New concepts on the pathogenesis of autoimmune diseases: a role for immune homeostasis, immunoregulation, and immunosenescence.

Complex autoimmune diseases are chronic conditions initiated by a loss of immunological tolerance to self-antigens. Despite many years of intense investigation, the etiopathogenic mechanisms initiating these chronic inflammatory conditions remain undefined. The relatively high prevalence and the clustering of multiple autoimmune diseases within individuals or within families suggest that rather common immune mechanisms may facilitate the development of autoimmune diseases. However, specific genetic or environmental factors seem to be necessary for triggering disease. Clearly, immune mechanisms, which are intended to protect from disease, fail or become dysregulatcd. In this review, we discuss the mechanisms of immune homeostasis, immune regulation, and immunosenescence. We focus on the merit, consequences, and/or shortcomings of these mechanisms and speculate on their possible involvement in autoimmune-disease development.