Analysis of allergic antibodies indicates that they have two constituents, lipids and proteins. Electrophoretic analyses reveal that they are displaced mostly as beta globulins. Experiments show that such lipido proteic antibodies lose their activity if broken into their constituents, neither the lipid fraction nor the protein alone being able to bind the antigen.

The study of the lipido proteic antibodies, brought us back to consider the role of the lipids in the immediate or prolonged first phase. Most, if not all the natural antigens have lipids and lipoproteins in their structure. As we have seen above, some of the fatty acids induce defense responses. The administration of fatty acids is followed by a leucopenia—especially a lymphopenia; administration of sterols, by a hyperleucocytosis. Some fatty acids, such as those obtained from the tubercle bacilli, induce characteristic lesions such as giant cells. There are both naturally present lipoproteins and those resulting from the bond of the body's freed fatty acids to the antigen, which seem to act as specific antigens, inducing the appearance of coagulant, allergic antibodies. Experiments, which we will discuss below, have shown that, while the specificity of the antibodies is highly related to the protein fraction, the allergic or immune character of the resulting response is due to the fact that lipido proteins are involved in these processes. The injection of the product resulting from the action in vitro of the acid lipidic constituents of an organism upon proteins of another species acts as an antigen inducing the early appearance of coagulant antibodies. The repeated injections of the product obtained through the action in vitro of foreign lipoacid fractions of various origins upon different body proteins also induces allergic response. Just as we have connected the appearance of the first diphasic phenomenon to hydrolytic enzymes and the prolonged form of the antiheterogeneous defense mechanism to the intervention of lipids, we relate the allergic body defense to the intervention of lipido proteic formations. The allergic stage of defense thus could be considered to be a lipido proteic defense response against lipido proteic antigens.

Neutralizing Antibodies

The unsuccessful fight of the organism against an antigen through the diphasic, lipidic or allergic responses often can evolve further, making use of a more effective measure which corresponds to another kind of antibody, different from the coagulant type. The characteristic of this second type is that it forms, specifically with the antigen against which it is manufactured, a new kind of bond, an antigen antibody complex, this time entirely nonnoxious to the organism. This complex is energetically so balanced as to correspond to the constants of respective levels of the body where it occurs. Through this new bond, the antigen is biologically neutralized in the sense that the resulting antigen antibody complex is entirely harmless.

This type of neutralizing or immune antibody usually appears on or after the 15th day following the moment when the organism has started to organize its defense against the antigen. It can occur whether the antigen is still present or not and whether it is free or bound to coagulant antibodies. It represents the best means through which the organism opposes the influence exercised by an antigen. The appearance of the neutralizing antibodies corresponds to the last stage, the immune one, in the defense mechanism. If the antigen has produced a clinical condition, the neutralization of the antigen by the new antibody results in the slow disappearance of morbid manifestations and a progressive return to normal. With or without prior clinical manifestations, the presence of the neutralizing antibody in the organism provides a potential weapon to prevent the same antigen from again causing trouble. This has led us to identify this part of the defense reaction as the "immune stage" of the defense mechanism.

The action of these neutralizing antibodies has been demonstrated beyond doubt through passive immunity. Their administration confers protection against the antigen. This action is limited to the antigen so long as it is not bound by another antibody. Clinically, neutralizing antibodies have a curative value if the antigen is present, inducing the primary toxic response. They have, also a preventive effect upon the allergic form of the disease if they are administered before the appearance of the coagulant antibodies.

Neutralizing antibodies are globulinic in nature. They are displaced in electrophoretic analyses as gamma globulins. Isolated as pure globulins, they do not lose their activity. This would differentiate them from the coagulant antibodies which, as previously noted, are lipido proteinic in nature.

The defense resources of organisms against antigens thus can be didactically separated into four fundamentally distinct groups: enzymatic hydrolytic, lipidic, lipoproteinic and proteinic. They correspond to distinct stages from the point of view of reactions induced and biological meaning. The first represents a primary, direct, immediate response characterized by a rapid nonspecific digestive process and followed by the exaggerated mobilization of repair processes. If the immediate response is inadequate, a second stage as a prolonged lipidic defense follows. Although it has a certain degree of specificity, this last response is still directed against a heterogeneous constitution of the agent as such. If unsuccessful in inactivating the agent, all these responses are followed by another defense stage in which action is taken against the antigen through more specific coagulant lipido proteinic antibodies and through the antiheterogeneous reaction to the resulting complex. With the last stage, which is characterized by the intervention of proteinic neutralizing protective immune antibodies, the fight against the antigen is usually concluded successfully. Table XI, below, summarizes this systematization of the defense response.