A theory of regulation and self‐nonself discrimination in an immune network

Abstract

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 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 β₂-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.