Tlaskalová-Hogenová H, Stĕpánková R, Tucková L, Farré M A, Funda D P, Verdú E F, Sinkora J, Hudcovic T, Reháková Z, Cukrowska B, Kozáková H, Prokesová L
Division of Immunology and Gnotobiology, Academy of Sciences of the Czech Republic, Prague.
Folia Microbiol (Praha). 1998;43(5):545-50. doi: 10.1007/BF02820817.
Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.
尽管目前对几种自身免疫性疾病的靶抗原和遗传基础有了更好的理解，但导致对自身成分耐受性丧失的初始事件仍然未知。对自身免疫现象最有吸引力的解释之一涉及各种感染，认为这是可能在遗传易感个体中引发该过程的自然事件。关于感染如何导致自身免疫的最被认可的解释基于“分子模拟”概念（自身抗原表位与环境抗原表位之间的相似性）。感染性刺激也可能通过诱导应激蛋白（热休克蛋白）、伴侣蛋白和移植抗原表达增加而参与自身免疫的发展，这会导致自身抗原的异常加工和呈递。超抗原被认为是诱导炎症反应并参与自身免疫机制发展和进程的最有效的细菌成分之一。长期以来人们已知宿主防御机制缺陷会使个体易受某些微生物引起的感染。微生物抗原排除受损可导致慢性免疫激活，进而影响对自身成分的耐受性。免疫系统某些成分的缺陷与自身免疫性疾病发生风险较高相关。利用动物模型研究具有免疫发病机制的人类疾病，为免疫调节因子和参与疾病发展的淋巴细胞亚群的影响提供了新见解。使用基因工程免疫缺陷小鼠模型进行研究得出的最惊人结论之一是免疫系统成分存在高度冗余。然而，当编码参与T细胞免疫调节功能的分子的基因被删除时，会出现肠道黏膜自发慢性炎症（类似于人类炎症性肠病）。令人惊讶的是，当将此类免疫受损动物置于无菌环境中时，肠道炎症并未发生。有人提出黏膜对正常菌群免疫反应受损在慢性肠道炎症发病机制中起关键作用。使用定殖有特定微生物群落的免疫缺陷模型分析免疫反应性，将有助于阐明负责管腔共生菌、黏膜免疫系统非特异性和特异性成分之间微妙平衡的不同免疫重要分子的作用方式。
