Chapter 3 - General Features of Autoimmune Disease

Abstract

Autoimmune diseases are common diseases in which loss of tolerance within the immune system results in pathologic immune responses that target either cellular or organ-specific self-antigens. There is a genetic tendency toward autoreactivity in affected individuals, and both innate and adaptive immune activation may contribute to disease. An important recent advance is the identification of genetic polymorphisms that contribute to risk in most autoimmune diseases and are associated with a variety of immune activation pathways; these associations have been informative about disease-specific pathogenesis and have led to the development of successful therapies for some diseases. A deeper understanding of the components of the innate and adaptive immune system has led to highly effective therapeutic targeting of cytokines, cell surface molecules, and intracellular signaling molecules with marked improvements in outcome in several autoimmune diseases. Fertile new avenues for research include mechanisms of regulation by regulatory immune cells, metabolic regulation of immune cell function, and immune activation by commensal bacteria that colonize humans. The goal of regulating autoimmunity without causing excessive immunosuppression remains elusive but is the holy grail of current research efforts.