Autoimmune processes resulting from perturbations of self-nonself recognition

The cellular events involved in the induction, maintenance and termination of experimentally induced immunologic tolerance have been used to better define the cellular and subcellular mechanisms of autoimmunity. Based on these cellular events a model of self-nonself discrimination is presented which assumes that 1) the degree of tolerance to self constituents is determined by the concentration of self antigens in the microenvironment of potential self reactive cells; 2) the induction and maintenance of tolerance to self in B cells require much higher concentrations of self antigens in this microenvironment than in T cells; and 3) self tolerance is a central unresponsive state resulting from clonal deletion. Using these basic assumptions, polyclonal activation of competent B cells, bypassing the requirement for direct activation of specific T cells was discussed as a possible mechanism for the circumvention of self tolerance. Several models of experimental autoimmunity were presented to support these putative mechanisms, and the possible role of regulatory cells in the initiation and progression of autoimmunity was discussed.