Bäumler C, Kim G O, Elkon K B
Hospital for Special Surgery, Weill Medical College of Cornell University, New York, USA.
Rev Immunogenet. 2000;2(2):283-90.
Homeostasis within the immune system is complicated by the need to selectively force the survival of potentially useful lymphocytes in the central lymphoid organs and of antigen-reactive cells in the periphery. Coupled with this requirement, is the need to delete strongly autoreactive cells in the thymus and bone marrow and downsize the foreign antigen-reactive cells following elimination of the pathogen. Homeostasis is achieved by coupling the fate of the cell to the integration of signals received through the antigen receptor, co-stimulatory receptors and cytokine receptors as well as members of the tumor necrosis factor receptor family that are highly specialized to promote survival or death of a cell. In this review, we briefly discuss how well-defined pathways that promote cell survival PI-3 kinase, Akt, Bcl-2 family and inhibitors of apoptosis (IAPs)-function within the cell. We discuss how cell death stimuli signal either the intrinsic, mitochondrial pathway of apoptosis or kill the cell through one of the six death receptors such as Fas (APO-1/CD95). Finally, the consequences of spontaneous and genetically engineered mutations within survival and death pathways are discussed in the context of predisposition to autoimmune disease and cancer.
免疫系统中的稳态很复杂，因为需要在中枢淋巴器官中选择性地促使潜在有用的淋巴细胞存活，并使外周的抗原反应性细胞存活。与此需求相伴的是，需要在胸腺和骨髓中清除强自身反应性细胞，并在病原体清除后缩减对外源抗原反应性细胞的规模。稳态是通过将细胞命运与通过抗原受体、共刺激受体、细胞因子受体以及肿瘤坏死因子受体家族成员接收的信号整合来实现的，这些受体高度专门化，可促进细胞存活或死亡。在本综述中，我们简要讨论促进细胞存活的明确途径——PI-3激酶、Akt、Bcl-2家族和凋亡抑制剂（IAPs）——在细胞内的功能。我们讨论细胞死亡刺激如何通过凋亡的内在线粒体途径发出信号，或通过六种死亡受体之一（如Fas（APO-1/CD95））杀死细胞。最后，在自身免疫性疾病和癌症易感性的背景下，讨论了存活和死亡途径中自发和基因工程突变的后果。
