Immunity in Plague: A Critical Consideration of Some Recent Studies

Abstract

Discussion and Summary: From the vast and somewhat unmanageable array of facts, there may be derived certain principles and laws which govern the immunity in bubonic and pneumonic plague. Considering the mechanism from a diversity of angles, it is recognized that phagocytosis is the most important mechanism which animals and man use in guarding against and disposing of a plague infection.2 The mesenchymal tissue cells are responsible not only for cellular immunity, but for humoral defense as well. Their cytoplasm, modified by effective contact with antigen, develops adaptive enzymes and thus circulating antibodies—agglutinins and specific fraction I precipitins—which in turn remove the antiphagocytic property of the slimy “envelope” of the plague bacillus. Cytologic and immunologic observations support this interpretation. The effectiveness of the mechanism and consequently the fate of the host are determined by the balance between the bacterial multiplication and the efficacy of the clearing mechanism. The following factors not clearly understood are suspected of impairing the orderly development of antibacterial immunity: (a) The endotoxins liberated by the disintegrating plague bacilli seriously poison the myocardium, adrenals and parenchymatous organs, and thus create vascular disturbances. (b) The soluble antigens set free, if excessive, block the action of the antibodies on the bacilli. (c) Genetic resistance of individual bacillary elements may permit escape from phagocytosis; slow multiplication of these resistant cells may be, in part, responsible for chronic plague accompanied by marasmus. It is generally accepted that the efficacy of the humoral phase of the immunity mechanism is determined by the existing concentration of antibodies. This aspect deserves brief discussion. Current articles on plague convey the impression that the concentration of serum antibodies in man recovered from plague or in animals actively immunized with avirulent strains or antigens is too low to be detected by the usual agglutination or mouse-protection test (as developed by Jawetz and Meyer). Provided suitable strains have been selected for agglutination and improvements in the protection test made (Meyer and Foster, 1948), even low concentrations of antibodies are demonstrable. Antibodies in varying concentrations have been demonstrated in the serum of monkeys, guinea pigs, mice and man recovered from infection or injected with any one of a diversity of antigens or avirulent cultures. Furthermore, the persistence of specific serum antibodies in low concentrations for several months has been proved. However, the blood concentration of the antibody does not necessarily indicate the state of immunity against plague. The physiologic activity and avidity of the cellular factors are so important that the availability of the antibody in the plasma is probably subordinate to the antibodies on the cells in the regional lymph nodes. In the natural process of plague infection the defenses, as studied in the cytogram, come into play in the following order: tissue, lymphatic system, blood stream and finally the reticulo-endothelial system. During the progress of these reactions, although specific antibodies are not demonstrable in the blood plasma, the antigenic stimulus on the antibody-producing cells previously in contact with the different antigenic plague proteins will respond vigorously. Man, as well as animals, injected with plague vaccine or certain particulate antigens apparently possesses the ability to mobilize antibodies in the local inflammatory exudate and regional lymph nodes, provided their cells have been adequately impressed. It is indeed significant that the immunity afforded by a virulent infection is greater than that conferred by vaccination with different avirulent strains, which in turn is more permanent than that produced by plague prophylactics consisting of antigens. Whether an infection in an immune animal stimulates the physiologic activity of the histiocytes and their related cells to produce antibodies more rapidly and more effectively than the susceptible animal has not as yet been determined. It is not unlikely that the immune state is further conditioned by an increased phagocytic capacity of the microphages and macrophages. Scattered observations indicate that individual and seasonal species-resistance to plague depends on the physiologic activity of the mesodermal tissues, not on any mysterious humoral lytic antibody.