Induction of a Specific Autoantibody Response Critical Component of Pathogenesis

Recent studies have demonstrated that apoptotic cells are a dominant toleragen for the immune system (Henson et al. 2001, Savill and Fadok 2000), with apoptosis occurring universally during development, homeostasis, and lymphocyte selection and actively inducing anti-inflammatory cytokine secretion on phagocytosis by macrophages (Hengartner 2000). Abnormalities in (a) the efficient, noninflammatory clearance of apoptotic cells or (b) the occurrence of unusual forms of apoptotic death that generate unique structures of autoantigens not generated during "tolerizing" apoptosis may render an individual susceptible to immunization with apoptotic cells. Examples of both mechanisms are dealt with in the following subsections.

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