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

European Journal of Immunology
G W Hoffmann

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 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.

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