Apoptosis

Epidemiology and Etiology:

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Common sites:

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Gross features:

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Histologic features:

· Chromatin condensation, fragmentation

· Cell shrinkage and cytoplasmic eosinophilia

· Cytoplasmic blebs and apoptotic bodies (membrane-bound)

· Lack of inflammation – local macrophages gobble them up

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· Intrinsic (mitochondrial) pathway:

· DNA damage -> p53 accumulation -> if repair fails -> increased Bax expression ->

· Withdrawal of growth factors -> decreased bcl-2, bcl-x -> increased Bax

· Bax opens mitochondrial membrane channels -> cytochrome C released -> combines with Apaf-1 to form apoptosome (“wheel of death”) -> activates caspases -> cleave proteins and activate endonucleases

· Extrinsic (death receptor) pathway

· Fas-ligand binds to Fas (CD95) or TNFR1 -> through FAS associated death domain (FADD) assembles death-inducing signaling complex (DISC) -> activates caspases

· Cytotoxic T-cell secretes perforin (pre forming) then delivers granzyme B -> activates aspases

· Both pathways:

· Thrombospondin (adhesive glycoprotein) on apoptotic boides recognized by macrophages

Other features:

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References:

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