>apoptosis of proliferating effector cells). Also occurs after exposure to injurious stimuli (e.g., radiation, toxins, hypoxia). Changes in proportions of anti- and pro- apoptotic factors lead to*mitochondrial permeability and cytochrome c release. BAX and BAK are pro- apoptotic proteins; Bcl-2 is anti-apoptotic. Bcl-2 prevents cytochrome c release by binding to and inhibiting Apaf-1. Apaf-1 normally induces the activation of caspases. If Bcl-2 is overexpressed (e.g., follicular lymphoma), then Apaf-1 is overly inhibited, leading to*caspase activation and tumorigenesis.Extrinsic pathway2 pathways: - Ligand receptor interactions (FasL binding to Fas [CD95J) and immune cell (cytotoxic T-cell release of perforin and granzyme B) Fas-FasL interaction is necessary in thymic medullary negative selection. Mutations in Fas increase numbers of circulating self-reacting lymphocytes due to failure of clonal deletion.After Fas crosslinks with FasL, multiple Fas molecules coalesce, forming a binding site for a death domain-containing adapter protein, FADD. FADD binds inactive caspases, activating them.">