Autoimmune hepatitis. Part A: pathogenesis.
Autoimmune hepatitis. Part A: pathogenesis.
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DOI：
10.1586/17474124.1.1.113
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发表时间：
2007-10-01
影响因子：
3.9
通讯作者：
Czaja, Albert J
中科院分区：
文献类型：
--
作者：
Czaja, Albert J
自身免疫性肝炎是触发抗原和有利于自身抗原呈递的遗传因素、影响免疫细胞活化和持久性的多态性、促进肝脏浸润细胞毒性T细胞增殖的细胞因子改变以及免疫调节细胞群（包括调节性T细胞和自然杀伤T细胞）的数量和功能的扰动的结果。触发表位可能是在多种传染性或毒性因子中常见的短序列肽。该表位和自身抗原之间的同源性（分子模拟）可以刺激交叉反应的体液和细胞应答。致敏的免疫细胞通过类似于外来抗原的自身抗原的不精确靶向（混杂行为）来延长和延续炎症。疾病的发生和临床表型可能与有利于长期暴露于本土病原体的遗传易感性因素有关，这些遗传因素在不同的地理区域和种族群体中可能存在差异。群体内的临床表型可以通过非疾病特异性的遗传多态性进一步修饰，并且影响免疫细胞活化、分化、增殖和程序性死亡（细胞凋亡）。自身免疫性肝炎是一种自身反应性模型，反映了免疫稳态所必需的反调节机制的多重干扰。
Autoimmune hepatitis is a consequence of a triggering antigen and genetic factors that favor the presentation of autoantigens, polymorphisms that affect immunocyte activation and durability, cytokine alterations that promote proliferation of liver-infiltrating cytotoxic T cells, and perturbations in the number and function of immune-regulatory cell populations, including T regulatory cells and natural killer T cells. The triggering epitope is probably a short sequence peptide that is common in multiple infectious or toxic agents. Homologies between this epitope and self-antigens (molecular mimicry) may stimulate humoral and cellular responses that are cross-reactive. Sensitized immunocytes extend and perpetuate the inflammation through imprecise targeting of self-antigens that resemble foreign antigens (promiscuous behavior). The occurrence and clinical phenotype of the disease may relate to genetic susceptibility factors that favor protracted exposure to indigenous etiological agents, and these genetic factors can vary in different geographical regions and ethnic groups. The clinical phenotype within a population can be modified further by genetic polymorphisms that are not disease specific and that affect immunocyte activation, differentiation, proliferation and programmed death (apoptosis). Autoimmune hepatitis is a model of autoreactivity that reflects multiple disturbances in the counter-regulatory mechanisms essential for immune homeostasis.