The basis of autoimmunity: an overview.
Autoimmune diseases represent a failure of control in the immune system. In recent years, our understanding of the mechanisms of action of both the innate and the specific immune responses has increased greatly. In particular, we now know much more about the nature of antigens recognized by lymphocytes, as well as how diversity of antigen receptors is generated, antigens and antigen receptors interact, and the cells of the immune system communicate. It is apparent that an inevitable consequence of the diversity of the potential response to antigen is self-reactivity. However, the relative infrequency with which pathological self-reactivity occurs implies the existence of effective control of immune responses. The conditions under which immune responses can be activated, and the factors which regulate their progression, have been subjected to detailed scrutiny. Several of the mechanisms involved in the removal or inactivation of self-reactive lymphocytes, the process of self-tolerance, are now understood. What is less clear are the conditions under which, and the mechanisms by which, this self-tolerance can break down, giving rise to autoimmunity. Several classes of explanation have been put forward to explain this failure of self-tolerance. Although they are of great theoretical interest, proof of their involvement in the pathogenesis of the major autoimmune diseases is largely lacking. A further expansion of our understanding of the mechanisms by which self-tolerance is normally maintained is still needed, in order to comprehend the pathways of breakdown of this tolerance in autoimmunity. Only then will sites and mechanisms for effective therapeutic intervention be identified.
Jones
D E
DE
Department of Medicine, University of Newcastle-upon-Tyne Medical School, UK.
Diamond
A G
AG
D000818:Animals; D001324:Autoantigens; D015551:Autoimmunity; D006649:Histocompatibility Antigens; D006801:Humans; D007108:Immune Tolerance; D007109:Immunity; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D006649:Histocompatibility Antigens; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell