Cellular Injury and Apoptosis

Programmed cell death is a complex biological process involving multiple signaling pathways. Autoimmunity can result from defects in multiple stages of apoptosis, ranging from mutant death receptors and ligands to biochemical alterations in death-inducing signaling. While defects in apoptosis of immunocompetent cells can lead to systemic autoimmunity, increased levels of apoptotic cells are also associated with autoimmunity. Ineffective recognition and clearance of apoptotic cells is also a cause of autoimmunity. In this chapter, we review the mechanisms of apoptosis, and the means by which abnormalities in this process can lead to self-immunization and to the development of autoimmunity. The role of necrotic cells in inducing autoimmunity is also discussed, as well as the role of immune complexes containing apoptotic cells in amplifying and perpetuating autoimmunization.