Ring G H, Lakkis F G
Veterans Affairs Medical Center, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30033, USA.
Semin Nephrol. 1999 Jan;19(1):25-33.
Autoimmunity results from a breakdown of physiological mechanisms responsible for maintaining tolerance to self-antigens. These mechanisms are traditionally divided into central and peripheral. T or B lymphocytes that bind to self-antigens with high avidity are deleted or rendered unresponsive during their ontogeny in generative lymphoid organs such as the thymus and the bone marrow (central tolerance). However, this elimination process is incomplete, and regulatory mechanisms that keep mature autoreactive lymphocytes in check are necessary for preventing autoimmunity (peripheral tolerance). Peripheral tolerance mechanisms include passive or activation-induced T and B cell apoptosis, anergy, ignorance, and perhaps suppression of autoreactivity by regulatory lymphocytes. Observations in humans and experimental animals with defined genetic mutations provide examples of autoimmune disorders arising from failure to maintain peripheral tolerance to self. However, multiple factors are necessary for the induction of autoimmunity. For example, bacterial and viral infections may precipitate autoimmune disease in genetically susceptible individuals by exposing autoreactive T cells to cross-reactive peptides (molecular mimicry) or by enhancing lymphocyte stimulation.
自身免疫是由于负责维持对自身抗原耐受性的生理机制出现故障所致。这些机制传统上分为中枢性和外周性。在胸腺和骨髓等生成性淋巴器官中发育过程中，与自身抗原高亲和力结合的T或B淋巴细胞会被清除或变得无反应（中枢耐受性）。然而，这个清除过程并不完全，因此需要有调控机制来控制成熟的自身反应性淋巴细胞，以预防自身免疫（外周耐受性）。外周耐受性机制包括被动或激活诱导的T细胞和B细胞凋亡、无反应性、忽视，以及可能由调节性淋巴细胞抑制自身反应性。对具有特定基因突变的人类和实验动物的观察提供了因未能维持对外周自身耐受性而引发自身免疫性疾病的例子。然而，自身免疫的诱发需要多种因素。例如，细菌和病毒感染可能通过使自身反应性T细胞接触交叉反应性肽（分子模拟）或增强淋巴细胞刺激，在遗传易感个体中引发自身免疫性疾病。
