Cell death recognition model for the immune system
Cell death recognition model for the immune system
复制标题
免疫系统的细胞死亡识别模型
DOI：
10.1016/j.mehy.2007.05.049
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发表时间：
2008-01-01
影响因子：
4.7
通讯作者：
Sun, Erwei
中科院分区：
文献类型：
--
作者：
Sun, Erwei
对于免疫系统来说，识别标志物或了解区分应积极响应的抗原和应耐受的抗原所需的规则是至关重要的。尽管过去50年来经典的自我-非我理论受到了“危险”模型、“传染性非我”模型等的挑战，但没有一种理论可以适用于所有人。细胞死亡不仅因为它在体内平衡中的作用，而且还因为它对免疫反应的决定性影响。不同的细胞死亡、凋亡或坏死方式，为免疫系统传递从根本上相反的驱动力，诱导耐受或启动适应性免疫反应。随着对细胞吞噬和细胞死亡过程认识的不断深入，作者提出了免疫系统的“细胞死亡”识别模型。在这个模型中有四个重要的原则。首先，只有从凋亡或坏死细胞脱落的抗原，而不是来自健康细胞的抗原，才能被提呈给幼稚的T细胞。其次，无论是凋亡细胞还是坏死细胞，但不是健康细胞，都可以吸引吞噬细胞，即树突状细胞(DC)或同时也是抗原提呈细胞(APC)的巨噬细胞，以清除死亡细胞。第三，巨噬细胞或DC驻留在非淋巴组织中，吞噬死亡/死亡细胞，迁移到淋巴组织，并向那里的初始T细胞递送抗原。第四，耐受或适应性反应不取决于抗原是自我还是非自我，而是取决于抗原提呈过程中细胞死亡的方式。重要的是，耐受和获得性免疫都是显性反应，细胞死亡对免疫反应的影响是它们之间的动态平衡。细胞死亡识别模型可以更容易地解释各种免疫现象，包括感染、自身耐受和自身免疫、肿瘤免疫以及移植排斥反应。研究细胞死亡介导的免疫反应的作用和机制，找出关键的调节因子，将有助于更好地理解免疫识别的途径，并为自身免疫、肿瘤、感染和移植的治疗提供新的策略。(C)2007爱思唯尔有限公司。保留所有权利。
It is essential for the immune system to recognize markers or understand rules required for discriminating antigens that should be actively responded to from those be tolerated. Although the classic self-nonself theory over the past five decades has been challenged by "danger" model and "infectious nonself" model, etc., no theories could fit for all. Cell death is important not only for its role in homeostasis, but also for its decisive effects on the immune responses. Different ways of cell death, apoptosis or necrosis, transmit fundamentally opposite driving forces for the immune system, inducing tolerance or initiating adaptive immune responses. The progress in understanding phagocytosis and process of apoptotic and necrotic cells leads the author to propose "cell death" recognition model for the immune system. Four principles are important in this model. First, only antigens shedding from apoptotic or necrotic cells rather than those from healthy cells, can be presented to naive T cells. Second, either apoptotic cells or necrotic cells, but not healthy cells, can attract phagocytes, namely dendritic cells (DC) or macrophages that are also antigen presenting cells (APC), to scavenge dead cells. Third, macrophages or DC residing in non-lymphoid tissues phagocytose dying/dead cells, migrate to lymphoid tissues and present antigens to naive T cells there. Fourth, tolerance or adaptive responses are not dependent on whether the antigens are self or nonself, but on the ways of cell death during antigen presentation. Importantly, tolerance and adaptive immunity are all dominant responses and the impact of cell death on immune responses is a dynamic balance between them. "Cell death" recognition model could more easily explain various immune phenomena, including infection, self tolerance and autoimmunity, tumor immunity as well as transplant rejection. Investigation into the roles and mechanisms of cell death mediated immune responses and finding out key modulators wilt prompt better understanding the ways of immune recognition and provide novel strategies for the management of autoimmunity, tumors, infections as well as transplantation. (C) 2007 Elsevier Ltd. All rights reserved.