apoptotic body

**Definition:** Apoptotic bodies are the final membrane-enclosed fragments of a cell dying by programmed cell death (apoptosis). Plasma membrane remains intact, so cell contents do not leak out.

**Formation (morphologic sequence):** 1. Cell shrinkage with dense, eosinophilic cytoplasm 2. Chromatin condensation (pyknosis) and nuclear fragmentation (karyorrhexis) 3. Membrane blebbing 4. Budding/fragmentation into apoptotic bodies containing cytoplasm, intact organelles, and ± nuclear fragments

**Pathways leading to their formation:** - **Intrinsic (mitochondrial):** DNA damage, growth factor withdrawal → BAX/BAK activation (inhibited by BCL-2/BCL-xL) → cytochrome c release → Apaf-1 apoptosome → caspase-9 → executioner caspases (3, 6, 7) - **Extrinsic (death receptor):** Fas ligand–Fas (CD95) or TNF–TNFR → FADD → caspase-8 → caspase-3 - **Cytotoxic T cell/NK cell:** perforin and granzyme B → caspase activation - Executioner caspases activate endonucleases (internucleosomal DNA cleavage → "ladder pattern" on gel electrophoresis) and cleave cytoskeletal proteins.

**Clearance:** - Cells display phosphatidylserine on the outer membrane leaflet (normally inner), plus annexin V binding and opsonins (e.g., C3b, thrombospondin) as "eat-me" signals. - Phagocytosed by macrophages or neighboring cells. - **No inflammation** (no release of cell contents, no neutrophil recruitment), in contrast to necrosis.

**Histology:** H&E shows round/oval, intensely eosinophilic cytoplasmic fragments with dense basophilic nuclear chromatin fragments. A classic example is the **Councilman body** in viral hepatitis (acidophilic body of apoptotic hepatocyte). Also seen in graft-versus-host disease, and in the thymus (negative selection).

**Apoptosis vs. necrosis:** | Feature | Apoptosis | Necrosis | |---|---|---| | Energy (ATP) | Required | Not required | | Cell size | Shrinks | Swells | | Membrane | Intact | Disrupted | | Inflammation | Absent | Present | | Pathologic/physiologic | Both | Always pathologic | | DNA | Ladder pattern | Random degradation (smear) |

**Physiologic examples:** Embryogenesis (interdigital webbing regression, Müllerian duct regression in males), hormone-dependent involution (endometrium shedding, post-lactation breast), deletion of autoreactive lymphocytes, and elimination of cells with DNA damage (p53-mediated).

**Pathologic examples:** Viral infections (hepatitis B/C, adenovirus), cytotoxic T-cell–mediated death, ischemic injury (mild), and neurodegeneration.

**Clinical correlations:** - **Too little apoptosis:** cancer (BCL-2 overexpression in follicular lymphoma t(14;18)), autoimmune disease (Fas/FasL mutations → autoimmune lymphoproliferative syndrome) - **Too much apoptosis:** neurodegenerative diseases, ischemia, AIDS (CD4+ T-cell depletion) - Defective clearance of apoptotic bodies (e.g., complement C1q deficiency) → persistence of nuclear antigens → **SLE**-like autoimmunity.

**High-yield pearls:** Apoptotic bodies = apoptosis hallmark; caspases are the executioners; phosphatidylserine flipping is the key "eat-me" signal; no inflammation.