Membrane repair and immunological danger
Membrane repair and immunological danger
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DOI：
10.1038/sj.embor.7400505
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发表时间：
2005-09-01
期刊：
影响因子：
7.7
通讯作者：
Andrews, NW
中科院分区：
文献类型：
--
作者：
Andrews, NW
只有当佐剂分子提供第二信号时，抗原才能引发有效的免疫应答。已经确定的是，当被抗原呈递细胞上的特异性受体识别时，外源获得的病原体相关分子模式实现这种佐剂作用。最近的证据表明存在另一类佐剂，这显然是从受损细胞释放。这种内源性佐剂被称为“危险”信号，可以提醒免疫系统注意导致细胞损伤的情况，但不一定是那些涉及感染的情况。内源性佐剂为针对肿瘤和自体组织产生的免疫应答提供了很好的解释，但考虑到细胞在体内受损的频率，很难解释如何避免免疫系统的持续激活。在这里，我们认为，细胞在其质膜上重新密封伤口的效率可能是耐受性和自身免疫之间平衡的一个重要因素。最近在synaptotagmin-VII缺陷小鼠中的观察表明，有缺陷的膜修复可能导致对机械损伤更敏感的组织中的自身免疫。
Antigens are able to elicit productive immune responses only when second signals are provided by adjuvant molecules. It is well established that exogenously acquired, pathogen-associated molecular patterns fulfil this adjuvant role when recognized by specific receptors on antigen-presenting cells. Recent evidence points to the existence of another class of adjuvant, which is apparently released from injured cells. Such endogenous adjuvants, referred to as 'danger' signals, could alert the immune system to situations that cause cell damage, but not necessarily those that involve infections. Endogenous adjuvants provide a good explanation for immune responses generated against tumours and autologous tissues, but it has been difficult to explain how a constant activation of the immune system is avoided, considering the frequency at which cells are injured in vivo. Here, we suggest that the efficiency with which cells reseal wounds in their plasma membrane might be an important factor in the balance between tolerance and autoimmunity. Recent observations in synaptotagmin-VII-deficient mice suggest that defective membrane repair could lead to autoimmunity in tissues that are more susceptible to mechanical injury.