Antigens

Antigens, in immunology, the name for substances that, when introduced into an animal organism, cause changes in the latter's fluids and cells that lead to the appearance and increase of selective reactive affinity of these cells and fluids to the given substance. Antigenic properties are possessed by far from every substance foreign to the organism, whether it is poisonous or harmless. Thus, for example, according to generally accepted views, only proteins foreign to the organism into which they are introduced possess antigenic properties. From a physicochemical point of view, an antigen represents a protein in a state of colloidal dispersion. To manifest its antigenic function, or in other words, to cause corresponding changes in the cells and fluids of the organism, such a protein must penetrate through the epithelial coverings that separate the internal parts of the organism from the external environment, and must possess the ability to dissolve, resp. be fixed, by the cellular or humoral systems of the organism. A protein that shows no reactive affinity to the latter is unable to produce the physicochemical changes characteristic of antigens in the organism. The changes themselves caused in the organism by antigens are expressed in the so-called specific immune reactions that arise between the antigens and the cellular-humoral systems of the organism. Morphologically, these reactions have a dual character: either coagulation or peptization (lysis) of the antigen (see Immunity). Reactions of the coagulation type include, for example, agglutination, precipitation, detoxification, opsonization, tropinization, capture of the antigen by phagocytes, and others. Reactions of the peptization type include lysis of microbes and foreign formed elements, as well as their digestion in the protoplasm of the phagocyte, and others. To this day, there is no generally accepted theory in immunology explaining the essence and origin of each of the listed reactions, and consequently, the action of antigens on the organism. The various theoretical premises with which different authors approach the study of the nature and mechanism of antigen action are reflected in the selection of factual material that determines the concept of antigens. A brief summary of this factual material gives the following. Proteins lacking aromatic radicals, for example, gelatin, also show no antigenic function (Wells, Landsteiner and others). Protamines, usually representing a complex of diamines and a small content of mono-amines, are also devoid of antigenic properties (Wells, Schmidt, Bennett). Thus, from a chemical side, the most important constituent part of a protein antigen is the aromatic radicals present in it (Obermeyer, Pick), with which the toxicity of the protein is associated (Vaughan), determining the antigenic action. A homologous protein, as a rule, is incapable of immunizing, although Doerr and others note the possibility in some cases of so-called "isoimmunization," that is, such immunization in which a protein of the same species as the immunized animal serves as the antigen. Abderhalden in his theory of protective enzymes (see Abderhalden's reaction) proves that in the blood and in individual organs of the animal organism there is constant enzymatic destruction of proteins of its own origin, as soon as these proteins denature, become "foreign" to the blood and to this or that organ. From this it is evident how important the physicochemical state of the protein antigen is. The main factor of antigenic action should be considered the large size of the protein molecule and the colloidal state of the protein. Any denaturation of a protein is accompanied by corresponding changes in its antigenic properties. For example, a protein treated with iodine, arsenic, formaldehyde, or coagulated by heating, when injected into animals, causes in their blood serum the appearance of immune reactions selectively directed at the correspondingly treated protein, and not observed with pure unchanged protein (Landsteiner, Jablon and others). The breakdown of the protein molecule is accompanied by the destruction of its antigenic properties. None of the fragments of this molecule shows the ability to act as an antigen. The addition to a protein antigen of various non-protein radicals or simple chemical substances that combine with the protein of a given animal transforms this protein into one foreign to its own species and causes in the latter organism specific protective reactions against such artificially altered protein. It is interesting that the blood serum of animals treated in this way reacts not only to the artificially altered own protein, but also to the non-protein radicals and chemical substances taken separately, with which the protein was treated and which are not antigenic in themselves (Uzle and others). With respect to a number of organic substances, such as hemoglobin, certain enzymes in purified form, lipoids, and others, the question of their ability to serve as antigens remains open and controversial. Neither fats, nor carbohydrates, nor alcohol, nor mineral poisons, nor alkaloids have until recently been considered antigens. However, the doctrine that the antigenic function is exclusively associated with protein cannot be considered flawless in terms of its substantiation by factual material, and the correctness of such an opinion is now disputed by some researchers (Barykin). Individual researchers, for example, Bang and Forsmann, working with lipoids, Angelis with aniline dyes, Barykin, Frize and Zilber with aniline dyes and colloidal iron, prove that the listed substances, like foreign protein, are capable of causing antigenic irritation of the animal organism, accompanied by immune serum reactions to these substances. Such a study of the nature of the so-called Forsman antigen showed that a lipoid in combination with a foreign protein, when injected into an animal, causes in its serum immune reactions not only to the combination: lipoid + protein, but also to the lipoid and to the protein taken separately. Hence, a whole new chapter was created in immunology about the so-called "haptens" (semi-antigens) of Landsteiner. These haptens, in their role in immunizing irritation, have an undeniable analogy with the purified enzymes of Bach, as well as with residual antigens of a carbohydrate nature (Zinsser and Parker), since both the former and the latter need protein for their activation. On the other hand, the well-known experiments of Weinland with parenteral administration of carbohydrates, to which the organism responds with a clear increase in its diastatic properties, then the experimental data of Barykin's laboratory, convince that parenteral administration, for example, of starch or a mixture of two semi-antigens, such as lecithin + cholesterol, or even pure colloidal paraffin, result in the organism's response reactions, no different from the classical reactions of immunity (precipitation, fixation of alexin). Kats showed that the organism responds with similar reactions to its immunization with colloidal iodine or even with a crystalloid - sodium iodide. The above-mentioned experimental works throw new light on the doctrine of the nature and mechanism of antigen action. They show that it would essentially be incorrect to contrast the state of the organism that expresses its immunity to the classical antigen-protein with the state that until now was not considered immunity, but was called the organism's habituation, its increased resistance, for example, to iodine, arsenic, cocaine, morphine, heavy metals, and others.