phagocytes, 177; digested by phagocytes, 181, 514–525, 536, 539–543 (_see_ Phagocytes, Phagocytosis); transformation into spherical granules, 198 (_see also_ Pfeiffer’s phenomenon); extracellular destruction of, 165, 212, 533–537, 542; modified growth in serums from immunised animals, 256, 259 (_see also_ Agglutination); specific diagnosis of, by modified growth, 256, 259; agglutination does not prevent growth of, 262; changes which they undergo in immunised animal, 289; attenuation of, 208, 286–289, 508; adjuvant and retarding functions of, 170, 426; antagonism between anthrax and certain, 323; antagonism between cholera vibrio and certain, 324; acidophile, 418; exfoliation of epidermis to get rid of, 406; localisation and arrest of, in the dermis, 406; destruction of toxins by, 427

Microphages, 77, 78, 79, 148, 152, 154, 162, 164, 172, 185, 245, 548; intervene specially against micro-organisms and in acute infections, 177, 196, 206, 549; source of bactericidal substance in body fluids, 187, 195; granular transformation of vibrios inside, 164, 165, 224 (_see also_ Pfeiffer’s phenomenon)

_Microsphaera_, 18

Milk, absorption of, 107; precipitins in the differentiation of various kinds of, 107, 568; of immunised animals, antitoxin in, 356; immunity conferred by mother’s, 449, 450, 452; transmission of agglutinative power by, 450

Milk-sugar, adaptation of yeasts to, 26

Mithridates, method of protecting himself against poisons, 343

Mollusca. _See also Helix_, _Phyllirhoë_, _Thetys_

Mollusca, natural immunity in, 134; liver of, an organ of second digestion, 59

Mongoose, immunity of, against snake venom, 339

Monkeys, immunised, with poor yield in antitoxin, 373; immunisation of, against diphtheria toxin, 373; transient acquired immunity against recurrent fever, 434

_Monospora_, parasite of _Daphnia_ disease, 131, 404, 520

Morphia, adaptation to, 343

Mouse, infection of, by swine erysipelas, 270, 307, 476; the only animal that acquires immunity by suckling, 450, 452; acquired immunity of, against typhoid, 230; natural immunity of, against diphtheria toxin, 204, 339

Mouse septicaemia, immunity of frog against, 141; phagocytosis in, 283; acquired immunity of rabbit against, 509

Mouth. _See_ Buccal cavity

Mucous membranes, immunity of the, 407–432; elimination of micro-organisms by the nasal, 410; protective function of the genital, 429

Mycoses, pulmonary, 413 (_see also_ Aspergillosis)

_Mygale._ _See_ Spiders

Myriapods. _See Scolopendra_

Myxomycetes, plasmodia of, 30, 545

Naegeli’s theory of immunity, 512

Nagana disease, 2, 4, 247, 316 (_see Trypanosoma_)

Narcosis. _See_ Opium

Nasal mucous membrane, elimination of organisms by, 410

_Nepenthes_, digestive juice of, 355

Nerve centres, susceptibility of, to toxins, 564

Neuroglia cells, their phagocytic function, 75

Neurotoxin, 116

Neutral red, reaction of, 13, 83, 181

Nuclein as a protective substance, 320; vaccinal against plague, 490

Nucleohiston, preventive action of, on diphtheria toxin, 365

Nutrition, certain diseases of, probably due to a parasite, 3; extra-buccal, 67, 69

_Oidium albicans_, growth of, in serum of immunised animals, 257

Omentum, glands of, 85; bactericidal power of extracts of, 195; phagocytosis of vibrios in, 224

Opium, its action on leucocytes, 225, 231, 236, 306, 307; its influence on immunisation by specific serums, 306; resistance of hedgehog to, 337

_Oryctes nasicornis._ _See_ Rhinoceros beetle

Osmotic pressure, adaptation of plants to, 37, 39, 566; as cause of bactericidal action of body fluids, 193, 213

Ovum in the Graafian follicle, immunity acquired by the, 448

Oxalic acid, function of, in plants, 37, 566

Oxydases, 96

Pancreatic digestion, 60, 63, 65

Pancreatic juice, antitoxic power of, 424

Pancreatic secretion, its adaptation to kind of food, 64, 65

Paralysis, general progressive, and syphilis, 435

_Paramaecia_, 13, 16, 17, 19

Parasites in infective diseases, 2, 9 (_see also_ Micro-organisms)

Pasteur’s theory of exhaustion of nutrient medium, 510–512; anthrax vaccines, 208, 470; modification of Willems’ method against pleuropneumonia, 477; vaccines against rabies, 462, 463–464; and Thuillier’s vaccines against swine erysipelas, 208, 473, 509

Pepsin in the urine, 65, 97; in the blood, 66, 563; antitoxic function of, 419; antiseptic action of, 417; chemical composition of, 109

Pessimism and fear of disease, 1, 569

Peyer’s patches, 61; protective function of, 428

_Peziza._ _See Sclerotinia_

Pfaundler’s reaction, 259

Pfeiffer’s phenomenon in cholera vibrio, 165, 192, 212–226, 251, 267, 268, 280, 301–307, 534–536; in spirillum of recurrent fever, 229; in typhoid bacillus, 230, 303, 304; in _Bacillus pyocyaneus_, 234, 307; different in immunised and in normal fluids, 251; conditions for its manifestation, 252, 253, 295, 534

Pfeiffer’s theory of immunity, 534

Phagocytes (_See also_ Leucocytes), amoeboid cells with digestive function, 7, 182, 547; in Sponges, 69; in Vertebrata, 73; various categories of, 74–79; of _Bipinnaria_ and _Phyllirhoë_, 70; chemiotaxis of, 79, 108, 133, 167, 177, 280; the source of the haemolytic ferment, 100; of osseous fishes, 135; of frog, 137; ingest living and virulent bacteria, 142, 177, 179–181, 558, 566; function of, 151, 157, 177, 181, 206, 547, 548, 566; mode of entry of microorganisms into, 177; acid reaction inside, 83, 182; action of opium on, 225, 231; theory of, and side-chain theory compared, 296–299, 538; in defence of animal against poisons, 393–400; in production of antitoxin, 400–402; in the defence of the skin, 407; attempts to reconcile theory of, with humoral theory, 539; history of theory of, 514–525, 539–543; stimulant action of, 532

Phagocytic crisis of Bordet, 314; ferments, 549–558; function of neuroglia cells, 75; organs, 85, 150, 292, 293, 537; of cricket, 133; of _Ascaris_, 547

Phagocytosis in osseous fishes, 135; in frogs, 137, 142; in fowl, 144, 282; in dog, 149, 151; in rat, 154, 157; in guinea-pig, 162, 163, 166, 170, 223; in horse, 245, 313; in rabbit, 159, 167, 169, 233, 239, 314; effect of removal of spleen on, 150; agents that prevent, 170–173 (_see also_ Opium); neutralisation of toxins not necessary for, 205, 289; and agglutination, 202, 242, 245; ensures natural immunity, 206; action of opium on, 225, 231, 236, 306, 307; action of rabbit’s serum on, 231; in acquired immunity, 220, 223–226, 245, 280–286, 295, 313; relation to fixatives in acquired immunity, 291, 295; in the immunity conferred by specific serums, 303–317; history of, and of the theory of phagocytes, 514–525, 539–543; its application in surgery, 568

Phagolysis, 80, 99, 165; prevention of, 99, 218, 219, 220, 230, 252, 304; its relation to extracellular destruction of bacteria and Pfeiffer’s phenomenon, 218–220, 230, 280, 295, 534; escape of cytases during, 95, 99, 102, 191, 197, 252, 551–554, 560

Philocytase, 91, 92

Phloridzin, its action on natural immunity, 150

_Phyllirhoë_, two modes of digestion in, 58; resorption by phagocytes of, 70

Pig. _See also_ Swine

Pig, protection of, against tetanus, 493

Pigeon, immunity of, against anthrax, 146; immunity of, against human tuberculosis, 147; immunity of, against influenza bacillus, 130, 554; its blood best culture medium for influenza bacillus, 130, 554; susceptible to swine erysipelas, 476; protective power of serum of, immunised against anthrax, 276, 277, 288; vaccination of, against anthrax, 276, 277

Pilocarpin augments production of antitoxin, 380

_Piroplasma bigeminum_, 247, 279

Plague, bubonic, rapid immunisation by serum, 312; protective influence of broth against, 321; production of antitoxic serum by, 401; infection by, through the nasal cavity, 409, 411; vaccinations against, 486–492; serum treatment in, 490–492; immunity against, when acquired and duration, 488, 489; statistics on vaccinations against, 488; prophylactic treatment against, 491; Reports of German and English Commissions on, 489

Planarians, digestion in, 49, 71, 82

Plants, immunity in multicellular, 29–39; cicatrisation of, 34; and osmotic pressure, 37, 39, 566; ravages of _Sclerotinia_ amongst cultivated, 32; action of manures on immunity of cultivated, 36; function of oxalic acid in, 37, 566

Plasma, Gengou’s method of preparing, 157, 190

Plasmas. _See also_ Body fluids, Serums

Plasmas, presence of fixatives in, 103; bactericidal power of, 190, 543

Plasmase (fibrin ferment), 95, 197, 550

Plasmodia, intracellular digestion in, 30, 545; chemiotaxis of, 30; adaptation of, to poisons, 30

Pleuropneumonia, bacterium of, 3, 130, 478, 569; vaccinations against, 477–479; action of serum from animals immunised against, 479; vaccinal methods used by savage races against, 506

Pneumococcus, modified growth of, in serums from immunised animals, 256, 262; vaccination against, 262; attenuated by serums from vaccinated animals, 287; agglutination of, 287

Pneumo-enteritis of swine, cocco-bacillus of, 259; action of serum of vaccinated rabbits on bacillus of, 260, 266, 287, 532; acquired immunity against, 260, 275, 311, 532

Pneumonia, fibrinous, relapses separated by periods of immunity, 434

Poisons. _See also_ Toxins

Poisons, absorption of, by leucocytes, 393–400

_Polyphagus euglenae_, 12

Potato attacked by _Bacillus coli_, 35

Precipitins in the blood serum, 68, 106, 107; use of, in medico-legal investigations, 107, 568; and in the differentiation of various kinds of milk, 107, 568

Predisposition or absence of immunity, 7

Preventive substances of Bordet (syn. fixatives), 266

Profetta, law of, 453

Protective or anti-infective property. _See also_ Antitoxic, Antitoxins, Blood, Body fluids, Serums

Protective property, origin of, in serums and other fluids, 291–294; differs from agglutinative, 268, 269, 294; of blood and other fluids in convalescents, 437–444

Protective action of normal serums, 317–320; of fats against toxins, 387; of leucocytes against poisons, 393–400; of flow of a fluid, 431

Protective function of the skin, 404–407; in the respiratory channels, 411–414; of the cornea, 409; of the saliva, 415; of the intestine, 422; of the bile, 424; of the liver, 427; of the lymphoid organs, 428; of the suprarenal capsules, 431; in the urinary organs, 431

Protective substance resistant to heat, 268; and so distinguished from bactericidal substance, 268; closely connected with fixative substance, 269, 294, 295, 561

Protective vaccinations, 454–504

_Proteus vulgaris_, susceptibility of leucocytes to, 166, 179, 201, 282; eosinophile transformation in, 198; modified growth in certain serums, 259

Protozoa, intracellular digestion in the, 13, 30, 49; adaptation of, to saline solutions, 23, 515; and to physical conditions, 26

Prussic acid, antidote to, 363

Pseudo-diphtheria bacilli, 444

Pseudo-eosinophile leucocytes, secretion by, 187, 542

Pseudo-immunity or resistance, 320

Pus, ferment in, 96

Pyrogallic acid, its action on natural immunity, 150

Rabbit, immunity of, against anthrax bacillus, 159; against streptococci, 167, 168; against tetanus bacillus, 169; against cholera vibrio, 424; against pleuropneumonia, 569; acquired immunity of, against pyocyanic disease, 232; against swine erysipelas, 236–239, 527; against anthrax, 239, 323; against streptococcus, 243–247, 284–286, 312, 314; against pneumo-enteritis, 260, 266, 275, 311, 532; against pneumococcus, 262; against a staphylococcus, 266; against hog cholera, 290; against mouse septicaemia, 509; phagocytosis in, 159, 167, 169, 233, 239, 314, 569; infection by streptococci in, 283; action of serum of vaccinated, on bacillus of pneumo-enteritis, 287; action of agglutinated pneumococci on, 287; vaccinated against hog cholera susceptible to its toxin, 290; immunised against anthrax by means of the erysipelas coccus, 323; immunised against anthrax by products of _Bacillus pyocyaneus_, 323; infection by anthrax prevented by Friedländer’s bacillus, 323; brain of, very susceptible to action of tetanus toxin, 383; reaction of, to atropin, 395

Rabies, action of anthrax bacillus on, 150; action of normal ox serum on, 365; action of bile on, 425; heredity of immunity against, 446; vaccinations against, 461–466; statistics of vaccinations against, 464–466; in domestic animals, vaccinations against, 466

Rat, immunity of, against anthrax bacillus, 152, 526; against diphtheria bacillus, 204; acquired immunity against _Trypanosomata_, 247–249, 316; against anthrax, 240; natural immunity of, against diphtheria toxin, 204, 339; bactericidal ferment of phagocytes of, 20, 157; phagocytosis in, 154, 157

Receptors, 93, 120, 296; over-production of, 121, 296, 562; antitoxic and philotoxic functions of, 120; theory of, _see_ Side-chain theory

Recurrent fever. _See_ Spirilla, _Spirochaete obermeyeri_

Recurrent fever, transient acquired immunity against, 434

Rennet, 109, 119

Reptilia. _See_ Alligator, Turtle, Snake, Lizard

Reptilia, natural immunity of, against tetanus toxin, 331–334

Resistance to disease, 8–10. _See_ Immunity, Pseudo-immunity

Resorption of micro-organisms, 46, 175 (_see also_ Immunity, cellular, Micro-organisms); of the formed elements, 47, 67–105; a true intracellular digestion, 85, 296; of cells in the Invertebrata, 70; of red corpuscles by phagocytes of the Vertebrata, 72, 80 (_see also_ Phagocytes, Phagocytosis); part played by macrophages in (_see_ Macrophages); and digestion closely related, 69, 85; of spermatozoa, 84, 100; of white corpuscles, 84 (_see also_ Leucocytes, Phagocytes); of albuminoid substances, 106–127; of cells and the phenomena in acquired immunity, 296

Respiratory channels, protection by the, 411–414; absorption of poisons by the, 414

Rhinoceros beetle, natural immunity in larvae of, 132, 209, 326, 329; susceptibility to cholera vibrio, 40, 133

Ricin, 344, 360, 446, 449

Rinderpest, action of bile on, 425, 466; vaccinations against, 466–468; Koch’s method of vaccination against, 466; Kolle and Turner’s method of “simultaneous vaccinations” against, 467

Ring-worm, mechanical factor in, 4

Robin (toxalbumin of _Robinia pseudacacia_), 365; serum of animals vaccinated against, antitoxic, 365; heredity of immunity against, 446

_Saccharomyces._ _See_ Yeasts

Saline solution (physiological) as a protective fluid, 320, 365

Saliva, microbicidal property of the, 415; antitoxic function of, on snake venom, 417; psychic influence on flow of, 62, 566

Saponin, haemolytic action of, 389; and cholesterin, 389; and antisaponic power, 390

_Saprolegnia._ _See_ Fungi

Sarcinae as adjuvant organisms, 426

Sarcinae, acidophile, 418

_Sclerotinia_, pathogenic action of, 32

_Scolopendra_, acquired immunity in, against anthrax, 209

Scorpion, natural immunity of, against tetanus toxin, 326; against its own poison, 327; antivenomous property of blood of, 328; supposed suicide of, 327

Scorpion serum, action of antivenomous serum on, 365

Scorpion venom, antitoxic action of crayfish blood against, 366

Scrofula in immunity against tuberculosis, 436

Secretion of bactericidal substance, theory of, 187–191, 533–537, 540, 542

Sensibilising substance of Bordet (fixative), 91, 199, 298, 535, 537, 557

Sensitiveness of plants to osmotic pressure, 37, 566

Septicaemia of goose. _See Spirochaete anserina_

Septicaemia of mouse. _See_ Mouse septicaemia

Septic vibrio, 170

Serums. _See also_ Blood, Body fluids, Humoral theory, Toxins

Serums, haemolysis by, 83, 87–95 (_see also_ Haemolysis); effect of injections of, 68; increasing haemolytic power of, 90; isotoxic, 104; absorption of, 106; antihaemotoxic, 111, 112; haemolytic or haemotoxic, 111, 112; anticoagulating, 190; anticytase, 115, 371; antispermotoxic, 116, 122–126; bactericidal properties of, 184, 190, 191, 192, 193, 206, 211, 226, 233, 238, 241, 243, 244, 260, 298, 554; influence of alkalinity or acidity on bactericidal action of, 196; agglutination of red blood corpuscles by, 258; agglutination of bacteria by, 256–265, 380; protective power of, in the immunised organism, 266–280, 287, 293, 295, 532; differs from bactericidal power, 268; and from agglutinative power, 268; and is not a measure of acquired immunity, 271, 274, 275; protective, may be only feebly antitoxic, 497; modified growth of bacteria in immunised, 256, 259 (_see also_ Agglutination); resistance to heat of protective substance of, 268; fixatives in protective, 269, 438; their origin, 294; protective and fixative substances contrasted, 269; relations of fixative and cytase in bactericidal action of, 298; stimulating action of, 270–274, 301, 308–320, 365; absence of protective power in specific, 270, 276–279; origin of protective power in, 291–294; theory of attenuation of micro-organisms by immune, 286–289; inactive specific, rendered active by addition of normal serum, 215, 268, 298, 302, 317; protective action of heated normal serum, 273, 318; protective action of non-specific, against toxins, 365; from convalescents, protective action of, 437–444; temporary immunity against micro-organisms conferred by specific, 301–317; conferred by normal, 317–320; conferred by fluids other than, 320–322; phagocytosis in the immunity conferred by specific, 303–306; influence of opium on immunisation by specific, 306; antivenomous action of, 334, 338, 358, 360, 361; antitoxic action of non-specific and normal, 365, 380; anti-arsenic, 390; antileucocidic, 359; antidiastatic, 361; testing and standardisation of antitoxic, 376, 476, 496–498

Sheath, protective. _See_ Membrane

Sheep, natural immunity of, against anthrax, 159, 289; acquired immunity of, against anthrax, 241–3, 289; bactericidal action of blood serum of, 241, 286; protective power of serum of, immunised against anthrax, 276; immunised with blood from dog affected by a haematozoon, 279; vaccination of, against sheep-pox, 460; against rabies, 466; against anthrax, 469; protection against tetanus in, 493; fate of anthrax bacilli in Algerian, 512

Sheep-pox (la clavelée), heredity of immunity against, 452; vaccinations against, 460–461

Side-chains or receptors, theory of, 120, 381–384, 538, 557, 562–563; compared with theory of phagocytes, 296–299, 538, 558

Silver, soluble salts of, absorbed by leucocytes, 400

Skin, immunity of the, 403–407; protective function of the, 404–407; phagocytes in the defence of the, 407

Small-pox, mortality from, in 18th century, 454; vaccinations against, 454–460; vaccination with calf lymph, 456; with contents of pustule of cow-pox, 455; vaccination statistics, 457–459

Snail. _See Helix pomatia_

Snake, natural immunity of, against snake venom, 333

Snake venom, natural immunity of snakes against, 333; of hedgehog against, 337; of mongoose against, 339; artificial immunity against, 345, 347; action of antivenomous serum on, 358, 360, 361; of other specific serums on, 365; of cerebral substance on, 386; protective substances against, 387; action of saliva on, 417; action of bile on, 425; vaccination methods of savage races against, 506

Spermatozoa, resorption of, 84, 100; action of spermotoxin on, 101, 116, 125

Spermotoxin, 101, 116, 125

Spiders, natural immunity of, against tetanus toxin, 326

Spirilla, natural immunity against, 159; acquired immunity against, 227–230, 434; living in stomach of dog, 177; acidophile, 418

_Spirochaete anserina_, 160

_Spirochaete obermeyeri_, 160; acquired immunity against, 227–230; Pfeiffer’s phenomenon in, 229

Spleen, function of, 62, 85; action of extract of, on tetanus toxin, 365; effect of removal of, 150, 293; as source of fixative substance, 295, 537

Spleen and other haematopoietic organs as source of protective substance, 292–294; as source of agglutinins, 264; are phagocytic organs, 85, 150, 292

Sponges, digestion of, 69, 517

Staining reactions of cells and micro-organisms, 13, 77, 83, 181, 183, 198, 213

Standardisation of antidiphtheria serums, 376, 496–498; Ehrlich’s method, 496; Pasteur Institute method, 496–497

Staphylococcus, acquired immunity against, 266, 532; protective action of normal serum against, 319

_Staphylococcus pyogenes_ in vagina, 430

Stellate cells of Kupffer, 75

Stimulant action. _See also_ Body fluids, Protective

Stimulant action of serums, 270–274, 301, 308–320, 365; of phagocytes, 532; of normal fluids of the body, 559

Stimulins and their action in serums, 270–274

Stöhr’s phenomenon, 429

Stomach, acidophile microbian flora of, 418

Streptococci, protective sheath formed by, 22; immunity against, 165, 179, 282, 284–286; phagocytosis in immunity against, 245, 313; acquired immunity against, 243–247, 313; agglutination by serum of, 244, 245; reaction of animal organism against, 245–247; antitoxin against, 205; and phagocytosis, 283; action of specific serums on, 287, 288, 312; protective action of various fluids against, 320, 321

Streptococcic serum, action of, on leucocidin, 359

Sturin, bactericidal action of, 183

Suprarenal capsules, protective function of, 431

Susceptibility. _See also_ Chemiotaxis, Hypersusceptibility, Irritability, Sensitiveness

Susceptibility of immunised animals to the specific toxin, 289; of frogs to tetanus toxin, 330; diminution of, in immunised animals, 374–376; in immunity, the part played by, 565; cellular, a general property of living beings, 565–566

Swine. _See_ Pig, Pneumo-enteritis

Swine erysipelas, acquired immunity against, 236–239, 254, 283, 527; agglutination of bacilli of, 262; specific serum of, will not prevent infection, 270; phagocytosis in, 283; action of immune serums on bacillus of, 288, 289; protective action of specific serum against, 307; method of testing strength of serums against, 476; vaccinations against, 473–477; Pasteur’s method, 473; Lorenz’s method, 475; “serum-vaccinations” method, 475; vaccines against, 208, 473, 509

Swine plague, 259, 260

_Synapta_, 518

Syphilis, immunity in, 435; and general progressive paralysis, 435; law of Profetta in immunity against, 453; law of Baumès-Colles in, 436; transmission of, 452

Tears, microbicidal function of the, 408

Testing of serums. _See_ Standardisation

Tetanolysin of Ehrlich, 349

Tetanospasmin, 362

Tetanus, immunisation against, 344, 347, 492–495; cerebral, in rabbit, 383, 391; difference between antitoxic action of living brain and that of cerebral emulsion on, 383; in fowl, 384; no antitetanic power in serum of convalescents, 443; vaccinations against, 492–495; vaccines against, 493; protective serum treatment against, 493–495

Tetanus antitoxin, hypothesis of nervous origin of, 381–385; nature of, 355; mode of action on toxin, 357, 381; of nerve centres locally restricted in its action, 382

Tetanus bacillus, natural immunity against, 169, 204

Tetanus toxin, natural immunity of spiders and scorpions against, 326; of larvae of _Oryctes_ and of cricket against, 329; of frog against, 330; of reptiles against, 331–334; of fowl against, 335; of hibernating animals against, 339; attenuation of, 344; localisation of, in vascular organs, 336; brain of rabbit very susceptible to action of, 383; fixation of, by substance of nerve centres, 382; by certain parts of brain and cord, 386, 391; by other cells, 391, 392; action of emulsions of frog’s brain on, 386; fixation of, by carmine, 388, 394; absorption of, by leucocytes, 393–395; action of extract of spleen on, 365; toxone (tetanolysin) of, 349, 362; local reaction to, in horse, 352; heredity of immunity against, 446, 448, 450

Texas fever, acquired immunity of Bovidae against, 247, 279; attenuation of parasite of, in the tick, 247; haematozoon in dog closely allied to that of, 279

_Thetys_, 517

Thymus gland, immunising power of, 293

Tick, attenuation of parasite of Texas fever in, 247

Tonsils, protective function of, 428

Torulae as adjuvant organisms, 426

Toxins, immunity against, 10; immunity of unicellular organisms against, 19; adaptation of bacteria to, 21–27; of yeasts to, 20, 26; of plasmodia to, 30; action of, on Infusoria, 19, 326; composition of, 120; neutralisation of, not necessary for phagocytosis, 205, 289; immunity against micro-organism not same as against toxin, 251, 290; protective fixation of, by nerve elements and other cells, 386–400; methods of immunisation by modified and unmodified, 345–347 (_see_ Immunisation); local reaction in immunisation against, 352; action of normal serums on, 365; of non-specific serums on, 365; protective action of fats against, 387; leucocytic reaction against, 393–400; absorption of, by the conjunctiva, 409; by the respiratory channels, 414; destruction of, by the intestinal organisms, 427; attenuation of, 344; natural immunity against, 325–341; artificial immunity against, 342–402; against bacterial, 343; against vegetable, 344, 365; heredity of immunity in phanerogamic, 446, 449; susceptibility of nerve centres to, 564

Toxoids, 349 (_see also_ Toxophore); immunisation by, 350

Toxones, 349, 362; method of immunisation by, 349

Toxophore atomic group in toxin (= toxoid), 120, 350, 384

_Trichinae_, mechanical action of, 3

Tristeza (syn. Texas fever), 247

_Tropidonotus._ _See_ Snake

_Trypanosoma_, 4, 129, 147; _brucei_, 9; _lewisi_, 173, 248

_Trypanosomata_, fate of, in refractory animal, 173; acquired immunity against, 247–249, 316; and agglutinative power, 278

Trypsin, antitoxic power of, 424

Tsetse fly, 4, 9, 129, 247

Tubercle bacillus, formation of sheath by, 22, 183

Tuberculin as a protective substance against cholera vibrio, 320

Tuberculosis, mechanical etiological factors in, 4

Tuberculosis, bacillus of, 22, 42, 143; avian, 41, 148, 149, 182; human, immunity of pigeon against, 147; acquired immunity in, 436; after scrofula, 436; Koch’s phenomenon in, 437

Tumours, malignant, probability of discovery of parasite of, 3; use of erysipelas streptococcus in, 434

Turtle, natural immunity of, against tetanus toxin, 332, 386

Typhoid, protective power of serum of convalescents from, 437–440; its agglutinative power, 439; serum-diagnosis of, 256, 257, 261, 439; immunity against, not acquired by suckling, 450; vaccinations against, 479, 481–486; Wright’s vaccine against, 482; bactericidal power of serum from persons immunised against, 483; statistics of vaccinations against, 483–485

Typhoid bacillus, 23, 143, 191, 198, 203; acquired immunity against, 230; attenuated Pfeiffer’s phenomenon in, 230, 303, 304; agglutination of, 260, 261, 380, 439; resistance to agglutinated, 263; protective action of serums against, 272–274, 293, 317, 319; origin of protective substance against, 292; of agglutinative property against, 294; protective action of various fluids against, 320; passes uninjured through stomach, 418; transmission by suckling, of agglutinative power against, 450

Typhoid infection, experimental, in laboratory animals, 230, 267; influence of anticytase serum on, 371; uncertainty of, by ingestion, 423

Typhoid septicaemia, experimental, heredity of immunity against, 447

Tyrosin, protective action of, 387

Unicellular organisms, immunity in, 11–28; infective diseases of, 12; irritability of, 27; adaptation of, to saline solutions, 23, 515

Unit, Ehrlich’s immunising, 373, 496

Urinary ferments, 66

Urinary organs, protective function in, 431

Urine as a protective fluid, 320, 431; pepsin in the, 65; amylase in the, 65

Vaccination. _See also_ Immunisation

Vaccinations, protective, 208, 241, 267, 454–504, 507; with attenuated micro-organisms, 509

Vaccine against fowl cholera, 208

Vaccines against anthrax, 208, 470, 509; against swine erysipelas, 208, 473, 509; against rabies, 208, 462, 463–464; against symptomatic anthrax, 471; against small-pox, 455–457, 507; against pleuropneumonia, 477; against cholera, 481; against plague, 487, 489, 490; against tetanus, 493

Vaccinia, supposed micro-organism of, 455–456

Vagina, autopurification of, 429

Variolisation, early use of, 455, 507

Venom. _See_ Snake venom

_Ver blanc_, syn. cockchafer larva

Vibrio. _See also_ Cholera vibrio, Massowah vibrio, Septic vibrio

Vibrios, acquired immunity against, 211–227; phagocytosis in immunity against, 220, 223–226; granular transformation of, 164, 165, 192, 212–226 (_see_ Pfeiffer’s phenomenon); bacteriolysis (agglutination) of, 256; susceptibility of animals vaccinated against, to the toxins, 290

_Vibrio metchnikovi_, acquired immunity against, 211, 226, 527, 531; modified growth of, in serums from immunised animals, 156, 262; action of, grown in serum of vaccinated animals, 287; perishes in intestine of dog, 422; action of microcytase on, in hypervaccinated guinea-pigs, 553

Viper. _See_ Snake, Snake venom

Viruses, attenuated, 208, 508; vaccination with, whose nature is as yet unknown. _See_ Small-pox, Sheep-pox, Rabies, Rinderpest

Vitellus of egg of immunised fowl, tetanus antitoxin present in, 356; immunity conferred by, 449

Warlomont’s calf lymph vaccine, 456

Weber-Fechner, law of, 27, 38, 566

Willem’s method of vaccination against pleuropneumonia, 477; Pasteur’s modification of, 477

Wright’s method of vaccination against typhoid, 482; method of testing bactericidal power of body fluids, 483

Yeast-cells, adaptation of, to poisons, 20, 26; to milk-sugar, 26; destruction of injected, by phagocytes, 172; Curtis’s pathogenic, 172; endotrypsin of, 197; autodigestion in, 197; soluble ferments of, 253

Yeasts, diseases due to, 2

Yolk. _See_ Vitellus

Zymase, 197, 550

CAMBRIDGE: PRINTED BY JOHN CLAY, M.A. AT THE UNIVERSITY PRESS.

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Footnote 1:

_Deutsche med. Wchnschr._, Leipzig, 1884, SS. 499, 519.

Footnote 2:

_Mitth. aus d. K. Gesundheitsamte_, Berlin, 1884, Bd. II, S. 421.

Footnote 3:

“On the Origin of Species,” 6th ed., London, 1872, Chapter XI, p. 277.

Footnote 4:

_Vrtljschr. f. gerichtl. Med._, Berlin, 1855, S. 102.

Footnote 5:

“Ueber Chytridium,” in _Monatsber. d. Berliner Akad._, 1855, June, No. 14.

Footnote 6:

Cohn’s “Beiträge zur Biologie der Pflanzen,” Breslau, 1876, Bd. II, S. 210.

Footnote 7:

For the parasites of Infusoria, cf. Bütschli in Bronn’s “Klassen und Ordnungen d. Thier-Reichs,” Leipzig, 1885—1889, Bd. I, SS. 872, 1823, 1944.

Footnote 8:

_Arch. d’anat. microsc._, Paris, 1898, t. II, p. 528.

Footnote 9:

Le Dantec, “Recherches sur la digestion intracellulaire,” Lille, 1891, p. 53.

Footnote 10:

Ehrlich u. Lazarus, “Die Anämie,” in Nothnagel’s “Specielle Pathologie u. Therapie,” Wien, 1898, Bd. VIII, I^{ter} Theil, S. 85; also “Pathology of the Blood,” authorised English translation, Cambridge, 1900, p. 125.

Footnote 11:

_Arch. f. Entwickelungsmech._, Leipzig, 1898, Bd. VII.

Footnote 12:

_Compt. rend. Acad. d. Sci._, Paris, 1901, t. CXXXIII, p. 244.

Footnote 13:

_Arch. de zool. expér._, Paris, 1889, 2^{me} série, t. VII, p. 446.

Footnote 14:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 148.

Footnote 15:

“Leçons sur la pathologie comparée de l’inflammation,” Paris, 1892, p. 24; “Lectures on the comparative pathology of inflammation,” authorised translation into English, London, 1893, p. 20.

Footnote 16:

“Leçons sur la pathologie comparée de l’inflammation,” p. 21; English edition, p. 17.

Footnote 17:

_Monatsber. d. Berl. Akad. d. Wissensch._, 1881, p. 388.

Footnote 18:

_Compt. rend. du Congrès internat. de Méd. tenu à Paris en 1900._ Section de bactériologie et de parasitologie.

Footnote 19:

“Sur l’immunité naturelle des organismes monocellulaires contre les toxines” _Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 465.

Footnote 20:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 801.

Footnote 21:

“Ueber die Ursache der Immunität von Ratten gegen Milzbrand,” in the _Centralbl. f. klin. Med._, Bonn, 1888, no. 38.

Footnote 22:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 872.

Footnote 23:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 641.

Footnote 24:

Metchnikoff, _Virchow’s Archiv_, 1884, Bd. XCVII, S. 510.

Footnote 25:

“Contribution à l’étude du sérum antistreptococcique,” _Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 177, Planche V.

Footnote 26:

_Arch. f. Hyg._, München u. Leipzig, 1900, Bd. XXXIX, S. 31.

Footnote 27:

“Entwickelungsgeschichte der mikroskopischen Algen und Pilze,” _Nov. Acta Acad. Caes. Leop. Carol._, 1854, t. XXIV, p. 1.

Footnote 28:

“Action des sels sur les infusoires,” _Arch. d’anat. microsc._, Paris, 1898, t. II, p. 595.

Footnote 29:

“On the acclimatisation of organisms to poisonous chemical substances,” _Arch. f. Entwickelungsmech._, Leipzig, 1895, Bd. II, S. 564.

Footnote 30:

_Ann. de l’Inst. Pasteur_, Paris, 1887, t. I, p. 465.

Footnote 31:

_Monit. scient. du D^r Quesnerille_, 1890, 1891, 1892, 1894.

Footnote 32:

“Traité de Microbiologie,” Paris, 1898, t. I, p. 238.

Footnote 33:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 417.

Footnote 34:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 139.

Footnote 35:

_Journ. R. Micr. Soc._, London, 1880, III, p. 1.

Footnote 36:

Davenport and Castle, _Arch. f. Entwickelungsmech._, Leipzig, 1895, Bd. II, S. 227.

Footnote 37:

_Untersuch. a. d. physiolog. Inst. d. Univ. Heidelberg_, 1878, Bd. II, S. 273.

Footnote 38:

_Flora_, Marburg, 1892, Bd. LXXVI, S. 182.

Footnote 39:

_Botan. Ztg._, Leipzig, 1884, S. 161.

Footnote 40:

[Stahl used plasmodia which had spread themselves on a substratum of wet filter paper applied to the inside of glass vessels, its lower edge touching the surface of the experimental fluid at the bottom of the vessel (Translator).]

Footnote 41:

The italics are M. Metchnikoff’s.

Footnote 42:

“Vergleichende Morphologie u. Biologie der Pilze, Mycetozoen u. Bacterien,” Leipzig, I^{te} Aufl., 1884; also authorised English translation, Oxford, 1887.

Footnote 43:

_Botan. Ztg._, Leipzig, 1886, SS. 377, 393, 409, 433, 449, 465.

Footnote 44:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 44.

Footnote 45:

“La cicatrisation chez les végétaux,” _Mém. couron. de l’Acad. roy. de Belgique_, Bruxelles, 1898, t. LVII.

Footnote 46:

Cf. Frank, “Die Krankheiten der Pflanzen,” Breslau, 2^{te} Aufl., 1895, Bd. I, S. 43.

Footnote 47:

“Recherches expérimentales sur les maladies des plantes,” _Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 1.

Footnote 48:

“Réaction osmotique des cellules végétales,” _Mém. couron. de l’Acad. roy. de Belgique_, Bruxelles, 1899.

Footnote 49:

“La cicatrisation,” _l.c._, p. 61.

Footnote 50:

_Untersuch. a. d. botan. Inst. zu Tübingen_, Leipzig, 1884, Bd. I, S. 363.

Footnote 51:

“Recherches sur les organismes inférieurs,” _Bull. de l’Acad. de Belgique_, 1888, 2^e série, t. XVI, V, 12.

Footnote 52:

_L.c._, p. 40.

Footnote 53:

[Probably a surface growth on a sloped agar tube (Transl.).]

Footnote 54:

“Etude expérimentale sur les glandes lymphatiques des invertébrés,” _Mélanges biol. de l’Acad. d. sc. de St-Pétersb._, 1894, t. XIII, p. 458.

Footnote 55:

“Ueber grünen Eiter,” Volkmann’s _Samml, klin. Vortr._, No. 62, Leipzig, 1893.

Footnote 56:

“Processus chimiques dans les intestins de l’homme,” _Arch. d. sc. biol. de St-Pétersb._, 1892, t. I, p. 539; _Ztschr. f. Hyg._, Leipzig, 1893, Bd. XV, S. 474.

Footnote 57:

Cited by Schimmelbusch, _l.c._

Footnote 58:

_Compt. rend. Acad. d. Sc._, Paris, 1892, t. II, p. 1226.

Footnote 59:

_Berl. klin. Wchnschr._, 1901, S. 163.

Footnote 60:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXIX, S. 548.

Footnote 61:

“Fermente und Mikroparasiten” in Ziemssen u. Pettenkofer’s “Handbuch der Hygiene,” Leipzig, 1883.

Footnote 62:

“Ueber die Schicksale der in’s Blut injicirten Mikroorganismen,” _Ztschr. f. Hyg._, Leipzig, 1886, Bd. I, S. 1.

Footnote 63:

_Ztschr. f. Hyg._, Leipzig, 1897, Bd. XXVI, S. 353.

Footnote 64:

_Arch. f. exper. Path._, Leipzig, 1897, Bd. XXXIX, S. 39.

Footnote 65:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXIX, S. 528.

Footnote 66:

_Ztschr. f. Hyg._, Leipzig, 1900, Bd. XXXIII, S. 261.

Footnote 67:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 415.

Footnote 68:

_Berl. klin. Wchnschr._, 1891, S. 505.

Footnote 69:

_Vratch_ (in Russian), St Petersburg, 1896, Nos. 8, 12.

Footnote 70:

_Centralbl. f. d. med. Wissensch._, Berlin, 1867, No. 31.

Footnote 71:

_Virchow’s Archiv_, 1869, Bd. XLVIII, S. 1.

Footnote 72:

_Compt. rend. Acad. d. Sc._, Paris, 1884, t. XCVIII, p. 749.

Footnote 73:

_Compt. rend. Soc. de biol._, Paris, 1900, p. 553.

Footnote 74:

_Virchow’s Archiv_, 1852, Bd. IV, S. 536.

Footnote 75:

“Handb. d. klin. Mikroskopie,” 1887, S. 108; _Gaz. med. lombarda_, 1871 and 1872; _Wien. medic. Jahrbücher_, 1872, S. 160.

Footnote 76:

“Grundzüge einer vergl. Physiologie der Verdauung,” Heidelberg, 1882.

Footnote 77:

G. H. Lewes, “Sea-side Studies,” Edin. and London, 1858, p. 216.

Footnote 78:

_Zool. Anz._, Leipzig, 1880, Jahrg. III, S. 261, and 1882, Jahrg. V, S. 310.

Footnote 79:

Metchnikoff, _Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 348.

Footnote 80:

_Bull. Acad. roy. de Belg._, Brux., 1893, t. XXV, p. 262, and _Arch. de Zool. expér._, Paris, 1893, 3^{me} série, t. I, p. 139.

Footnote 81:

“Etudes de physiologie sur les Actinies,” Charkoff, 1895 (in Russian).

Footnote 82:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 352.

Footnote 83:

Address delivered before the _Société des médecins russes_ at St Petersburg. _Gaz. clin. de Botkine_, 1900.

Footnote 84:

“Physiologie du suc intestinal,” Saint-Pétersbourg, 1899 (Thesis, in Russian).

Footnote 85:

_Arch. d. sc. biol._, St.-Pétersb., 1893, t. II, p. 698.

Footnote 86:

Cf. _Bull. Acad. de méd._, Paris, 1901, p. 17.

Footnote 87:

_Arch. d. sc. biol._, St.-Pétersb., 1899, t. VII, p. 1.

Footnote 88:

_Arch. d. sc. biol._, St.-Pétersb., 1893, t. II, p. 219.

Footnote 89:

_Virchow’s Archiv_, 1893, Suppl. to Bd. CXXXI, S. 142. The question of urinary ferments is summarised in Neubauer u. Vogel’s “Analyse des Harns,” Wiesbaden, 10^{te} Aufl., 1898, S. 599.

Footnote 90:

_Compt. rend, du XIII^e Congrès internat. de Méd._, Paris, 1901. Leube, “Ueber extrabuccale Ernährung,” in “Deutsche Klinik am Eingange d. XX. Jahrhunderts,” Wien u. Leipzig, 1901, I, S. 64.

Footnote 91:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 406.

Footnote 92:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 225.

Footnote 93:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1900, I^{te} Abt., Bd. XXVIII, S. 237.

Footnote 94:

_Deutsche med. Wchnschr._, Leipzig, 1900, S. 734.

Footnote 95:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 49.

Footnote 96:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 17.

Footnote 97:

The resorption of the red blood corpuscles by the phagocytes of larvae of starfish (_Bipinnaria_) and of _Phyllirhoë_ has been described in my paper on intracellular digestion in the Invertebrates in _Arb. a. d. Zool. Inst. d. Univ. Wien_, 1883, Bd. V, Hft. 2, S. 141.

Footnote 98:

I have only been able to discover the haemolytic property of the serums of _Cyprinus_ after the third injection of guinea-pig’s blood.

Footnote 99:

_Virchow’s Archiv_, 1870, Bd. XLIX, S. 66.

Footnote 100:

Soudakewitch, _Ziegler’s Beitr. z. path. Anat._, Jena, 1888, Bd. II, S. 129, and Babes, “Untersuchungen über den Leprabacillus,” Berlin, 1898, S. 58.

Footnote 101:

Marinesco, _Compt. rend. Soc. de Biol._, Paris, 1896, p. 726.

Footnote 102:

_Arch. f. mikr. Anat._, Bonn, 1899, Bd. LIV, S. 254.

Footnote 103:

Ehrlich u. Lazarus, “Die Anaemie,” in Nothnagel’s “Specielle Pathologie u. Therapie,” Wien, 1898, Bd. VIII, I^{ter} Theil, S. 49. Cf. the authorised English translation, “Histology of the Blood,” Cambridge, 1900, p. 74.

Footnote 104:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 301.

Footnote 105:

_Arch. de méd. expér._, Paris, 1901, t. XIII, p. 1.

Footnote 106:

_Fortschr. d. Med._, Berlin, 1888, Bd. VI, S. 460; “Die Entstehung der Entzündung,” Leipzig, 1891.

Footnote 107:

_Journ. publ. par la Soc. roy. d. Sc. méd. et nat. de Bruxelles_, 1890, 3 Feb.

Footnote 108:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 742.

Footnote 109:

Krompecher (_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1900, Bd. XXVIII, S. 588) has obtained a serum which was even capable of altering the nuclei of the red corpuscles of the frog. These nuclei must be much less resistant than those of the red blood corpuscles of birds, such as the goose, fowl and pigeon.

Footnote 110:

Some years ago it was proposed to give the name of cytase to the ferments which digest cellulose. Thus Laurent, in the work analysed in the second chapter, applies it to the ferment secreted by the bacilli which attack the vegetable membrane. We think that the cellulose ferment should be designated by the name of _cellulosase_ and that the name of cytase would be more suitable for a soluble ferment which digests the cells.

Footnote 111:

_Arch. de méd. expér._, Paris, 1891, t. III, p. 720.

Footnote 112:

_Verhandl. d. X. Congr. f. inn. Med._, Wiesbaden, 1892.

Footnote 113:

_München. med. Wchnschr._, 1900, S. 1193.

Footnote 114:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 273; 1901, t. XV, p. 312.

Footnote 115:

_Berl. klin. Wchnschr._, 1899, SS. 6 and 481.

Footnote 116:

Ehrlich and Morgenroth, “Ueber Haemolysine,” II, _Berl. klin. Wchnschr._, 1899, S. 481. The following are the combinations found by these observers: heated calf’s serum with normal serum dissolves the red blood corpuscles of the guinea-pig; heated rabbit’s serum plus sheep’s serum dissolves the red blood corpuscles of the sheep; heated serum of rabbit with the addition of goat’s serum dissolves the red corpuscles of the goat; heated sheep’s serum with guinea-pig’s serum produces haemolysis of the red corpuscles of the guinea-pig.

Footnote 117:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1901, Bd. XXIX, S. 175.

Footnote 118:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 688.

Footnote 119:

Among the synonyms of this substance, resistant to the action of heat, we may mention the following: haemolytic antibody, preventive substance, immunising body (Immunkörper of Ehrlich), amboceptor (Ehrlich), philocytase (Metchnikoff), desmon (London), copula (P. Müller).

Footnote 120:

_München. med. Wchnschr._, 1900, S. 677.

Footnote 121:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 656.

Footnote 122:

_Arch. d. sc. biol._ (russes), 1901, t. VIII, pp. 281 and 323.

Footnote 123:

_München. med. Wchnschr._, 1900, S. 1193.

Footnote 124:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 688; 1899, t. XIII, p. 273.

Footnote 125:

_Berl. klin. Wchnschr._, 1899, SS. 6 and 481.

Footnote 126:

_Berl. klin. Wchnschr._, 1900, S. 682.

Footnote 127:

_Deutsche med. Wchnschr._, Leipzig, 1890, S. 389.

Footnote 128:

_Arch. russes d. path._, etc., St.-Pétersb., 1900, t. IV, p. 402.

Footnote 129:

“Die Entstehung der Entzündung,” Leipzig, 1891, S. 508.

Footnote 130:

_Compt. rend. Soc. de Biol._, Paris, 1899, p. 568.

Footnote 131:

“Les Oxydases dans la série animale,” Paris, 1897.

Footnote 132:

Stadelmann, _Ztschr. f. Biol._, München, 1887, Bd. XXIV, S. 226; 1888, Bd. XXV, S. 208; Patella, _Ann. univ. di med. e chir._, Milano, 1887. (Cited by Huppert in Neubauer u. Vogel’s _Analyse des Harns_, x^{te} Aufl., Wiesbaden, 1898, S. 599.)

Footnote 133:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1901, Bd. XXIX, S. 531.

Footnote 134:

Sawtchenko (_Arch. russes de Path._, etc., St. Pétersb., 1901, t. XI, p. 455) has observed that leucocytes, after they have absorbed the specific fixative, acquire the property of ingesting red blood corpuscles with extraordinary rapidity. Tarassewitch was able to confirm this fact.

Footnote 135:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1899, Bd. XXV, S. 546.

Footnote 136:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 738.

Footnote 137:

_Deutsche med. Wchnschr._, Leipzig, 1900, S. 61.

Footnote 138:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 369.

Footnote 139:

_Ibid._, p. 577.

Footnote 140:

_Berl. klin. Wchnschr._, 1900, S. 453.

Footnote 141:

We have given a sketch of the actual state of this question of cell poisons or cytotoxins in the _Revue générale des sciences pures et appliquées_, 1901, p. 1.

Footnote 142:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 413.

Footnote 143:

Deutsch, _Compt. rend. XIII congrès internat. de Méd. de Paris_, and _Centralbl. f. Bacteriol. u. Parasitenk._, I^{te} Abt., Jena, 1901, t. XXIX, S. 661; Uhlenhuth, _Deutsche med. Wchnschr._, Leipzig, 1901, S. 82; Wassermann u. Schütze, _Berl. klin. Wchnschr._, 1901, S. 187; [Nuttall and Dinkelspiel, _Journ. of Hyg._, Cambridge, 1901, Vol. I, p. 367; Nuttall, _Brit. Med. Journ._, London, 1902, I, p. 825].

Footnote 144:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 240.

Footnote 145:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVI, S. 5.

Footnote 146:

[Myers, _Lancet_, London, 1900, II, p. 98, and _Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1900, Bd. XXVIII, S. 237.]

Footnote 147:

_Compt. rend. Soc. de biol._, Paris, 1901, p. 51.

Footnote 148:

_Zeitschr. f. physiol. Chem._, Strassburg, 1901, Bd. XXXII, S. 291.

Footnote 149:

_Virchow’s Archiv_, Berlin, 1893, Bd. CXXXI, S. 32.

Footnote 150:

_Zeitschr. f. Hyg._, Leipzig, 1894, Bd. XVIII, S. 83.

Footnote 151:

_München. med. Wchnschr._, 1898, 15 August.

Footnote 152:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1899, Bd. XXVI, S. 349 and 1900, Bd. XXVII, S. 721.

Footnote 153:

“Étude sur la présure et l’antiprésure.” Sceaux, 1900. (_Thèse d. l. Faculté d. Sc. de Paris_, no. 4.)

Footnote 154:

_Arch. internat. de Pharmacodyn._, Bruxelles et Paris, 1898, t. III and IV.

Footnote 155:

_Berl. klin. Wchnschr._, 1898, S. 152.

Footnote 156:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 406.

Footnote 157:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 785.

Footnote 158:

_Ibid._ 1899, t. XIII, p. 285.

Footnote 159:

_Ibid._, Paris, 1900, t. XIV, p. 270.

Footnote 160:

_Berl. klin. Wchnschr._, 1900, S. 684. Ehrlich, “Croonian Lecture,” _Proc. Roy. Soc. London_, 1900, Vol. LXVI, p. 424.

Footnote 161:

_Berl. klin. Wchnschr._, 1901, S. 570.

Footnote 162:

_Deutsche med. Wchnschr._, Leipzig, 1900, S. 431.

Footnote 163:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1901, Bd. XXIX, S. 175.

Footnote 164:

_Berl. klin. Wchnschr._, 1901, S. 251.

Footnote 165:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVI S. 190.

Footnote 166:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 5.

Footnote 167:

_Ibid._, p. 583.

Footnote 168:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 833.

Footnote 169:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1899, Bd. XXVI, S. 352.

Footnote 170:

_Virchow’s Archiv_, Berlin, 1893, Bd. CXXXI, S. 5.

Footnote 171:

_Klin. Jahrb._, Jena, 1897, Bd. VI, S. 299; “Croonian Lecture,” _Proc. Roy. Soc. London_, 1900, Vol. LXVI, p. 424. Ehrlich, Lazarus u. Pincus, “Leukaemie, etc.” in Nothnagel’s _Specielle Pathologie u. Therapie_, Wien, 1901, Bd. VIII, Schlussbetrachtungen, S. 163.

Footnote 172:

Bordet, _Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 499; von Dungern, _München. med. Wchnschr._, 1900, S. 678.

Footnote 173:

_Berl. klin. Wchnschr._, 1901, S. 255.

Footnote 174:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 833.

Footnote 175:

_Brit. Med. Journ._, London, 1897, II, p. 1786; 1898, I, p. 550. _Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 136.

Footnote 176:

_Ztschr. f. Hyg._, Leipzig, 1893, Bd. XIII, S. 357.

Footnote 177:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 240.

Footnote 178:

_Virchow’s Archiv_, Berlin, 1884, Bd. XCVI, S. 177.

Footnote 179:

[English translation, pp. 83–86.]

Footnote 180:

_Bull. Acad. d. sc. de St Pétersb._, 1894, t. XIII, p. 437.

Footnote 181:

_Compt. rend. Acad. d. sc._, Paris, 1886, t. CIII, p. 952.

Footnote 182:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1889, Bd. V, S. 5.

Footnote 183:

_Ann. de l’Inst. Pasteur_, Paris, 1894, t. VIII, p. 696.

Footnote 184:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 301.

Footnote 185:

Cohn’s “Beiträge zur Biologie der Pflanzen,” Breslau, 1876, Bd. II, S. 300.

Footnote 186:

_Compt. rend. Acad. d. sc._, Paris, 1882, t. XCIV, p. 1605.

Footnote 187:

_Virchow’s Archiv_, Berlin, 1884, Bd. XCVII, S. 502.

Footnote 188:

_Centralbl. f. klin. Med._, Bonn, 1888, S. 516.

Footnote 189:

“Untersuch. über d. Immunität d. Frosches gegen Milzbrand,” Ziegler’s _Beitr. z. path. Anat._, Jena, 1888, Bd. III, S. 357.

Footnote 190:

“Beiträge z. Kritik der Metschnikoff’schen Phagocytenlehre,” Inaug. Diss., Königsberg, 1889.

Footnote 191:

_Ztschr. f. Hyg._, Leipzig, 1888, Bd. IV, S. 353.

Footnote 192:

_Virchow’s Archiv_, Berlin, 1888, Bd. CXIV, S. 466.

Footnote 193:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 362.

Footnote 194:

_Arb. a. d. k. Gsndhtsamte_, Berlin, 1894, Bd. IX, S. 497.

Footnote 195:

_Ziegler’s Beitr. z. path. Anat._, Jena, 1890, Bd. VIII, S. 203.

Footnote 196:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1889, Bd. VI, SS. 481 and 529; _Fortschr. d. Med._, Berlin, 1896, Bd. VIII, S. 665; _Ztschr. f. klin. Med._, Berlin, 1891; “Ueber Immunität u. Schutzimpfung,” Schneidemühl’s _Thiermed. Vorträge_, 1892, Bd. II.

Footnote 197:

_Bull. Acad. de méd._, Paris, 1878, p. 440.

Footnote 198:

_Virchow’s Archiv_, Berlin, 1887, Bd. CIX, S. 365.

Footnote 199:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 570.

Footnote 200:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 362.

Footnote 201:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVIII, S. 189.

Footnote 202:

“Untersuchungen ü. die Immunität d. Tauben,” Königsberg, 1889; _Ziegler’s Beitr. z. path. Anat._, Jena, 1890, Bd. VII, S. 49.

Footnote 203:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 38; p. 65.

Footnote 204:

_Ztschr. f. Hyg._, Leipzig, 1892, Bd. XII, S. 348.

Footnote 205:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 426.

Footnote 206:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 561.

Footnote 207:

_Arch. de méd. expér. et d’anat. path._, Paris, 1889, t. I, p. 325.

Footnote 208:

_Virchow’s Archiv_, Berlin, 1887, Bd. CIX, S. 365.

Footnote 209:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 520.

Footnote 210:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 13.

Footnote 211:

_Ann. de l’Inst. Pasteur_, Paris, 1889, t. III, p. 577.

Footnote 212:

_Ztschr. f. Hyg._, Leipzig, 1888, Bd. IV, S. 353.

Footnote 213:

_Ann. de l’Inst. Pasteur_, Paris, 1887, t. I, p. 43.

Footnote 214:

“Untersuchungen ü. die Ursachen der angeborenen u. erworbenen Immunität,” Berlin, 1891, S. 111.

Footnote 215:

_La Cellule_, Lierre et Louvain, 1893, t. IX, p. 337.

Footnote 216:

“Zur Lehre von den Geschswülsten und Infectionskrankheiten,” Wiesbaden, 1899.

Footnote 217:

_Centralbl. f. Bacteriol, u. Parasitenk._, I^{te} Abt., Jena, 1900, Bd. XXVII, SS. 10 und 517.

Footnote 218:

_La Cellule_, Lierre et Louvain, 1894, t. X, p. 7.

Footnote 219:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 68.

Footnote 220:

_Virchow’s Archiv_, Berlin, 1884, Bd. XCVII, S. 516.

Footnote 221:

_Centralbl. f. klin. Med._, Bonn, 1888, No. 38.

Footnote 222:

“Infectionsschutz und Immunität” in Eulenberg’s “Real-Encyclopädie d. ges. Heilkunde,” III^{te} Aufl. (_Encyclop. Jahrbücher_), Wien, 1900, Bd. IX, S. 196.

Footnote 223:

_Centralbl. f. Bacteriol. u. Parasitenk._, Jena, 1888, Bd. IV, SS. 710, 737.

Footnote 224:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 193.

Footnote 225:

_Centralbl. f. Bacterial. u. Parasitenk._, Jena, 1891, Bd. IX, SS. 336, 372.

Footnote 226:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 479.

Footnote 227:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 865.

Footnote 228:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 232.

Footnote 229:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 145.

Footnote 230:

“Om Mjältbrand hos Höns,” Stockholm, 1897.

Footnote 231:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 564.

Footnote 232:

_Arch. russes de pathol._ etc., St Pétersb., 1900, t. IX, p. 578; and Sawtchenko et Melkich, _Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 502.

Footnote 233:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 448.

Footnote 234:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVIII, S. 1.

Footnote 235:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 177.

Footnote 236:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 104.

Footnote 237:

_Arch. de méd. expér. et d’anat. path._, Paris, 1898, t. X, p. 253.

Footnote 238:

_Ziegler’s Beitr. z. path. Anat._, Jena, 1899, Bd. XXV, S. 206.

Footnote 239:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 1; 1892, t. VI, p. 385; 1893, t. VII, p. 755.

Footnote 240:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 179.

Footnote 241:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 202.

Footnote 242:

_Centralbl. f. Bacteriol. u. Parasitenk._, Jena. 1897, Bd. XXI, S. 147.

Footnote 243:

_Arch. de méd. expér. et d’anat. path._, Paris. 1897, t. IX, p. 881.

Footnote 244:

_Arch. f. Hyg._, München u. Leipzig, 1896, Bd. XXVII, S. 234.

Footnote 245:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 770.

Footnote 246:

_Ibid._, 1896, t. X, p. 448.

Footnote 247:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 673.

Footnote 248:

_Arch. f. mikr. Anat._, Bonn, 1893, Bd. XLII, S. 146.

Footnote 249:

_Ztschr. f. Hyg._, Leipzig, 1899. Bd. XXXI, S. 507. See review by Podwyssotsky in the _Arch. russes de Path._, St Pétersb., 1899, t. VIII, p. 257.

Footnote 250:

_Arb. a. d. zool. Inst. d. Univ. Wien_, 1883, tom. V, S. 160.

Footnote 251:

_Biol. Centralbl._, Erlangen, 1883–4, Bd. III, S. 562.

Footnote 252:

_Compt. rend. Acad. d. sc._, Paris, 1880, t. XC, p. 952.

Footnote 253:

_Ann. de l’Inst. Pasteur_, Paris, 1887, t. I, p. 325.

Footnote 254:

_Arch. f. mikr. Anat._, Bonn, 1900, Bd. LVI, S. 868.

Footnote 255:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 928.

Footnote 256:

“Leçons sur la pathologie comparée de l’Inflammation,” Paris, 1892, p. 193; authorised English translation, London, 1893, p. 162.

Footnote 257:

_Arch. f. Physiol._, Leipzig, 1894, S. 200.

Footnote 258:

_Jahresb. d. schles. Gesellsch. f. vaterl. Cultur_, Breslau, 1874.

Footnote 259:

_Deutsche med. Wchnschr._, Leipzig, 1886, S. 617; 1887, S. 745.

Footnote 260:

_Ztschr. f. Hyg._, Leipzig, 1888, Bd. IV, S. 208.

Footnote 261:

_Ztschr. f. Hyg._, Leipzig, 1888, Bd. IV, S. 353.

Footnote 262:

“Les microbes pathogènes,” Paris, 1892.

Footnote 263:

_Arch. f. Hyg._, München u. Leipzig, 1890, Bd. 10, S. 84; _Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1889, Bd. V, S. 817, and Bd. VI, SS. 1, 561; 1890, Bd. VIII, S. 65.

Footnote 264:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1889, Bd. VI, S. 481; _Ztschr. f. klin. Med._, Berlin, 1891, Bde XVIII, XIX.

Footnote 265:

_Ann. de l’Inst. Pasteur_, Paris, 1889, t. III, p. 670.

Footnote 266:

_La Cellule_, Lierre et Louvain, 1894, t. X, p. 7.

Footnote 267:

_München, med. Wchnschr._, 1894, S. 717.

Footnote 268:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 462.

Footnote 269:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVII, S. 272.

Footnote 270:

_Deutsche med. Wchnschr._, Leipzig, 1899, S. 687.

Footnote 271:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 68.

Footnote 272:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1892, Bd. XII, SS. 777, 809; 1893, Bd. XIV, S. 852.

Footnote 273:

_Proc. Roy. Soc. London_, 1892, Vol. LII, p. 267; _Phil. Trans._, London, 1894, (B) Vol. 185, pt. I, p. 279.

Footnote 274:

_München. med. Wchnschr._, 1894, S. 717 and 1897, S. 1320.

Footnote 275:

_Arch. f. Hyg._, München u. Leipzig, 1895, Bd. XXV, S. 105; 1897, Bd. XXVIII, S. 312. _Berl. klin. Wchnschr._, 1896, S. 864.

Footnote 276:

_Arch. f. Hyg._, München u. Leipzig., 1897, Bd. XXXI, p. 1; 1899, Bd. XXXV, S. 135. _München. med. Wchnschr._, 1898, SS. 353, 1109.

Footnote 277:

_Arch. f. Hyg._, München u. Leipzig, 1900, Bd. XXXVII, S. 290.

Footnote 278:

_Arch. f. Hyg._, München u. Leipzig, 1901, Bd. XL, S. 382.

Footnote 279:

_Arch. f. Hyg._, München u. Leipzig, 1895, Bd. XXV, S. 105; _Berl. klin. Wchnschr._, 1896, S. 864.

Footnote 280:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 232.

Footnote 281:

_Ibid._, p. 129.

Footnote 282:

_Deutsche med. Wchnschr._, Leipzig, 1901, S. 4.

Footnote 283:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 209.

Footnote 284:

Since Nuttall’s first paper appeared a certain bactericidal action of the aqueous humour has been observed. This fact should be taken into consideration in the study of the question of the phagocytic origin of the bactericidal substance of the body fluids. If this substance really comes from the phagocytes, it should not be found in the transparent aqueous humour that contains no, or almost no, leucocytes. Now this fluid sometimes destroys a certain number of micro-organisms. This apparent contradiction is explained by the fact that the bactericidal action may be exercised by all kinds of fluids, such as physiological salt solution, nutritive broths, etc. The bactericidal property of the aqueous humour comes into this category. Its action is, as a rule, much more feeble than the action of serums and exudations and is not modified by heating to 55°–56° C. In certain aqueous humours, a little cytase, or true bactericidal substance, may come into play, for we find aqueous humours which coagulate and which, when centrifugalised, show a small deposit of leucocytes. These results have been obtained by Mme. Metchnikoff.

It must not be forgotten also that, even in the bactericidal action of blood serums, a certain factor is the change of medium which the micro-organisms experience with the plasmolytic phenomena which follow. But it is not possible to ascribe to this factor the whole of the bactericidal property of serums and exudations, as is done by Baumgarten (_Arb. a. d. pathol.-anat. Inst. zu Tübingen_, 1899, Bd. III, S. 1, and _Berl. klin. Wchnschr._, 1900, SS. 136, 162, 192), and his pupils Jetter and Walz supported by A. Fischer (_Ztschr. f. Hyg._, Leipzig, 1900, Bd. XXXV, S. 1). The idea of reducing the destruction of bacteria in serums and exudations to the effect of osmotic pressure has been recently elaborately analysed by v. Lingelsheim (_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVII, S. 131). With great justness he comes to the conclusion that “the existence in extravascular blood or in serum, of bactericidal substances acting as soluble ferments can now no longer be denied” (p. 167). In studying this question we must not lose sight of the fact that these bactericidal substances (alexines, complements, or cytases) give rise to the production in the animal organism of antagonistic substances as described by us in the 5th Chapter.

Footnote 285:

_Verhandl. d. Congresses f. inn. Med._, Wiesbaden, 1892, S. 273.

Footnote 286:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 257; 1901, t. XV, p. 312.

Footnote 287:

_Berl. klin. Wchnschr._, 1900, SS. 453, 677.

Footnote 288:

_Deutsche med. Wchnschr._, Leipzig, 1900, S. 790.

Footnote 289:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 303.

Footnote 290:

_Arch. f. Hyg._, München u. Leipzig, 1899, Bd. XXXV, S. 199.

Footnote 291:

_Arch. f. Hyg._, München u. Leipzig, 1901, Bd. XL, S. 375.

Footnote 292:

_Ztschr. f. Biol._, München u. Berlin, 1900, Bd. XL, S. 117.

Footnote 293:

_Sitzungsb. d. naturforsch. Gesellsch. zu Marburg_, 1900.

Footnote 294:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 295.

Footnote 295:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1899, I^{te} Abt., Bd. XXVI, S. 344.

Footnote 296:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 289.

Footnote 297:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 107.

Footnote 298:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1899, t. VI, p. 299; _Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 642.

Footnote 299:

_Compt. rend. Soc. de biol._, Paris, 1891, p. 464.

Footnote 300:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1894, Bd. XVI, S. 415.

Footnote 301:

Article “Immunität” in the 3rd edition of Eulenburg’s _Real-Encyclopädie_, Wien, 1896.

Footnote 302:

_Deutsche med. Wchnschr._, Leipzig, 1894, S. 120 (of Vereins-Beilage).

Footnote 303:

[_Journ. Exper. Med._, New York, 1896, Vol. I, p. 543.]

Footnote 304:

[_Journ. Path. and Bacteriol._, Edin. and London, 1896, Vol. III, p. 328; _Lancet_, London, 1899, Vol. II, p. 332; _Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1899, I^{te} Abt., Bd. XXVI, S. 548.]

Footnote 305:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVI, S. 299.

Footnote 306:

_Arch. de zool. expér._, Paris, 1895, 3^e série, t. III, p. 591.

Footnote 307:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 314.

Footnote 308:

_Ztschr. f. Hyg._, Leipzig, 1890, Bd. VIII, S. 412.

Footnote 309:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVII, S. 355, and _Deutsche med. Wchnschr._, Leipzig, 1896, SS. 97, 119.

Footnote 310:

_Ztschr. f. Hyg._, Leipzig, 1900, Bd. XXXV, S. 1.

Footnote 311:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 433.

Footnote 312:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 462.

Footnote 313:

“Contribution à l’étude du sérum chez les animaux vaccinés,” _Ann. Soc. d. sc. nat. et méd. de Bruxelles_, 1895, t. IV.

Footnote 314:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 308.

Footnote 315:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVI, S. 287.

Footnote 316:

_Deutsche med. Wchnschr._, Leipzig, 1896, S. 120.

Footnote 317:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1896, Bd. XX, S. 761.

Footnote 318:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 767.

Footnote 319:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 375.

Footnote 320:

_Ann. de. l’Inst. Pasteur_, Paris, 1898, t. XII, p. 199.

Footnote 321:

_Ann. Soc. d. sc. méd. et nat. de Bruxelles_, 1895, t. IV.

Footnote 322:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 894.

Footnote 323:

_München. med. Wchnschr._, 1896, SS. 277 and 310.

Footnote 324:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 273.

Footnote 325:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 288.

Footnote 326:

[_Trans. Seventh Internat. Congr. of Hyg. and Demogr._ London, 1892, Vol. II. p. 179;] _Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 465.

Footnote 327:

_Arch. russes de Pathol._, etc., St Pétersb., 1900, t. IX, p. 584; Sawtchenko et Melkich, _Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 503.

Footnote 328:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXI, S. 203.

Footnote 329:

_Ibid._ 1887, Bd. II, S. 110.

Footnote 330:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 755.

Footnote 331:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVII, S. 173.

Footnote 332:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 209.

Footnote 333:

_Compt. rend. Soc. de biol._, Paris, 1889, pp. 250, 330, 627; 1890, pp. 203, 332, 195.

Footnote 334:

“Les microbes pathogènes,” Paris, 1892.

Footnote 335:

_Centralbl. f. Bakteriol. u. Parasitenk._, I^{te} Abt., Jena, 1900, Bd. XXVIII, S. 577.

Footnote 336:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXII, S. 263.

Footnote 337:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 298.

Footnote 338:

_Fortschr. d. Med._, Berlin, 1888, Bd. VI, S. 729.

Footnote 339:

_Ann. de l’Inst. Pasteur_, Paris, 1889, t. III, p. 289.

Footnote 340:

_Arch. f. Hyg._, München u. Leipzig, 1891, Bd. XII, S. 275.

Footnote 341:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXII, S. 515; _Deutsche med. Wchnschr._, Leipzig, 1898, S. 49; _Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVIII, S. 38.

Footnote 342:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 481.

Footnote 343:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 295.

Footnote 344:

_Virchow’s Archiv_, Berlin, 1884, Bd. XCVII, S. 502.

Footnote 345:

_Virchow’s Archiv_, Berlin, 1888, Bd. CXIV, S. 465.

Footnote 346:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 805.

Footnote 347:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 881.

Footnote 348:

_Ann. de l’Inst. Pasteur_, Paris, 1887, t. I, p. 42.

Footnote 349:

_Ztschr. f. Hyg._, Leipzig, 1888, Bd. IV, S. 353.

Footnote 350:

_Ztschr. f. Hyg._, Leipzig, 1899, Bd. XXXI, S. 89.

Footnote 351:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1899, Vol. VI, pp. 303, 338.

Footnote 352:

“Infectionsschutz und Immunität” in Eulenburg’s “Real-Encyclopädie d. ges. Heilkunde,” III^{te} Aufl. (_Encyclop. Jahrbücher_), Wien, 1900, Bd. IX, S. 202.

Footnote 353:

_Compt. rend. Soc. de biol._, Paris, 1891, p. 538; 1895, pp. 124, 224; _Rev. de méd._, Paris, 1892.

Footnote 354:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 593.

Footnote 355:

_La Cellule_, Lierre et Louvain, 1895, t. XI, p. 175; _Bull. Acad. roy. de méd. de Belg._, Bruxelles, 1895, No. 11.

Footnote 356:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 194.

Footnote 357:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1899, Vol. VI, p. 73; Behring’s “Beitr. z. experim. Therapie,” 1899, Bd. I.

Footnote 358:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 192.

Footnote 359:

_Bulletin No. 1, Bureau of Animal Industry, U.S. Dep. of Agric._, Washington, 1893.

Footnote 360:

“Reisebericht über Rinderpest etc.,” Berlin, 1898.

Footnote 361:

_Rec. de méd. vét._, Paris, juillet, 1900, and _Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 121.

Footnote 362:

_Ztschr. f. Hyg._, Leipzig, 1899, Bd. XXX, S. 251.

Footnote 363:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 673.

Footnote 364:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 462.

Footnote 365:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 289.

Footnote 366:

_Centralbl. f. Bacteriol. u. Parasitenk._, Jena, 1896, I^{te} Abt., Bd. XIX, S. 191.

Footnote 367:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVI, S. 9.

Footnote 368:

_München. med. Wchnschr._, 1892, SS. 119, 982.

Footnote 369:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 647.

Footnote 370:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 289.

Footnote 371:

_Compt. Rend. Soc. de Biol._, Paris, 1889, p. 667.

Footnote 372:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 473.

Footnote 373:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 462.

Footnote 374:

_München. med. Wchnschr._, 1896, S. 285 [cf. also Durham, _Journ. Path. and Bacteriol._, Edin. and London, 1897, Vol. IV, p. 13, and 1901, Vol. VII, p. 240; _Brit. Med. Journ._, London, 1898, Vol. II, p. 588].

Footnote 375:

_Wien. klin. Wchnschr._, 1896, SS. 183, 204.

Footnote 376:

_Bull. Soc. méd. d. hôp._, Paris, 1896, 26 juin [_Semaine méd._, Paris, 1896, p. 259].

Footnote 377:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 225.

Footnote 378:

_Rev. gén. d. sc. pures et appliq._, Paris, 1896, t. VII, p. 770.

Footnote 379:

_Wien. klin. Wchnschr._, 1899, S. 1.

Footnote 380:

_Ann. de. l’Inst. Pasteur_, Paris, 1898, t. XII, p. 688.

Footnote 381:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 289.

Footnote 382:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1894, Bd. XVI, S. 235.

Footnote 383:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena. I^{te} Abt., 1898, Bd. XXIII, SS. 9, 71, 131.

Footnote 384:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVIII, S. 406.

Footnote 385:

_Fifteenth Ann. Rep. of the Bureau of Animal Industry for 1898_, Washington, 1899, p. 348, Pl. XI.

Footnote 386:

Widal et Sicard, _Bull. et Mém. Soc. méd. d. hôp._, Paris, 1896, p. 684 [_Semaine méd._, Paris, 1896, p. 514].

Footnote 387:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 411.

Footnote 388:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 277.

Footnote 389:

_Arch. f. Hyg._, München u. Leipzig, 1898, Bd. XXXIII, S. 124.

Footnote 390:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 260.

Footnote 391:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 225.

Footnote 392:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 481.

Footnote 393:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 209.

Footnote 394:

_Arch. de méd. expér. et d’anat. path._, Paris, 1896, 1^{re} série, t. VIII, p. 759.—Bensaude, “Le phénomène de l’agglutination des microbes,” Paris, 1897, p. 252.

Footnote 395:

_Compt. rend. Soc. de biol._, Paris, 1897, p. 104.

Footnote 396:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 376.

Footnote 397:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVII, S. 272.

Footnote 398:

_Ztschr. f. Hyg._, Leipzig, 1899, Bd. XXX, S. 19.

Footnote 399:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1899, vol. VI, p. 299.

Footnote 400:

_Compt. rend. Acad. d. Sc._, Paris, 1888, t. CVII, p. 750.

Footnote 401:

Behring u. Kitasato, _Deutsche med. Wchnschr._, Leipzig, 1890, S. 1113.

Footnote 402:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 299.

Footnote 403:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVI, S. 268; 1894, Bd. XVIII, S. 1.

Footnote 404:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXI, S. 203; _Deutsche med. Wchnschr._, Leipzig, 1896, SS. 185, 735.

Footnote 405:

“La sérothérapie de la fièvre typhoïde,” Bruxelles, 1896.

Footnote 406:

_Bull. Soc. méd. d. hôp._, Paris, 1893, 27 janvier.

Footnote 407:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1896, I^{te} Abt., Bd. XIX, S. 51; _Festschr. z. 100 jähr. Stiftungsfeier d. med. chir. Friedr. Wilh. Instituts_, 1895.

Footnote 408:

_Hygien. Rundschau_, Berlin, 1894, IV Jahrg., SS. 97, 145.

Footnote 409:

_Berl. klin. Wchnschr._, 1899, S. 6.

Footnote 410:

“Typhusepidemien und Trinkwasser,” Jena, 1898, S. 26.

Footnote 411:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 298.

Footnote 412:

_Berl. klin. Wchnschr._, 1892, S. 970.

Footnote 413:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII p. 411.

Footnote 414:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVI, S. 268.

Footnote 415:

See Lazarus, _Berl. klin. Wchnschr._, 1892, S. 1072.

Footnote 416:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXIII, S. 149.

Footnote 417:

_Ann. de l’Inst. Pasteur_, Paris, 1902, t. XVI, p. 94.

Footnote 418:

_Deutsche med. Wchnschr._, Leipzig, 1901, S. 4.

Footnote 419:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 209.

Footnote 420:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXI, S. 203.

Footnote 421:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 300.

Footnote 422:

_Ztschr. f. Hyg._, Leipzig, 1895, Bd. XIX, S. 82.

Footnote 423:

[_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1895, Bd. XVIII, S. 744]; _Rir. d’Ig. e San. Pubbl._, Torino, 1896, t. VII, nos. 18–19; _ibid._ 1901, t. XII, p. 212.

Footnote 424:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 785.

Footnote 425:

_Ztschr. f. Hyg._, Leipzig, 1897, Bd. XXV, S. 301.

Footnote 426:

_Ztschr. f. Hyg._, Leipzig, 1899, Bd. XXXI, S. 89.

Footnote 427:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 769.

Footnote 428:

_Ztschr. f. Hyg._, Leipzig, 1897, Bd. XXIV, S. 327.

Footnote 429:

_Deutsche med. Wchnschr._, Leipzig, 1900, S. 781.

Footnote 430:

“La Malaria secondo le nuove recherche,” Roma, 1899, p. 86 [translated into English by Eyre from the 2nd Italian edition under the title “Malaria according to the new researches,” London, 1900]. “Die Malaria” [German translation of same] in Behring’s “Beiträge z. exper. Therapie,” 1900, Bd. I, Hft. 3.

Footnote 431:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 343.

Footnote 432:

“La ‘Tristeza’ ou Malaria bovine dans la République Argentine,” Buenos Ayres, 1900, p. 142.

Footnote 433:

_Bull. Soc. centr. de méd. vétérin._, Paris, 1900, séances des 12 et 26 juillet.

Footnote 434:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 321.

Footnote 435:

_Ann. de l’Inst. Pasteur_, Paris, 1894, t. VIII, p. 1; _Arch. de méd. expér._, Paris, 1898, t. X, p. 725; _Arch. russes de Path._ &c., St Pétersb., 1898.

Footnote 436:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 615.

Footnote 437:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, p. 802.

Footnote 438:

“Untersuchungen über die Aetiologie der Wundinfectionskrankheiten,” Leipzig, 1878. [Translated into English in the New Sydenham Society’s Series, London, 1880, Vol. LXXXVIII, under the title “On Traumatic Infective Diseases.”]

Footnote 439:

_Arb. a. d. K. Gsndhtsamt._, Berlin, 1885, Bd. I, S. 46.

Footnote 440:

_Arb. a. d. K. Gsndhtsamt._, Berlin, 1885, Bd. I, S. 57.

Footnote 441:

_Compt. rend. Acad. d. sc._, Paris, 1883, t. XCVII, p. 1163.

Footnote 442:

_La Cellule_, Lierre et Louvain, 1895, t. XI, p. 177.

Footnote 443:

_Ann. de l’Inst. Pasteur_, Paris, 1887, t. I, p. 42.

Footnote 444:

_Compt. rend. Soc. de biol._, Paris, 1889–1891.

Footnote 445:

“Essai d’une théorie de l’infection.” Berlin, 1890.

Footnote 446:

Charrin, _Compt. rend. Soc. de biol._, Paris, 1890, pp. 203, 332; Roger, _ibid._, 1890, p. 573, and _Rev. gén. d. sc. pures et appliq._, Paris, 1891, p. 410.

Footnote 447:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 273.

Footnote 448:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 231.

Footnote 449:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 177.

Footnote 450:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 481.

Footnote 451:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 769.

Footnote 452:

_Compt. rend. Acad. d. sc._, Paris, 1880, t. XC, p. 1033.

Footnote 453:

_Compt. rend. Soc. de biol._, Paris, 1899, p. 432.

Footnote 454:

_Compt. rend. Acad. d. sc._, Paris, 1880, t. XC, p. 1526.

Footnote 455:

_Compt. rend. Soc. de biol._, Paris, 1890, p. 294.

Footnote 456:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 563.

Footnote 457:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 295.

Footnote 458:

_Berl. klin. Wchnschr._, 1891, p. 157.

Footnote 459:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVII, S. 272.

Footnote 460:

_Berl. klin. Wchnschr._, 1898, S. 209.

Footnote 461:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 689.

Footnote 462:

Ehrlich, Lazarus u. Pinkus, “Leukaemie, etc.” in Nothnagel’s “Specielle Pathologie u. Therapie,” Wien, 1901, Bd. VIII, I Theil, III Heft. Schlussbetrachtungen. S. 163.

Footnote 463:

_München. med. Wchnschr._, 1901, p. 697.

Footnote 464:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 315.

Footnote 465:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 193.

Footnote 466:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXI, S. 203.

Footnote 467:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 773.

Footnote 468:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 453.

Footnote 469:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 371.

Footnote 470:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 290.

Footnote 471:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 312.

Footnote 472:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 492.

Footnote 473:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 289.

Footnote 474:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 800.

Footnote 475:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1899, I Abt., Bd. XXVI, S. 428.

Footnote 476:

_Ztschr. f. Hyg._, Leipzig, 1899, Bd. XXXI, S. 110.

Footnote 477:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 308.

Footnote 478:

Marmorek, _Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 593.

Footnote 479:

_La Cellule_, Lierre et Louvain, 1895, t. XI, p. 175, and _Bull. Acad. roy. de méd. de Belg._, Bruxelles, 1895.

Footnote 480:

_Bull. Acad. roy. de méd. de Belg._, Bruxelles, 1896.

Footnote 481:

_Habilitations-Schrift_, Marburg, 1899, and in von Behring’s “Beiträge zur experimentellen Therapie,” 1899, Bd. I, S. 40.

Footnote 482:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 177.

Footnote 483:

_Ztschr. f. Hyg._, Leipzig, 1899, Bd. XXX, S. 251.

Footnote 484:

Laveran, “Titres et travaux scientifiques,” Paris, 1901, p. 39. _Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 673.

Footnote 485:

_Deutsche med. Wchnschr._, Leipzig, 1900, S. 285.

Footnote 486:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 225.

Footnote 487:

_Deutsche med. Wchnschr._, 1901, S. 4.

Footnote 488:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVI, S. 287.

Footnote 489:

“La Sérothérapie de la fièvre typhoïde,” Bruxelles, 1896, p. 69.

Footnote 490:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVII, S. 199.

Footnote 491:

_Compt. rend. Acad. d. sc._, Paris, 1877, t. LXXXV, p. 107.

Footnote 492:

_Arch. f. Hyg._, München u. Leipzig, 1887, Bd. VI, S. 442.

Footnote 493:

_Virchow’s Archiv_, Berlin, 1887, Bd. CVIII, S. 494.

Footnote 494:

_London Medical Record_, 1887.

Footnote 495:

_Compt. rend. Acad. d. sc._, Paris, 1889, t. CVIII, p. 713.

Footnote 496:

_Ann. d. Microgr._, Paris, 1889, p. 465.

Footnote 497:

_Compt. rend. Acad. d. sc._, Paris, 1889, t. CIX, p. 985.

Footnote 498:

_Ann. de l’Inst. Pasteur_, Paris, 1890, t. IV, p. 689.

Footnote 499:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVIII, S. 177.

Footnote 500:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1893, Bd. XIII, S. 426.

Footnote 501:

_Proc. Roy. Soc. London_, 1887, Vol. XLII, p. 17.

Footnote 502:

_Compt. rend. Soc. de biol._, Paris, 1893, pp. 294, 618; 1898, p. 344. “Le tétanos,” Paris, 1899, p. 25.

Footnote 503:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 597.

Footnote 504:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1900, Vol. VII, p. 265.

Footnote 505:

“Traité sur le venin de la vipère,” Florence, 1781.

Footnote 506:

_Arch. de physiol. norm. et path._, Paris, Année XXVI, 1894, p. 423.

Footnote 507:

“Le venin des serpents,” Paris, 1896, p. 40.

Footnote 508:

“Allgemeine Therapie der Infectionskrankheiten,” Berlin u. Wien, 1899, S. 992.

Footnote 509:

_Compt. rend. Soc. de biol._, Paris, 1891, p. 462; _Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 229.

Footnote 510:

Article: _Infectionsschutz und Immunität_ in Eulenburg’s “Real-encyclopädie d. ges. Heilkunde” (Encyclop. Jahrbücher), Wien, 1900, Bd. IX, S. 203.

Footnote 511:

_Deutsche med. Wchnschr._, Leipzig, 1898, S. 373.

Footnote 512:

_Vrach_, St Petersburg, 1897, p. 964.

Footnote 513:

_Compt. rend. Soc. de biol._, Paris, 1899, p. 77; _Bull. Muséum d. hist. nat._, Paris, 1895, t. I, p. 294.

Footnote 514:

_Deutsche med. Wchnschr._, Leipzig, 1898, S. 629.

Footnote 515:

_Compt. rend. Soc. de biol._, Paris, 1895, p. 639.

Footnote 516:

_Bull. Muséum d’hist. nat._, Paris, 1896, t. II, p. 100.

Footnote 517:

“Le venin des serpents,” Paris, 1896, p. 43.

Footnote 518:

The temporary immunity of the marmot (amongst mammals) against tetanus toxin must be considered separately. According to Billinger and Dönitz the marmot is insusceptible to this poison during its winter sleep. But once it is awakened it readily contracts tetanus. H. Meyer, Halsey and Ransom have observed the same fact in hibernating bats that have been waked up. In these cases the immunity is dependent on the low temperature which approximates these examples to that of the natural immunity of the frog against the same toxin.

Footnote 519:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1894, Bd. XVI, S. 415.

Footnote 520:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 225.

Footnote 521:

“Allgemeine Therapie der Infectionskrankheiten,” Berlin u. Wien, 1899, S. 982.

Footnote 522:

“Essai d’une théorie de l’infection,” Berlin, 1890; “Les microbes pathogènes,” Paris, 1892, p. 33.

Footnote 523:

_Ann. de l’Inst. Pasteur_, Paris, 1888, t. II, p. 629; 1899, t. III, p. 273.

Footnote 524:

_Berl. klin. Wchnschr._, 1890, S. 717.

Footnote 525:

_Berl. klin. Wchnschr._, 1890, No. 11.

Footnote 526:

_Berl. klin. Wchnschr._, 1890, No. 49.

Footnote 527:

_Deutsche med. Wchnschr._, Leipzig, 1890, SS. 1145, 1245.

Footnote 528:

_Deutsche med. Wchnschr._, Leipzig, 1891, SS. 976, 1218.

Footnote 529:

_Compt. rend. Soc. de biol._, Paris, 1894, p. 111.

Footnote 530:

_Compt. rend. Soc. de biol._, Paris, 1894, pp. 120, 204. [Cf. also Fraser, _Brit. Med. Journ._, London, 1895, Vol. I, p. 1309 and II, p. 416; _Nature_, London, 1896, Vol. LIII, p. 571.]

Footnote 531:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 683.

Footnote 532:

“Le venin des serpents,” Paris, 1896, p. 54.

Footnote 533:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 316.

Footnote 534:

_Berl. klin. Wchnschr._, 1890, No. 49.

Footnote 535:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 225.

Footnote 536:

_Compt. rend. Acad. d. sc._, Paris, 1894, t. CVIII, p. 288; _Compt. rend. Soc. de biol._, Paris, 1894, p. 111.

Footnote 537:

_Deutsche med. Wchnschr._, Leipzig, 1890, SS. 1145, 1245.

Footnote 538:

_Bull. Acad. de méd._, Paris, 1895, t. XXXIV, p. 216.

Footnote 539:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXI, S. 485.

Footnote 540:

“On the preparation of a potent antidiphtheria serum,” St Pétersbourg, 1897 (in Russian) [cf. _Berl. klin. Wchnschr._, 1897, S. 720].

Footnote 541:

“Allgemeine Therapie der Infectionskrankheiten,” Berlin u. Wien, 1899, S. 1093.

Footnote 542:

_Deutsche med. Wchnschr._, Leipzig, 1898, S. 597.

Footnote 543:

_Ztschr. f. Hyg._, Leipzig, 1897, Bd. XXIV, S. 425.

Footnote 544:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, pp. 568, 801.

Footnote 545:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVI, S. 325.

Footnote 546:

_Compt. rend. du Congrès internat. de méd. de Paris_ (Section de bactériologie et parasitologie), 1901, p. 40.

Footnote 547:

_Compt. rend. du Congrès internat. de méd. de Paris_ (Section de bactériologie et parasitologie), 1901, p. 45; _Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVII, S. 250.

Footnote 548:

_Deutsche med. Wchnschr._, Leipzig, 1895, S. 457.

Footnote 549:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 257.

Footnote 550:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXII, S. 312.

Footnote 551:

“Allgemeine Therapie der Infectionskrankheiten,” Berlin u. Wien, 1899, S. 1052.

Footnote 552:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 318.

Footnote 553:

_Arch. de méd. expér. et d’anat. path._, Paris, 1897, t. IX, p. 770.

Footnote 554:

_Journ. de physiol. et de path. gén._, Paris, 1900, t. II, p. 973.

Footnote 555:

_Deutsche med. Wchnschr._, Leipzig, 1890, S. 1113.

Footnote 556:

“Die praktischen Ziele der Blutserumtherapie,” Leipzig, 1892, S. 52.

Footnote 557:

_Ztschr. f. physiol. Chem._, Strassburg, 1901, Bd. XXXII, S. 318.

Footnote 558:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 81.

Footnote 559:

_Ztschr. f. Hyg._, Leipzig, 1892, Bd. XII, S. 183.

Footnote 560:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVIII, S. 248.

Footnote 561:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 324.

Footnote 562:

_Compt. rend. Soc. de biol._, Paris, 1891, p. 462; _Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 229.

Footnote 563:

_Arch. f. exper. Path. u. Pharmakol._, Leipzig, 1893, Bd. XXXI, S. 371.

Footnote 564:

_Berl. klin. Wchnschr._, 1893, S. 1266.

Footnote 565:

_München, med. Wchnschr._, 1893, S. 480.

Footnote 566:

_Ann. de l’Inst. Pasteur_, Paris, 1894, t. VIII, p. 725.

Footnote 567:

“Le venin des serpents,” Paris, 1896, p. 58.

Footnote 568:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXII, S. 263.

Footnote 569:

_La Cellule_, Lierre et Louvain, 1896, t. XI, p. 359; _Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 580.

Footnote 570:

_Arch. f. Hyg._, München u. Leipzig, 1897, Bd. XXX, S. 348.

Footnote 571:

Gheorghiewsky, _Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 298.

Footnote 572:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVI, S. 330.

Footnote 573:

[At a meeting held at St Bartholomew’s Hospital, London, cited by Stephens and Myers in _Journ. Path. and Bacteriol._, Edin. and London, 1898, vol. V, p. 280.]

Footnote 574:

_Fortschr. d. Med._, Berlin, 1897, Jahrg. XV, S. 41.

Footnote 575:

_Proc. Roy. Soc. London_, 1898, Vol. LXIII, p. 423.

Footnote 576:

_Klin. Jahrbuch._, Berlin, 1897, Bd. VI, S. 13 [of reprint].

Footnote 577:

_Fortschr. d. Med._, Berlin, 1897, Jahrg. XV, S. 657; _München. med. Wchnschr._, 1898, S. 321.

Footnote 578:

“Experimentelle Untersuchungen über die Grenzen der Heilungsmöglichkeit des Tetanus,” Marburg, 1895, SS. 14, 21.

Footnote 579:

Lubarsch u. Ostertag’s “Ergebnisse d. allgem. Pathologie u. patholog. Anatomie,” Wiesbaden, IV Jahrg. (for 1897), S. 121.

Footnote 580:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1896, Vol. III, p. 77.

Footnote 581:

_Ztschr. f. Hyg._, Leipzig, 1895, Bd. XX, S. 210.

Footnote 582:

_Centralbl. f. inn. Med._, Leipzig, 1895, Jahrg. XVI, SS. 913, 937.

Footnote 583:

_Arch. f. exper. Path. u. Pharmakol._, Leipzig, 1896, Bd. XXXVII, S. 191.

Footnote 584:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 703.

Footnote 585:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 225.

Footnote 586:

“Die Werthbemessung d. Diphtherieheilserums” (_Klin. Jahrb._, Berlin, 1897, p. 20 of reprint).

Footnote 587:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 98.

Footnote 588:

_Deutsche med. Wchnschr._, Leipzig, 1893, S. 1253; “Allgemeine Therapie der Infectionskrankheiten” in Eulenburg u. Samuel’s “Lehrb. d. allg. Therapie,” Berlin u. Wien, 1899, Bd. III, S. 1051.

Footnote 589:

_Berl. klin. Wchnschr._, 1901, S. 157.

Footnote 590:

_Ztschr. f. Hyg._, Leipzig, 1895, Bd. XIX, S. 109.

Footnote 591:

“Allgemeine Therapie der Infectionskrankheiten,” in Eulenburg u. Samuel’s “Lehrb. d. allg. Therapie,” Berlin u. Wien, 1899, Bd. III.

Footnote 592:

“Experimentelle Untersuchungen über die Grenzen der Heilungsmöglichkeit des Tetanus,” Marburg, 1895, SS. 18, 19.

Footnote 593:

_Berl. klin. Wchnschr._, 1901, S. 157.

Footnote 594:

_Ztschr. f. Heilk._, Berlin, 1901, Bd. XXII, S. 1.

Footnote 595:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVII, S. 194.

Footnote 596:

_Compt. rend. Soc. de biol._, Paris, 1891, p. 464.

Footnote 597:

_Berlin klin. Wchnschr._, 1901, S. 157. The idea of immunising monkeys against diphtheria was suggested to von Behring by the fact that the immunity conferred by serums was the more durable the nearer the relation between the serum used and the blood of the species which receives the protective injection. Von Behring supposed that the diphtheria antitoxin, introduced into the human body, would be maintained there longer, if the antitoxic serum injected came from monkeys, species much nearer man than is the horse, the usual source of antidiphtheria serum. The immunity conferred by this horse serum is generally of very short duration.

Footnote 598:

Ehrlich’s antitoxic unit is adopted by most investigators not only in Germany, but also in other countries. This unit corresponds to 1 c.c. of serum capable of neutralising 100 lethal doses of a standard toxin, i.e. that used to establish the first standard of antitoxin. The serum must be injected after being mixed _in vitro_ with the toxin. The neutralisation must be complete and give rise to no symptom of intoxication.

Footnote 599:

These observations were communicated to me by M. Prevôt, the director of the serotherapeutic station of the Pasteur Institute at Garches.

Footnote 600:

_Deutsche med. Wchnschr._, Leipzig, 1893, SS. 1253, 1254.

Footnote 601:

Article “Immunität” in Eulenburg’s _Realencyclopädie_, III^{te} Aufl., Wien, 1896; see also his “Allgemeine Therapie d. Infectionskrankheiten,” in Eulenburg u. Samuel’s “Lehrb. d. allg. Therapie,” Berlin u. Wien, 1899, Bd. III, SS. 996, 997.

Footnote 602:

_Op. cit. supra_ p. 370, S. 19.

Footnote 603:

_München. med. Wchnschr._, 1893, S. 380.

Footnote 604:

“Immunität” in Weyl’s “Handbuch der Hygiene,” Jena, 1897, Bd. IX, S. 48.

Footnote 605:

_München. med. Wchnschr._, 1898, p. 321.

Footnote 606:

_Deutsche med. Wchnschr._, Leipzig, 1891, SS. 976, 1218; [_Ztschr. f. Hyg._, Leipzig, 1892, Bd. XII, S. 183].

Footnote 607:

“Allgemeine Therapie der Infectionskrankheiten” in Eulenburg u. Samuel’s “Lehrbuch der allgemeine Therapie,” Berlin u. Wien, 1899, Bd. III, S. 997.

Footnote 608:

_Journ. Path. and Bacteriol._, Edin. and London, 1900, Vol. VI, p. 180.

Footnote 609:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 82.

Footnote 610:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 763.

Footnote 611:

_Op. cit. supra_, p. 363, IV Jahrg., S. 122.

Footnote 612:

_Compt. rend. Acad. d. sc._, Paris, 1898, t. CXXVI, p. 1229.

Footnote 613:

_Ztschr. f. Hyg._, Leipzig, 1897, Bd. XXIV, S. 514.

Footnote 614:

“Die Werthbemessung des Diphtherieheilserums” (_Klin. Jahrb._, Berlin, 1897, Bd. VI), SS. 13–17 of reprint.

Footnote 615:

_Berl. klin. Wchnschr._, 1898, S. 5.

Footnote 616:

_Deutsche med. Wchnschr._, Leipzig, 1898, S. 68.

Footnote 617:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 91.

Footnote 618:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, pp. 81, 263.

Footnote 619:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 156.

Footnote 620:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 225.

Footnote 621:

_München. med. Wchnschr._, 1898.

Footnote 622:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 801.

Footnote 623:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 81.

Footnote 624:

_Compt. rend. Soc. de biol._, Paris, 1898, p. 602.

Footnote 625:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 238.

Footnote 626:

_l.c._ p. 343.

Footnote 627:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXVII, S. 213.

Footnote 628:

_Compt. rend. Acad. d. sc._, Paris, 1897, p. 1053; and 1898, p. 431; _Compt. rend. Soc. de biol._, Paris, 1897, p. 1057; and 1898, p. 153.

Footnote 629:

_Ann. de l’Insl. Pasteur_, Paris, 1899, t. XIII, p. 126.

Footnote 630:

_Deutsche med. Wchnschr._, Leipzig, 1901, S. 194.

Footnote 631:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 244.

Footnote 632:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 465.

Footnote 633:

_Arch. internat. de Pharmacodyn._, Gand et Paris, 1900, vol. VII, p. 65.

Footnote 634:

_Semaine méd._, Paris, 1899, p. 411.

Footnote 635:

_Deutsche med. Wchnschr._, Leipzig, 1897, S. 428.

Footnote 636:

_l.c._ p. 229.

Footnote 637:

_Compt. rend. Congrès internat. de Médicine de Paris_, Section de bactériologie et de parasitologie, Paris, 1891, p. 30.

Footnote 638:

_München. med. Wchnschr._, 1898, S. 321.

Footnote 639:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 808.

Footnote 640:

“Les réactions leucocytaires, vis-à-vis de certaines toxines,” Paris, 1894.

Footnote 641:

_Ann. de l’Inst. Pasteur_, Paris, 1891, t. V, p. 1.

Footnote 642:

“Cinquantenaire de la Société de Biologie,” Volume jubilaire, Paris, 1899, p. 202.

Footnote 643:

The rapid disappearance of poisons from the blood is proved also by the experiments of von Behring, Dönitz, Decroly and Rousse (_Arch. internat. de Pharmacodyn._, Gand et Paris, 1899, t. VI, p. 211) on snake venom and diphtheria and tetanus toxins, as likewise by those of Heymans and Masoin (_Ibid._, 1901, t. VIII, p. 1) on the malonic and pyrotartaric nitrites. These poisons, within a few minutes of their injection into the veins, are absorbed by the cell elements.

Footnote 644:

“Contribution à l’étude physiologique du leucocyte,” Paris, 1901, p. 39.

Footnote 645:

_Ann. de l’Inst. Pasteur_, Paris, 1894, t. VIII, p. 719.

Footnote 646:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, pp. 49, 209.

Footnote 647:

See Besredka, _op. cit._, p. 50, for its approximate composition and distinction from ordinary yellow trisulphide.

Footnote 648:

_Arb. d. pharmak. Instit. z. Dorpat_, 1893, 1894, Bde VII-X.

Footnote 649:

_Ann. de l’Inst. Pasteur_, Paris, 1894, t. VIII, p. 719.

Footnote 650:

Lubarsch u. Ostertag’s _Ergebnisse d. allg. Path._, Jahrg. IV for 1897, Wiesbaden, 1899, S. 107.

Footnote 651:

_Arb. d. pharmak. Instit. z. Dorpat_, 1893, Bd. IX, S. 27.

Footnote 652:

Communication to the XIIIth Intern. Congress of Medicine in Paris, 1900.

Footnote 653:

“Les toxines microbiennes et animales,” Paris, 1896.

Footnote 654:

In Bouchard’s _Traité de Pathologie générale_, Paris, 1900, t. III, 2^{me} partie, article “Inflammation.”

Footnote 655:

Römer’s recent researches (_Arch. f. Ophth._, Leipzig, 1901, Bel. LII, S. 72) on anti-abrin accord very well with our hypothesis. He was able to demonstrate that the spleen, the bone-marrow, and the conjunctiva of the eye, when submitted to the influence of abrin, contain a notable quantity of anti-abrin. Now these three organs are very rich in phagocytes.

Footnote 656:

_Virchow’s Archiv_, Berlin, 1884, Bd. XCVI, S. 192.

Footnote 657:

_Arch. de Biol._, Gand et Leipzig, 1893, t. XIII, p. 245.

Footnote 658:

_Ann. de dermat. et de syph._, Paris, 1900, t. X, p. 729.

Footnote 659:

von Graefe’s _Arch. f. Ophth._, Leipzig, 1894, Bd. XL, S. 130.

Footnote 660:

Deutschmann’s _Beitr. z. Augenheilk_, Hamburg u. Leipzig, 1893, Hft. VIII.

Footnote 661:

_op. cit. supra._

Footnote 662:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 210.

Footnote 663:

_Arch. d’anat. microsc._, Paris, 1898, t. II, pp. 44, 177.

Footnote 664:

[_Med.-Chir. Trans._, London, 1895, Vol. LXXVIII, p. 239]; _The Lancet_, London, 1896, Vol. I, p. 86; _Brit. Med. Journ._, London, 1896, Vol. I, p. 137.

Footnote 665:

_Compt. rend. Soc. de biol._, Paris, 1893, p. 756.

Footnote 666:

_München. med. Wchnschr._, 1896, S. 730.

Footnote 667:

Batzaroff, “La pneumonie pesteuse expérimentale,” _Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 385.

Footnote 668:

“La Lèpre,” Paris, 1894.

Footnote 669:

_München. med. Wchnschr._, 1897, S. 1063.

Footnote 670:

_Presse méd._, Paris, 1899, 8 avril.

Footnote 671:

“Untersuchungen über Staubinhalation,” Leipzig, 1885.

Footnote 672:

“Eingangspforten der Infectionsorganismen,” Berlin, 1881.

Footnote 673:

_Mitth. aus der Brehmer’schen Heilanstalt_, 1899, S. 297.

Footnote 674:

“Experim. Unters. ii. d. Eindringen path. Microorganismen,” Königsberg, 1888, [and in Ziegler’s _Beitr. z. path. Anat._, Jena, 1888, Bd. II, S. 411].

Footnote 675:

_Arch. f. Hyg._, München u. Leipzig, 1887, Bd. VIII, S. 145.

Footnote 676:

Baumgarten’s _Arb. auf d. Geb. d. path. Anat._ etc., Braunschweig, 1892, Bd. I, S. 450.

Footnote 677:

“Der Untergang pathog. Schimmelpilze im Körper,” Bonn, 1887.

Footnote 678:

“Die acute Entzündung der Lunge,” Bonn, 1886.

Footnote 679:

“Ueb. d. Untergang des Staphylococcus,” etc., Bonn, 1887.

Footnote 680:

_Ann. de l’Inst. Pasteur_, Paris, 1889, t. III, p. 337.

Footnote 681:

_Compt. rend. Soc. de biol._, Paris, 1897, p. 265.

Footnote 682:

“Die Mikroorganismen der Mundhöhle,” Leipzig, 2^{te} Aufl., 1892.

Footnote 683:

“La saliva umana,” Siena, 1891, and _Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1891, Bd. X, S. 817.

Footnote 684:

_op. cit._

Footnote 685:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 545.

Footnote 686:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 510.

Footnote 687:

“Allgemeine Therapie der Infectionskrankheiten,” in Eulenburg u. Samuel’s “Lehrb. d. allg. Therapie,” Berlin u. Wien, 1899, Bd. III, S. 980.

Footnote 688:

_Arch. de méd. expér. et d’anat. path._, Paris, 1889, t. I, p. 370.

Footnote 689:

_Deutsche med. Wchnschr._, Leipzig, 1885, no. 49.

Footnote 690:

Amongst this acidophile flora one species merits particular attention. This is a spirillum, discovered by Bizzozero in the mucous membrane of the stomach of the dog. Salomon (_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1896, Bd. XIX, S. 433) has studied this organism, not only in the dog, but in the cat and Norway rat. Multiplying on the mucous membrane, the very mobile spirillum penetrates into the epithelial cells or is met with inside vacuoles. These latter being in communication with the external medium, the spirilla can readily penetrate by the openings. This fact has, then, nothing in common with phagocytosis, where it is the cell which ingests the micro-organisms by means of its amoeboid movements.

Footnote 691:

Von Volkmann’s _Samml. klin. Vortr._, Leipzig, 1898, no. 38, S. 290.

Footnote 692:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 510.

Footnote 693:

_Compt. rend. Soc. de biol._, Paris, 1892, p. 153.

Footnote 694:

_Compt. rend. Soc. de biol._, Paris, 1897, p. 830, and Charrin, “Les défenses naturelles de l’organisme,” Paris, 1898, p. 128.

Footnote 695:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1898, Bd. XXIII, SS. 840, 880.

Footnote 696:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 517.

Footnote 697:

_Deutsche med. Wchnschr._, Leipzig, 1891, SS. 976, 1218.

Footnote 698:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1896, Bd. XIX, S. 442.

Footnote 699:

_Berl. klin. Wchnschr._, 1900, S. 553.

Footnote 700:

_Compt. rend. Acad. d. sc._, Paris, 1880, t. XCI, p. 86.

Footnote 701:

_Fortschr. d. Med._, Berlin, 1888, Bd. VI, S. 809.

Footnote 702:

_Compt. rend. Soc. de biol._, Paris, 1894, p. 38.

Footnote 703:

_Brit. Med. Journ._, London, 1897, Vol. II, p. 595.

Footnote 704:

_Compt. rend. Soc. de biol._, Paris, 1898, p. 1057.

Footnote 705:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 345.

Footnote 706:

_Deutsche med. Wchnschr._, Leipzig, 1897, SS. 225, 241.

Footnote 707:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1898, Abt. I, Bd. XXIII, S. 782.

Footnote 708:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 506.

Footnote 709:

Perhaps the intestinal micro-organisms also play a part in the immunity of the animal against Entozoa. Many of the examples of this immunity are very striking. Certain intestinal worms can live only in the digestive canal of a single or of a very small number of species of animals. When we feed rabbits with a quantity of the cysticerci of the pig these pass living into the small intestine and are there transformed into true scolices. But, instead of reproducing themselves, they are expelled and never give rise to the development of taeniae. The immunity against intestinal parasites has never been made the object of special study, and it is only as a pure hypothesis that I offer this suggestion as to the part played by the micro-organisms of the intestinal flora.

Footnote 710:

_Ann. de l’Inst. Pasteur_, Paris, 1894, t. VIII, p. 549.

Footnote 711:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 802.

Footnote 712:

_Compt. rend. Soc. de biol._, Paris, 1897, p. 545.

Footnote 713:

_Arch. de Sci. biol._, St Pétersbourg, 1892, t. I.

Footnote 714:

“Les défenses naturelles de l’organisme,” Paris, 1898.

Footnote 715:

_Deutsche med. Wchnschr._, Leipzig, 1885, S. 197.

Footnote 716:

_Centralb. f. d. med. Wissensch._, Berlin, Jahrg, 1885, S. 801.

Footnote 717:

_Gior. internaz. d. sc. med._, Napoli, 1886, p. 318.

Footnote 718:

_Quart. Journ. Micr. Sc._, Lond., 1890, Vol. XXX, n.s., p. 481.

Footnote 719:

_Virchow’s Archiv_, 1884, Bd. XCVII, S. 211.

Footnote 720:

“Bakteriologie des weiblichen Genitalkanals,” Leipzig, 1897.

Footnote 721:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 842.

Footnote 722:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 699.

Footnote 723:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 65.

Footnote 724:

“Die Etiologie des Erysipels,” Berlin, 1883.

Footnote 725:

_Deutsche med. Wchnschr._, Leipzig, 1900, SS. 781, 801.

Footnote 726:

_Virchow’s Archiv_, 1900, Bd. CLXII, S. 222.

Footnote 727:

Address given at the XIIth International Congress of Medicine at Moscow, 1897.

Footnote 728:

See Hudalo, _Ann. de dermat. et de syph._, Paris, 1891, t. II, pp. 353, 470.

Footnote 729:

_Deutsche med. Wchnschr._, Leipzig, 1891, S. 101.

Footnote 730:

_Ann. de l’Inst. Pasteur_, Paris, 1892, t. VI, p. 773.

Footnote 731:

_Ztschr. f. Hyg._, Leipzig, 1896, Bd. XXI, S. 213.

Footnote 732:

_Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 289.

Footnote 733:

_Bull. et mém. Soc. méd. d. hôp. de Paris_, 1901, 20 juin, p. 624.

Footnote 734:

“Le phénomène de l’agglutination des microbes,” Paris, 1897, p. 76.

Footnote 735:

_Presse méd._, Paris, 1896, No. 83.

Footnote 736:

_Deutsche med. Wchnschr._, Leipzig, 1892, S. 827.

Footnote 737:

_Berl. klin. Wchnschr._, 1892, S. 1072; 1893, S. 1241.

Footnote 738:

_Berl. klin. Wchnschr._, 1892, S. 1267.

Footnote 739:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVI, S. 308.

Footnote 740:

_Ztschr. f. Hyg._, Leipzig, 1893, Bd. XIV, S. 42.

Footnote 741:

_Hyg. Rundsch._, Berlin, 1895, S. 145.

Footnote 742:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 417.

Footnote 743:

_München. med. Wchnschr._, 1898, S. 363.

Footnote 744:

_Deutsche med. Wchnschr._, Leipzig, 1898, S. 247.

Footnote 745:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1893, Bd. XIII, S. 153.

Footnote 746:

_Deutsche med. Wchnschr._, Leipzig, 1894, SS. 899, 936.

Footnote 747:

_Deutsche med. Wchnschr._, Leipzig, 1895, S. 400.

Footnote 748:

_Ztschr. f. Hyg._, Leipzig, 1895, Bd. XIX, S. 408.

Footnote 749:

_Prag. med. Wchnschr._, 1896.

Footnote 750:

_Ann. de l’Inst. Pasteur_, Paris, 1888, t. II, p. 69.

Footnote 751:

_Ztschr. f. Hyg._, Leipzig, 1892, Bd. XII, S. 183; Brieger u. Ehrlich, _Deutsche med. Wchnschr._, 1892, S. 393.

Footnote 752:

_Ztschr. f. Hyg._, Leipzig, 1894, Bd. XVIII, S. 57.

Footnote 753:

_Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1893, Bd. XIII, S. 81; _Deutsche med. Wchnschr._, Leipzig, 1892, S. 394.

Footnote 754:

_Compt. rend. Acad. d. sc._, Paris, 1893, t. CXVII, p. 365; _Rev. gén. d. sc. pures et appliq._, Paris, 1896, p. 1.

Footnote 755:

_Festschr. z. 100-jahr. Stiftungsf. d. med. chir. Friedr. Wilhelms-Instituts_, Berlin, 1895.

Footnote 756:

_Ann. de l’Inst. Pasteur_, Paris, 1896, t. X, p. 65.

Footnote 757:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 129.

Footnote 758:

_Arch. d. Sci. biol._, St Pétersbourg, 1901, t. VIII, p. 211.

Footnote 759:

_Arch. d. Sci. biol._, St Pétersbourg, 1901, t. VIII, p. 421.

Footnote 760:

_Compt. rend. Soc. de biol._, Paris, 1897, p. 804.

Footnote 761:

_Compt. rend. Soc. de biol._, Paris, 1897, p. 950.

Footnote 762:

_Semaine méd._, Paris, 1896, p. 303.

Footnote 763:

_Ztschr. f. Hyg._, Leipzig, 1901, Bd. XXXVII, S. 323.

Footnote 764:

“Le charbon bactérien,” Paris, 1883, p. 184.

Footnote 765:

_Compt. rend. Acad. d. sc._, Paris, 1868, t. LXVI, pp. 289, 317, 359.

Footnote 766:

_Virchow’s Archiv_, 1872, Bd. LV, S. 229.

Footnote 767:

_Monatssch. f. prakt. Dermat._, Hamburg, 1887; “Die Protozoen als Krankheitserreger,” Jena, 1891, S. 184.

Footnote 768:

_Arch. per le sc. med._, Torino, 1892, t. XVI, p. 403.

Footnote 769:

_Ann. de l’Inst. Pasteur_, Paris, 1897, t. XI, p. 289.

Footnote 770:

_Deutsche med. Wchnschr._, Leipzig, 1901, S. 130; _Brit. Med. Journ._, London, 1901, Vol. I, p. 448.

Footnote 771:

_Deutsche med. Wchnschr._, Leipzig, 1901, S. 261.

Footnote 772:

“Die Geschichte der Pocken und der Impfung,” von Coler’s _Bibliothek_, Berlin, 1901.

Footnote 773:

_Lancet_, London, 1901, Vol. II, p. 796.

Footnote 774:

_Médecine moderne_, Paris, 1896, p. 441.

Footnote 775:

Nocard et Leclainche, “Les maladies microbiennes des animaux,” 2^e édition, Paris, 1898, pp. 464, 469.

Footnote 776:

Report by Viala in the _Ann. de l’Inst. Pasteur_, Paris, 1901, t. XV, p. 445. There will be found in Marie’s work, “La rage” (_Collection des aides-mém._, Paris, 1900), many details on antirabic vaccination.

Footnote 777:

According to Krajouchkine, in the _Arch. d. Sci. biol._, St Pétersbourg, 1901, t. VIII, p. 349.

Footnote 778:

According to Marx in _Klin. Jahrb._, Berlin, 1900, Bd. VII, S. 1.

Footnote 779:

_Ann. de l’Inst. Pasteur_, Paris, 1888, t. II, p. 341.

Footnote 780:

_Compt. rend. Acad. d. sc._, Paris, 1881, t. XCIII, p. 284.

Footnote 781:

_Deutsche med. Wchnschr._, Leipzig, 1897, SS. 225, 241.

Footnote 782:

_Ztschr. f. Hyg._, Leipzig, 1898, Bd. XXIX, S. 309.

Footnote 783:

_Ann. de l’Inst. Pasteur_, Paris, 1899, t. XIII, p. 319; 1901, t. XV, p. 715.

Footnote 784:

_Rec. de méd. vét._, Paris, 1901, pp. 48, 115.

Footnote 785:

_Report on an experim. Investig. of the method of Inoculation against Rinderpest_, Calcutta, 1900; _Ztschr. f. Hyg._, Leipzig, 1900, Bd. XXXV, S. 59.

Footnote 786:

Nencki, Sieber and Wyznikiewicz, _Arch. internat. de Pharmacodyn._, Gand et Paris, 1899, vol. V, p. 475.

Footnote 787:

J. Mendez, _Anal. d. Circ. Med. Argent._, Buenos Aires, 1901, t. XXIV, Nos. 5, 6.

Footnote 788:

On the methods of vaccination against anthrax see Chamberland, “Le charbon et la vaccination charbonneuse,” Paris, 1883.

Footnote 789:

“Le charbon bactérien,” Paris, 1883; 2^e édition, 1887.

Footnote 790:

_Ann. de l’Inst. Pasteur_, Paris, 1900, t. XIV, pp. 202, 513.

Footnote 791:

_Compt. rend. Acad. d. sc._, Paris, 1883, t. XCVII, p. 1163.

Footnote 792:

_Arch. f. Hyg._, München u. Leipzig, 1891, Bd. XII, S. 275.

Footnote 793:

_Deutsche thierärztl. Wchnschr._, Karlsruhe, 1893, Bd. I, SS. 41, 85; _Centralbl. f. Bakteriol. u. Parasitenk._, Jena, 1893, Bd. XIII, S. 357; _Deutsche Ztschr. f. Thiermed._, Leipzig, 1894, Bd. XX, S. 1.

Footnote 794:

_Rev. vét._, Toulouse, 1900, t. LVII, p. 346.

Footnote 795:

_Rev. vét._, Toulouse, 1901, t. LVIII, p. 149.

Footnote 796:

_Deutsche thierärztl. Wchnschr._, Karlsruhe, 1901, No. 6.

Footnote 797:

_Ann. de l’Inst. Pasteur_, Paris, 1898, t. XII, p. 240; _Cinquanten. d. l. Soc. d. biol._, Paris, 1899, p. 440; Dujardin-Beaumetz, “Le microbe de la péripneumonie,” Thèse de Paris, 1900.

Footnote 798:

In 1884, in the Department of the Basses-Pyrenées, the Willems’ method of inoculation was carried out on 1354 Bovidae; of this number 10 died and 45 lost their tails completely. In 1901, in the same department, 2800 Bovidae were inoculated with pure cultures, only 1 died and 9 lost their tails.

Footnote 799:

“L’inoculation préventive contre le choléra morbus asiatique” (translated from the Spanish), Paris, 1893.

Footnote 800:

“Anti-cholera Inoculations in India,” _Indian Med. Gaz._, Calcutta, 1895, No. 1. [Also Report to the Gov. of India, Calcutta, 1895.]

Footnote 801:

_Ann. de l’Inst. Pasteur_, Paris, 1893, t. VII, p. 579.

Footnote 802:

_Deutsche med. Wchnschr._, Leipzig, 1896, S. 735.

Footnote 803:

Wright and Leishman, _Brit. Med. Journ._, London, 1900, Vol. I, p. 122; [Wright, “A short treatise on anti-typhoid inoculation,” London, 1904].

Footnote 804:

_Brit. Med. Journ._, London, 1901, Vol. I, p. 84.

Footnote 805:

_Lancet_, London, 1901, Vol. I, p. 399.

Footnote 806:

_Lancet_, London, 1901, Vol. I, p. 1272.

Footnote 807:

_Brit. Med. Journ._, London, 1900, Vol. I, p. 1456.

Footnote 808:

_Gaz. clin. de Botkine_, St Pétersb., 1899, p. 1911 (in Russian).

Footnote 809:

_Ann. de l’Inst. Pasteur_, Paris, 1895, t. IX, p. 589.

Footnote 810:

_Brit. Med. Journ._, London, 1897, Vol. I, p. 1461; _Indian Med. Gaz._, Calcutta, 1897, Vol. XXXII, p. 201.

Footnote 811:

“Joint Report on the Epidemic of Plague in Lower Damaun,” Bombay, 1897.

Footnote 812:

_Arb. a. d. K. Gsndhtsamte_, Berlin, 1899, Bd. XVI, S. 331.

Footnote 813:

“Report of the Indian Plague Commission,” London, 1901, Vol. V,