How apoptosis got the immune system in shape

Abstract

The discovery that apoptosis is an integral component of normal development has facilitated the widespread recognition that cell death is not at all inimical to life. For much of our lifetime the body maintains a cellular homeostasis persisting until, ultimately, it is broken during the aging process. However, unlike the body as a whole, fluctuations at any age in this cellular balance are frequent in the immune system, which responds to infections via massive clonal expansions and elimination of reactive T and B cells. Moreover, cell death also plays a key, and essential, role in the education of immune cells in the thymus and the bone marrow, where autoreactive cells are eliminated, thereby establishing tolerance to self tissues. Furthermore, the mechanism by which cytotoxic T and NK cells kill virus infected or transformed target cells is by inducing apoptotic cell death. Thus, cell death, and in particular apoptosis, is an integral facet of almost all aspects of immune function. Failure to execute apoptosis appropriately has dire consequences leading to the development of autoimmune disease and malignant growth. This narration provides a historical overview of the impact that the discovery of apoptosis had on the understanding of the function of the immune system. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.