These observers introduce the same quantity of streptococci below the skin of the ear of normal and of vaccinated rabbits. In the first there is soon produced a very marked oedema of the ear, in which may be seen a number of streptococci and of leucocytes that have not ingested any micro-organisms. In the second the oedema does not develop, but at the seat of invasion a number of leucocytes come up and these soon ingest the streptococci. As we see, the phenomena manifest themselves here just as they do with the anthrax bacillus and many other micro-organisms when under analogous conditions. Denys and Leclef, indeed, recognise that, below the skin of the ear of vaccinated rabbits, the small quantity of exudation fluid is not sufficient to enable us to accept it as capable of exerting any considerable influence as regards humoral properties. Nevertheless, they think that the “serum” of this fluid may exercise a certain action, but they furnish no proof of this, and seem to ignore the fact that the plasma of the subcutaneous exudation is far from being identical with blood serum obtained outside the animal. At present it is well known that this latter fluid contains cytases which are absent from the plasmas. Now, the feeble bactericidal action, if this really exists as regards the streptococcus, must be attributed to the microcytase which has escaped from the leucocytes at the time of the preparation of the serum.

To sum up, the example studied by Denys and Leclef clearly comes under the general law of phagocytic reaction in acquired immunity against micro-organisms. It is impossible to deny that the superactivity of the phagocytes which is always found in this immunity, although readily observed, cannot be demonstrated in a rigorous fashion outside the fluids which bathe the cells. There are, however, very important analogies which may be invoked in favour of this thesis. We have already cited in our fifth chapter Delezenne’s experiments on the digestion of gelatine by the leucocytes of the dog, which show in the most demonstrative fashion that these cells accustom themselves to bring about this digestion more and more quickly and this quite independently of any humoral influence.

For some time past there has been no doubt as to the fundamental fact that the phagocytes in immunised animals seize and destroy living micro-organisms. Several attempts have been made to show that such destruction of these bacteria takes place solely by the body fluids, and that the phagocytes intervene only as “scavengers” to carry off the dead bodies of the micro-organisms. The numerous observations, described in the preceding chapter, absolve us from again entering into a discussion of this question. Moreover, the majority of these opponents now recognise that micro-organisms are ingested in a living state by the phagocytes of immunised animals. Some, however, have expressed the opinion that these living micro-organisms, before becoming the prey of the phagocytes, must undergo some preliminary attenuation of virulence through the action of the body fluids. Hence the theory of the attenuating power of the fluids of the body, maintained especially by Bouchard and his pupils. During the course of our exposition of the facts concerning acquired immunity, we have several times had occasion to speak of the virulence of micro-organisms in the immunised animal. Here, therefore, we may confine ourselves to a brief summary of the observations collected on this point.

Having observed that the anthrax bacillus, when developed in the blood of immunised sheep, was incapable of giving fatal anthrax to rabbits, I expressed^[443] the opinion that under these conditions its virulence had become attenuated. Later, analogous changes were shown by Charrin^[444] in the Bacillus pyocyaneus when cultivated in the serum of immunised animals. Bouchard^[445], generalising on these data, arrived at the following theory of vaccination. “The inoculation of a strong virus into a vaccinated animal is equivalent to the inoculation of an attenuated virus. The attenuation, however, instead of being done beforehand in the laboratory, is brought about in the tissues of the vaccinated animal” (p. 18). Charrin and Roger^[446] upheld this view, and the latter offered several new arguments in support of it. He observed that animals inoculated with pneumococci and streptococci grown in the blood serum of vaccinated animals, contracted a transient and benign disease merely, whilst the control animals, inoculated with the same micro-organisms, cultivated in normal serum, always died from generalised infection.

The discovery of the protective property of serums has thrown a new light upon these experiments. We must now ask ourselves: Does the innocuousness of micro-organisms depend not on the attenuation of the virus, but rather on the protective action of the serum itself? When, in the course of my researches on the Gentilly cocco-bacillus, I found that this organism, cultivated in the serum of vaccinated rabbits, became much less pathogenic than when it was grown in the serum of normal rabbits, I set myself to answer this question. Simple filtration through paper was sufficient to rid the organism of the serum in which it had grown. The inoculation of cocco-bacilli thus treated proved at once that their virulence was in no degree modified, and that it was the intervention of the serum that prevented the micro-organism from setting up the rapidly fatal disease. Issaeff^[447], who, in my laboratory, carried out the investigation, was able to extend this to the pneumococcus. He obtained agglutinated cultures in the serum of vaccinated rabbits, and he compared their activity by injecting them (1) with, and (2) without their culture medium. The difference was very marked. In the first case the infection produced was much slower in its course than in the second. The virulence of the washed pneumococci was found to be the same whether they came from a culture in normal serum or from one in immunised serum. Sanarelli^[448] obtained the same result with Gamaleia’s vibrio. The vibrios when grown in the serum of vaccinated guinea-pigs proved to be very virulent so soon as they were freed from the fluid in which they were grown. Later, similar demonstrations were given by Bordet^[449] and Mesnil^[450] with respect to streptococci and to the bacilli of swine erysipelas. We must, then, conclude that we have here to do with a general law. Some experiments made by de Nittis^[451] might seem to indicate an exception to such a law. He observed that anthrax bacilli when grown in the serum of vaccinated pigeons lost a part of their virulence. It must not be forgotten, however, that he grew his cultures under special conditions; the bacillus was grown for several days at 42° C., this in itself being quite sufficient to bring about a certain attenuation of virulence.

The theory of the attenuating action of the body fluids, based on the attenuation of the virus in the serum of vaccinated animals, can no longer be maintained, as it is a well-established fact that the serum, obtained outside the body, is a fluid differing in character and properties from the plasma of the living animal. We have seen up to what point this demonstration has shaken the theory of the bactericidal action of the body fluids.

It cannot be doubted that a micro-organism may undergo a certain weakening in virulence, as well as in certain other functions, in the body of the animal that has acquired immunity. But the question must be put: Is this effect obtained as the result of humoral or of cellular action? As a general rule, exudations obtained from vaccinated animals, and containing living micro-organisms, are found to be virulent when inoculated directly into susceptible animals. This fact was established by Pasteur^[452] when he first carried out his researches on acquired immunity against fowl cholera. He showed that the exudations of vaccinated fowls set up a fatal disease in normal fowls, without there being the least evidence of any attenuation of the micro-organism. The same applies to the Gentilly cocco-bacillus and to the anthrax bacillus in a very great majority of examples. De Nittis observed that the exudations of immunised pigeons produced a fatal infection in the guinea-pig and in the mouse. In the immunised guinea-pig, on the other hand, he found that the exudations soon became innocuous for these animals. This alteration, however, must be attributed not to the body fluids (which exhibit no protective or attenuating power) but to the action of the cells.

With the object of gaining some idea of the changes that the micro-organisms undergo in the immunised animal, Vallée^[453] carried out a series of experiments on rabbits vaccinated against the bacillus of swine erysipelas. He enclosed these bacilli in sacs of collodion which he introduced into the peritoneal cavity of susceptible rabbits and of others that were hyperimmunised. The bacillus developed well in both cases. It gave homogeneous non-agglutinated cultures in the sacs placed in normal animals, whilst in the sacs introduced into the peritoneal cavity of hyperimmunised rabbits the bacilli grew into agglutinated filaments. This proves that the wall of the sacs permitted of the passage of the active substances elaborated in the immunised animal. Different from the point of view of agglutination, the cultures likewise exhibited a considerable difference in their pathogenic activity. The cultures developed in the sacs in hyperimmunised rabbits were found to be much more virulent than those grown in the sacs in control animals. This augmentation of virulence depends, probably, on the influence of the active substances which pass through the walls of the sacs. In any case, this experiment affords further confirmation of the impossibility of maintaining the theory of the attenuation of micro-organisms by the fluids of an animal enjoying acquired immunity.

Since the discovery of the antitoxic property of the fluids of the body, it has been accepted that its manifestation was indispensable for the acquisition of immunity. It was thought that in order to get rid of pathogenic micro-organisms the animal had first to develop the means of neutralising their toxins. These substances once prevented from exerting their toxic action, the micro-organisms were left without their weapon of attack and found themselves reduced to the condition of simple saprophytes. It was accepted, therefore, that an effective antitoxic power was always to be found in the fluids of animals that had acquired immunity. Against this explanation, however, are certain established facts. Chauveau^[454] had observed that Algerian sheep, whose natural immunity was further strengthened by considerable doses of anthrax bacilli, exhibited a susceptibility to injections of anthrax blood quite as marked as that of normal sheep. The immunity against the virus, then, did not progress pari passu with that against the poison. Later, Charrin and Gamaleia^[455] furnished important data on this subject. They showed that animals vaccinated against the Bacillus pyocyaneus and the vibrios of Koch and Gamaleia were even more susceptible to intoxication by the soluble products of these micro-organisms than were normal animals which had acquired no immunity against the corresponding bacteria. Shortly afterwards this observation was confirmed by Selander^[456], in his work on hog cholera, carried out under Roux’s direction. Rabbits vaccinated against the cocco-bacillus of this disease resisted infection by the virus, but died as a result of the exhibition of the same doses of toxin that killed normal rabbits. I^[457] was able not only to verify this, but to add to it the further fact that the blood serum of vaccinated rabbits, although markedly protective against infection, exercised not the slightest antitoxic action.

When, later, R. Pfeiffer set himself to study the immunity of animals against the cholera vibrio, he, along with his collaborators, was able to furnish numerous data confirming the hypothesis that animals thoroughly vaccinated against this vibrio had not thereby become more resistant to its toxin and that their anti-infective serum exhibited no antitoxic power. These results have been confirmed repeatedly and must be regarded as fully established.

Von Behring here recognised a general law which, with the aid of his collaborators, he attempted to develop. We owe to him the knowledge that the susceptibility, augmented as regards the toxins, of animals vaccinated against micro-organisms, might even serve in doubtful cases to reveal the presence of their bacterial poisons. Culture products when deprived of micro-organisms often set up no poisoning in normal animals susceptible to infection. From this fact it is generally concluded that the toxin is not present in the products in question. But animals of the same species when immunised against infection by the micro-organism, owing to their “hypersusceptibility,” react much more delicately and allow of the demonstration of the presence of bacterial poisons in fluids inactive for unvaccinated animals.

In collaboration with Kitashima^[458], von Behring immunised guinea-pigs against the diphtheria bacillus, and demonstrated that two or three injections of diphtheria toxin were quite sufficient to render these animals refractory to infection by the diphtheria bacillus though they became more susceptible to intoxication. Von Behring considers that this augmentation of susceptibility to the diphtheria poison may be a means of rendering the local reaction of the living elements at the point of introduction of the bacilli more active.

In any case, it is beyond question that acquired immunity against microbial infection is quite independent of the resistance against the toxins of the corresponding micro-organism. An antitoxic manifestation of any kind, therefore, cannot be regarded as necessary for the development of immunity against the micro-organism.

Of all the humoral properties developed in acquired immunity against micro-organisms, the fixative power and the protective power are the most constant. It might naturally be suggested, as a result of this observation, that these two powers are indispensable for the manifestation of phagocytosis for the purpose of destroying and of ridding the animal of the pathogenic organisms. It is quite possible to understand how, under these conditions, the idea has been put forward that anti-infective acquired immunity is the result of two different factors: in the first place, a humoral property independent of the phagocytes and, in the second place, the phagocytes themselves. But the part played by these cells cannot be accepted as purely secondary—a view which has been advanced and defended again and again. This question is of such importance that it is reasonable to ask whence come the humoral properties, such as the fixative power and the protective power, factors of such far-reaching influence in anti-infective immunity?

Thanks to the work of several investigators this question may now be answered. Pfeiffer and Marx^[459] first supplied important information concerning the origin of the protective property. Into rabbits they made subcutaneous inoculations of cholera vibrios, killed by heat (70° C.), and then examined, most minutely, the protective power of the blood and of extracts from various organs. Examining, separately, the protective power of the serum and that of the layer of leucocytes deposited in tubes, Pfeiffer and Marx were unable to find any marked difference. Nor did they ever obtain any definite effect with leucocytes collected from pleuritic exudations. From these observations they concluded that the leucocytes of the blood could not be regarded as the source of the protective substance (or “cholera antibody”). At a period when the serum as yet exhibited an insignificant protective power or none at all, the extract from the spleen often exerted an action of the most marked character. In an experiment in which the rabbit was killed 48 hours after the injection of the vibrios, 0·3 c.c. of the serum was incapable of preventing fatal infection of a guinea-pig, whereas 0·03 c.c. of an extract of the spleen exerted a marked protective effect. From this and similar experiments, Pfeiffer and Marx conclude that the spleen is the principal source of the protective substance. In order to verify this observation they injected killed cholera cultures into rabbits which had previously been deprived of their spleens, but the asplenic rabbits still produced the same amount of protective substance, and these two observers were led to conclude that the lymphatic glands and the bone-marrow might also serve as the sites of origin of this substance.

It is only during the first few days, however, that these organs exhibit a protective power greater than that of the blood. Three or four days after the injection of the vibrios the blood serum becomes richer in protective substance; the organs contain much less of it. This condition is maintained for some time, after which the blood in turn begins to get impoverished.

Pfeiffer and Marx put to themselves the question: Is the marked protective power of the spleen due to the production of preventive substance by this organ, or is it to be explained by an accumulation in the spleen of this substance manufactured elsewhere? With the object of obtaining an answer to this question they injected protective serum from other individuals into rabbits, when they found that the protective substance showed not the slightest tendency to accumulate in the spleen. These authors were compelled to conclude, therefore, that the spleen and other haematopoietic organs (lymphatic glands and bone-marrow) are the real seats of the production of the protective substance. We may add that these organs are also the phagocytic organs par excellence, that is to say, the centres which serve not only for the development of phagocytes but which contain a large number of the adult elements capable of exercising the phagocytic function.

Almost simultaneously with Pfeiffer and Marx, A. Wassermann^[460], in collaboration with Takaki, undertook similar researches on the origin of the substance protective against the typhoid cocco-bacillus. The outcome of this work was that “it was the bone-marrow, the spleen, and the lymphatic system, including the thymus gland, which exhibited immunising power against the bacillus of typhoid fever, whilst the other organs, the blood, brain, spinal cord, muscles, liver, kidney, etc., did not at this stage show any marked specific property.”

As these observations on the production of protective substance in the phagocytic organs was one of essential importance in connection with the problem of acquired immunity, I asked M. Deutsch^[461], working in my laboratory, to carry out a series of experiments on this subject. Using guinea-pigs, he injected into the peritoneal cavity cultures of the typhoid bacillus killed by heat (66° C.). A few days later the serum had become distinctly protective. At this stage, and even before the appearance of this property in the blood, Deutsch killed some of his animals and carefully measured the protective power of the extract of the various organs. He began by confirming the result obtained by Pfeiffer and Marx as to the non-production of the protective substance in the peritoneal exudation. Usually this fluid was insufficient to protect normal guinea-pigs against typhoid infection. In a few experiments only was the exudation found to be as protective as the blood serum; in most of the others, the blood serum was much more active than the fluid of the exudation. The spleen was the organ which exhibited the greatest protective power, and in nearly one-half of the cases it was more active than was the blood. The bone-marrow sometimes gave analogous though much less marked results. The spleen consequently must be looked upon as the principal seat of the production of the protective substance.

Having confirmed this observation of Pfeiffer and Marx and of Wassermann and Takaki, Deutsch tried to obtain the protective property in guinea-pigs deprived of their spleens. The experiment was quite successful, and here again his result agreed with that obtained by Pfeiffer and Marx. Guinea-pigs from which the spleen had been removed developed the protective property just as well as did the control animals; in the former the bone-marrow was found to be specially active.

When Deutsch, instead of removing the spleen from his guinea-pigs before the injection of the micro-organisms, did so some (3–5) days afterwards, there often occurred a marked diminution in the amount of the protective substance produced. We must conclude, therefore, that soon after inoculation there appears in the spleen a phenomenon which is associated with the development of the protective power. The most simple explanation of these facts is that the micro-organisms injected into the peritoneal cavity and soon afterwards seized by the phagocytes (for the most part by the microphages), are carried to the phagocytic organs, particularly the spleen, lymphatic glands, and bone-marrow. In those animals whose spleens are left intact a large number of these microphages loaded with micro-organisms make their way into this organ, a fact confirmed by direct observation. When the spleen is removed the microphages must necessarily betake themselves to other phagocytic organs. As the micro-organisms undergo intracellular digestion in the phagocytes, it is very difficult, if not impossible, to follow them for any length of time after they have been ingested, but the analogy with the phenomena of the resorption of red blood corpuscles, described in Chapter IV, justifies us in concluding that in the case of micro-organisms matters go on in much the same way. These organisms, seized at the seat of inoculation by the phagocytes, are transported by these cells, in their peregrination through the organs, into the general circulation. The interpretation I have just given has been accepted by Deutsch.

This observer wished also to come to some conclusion as to the origin of the agglutinative property so well developed in the fluids of animals inoculated with the typhoid cocco-bacillus. He did not succeed in solving this question, but he was able to demonstrate the undoubted difference between this property and the protective power. The facts brought forward by Deutsch must, therefore, be ranged alongside the many others, reported on above, which demonstrate in the most conclusive fashion that these two powers of the body fluids are essentially distinct.

Such concordant results obtained by all investigators who have studied the origin of the protective power warrant the conclusion that it is the elements of the phagocytic organs, that is to say, the phagocytes themselves, which produce the protective substance. But it will be asked: Can we therefore accept the fixative substance or fixative as being derived from the same source? When the experiments I have just summarised were carried out the fixatives were not as yet sufficiently known and were confounded with the protective substances. Nevertheless, there can be no doubt as to what the answer to the question just put must be. In the account of the experiments of Pfeiffer and Marx we find very precise statements as to the granular transformation of the vibrios. Thus, they observed on several occasions that an extract of the spleen set up this transformation in a particularly distinct and rapid fashion at a period when the blood and serum, used in a much stronger dose, were incapable of producing the same effect. Now, as Pfeiffer’s phenomenon is a visible manifestation of the action of the specific fixative, it cannot be doubted that the spleen is really the principal seat of development of the fixative substance before it makes its appearance in the blood.

Before concluding this chapter we must review very briefly the principal phenomena associated with acquired immunity against micro-organisms. The extracellular destruction of these parasites takes place in the living animal under special conditions only, when the phagocytes suffer a temporary injury (phagolysis) and allow their microcytases to escape. These latter by no means represent attributes of the body fluids, as is even yet maintained by some writers. These soluble ferments are connected with the phagocytes and represent the ferments of intracellular digestion. The cytases undergo no modification during the process of immunisation and correspond to those which act in natural immunity.

The agglutinative substance often present in the normal fluids of the body becomes much more developed in those of immunised animals. It is truly humoral, as it circulates in the plasmas and passes into the fluid exudations and transudations. But the part played by it in immunity is very restricted.

The protective and fixative properties, most often closely connected with each other, are very markedly developed in an animal enjoying acquired immunity. They may act upon the micro-organisms which become permeated by the fixative substance, or upon the infected animal by stimulating its defensive reaction, but they are incapable of affecting the vitality or virulence of the micro-organism. The two properties (protective and fixative) reside in the fluids of the body, but they are functions of the cell products. The elements of the phagocytic organs (spleen, bone-marrow, lymphatic glands), or phagocytes, produce the specific protective and fixative substances which pass thence into the plasmas.

The phagocytic reaction is very general in acquired immunity. The phagocytes which have a very imperfect antimicrobial function or none at all, become, as the result of vaccination, much more active. They exhibit a very marked positive chemiotaxis and acquire the faculty of digesting micro-organisms in a greatly intensified degree. It is with the increase of this digestive power that we have connected the over-production by the phagocytes of the fixative and protective substances which are excreted in large quantities by these cells and pass into the fluids of the animal. As these substances are phagocytic products it may be readily conceived that in certain examples of acquired immunity the animal overcomes the micro-organisms without the protective substances being found in the fluids. It is sufficient that it is in the possession of the phagocytes, which may retain it within themselves and not throw it off into the circulation.

From this account it will be seen that the phenomena, in acquired immunity against micro-organisms, are merely a more or less stereotyped copy of those that are presented in the animal after the resorption of cells. There, also, we have intracellular digestion with over-production of specific fixatives, part of which are excreted and thus pass into the plasmas. In the resorption of cells there is also a double action of cytases and fixatives; but in this case the macrocytases intervene, whilst in the resorption of micro-organisms this function is performed by the microcytases. The fixatives in the two cases are very different from the point of view of their action, for they are specific; but the cells which act in their production belong, in both cases (resorption of animal cells and of micro-organisms), to the category of phagocytes.

It is often maintained that the theory I have just summarised is fundamentally opposed to the theory of side-chains or receptors formulated by Ehrlich^[462]. This view I cannot accept. Applied to acquired immunity against micro-organisms this theory may be summed up as follows. The micro-organisms, when inoculated in a non-lethal but immunising dose, combine with certain cells of the animal. The receptors of the micro-organisms find corresponding receptors in these cells, but, when once combined, the receptors of the cells become incapable of fulfilling their normal nutritive function. The cells, thus deprived of their receptors, reproduce such an enormous quantity of them that a portion is excreted into the surrounding medium and passes into the plasmas. These receptors, originating from cells, but which have become constituent parts of the body fluids, are nothing but the fixatives or intermediary bodies, or the amboceptors of Ehrlich. On a fresh arrival of the same micro-organisms, they meet with, in the fluid of the exudations, numerous amboceptors which combine with the corresponding receptors of the micro-organisms, without, however, destroying them or interfering with their vitality. As these amboceptors possess still a second affinity, that for the molecules of the cytases, or the “complements” of Ehrlich, the micro-organisms can be placed in contact with these soluble ferments. Without the intervention of the fixatives, the combination of the body of micro-organisms with the cytase can never take place, because the receptors of the micro-organisms are not adapted to those of the cytases. When the molecules of these ferments are found in the plasmas in a free state, they can be attacked by the corresponding group of the amboceptors.

Let us compare the theory we have just sketched with that described further back. The micro-organisms, inoculated with a non-lethal but immunising dose, are, as we have seen, ingested by the phagocytes and afterwards digested within them. This intracellular digestion is followed by the over-production of the specific fixative, of which a part is excreted and passes into the plasmas. These are the results of the well-established experimental data described in this chapter. Ehrlich’s theory is in no way in opposition to this; it simply attempts to penetrate more deeply into the mechanism of the phenomena observed as taking place between the micro-organism and the cell. The act which we simply term intracellular digestion is divided by Ehrlich into its constituent parts. According to him there is a combination of the fixative, on the one hand, with the molecule of the micro-organism, on the other, with that of the soluble ferment or cytase. According to Ehrlich it is the amboceptors of the cells which become detached in order to furnish the fixative that circulates in the plasmas. For us there is simply an over-production of one of the two ferments of intracellular digestion, without defining more exactly what constituent part of this ferment passes into the circulation. The two theories may supplement each other but are in no way contradictory in principle. There is only a single important point wherein they do not accord. Ehrlich thinks that the cytases are always free in the body fluids and that the cells, in order to exert a digestive action on the micro-organisms, must previously seize their molecules by means of one of the groups of their amboceptors. We, on the contrary, have developed the idea that the cytases are only free in the animal during phagolysis and that under normal conditions the cytases remain closely bound up with the phagocytes. This statement is based upon a large number of well-established experimental facts and must therefore be accepted as proved. It does not, however, affect any fundamental principle of Ehrlich’s theory. On the other hand the bases of Ehrlich’s theory affect none of the main features of the theory I have developed. The doctrine which regards acquired immunity as a particular case of resorption may be reconciled with the conception of amboceptors. But it accords equally well with Bordet’s conception, according to which the fixatives act not as intermediary substances between the micro-organism and the cytase, but as substances which sensitise the micro-organisms for the penetration of the digestive ferment. This delicate question has not yet been definitely settled, but Bordet’s experiments described in Chapter IV are greatly in favour of this view.

Neisser and Wechsberg^[463] have tried to obtain some idea of the manner in which the fixatives act on the micro-organisms and have recorded a series of very interesting facts. They have shown that these substances only bring about the destruction of bacteria when they are in certain relations with the cytase. Mixtures of fixatives and cytases in which the former are found in excess not only do not kill the micro-organisms but even allow them to develop abundantly. To attain this result Neisser and Wechsberg mixed constant quantities of bacteria and normal serum containing cytase with variable quantities of the serum of immunised animals heated to 56° C. As we know, this specific serum, as the result of being thus heated, is deprived of its cytases, but may be readily made active again by the addition of normal, unheated serum. This paradoxical fact, demonstrated by Neisser and Wechsberg can, in their opinion, be explained only by Ehrlich’s theory of amboceptors. When these bodies with double affinities are found in too large quantity as regards the cytase, it may happen that one part only of those which combine with the receptors of the micro-organisms succeed in linking to themselves the molecules of the active ferment. The amboceptor being by itself incapable of destroying the micro-organism, can be injurious to it only on condition that it brings cytase. Consequently as the amount of this cytase is too small for the much larger number of amboceptors we can readily conceive that the micro-organisms may profit thereby and remain alive. This interpretation is certainly very ingenious, but nothing proves that it corresponds with the real state of things. Neisser and Wechsberg have themselves observed that the serum of the normal goat can also prevent the bactericidal action of the cytase. In this case, however, they suggest the intervention of an anticytase of this normal serum. The same explanation might perhaps serve also to explain the preventive action of the serum of immunised animals. We know that anticytases are found frequently enough in the various serums and that they undergo great variations, according to the conditions present in the animals furnishing the blood.

In any case, it is evident that the theory of receptors must in no way be regarded as the antithesis of the theory of phagocytosis. This latter quite retains its right to affirm that, in acquired immunity against micro-organisms, phagocytes play the most general and important part. They hold back the cytases which are capable of ridding the animal of micro-organisms from destroying them. It is further these same cells that produce and excrete the fixative and protective substances. The free fixatives may attack the micro-organisms in the body fluids but they are incapable of depriving them of life or even of virulence. The cytases, after escaping from the phagocytes, may certainly, in collaboration with the fixatives, destroy a certain number of the micro-organisms, but only in special cases met with, no doubt, but only rarely, under natural conditions. On the other hand, the phagocytes in the animal which enjoys acquired immunity constantly fulfil the function of seizing the micro-organisms and of submitting them in their interior to the combined action of fixatives and cytases.

Acquired immunity, like natural immunity against micro-organisms, presents merely special phases of intracellular digestion.