Mostarica-Stojković Marija
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade.
Srp Arh Celok Lek. 2005 Oct;133 Suppl 1:9-15. doi: 10.2298/sarh05s1009m.
The main function of the immune system is to protect the body by responding to invading microorganisms. Immunologic tolerance is the basic property of the immune system that provides for self/non-self discrimination so that the immune system can protect the host from external pathogens without reacting against itself. Central tolerance is achieved by the clonal deletion of self-reactive lymphocytes expressing receptors with high avidity for self. Autoreactive lymphocytes which escaped selection in the central lymphoid organs are present in the peripheral repertoire but but are kept under control by multiple diverse peripheral tolerance mechanisms acting either directly on the self-reactive T cell (T-cell intrinsic) or indirectly via additional cells (T-cell extrinsic). Intrinsic mechanisms include ignorance of autoantigens, anergy, phenotype skewing or activation-induced cell death of autoreactive T lymphocytes, while extrinsic mechanisms act through immature and/or tolerogenic dendritic cells as well as different types of regulatory cells. Autoimmune diseases are associated with humoral or cell-mediated immune reactions against one or more of the body's own constituents. Activation and clonal expansion of autoreactive lymhocytes is a crucial step in the pathogenesis of autoimmune diseases. They result from the complex interactions between genetic traits and environmental factors, among which infections are the most likely cause. Several basic mechanisms may be operating whereby an infectious agent actually induces apparent autoimmne reactivity including molecular mimicry, bystander activation, induction of costimulation, polyclonal activation, altered processing and expression of cryptic antigens. Although many questions regarding autotolerance and etiop athogenestis of autoimmunity have yet to be resolved, it is evident that multiple overlapping pathways are operative in establishing, maintaining and breaking autotolerance, as well as during the initiation, progression, and final effector phases of autoimmunity.
免疫系统的主要功能是通过对入侵微生物作出反应来保护身体。免疫耐受是免疫系统的基本特性，它能实现自我/非自我识别，从而使免疫系统能够保护宿主免受外部病原体的侵害，而不会对自身产生反应。中枢耐受是通过对表达高亲和力自身受体的自身反应性淋巴细胞进行克隆清除来实现的。在中枢淋巴器官中逃脱选择的自身反应性淋巴细胞存在于外周库中，但受到多种不同的外周耐受机制的控制，这些机制要么直接作用于自身反应性T细胞（T细胞内在机制），要么通过其他细胞间接作用（T细胞外在机制）。内在机制包括对自身抗原的忽视、无反应性、表型偏移或自身反应性T淋巴细胞的活化诱导细胞死亡，而外在机制则通过未成熟和/或耐受性树突状细胞以及不同类型的调节细胞发挥作用。自身免疫性疾病与针对身体自身一种或多种成分的体液或细胞介导的免疫反应有关。自身反应性淋巴细胞的活化和克隆扩增是自身免疫性疾病发病机制中的关键步骤。它们是由遗传特征和环境因素之间的复杂相互作用引起的，其中感染是最可能的原因。几种基本机制可能在起作用，通过这些机制，一种感染因子实际上会诱导明显的自身免疫反应性，包括分子模拟、旁观者活化、共刺激诱导、多克隆活化、隐蔽抗原的加工和表达改变。尽管关于自身耐受和自身免疫性疾病的病因学仍有许多问题有待解决，但很明显，多种重叠途径在建立、维持和打破自身耐受以及在自身免疫性疾病的起始、进展和最终效应阶段都发挥着作用。
