Chapter 33 of 37 · 2253 words · ~11 min read

Chapter XII.) Now, since in hereditary transmission the antitoxin passes

over with the blood plasma of the same species, whilst in the experiments on antitoxic immunity it is generally injected with the serum of a different species, it is easy to understand that the former should persist for a longer period than the latter. It is, therefore, very probable that this immunity of the offspring from vaccinated mothers is not in any way a case of true hereditary immunity, but is due simply, as maintained by Ehrlich, to the passage of ready prepared antibodies from the mother to the foetus. In the immunities against diphtheria and tetanus we have the direct passage of antitoxins; in transmitted immunity against infection by the vibrios of Koch and Gamaleia, so carefully studied by Vaillard, we have, very probably, the passage of corresponding fixatives from the mother to the foetus.

[Sidenote: [470]]

Dzierzgowsky[758] in a recent study on hereditary immunity denies the passage of antibodies and toxins through the placenta. He thinks that the foetus does not acquire its immunity through the blood of the mother, but at a very much earlier period. The ovum contained in the Graafian follicle would, according to this observer, come in contact with a fluid very rich in antitoxin, whence it might imbibe the necessary amount of this antibody to ensure the immunity of the new-born animal. Dzierzgowsky bases this opinion on experiments in which antidiphtheria serum injected into pregnant goats and dogs did not produce any antitoxic power in the blood of the foetus. But in the experiments on these animals the injections consisted of the serum of the horse—a different species. This must modify, profoundly, the conditions of the passage of the antitoxin through the placenta.

Dzierzgowsky made a single experiment upon a mare, immunised with diphtheria toxin, and its foal. Whilst the serum of the former was markedly antitoxic, that of the foal did not possess this property in the slightest degree. Hence the conclusion that the antitoxin of the mother had not passed into the blood of the foetus. But the blood of the foal was not withdrawn until some ten months after birth. Now, as the so-called hereditary immunity only lasts for a very short time Dzierzgowsky’s experiment supplies no evidence against the passage of antitoxin through the placenta.

In order to prove that the immunity against toxins may really be acquired by the ovum, Dzierzgowsky[759] carried out a series of experiments with the eggs of fowls immunised against diphtheria toxin. The yolk of the egg, in accordance with the discovery made by F. Klemperer, contained antitoxin; and this antitoxin passed into the blood of the hatched chickens. These facts, though in themselves very interesting, cannot be used to refute the view that antitoxins pass through the mammalian placenta. It is true that this view is perhaps not yet completely proved, but it accords well with all the known facts. Thus, the frequent presence of diphtheria antitoxin in the blood of new-born infants is explained much better on the assumption that it passes through the placenta than that it is due to an immunisation of the ovum surrounded, in the Graafian follicle, by antitoxic fluid. It is difficult to conceive how this immunity could be so fully retained during the nine months of pregnancy.

[Sidenote: [471]]

In support of his interpretation of the phenomenon of immunity transmitted by the mother to her progeny Ehrlich invokes his beautiful discovery of the immunity conferred by the maternal milk. A vaccinated female is capable of communicating to her young a portion of the antibodies manufactured in her organism, not only by the blood channels, but also, in certain cases, by the milk with which she feeds her young.

[Sidenote: [472]]

The transmission of antitoxins by milk has been demonstrated by Ehrlich, and this has since been confirmed by many observers (see Chapter XII). When Ehrlich found that the immunity of the progeny is retained for a longer time than is that which is conferred by injections of antitoxic serum, he conceived the idea of investigating whether the cause of more prolonged retention did not reside in the transmission of the maternal antitoxin by the milk. With the object of verifying this he took, at the moment when they had given birth to young, unvaccinated mice and mice that had been vaccinated against various toxins (ricin, abrin, tetanotoxin). He so changed the progeny that the vaccinated mothers nourished the young born of the normal mice, whilst the normal mothers suckled the offspring of the vaccinated mice. The result of these ingenious and delicate experiments fully confirmed his anticipations. The vaccinated mice transmitted their immunity not only to the young ones to which they had given birth but also to those they had merely nourished with their milk. This observation proved, to demonstration, that the antitoxins are absorbed by the alimentary canal, a very important fact from several points of view. Later researches have shown that only very young mice are capable of assimilating antitoxin through the intestinal wall. Adult mice, fed by Ehrlich with quantities of antitoxic milk, acquired neither immunity nor any antitoxic property of the blood. Later, Vaillard (_l.c._) was able to show that even the young of other species of animals such as the guinea-pig and the rabbit are incapable of appropriating the antitoxins from milk by the alimentary canal. He repeated Ehrlich’s experiments with new-born guinea-pigs and rabbits which he caused to be suckled by mothers vaccinated against tetanus. These young rodents, so treated, were found to possess no immunity whatever; they were not able, therefore, to absorb the antitoxin found in the milk of their nurses. Remlinger (_l.c._) made similar experiments with young guinea-pigs and rabbits suckled by foster mothers which had been vaccinated against the coccobacillus of typhoid fever. As in Vaillard’s experiments, the result was negative, the milk of the foster mother did not communicate any refractory condition to the nurselings. Remlinger drew the same conclusion from his researches on the transmission of the agglutinative property of the body fluids. When female rabbits and guinea-pigs are vaccinated during gestation the young ones acquire, along with the immunity against the typhoid coccobacillus, a certain agglutinative power of the blood serum. When, however, these vaccinated females suckle the progeny of non-vaccinated mothers the agglutinative power of the milk of the foster mother never passes into the blood of the nurselings. Some years before this, Widal and Sicard[760] had demonstrated the same fact that young rabbits and new-born kittens, when fed with agglutinative milk, acquired no power of agglutinating the typhoid coccobacillus. They agreed with Ehrlich, however, that the blood serum of young mice fed with agglutinative milk acquired the power of agglutinating the typhoid micro-organism.

[Sidenote: [473]]

As it was important to determine whether the human subject was capable of acquiring a certain immunity by absorbing antibodies contained in the milk, the study of this question was taken up, especially from the point of view of agglutinative power. Although the relations of this agglutinative power with immunity are very problematical it would be interesting, bearing in mind the analogy between the agglutinative, antitoxic, and protective properties, to ascertain whether the ingestion of agglutinative milk can confer any agglutinative property on the blood serum. Numerous researches in this direction were carried out in connection with typhoid fever. Widal and Sicard (_l.c._) caused a person to drink daily (for a period of three weeks) half a litre of milk coming from an immunised goat, a milk which powerfully agglutinated the typhoid coccobacillus. The blood, examined on several occasions, never showed the slightest agglutinative power. This experiment goes to prove that, in the adult human subject, the agglutinin does not pass from the alimentary canal into the circulation. May it not perhaps be otherwise in infants which are fed on milk only? An observation by Landouzy and Griffon[761] seemed to confirm this supposition. They first demonstrated the agglutinative power of the blood serum in a woman who had contracted typhoid fever three months after her lying-in. Being a mild attack the woman continued to suckle her child during the whole course of the fever. On examination of the blood of the infant it was found that the serum agglutinated the micro-organism of typhoid fever. These observers did not measure the agglutinative power of the blood, either in the infant or in the mother. This omission deprives their observation of value since it is now recognised that normal human blood fairly frequently exhibits some power of agglutinating the typhoid coccobacillus. For diagnostic purposes it is necessary, therefore, always to measure this power in order to be sure that it is higher than that of the normal blood.

It is all the more difficult to draw any positive conclusion from the observations of Landouzy and Griffon because in several similar cases the result has been entirely different. Thus Achard and Bensaude[762] have shown that the blood of an infant, suckled by a nurse attacked by typhoid fever and whose serum became distinctly agglutinative, was incapable of bringing about clumping of the typhoid coccobacilli. Schumacher[763], working in Fraenkel’s laboratory in Halle, studied a case with very great care. A woman gave birth at full term to an infant whose blood serum exhibited a certain agglutinative power. The mother suckled the infant from its birth. Although her milk manifested a very considerable agglutinative property, the blood of the child exhibited not only no increase in agglutinative power but a marked diminution. The agglutinin of the maternal blood had not passed into the fluids of the child.

[Sidenote: [474]]

From the point of view of the impossibility of acquiring immunity by suckling, therefore, the human subject may be grouped with the guinea-pig, rabbit and cat. Up to the present the mouse is the only exception. It would be very important, with the object of finding a means of communicating immunity by way of the intestine, to study the precise conditions which govern this phenomenon. In hereditary immunity, or rather in what appears to be such, those cases where the new-born animal exhibits a resisting power induced by the vaccination to which it has been subjected in the womb of the mother must be borne in mind. We have already cited the example given by Remlinger of rabbits and guinea-pigs born refractory against the typhoid coccobacillus, which had been injected into the mother animals. In those cases where the vaccination of the mothers has been carried out during the period of gestation the immunity of the young ones is more permanent than when it was completed before that period. Into this same group come those cases where women, vaccinated during the course of pregnancy, give birth to infants refractory to vaccine. Similar facts have been reported by veterinary surgeons with regard to sheep-pox; Arloing, Cornevin, and Thomas[764] have offered similar demonstrations with regard to symptomatic anthrax.

These results may be more or less closely associated with those where the child attacked by an infective disease immunises the mother. Such facts are rare. We know that a healthy mother may give birth to a syphilitic child; the affected father introducing the virus with the sperm, the contaminated foetus contracts the disease and the new-born infant is syphilitic. According to Ehrlich and Hubener (_l.c._ p. 54), the foetus instead of infecting the mother sets up in her a refractory condition. It must be confessed that as yet we do not understand the mechanism of this immunity; but in any case we have here to do with an example of immunity naturally acquired under very special conditions.

Here again must be recognised another form of immunisation:—where the child born of a syphilitic mother remains healthy and contracts syphilis neither by the breast nor through the kisses of the mother. Here, undoubtedly, we have an immunity against syphilis acquired in the womb of the mother, who may, however, readily communicate her disease to other persons by means which are without effect on her own infant. This example comes under the law of Profetta. Here again the mechanism of the acquired immunity is absolutely unknown.

[Sidenote: [475]]

It must be admitted that, generally, we are still very imperfectly informed concerning immunity as acquired by natural paths. In cases where this immunity is developed as the result of an attack of an infective disease the phenomena observed closely resemble those that have been observed after vaccination by living, fully active, or attenuated viruses, by micro-organisms which have been killed, or by the products of these micro-organisms. These vaccinations which bring about isopathic (von Behring) or active (Ehrlich) immunity give rise to transient and mild diseases and are confined almost completely to the diseases contracted by natural means which terminate in recovery and give rise to a refractory condition. The immunisation of the foetus comes into the same series.

On the other hand, the immunity which was believed to be hereditary and which results merely from the direct passage of the antibodies of the blood or of the milk of the mother to the foetus and to the child come into a group of cases characterised by what Ehrlich has termed a condition of passive immunity. We have already discussed (Chapter X) the thesis that this term “passive” is applicable only in rare cases. Most frequently it is necessary that the living cells of the organism which receives the antibodies—antitoxin, fixatives or others—should contribute their quota in order to ensure the refractory condition. This rule is undoubtedly applicable to the examples of immunity acquired by the new-born progeny of unaffected mothers.