A theory of regulation and self-nonself discrimination in an immune network.
A mechanism is suggested for the regulation of the immune response that involves antigen-binding and anti-idiotypic lymphocytes. The cross-linking of receptors is postulated to be a general mechanism for triggering T cells, B cells and cytotoxic effector cells (e.g. macrophages). A key role in regulation is ascribed to antigen-specific T cell-dependent factors, which are assumed to be able to block the receptors of both T cells and B cells of the anti-idiotypic specificities. The simple postulates of the model lead to feasible mechanisms for the helper, suppressor and killer roles of T cells, cellular and humoral immune responses, low zone tolerance and the tolerogenic effects of monomers, immune memory, antigenic competition, the abrogation of tolerance with cross-reacting antigens, the usefulness of the switch from IgM to IgG, and self-tolerance to both serum antigens and cell surface antigens. Biological roles are suggested for one of the Ia antigens and beta 2-microglobulin. The theory leads to a number of predictions, which can be tested experimentally. A simple mathematical model is included, which provides an indication of how the theory may be further developed on a quantitative basis.
Hoffmann
G W
GW
Basel Institute for Immunology, 487, Grenzacherstrasse, CH-4058 Basel, Switzerland.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D000941:Antigens / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001324:Autoantigens / Q000145:classification / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D000954:Antigens, Surface; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011948:Receptors, Antigen, T-Cell