In the defense processes, another factor intervenes to produce differences between responses at different levels—the special affinity of antigens for various cells, tissues or organs. This affinity will determine not only the level but also the individual entities where manifestations will occur. It has to be emphasized that the independence of the levels or of groups of entities in an organism goes so far as to allow the defense processes to progress to different stages. While defense processes at the tissular level, for instance, cannot go beyond the stage of prolonged lipidic response, those at the organic or systemic level can arrive at the allergic stage. We will see below the importance of this unequal response of the different levels.

The unequal capacity of different tissues to manufacture allergic antibodies could be postulated to explain the propensity for local allergic conditions. The ectodermic system appears especially inclined to allergic responses, as seen for the skin. We tried to relate this to the natural richness of these organs in sterols. This would explain the fact that the brain, which is richest in sterols, seems to show the earliest allergic manifestations, which could be interpreted as resulting from early or more constant appearance of coagulant antibodies.

Besides these differences in the responses of various entities, an important factor intervenes in the induction of localized allergic manifestations. It corresponds to unequal affinity of the antigen itself for various entities. This would localize the antigen in cells, tissues or organs so that when coagulated antibodies do appear, the noxious allergic complex will be formed locally in the same entities. It seems that this localization of the antigen, such as upon nerves, kidney, lung, etc., is more important than the capacity to produce antibodies in determining predilection of pathological processes for specific cells, tissues or organs.

One of the most interesting aspects of the defense mechanism is the relationship between successive steps. We could show, generally, that an intensive response in one step represents a favorable condition for appearance of an intensive response in the next step. It is a known fact that manufacture of immune antibodies is influenced by an inflammatory process. This is the reason for the customary injection of tapioca, for instance, in horses during their immunization for the production of therapeutic sera. We could show that injections of lipids, lipid acids or insaponifiable fraction of placenta, or of organs of animals of the same species for instance, manifestly hasten the appearance of the next step in the defense against the microbe.

It seems clear that under the influence of the lipids used, the agglutinins appear in blood earlier and their amount increases more rapidly than in the control animals.

Antigenic Factors

The intervention of different mechanisms in the defense has led to the supposition that each one would be induced by relatively specific factors present either in the antigen itself or appearing during the defense processes.

An analysis of this aspect of the problem of the defense has brought further interesting information.

The intervention of the first mechanism, that of hydrolytic enzymes acting through a process similar to digestion, would have as aim to break down the antigen itself as well as the groups resulting from the bond between antigen and body constituents, especially proteins. By analogy with the process of digestion, the factor present in the body which would induce this response would correspond to abnormally low number of micelles. The low number of micelles present is revealed by a cryoscopic index near zero. The digestive defense mechanism would thus intend to lower this cryoscopic index back to its normal values or even below them.

The second mechanism, that of the lipidic intervention, would have two aims. One, to act against free lipids either present in the antigen or resulting from the hydrolytic action upon fats, and second, to bind hydrosoluble constituents into complexes with a lower hydrosolubility, and consequently with lower diffusion capacity through the aqueous media of the organism. This concerns the antigen as well as the products resulting from the lytic intervention. The bond would take place through the active polar part of the lipid molecules.

The third mechanism is characterized by the intervention of the allergic antibodies with the aim of binding the antigen in higher complexes. The lipido proteic antibodies will oppose a lipido proteic fraction present in the antigen itself or resulting from the bond between lipids liberated in the second mechanism and proteins of the antigen or of the body. The coagulant effect would result from the bond through the polar and nonpolar groups of the lipido proteic antibodies and those of the lipido proteic antigenic factors.

For the fourth mechanism, characterized by the protective antibodies, the antigenic factor would be represented by the proteic constituents of the antigen, which leads to an antireplication in the specific antibodies.

It should be noted that in the complex defense mechanism the results of the intervention of a defense process represent antigenic factors for the next step. The presence of products of the enzymatic digestion leads to the intervention of the lipidic phase, largely aimed to immobilize and inactivate them; the bond between lipids and antigen leads to the appearance of the allergic lipido proteic antibodies. Possibly, the occurring lipido proteic complexes would intervene, facilitating the appearance of the protective antibodies. The idea that successive antigenic factors would induce the appearance of different steps in the defense mechanism, has led to a series of studies with the aim to obtain desired reactions through the use of such antigenic factors. We will describe here very briefly several such applications which were interesting also because of the practical results obtained.