The immune system can function normally only if it discriminates between self and nonself. In the view of N.R. Sinclair and A. Panoskaltsis, outlined here, this discrimination is based primarily on whether the antigen is distributed widely (self) or narrowly (nonself). If antigen is widely distributed, it will lead to inhibition of immune responses due to the generation of complexes made up of antigen and end product (either antibody or effector cell), which bind to responding antigen-specific cells and inactivate them. If antigen is narrowly distributed, being present only on cells that can present antigen without end product feedback signals, immune responses are stimulated. All processes that lead to disappearance of antigen from nonimmunogenic sites, collectively termed mechanisms of antigen depresentation, do not occur with continually synthesized self antigens. Autoimmunity occurs when mechanisms involved in feedback inhibition by antigen plus end product fail to function normally.
Bibliographical noteFunding Information:
we acknowledge the support of the Arthritis Society of Canada and the J.P. Bickell Foundation.