The basis of autoimmunity: Part I. Mechanisms of aberrant self-recognition.
The basis of autoimmunity: Part I. Mechanisms of aberrant self-recognition.
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自身免疫的基础：第一部分。异常自我识别的机制。
DOI：
10.1016/0167-5699(95)80095-6
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
Theofilopoulos,AN
中科院分区：
文献类型：
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作者：
Theofilopoulos,AN
在这个由两部分组成的系列文章中，Argyrios N. Theofilopoulos总结了自身免疫领域的现状。第一部分整合了自身免疫性疾病的集体机制理论。关于器官特异性疾病，最直接的解释是，这些疾病是由针对自身抗原的不适当的常规免疫反应引起的，而这种免疫反应从未建立起耐受性。类似的机制可能在系统性自身免疫中起作用，但其他异常，如细胞凋亡机制的缺陷也可能被调用。第二部分将讨论易患自身免疫综合征的遗传因素。长期以来，人们一直假设免疫系统的发展本质上是三位一体的：无用的细胞被丢弃，有用的细胞被保留，危险的细胞被破坏或失活。近年来，对转基因和内源性超抗原（SAg）表达小鼠的研究强烈表明，这一假设基本上是正确的，最终结果可能取决于抗原受体与自身成分的反应程度。具体来说，随着T细胞在胸腺中成熟，那些重排并显示具有一定亲和力/亲和力的自身主要组织相容性复合体（MHC）和肽反应性T细胞受体（TCRs）的细胞在胸腺中得到维持和繁殖（阳性选择）；但是，在它们输出到外周之前，那些具有危险的高亲和力/亲和性受体的受体被淘汰或失活（负选择）1-3。与膜结合的自身抗原或可溶性自身抗原反应的新生B细胞的消除或失活也分别有文献记载4,5。因此，通过这些编辑过程，达到了一种自我容忍的状态。然而，尽管最近获得了大量有关自身耐受机制的信息，但我们对导致致病性自身免疫的机制的理解仍然是零碎和不完整的。然而，这一领域的最新进展已经开始拼凑这一谜题缺失的部分。这篇综述的目的是综合广泛分散的概念
In this two-part series, Argyrios N. Theofilopoulos summarizes the current state of affairs in the field of autoimmunity. Part I integrates the collective mechanistic theories of autoimmune diseases. The most straightforward explanation to emerge with regard to organ-specific diseases is the concept that these are caused by inappropriate, yet conventional, immunological responses against self-antigens for which tolerance has never been established. A similar mechanism may be operative in systemic autoimmunity, but other abnormalities such as defects in the apoptosis machinery may also be invoked. Part II will address the genetic contributions predisposing to autoimmune syndromes.It has long been hypothesized that the development of the immune system is triadic in nature: useless cells are discarded, useful cells are retained and dangerous cells are destroyed or inactivated. In recent years, studies with transgenic and endogenous superantigen (SAg)-expressing mice have strongly suggested that this hypothesis is essentially correct, with the ultimate outcome likely to be dependent on the degree with which antigen receptors react with self-constituents. Specifically, it appears that, as T cells mature in the thymus, those that rearrange and display self major histocompatibility complex (MHC) and peptide-reactive T-cell receptors (TCRs) of a certain affinity/avidity are maintained and propagated within the thymus (positive selection); but, prior to their export to the periphery, those with receptors of dangerously high affinity/avidity are eliminated or inactivated (negative selection) 1-3. Elimination or inactivation of emerging B cells reactive with membrane-bound self-antigens or soluble selfantigens, respectively, has also been documented 4, 5. Thus, through these editing processes, a state of selftolerance is achieved. However, despite the recent acquisition of extensive information relating to the mechanisms of self-tolerance, our understanding of the mechanisms leading to pathogenic autoimmunity is still fragmentary and incomplete. Nevertheless, recent advances in this area have begun to assemble the missing pieces of the puzzle. The purpose of this review is to synthesize the widely dispersed concepts