Self, non-self, and danger: a complementary view.
Self, non-self, and danger: a complementary view.
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DOI：
10.1007/0-387-34134-x_6
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发表时间：
2006
影响因子：
--
通讯作者：
J. Köhl
中科院分区：
文献类型：
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作者：
J. Köhl
免疫系统的主要目的是保证身体的功能完整性。因此，它需要认识到可能危及功能体完整性的潜在威胁，并消除这些威胁。这种观点要求传感器能够识别各种潜在的危险。最初，免疫学家认为一切非自我的东西都是威胁，尤其是病原微生物。反之亦然，这个模型意味着自我衍生的分子是无害的，免疫系统的设计是为了区分自我和非自我1，2。重要的是，免疫主要被认为是细胞免疫，忽视了包括补体在内的先天免疫的“非特异性”免疫应答。正如我们今天所知道的，这种观点肯定是过于简单化了，因为免疫系统可以识别自我，并促进针对自身衍生分子的强烈炎症反应，最终导致自身免疫。显然，抗原呈递细胞（APC）随机地在其周围取样分子，将这些抗原呈递给T细胞，并通过共刺激信号激活T细胞，这表明细胞免疫本身不能区分自体和非自体，这一困境的一个漏洞是由以下建议提供的，即生殖编码结构可能存在于识别保守的病原体相关分子模式的APC上，并且只有这种识别允许APC诱导T细胞活化3。这种感染性非自身（INS）模型激发了对先天免疫研究的新兴趣，导致发现了Toll样受体（TLR），它识别各种微生物上的保守结构。显示DC上的TLR活化诱导共刺激分子的上调和T细胞活化细胞因子的分泌的数据支持非感染性自身与感染性非自身辨别的模型4。然而，七-
The main purpose of the immune system is to guarantee the functional integrity of the body. As such it needs to recognize potential threats that could jeopardize functional body integrity and to eliminate such threats. This view demands sensors able to identify all kinds of potential danger. Initially, immunologists considered everything that is non-self as a threat, in particular pathogenic microorganisms. Vice versa, this model implied that self-derived molecules are innocuous and that the immune system is designed to discriminate self from non-self1, 2. Importantly, immunity was mainly considered as cellular immunity, neglecting “unspecific” immune responses of innate immunity, including complement. As we know today, this view is certainly oversimplified as the immune system can recognize self and promote strong inflammatory responses against self-derived molecules, eventually leading to autoimmunity. Clearly, antigenpresenting cells (APCs) randomly sample molecules in their surroundings, present those antigens to T cells, and activate T cells through costimulatory signals, suggesting that cellular immunity per se cannot discriminate between self and non-self.A loophole for this dilemma was provided by the suggestion that germlineencoded structures may exist on APCs that recognize conserved pathogenassociated molecular patterns and that only this recognition licenses APCs to induce T cell activation3. This infectious non-self (INS) model fueled new interest in innate immunity research, resulting in the discovery of Toll-like receptors (TLR) that recognize conserved structures on all sorts of microorganisms. Data showing that TLR activation on DCs induces upregulation of costimulatory molecules and secretion of T cell-activating cytokines supported the model of non-infectious self versus infectious non-self discrimination4. However, sev-