APOPTOSIS-PARAMEDICAL LECTUR for teaching everdayE.pptx

apoptosis importance

1. APOPTOSIS PRESENTER- DR. PANKHURI GUPTA

2. DEFINITION Apoptosis is a ‘programmed cell death ’. Apoptosis=falling off or dropping off, like leaves or petals)

3. Apoptosis is responsible for mediating cell death in a wide variety of physiological and pathological processes

4. PHYSIOLOGICAL Organized cell destruction in sculpting of tissues during development of embryo. Physiologic involution of cells in hormone-dependent tissues e.g. endometrial shedding, regression of lactating breast after withdrawal of breast-feeding. Normal cell destruction followed by replacement proliferation such as in intestinal epithelium. Involution of the thymus in early age

5. PATHOLOGICAL- Cell death in tumors exposed to chemotherapeutic agents . Cell death by cytotoxic T cells in immune mechanisms such as in graft-versus-host disease and rejection reactions. Progressive depletion of CD4+T cells in the pathogenesis of AIDS. Cell death in viral infections e.g. formation of Councilman bodies in viral hepatitis. In degenerative diseases of CNS e.g. in Alzheimer’s disease, Parkinson’s disease, and chronic infective dementias. Heart diseases e.g. in acute myocardial infarction (20% necrosis and 80% apoptosis).

6. MORPHOLOGY 1 . Involvement of single cells or small clusters of cells in the background of viable cells. 2 . Apoptotic cells are round to oval shrunken masses of intensely eosinophilic cytoplasm ( mummified cell) containing shrunken or almost-normal organelles. 3 . Nuclear chromatin is condensed under the nuclear membrane i.e. pyknosis. 4 . The cell membrane may show blebs or projections on the surface. 5 . There may be formation of membrane-bound near spherical bodies containing condensed organelles around the cell called apoptotic bodies. 6 . Characteristically, unlike necrosis, there is no acute inflammatory reaction around apoptosis. 7 . Phagocytosis of apoptotic bodies by macrophages takes place at varying speed. There may be swift phagocytosis , or loosely floating apoptotic cells

7. Apoptotic bodies in the layer of squamous mucosa

8. MOLECULAR MECHANISM OF APOPTOSIS Initiators of apoptosis- All cells have inbuilt mechanisms for cell survival and signals of cell death; it is the loss of this balance that determines survival or death of a cell . Withdrawal of normal cell survival signals e.g. absence of certain hormones, growth factors, cytokines Agents of cell injury e.g. heat, radiation, hypoxia, toxins, free radicals Agents of cell injury e.g. heat, radiation, hypoxia, toxins, free radicals

9. 2 . Initial steps in apoptosis- After the cell has been initiated into self-destruct mode, cell death signaling mechanisms gets activated from intrinsic (mitochondrial) and extrinsic (cell death receptor initiated) pathways. However, finally mediators of cell death are activated caspases. Caspases are a series of proteolytic or protein-splitting enzymes which act on nuclear proteins and organelles containing protein components .

10. Intrinsic (mitochondrial) pathway Extrinsic( cell death receptor initiated) pathway

11. The intrinsic (mitochondrial) pathway of apoptosis . ( A ) Cell viability is maintained by the induction of anti-apoptotic proteins. The proteins maintain the integrity of mitochondrial membranes and prevent leakage of mitochondrial proteins. ( B ) Loss of survival signals, DNA damage, and other insults activate sensors that antagonize the anti-apoptotic proteins and activate the pro-apoptotic proteins BAX and BAK, which form channels in the mitochondrial membrane. The subsequent leakage of cytochrome c (and other proteins, not shown) leads to caspases activation and apoptosis.

12. The extrinsic (death receptor–initiated) pathway of apoptosis , illustrated by the events following Fas engagement. FADD: Fas- associated death domain; FasL , Fas ligand.

13. 3 . Final phase of apoptosis- The final culmination of either of the two mechanisms is activation of caspases . Mitochondrial pathway activates caspase – 9 and death receptor pathway activates caspases-8 and 10. Other caspases which actively partake in the apoptotic process are caspases-3 and 6. These caspases act on various components of the cell such as DNAase and nuclear matrix proteins and lead to proteolytic actions on nucleus, chromatin clumping, cytoskeletal damage, disruption of endoplasmic reticulum, mitochondrial damage, and disturbed cell membrane.

14. 4 . Phagocytosis- The dead apoptotic cells develop membrane changes which promote their phagocytosis. Phosphatidyl serine and thrombospondin molecules which are normally present on the inside of the cell membrane, appear on the outer surface of the cells in apoptosis, which facilitate their identification by adjacent phagocytes and promotes phagocytosis. The phagocytosis is rapid and is unaccompanied by any inflammatory cells