APOPTOSIS : APOPTOSIS Apoptosis—Coordinated and internally programmed cell death in physiological and pathological conditions.
Differs from necrosis
No inflammatory reaction
Apoptosis seen in : Apoptosis seen in Physiological
During embryogenesis
Hormone dependant-endometrial shedding, lactating breast after weaning
Atrophy of thymus Pathological
Injury due to heat,
Radiation,
Cytotoxic drugs, for cancer,
Tumour cells,
Autoimmune diseases
Morphological changes : Morphological changes Involves single cell or cluster of cells
Oval masses with intensely pink cytoplasm
Nuclear chromatin condensed and aggregated peripherally under nuclear membrane in various shapes and sizes
Ultimately karyorrhexis occurs
Slide 4 : With E.M. it appears as fragmentation of DNA into nucleosome like pieces formed due to activation of endonucleases
Cells shrink, form cytoplasmic buds and fragment into apoptotic bodies
There is no inflammatory reaction but apoptotic bodies are phagocytosed by macrophages
Mechanism of apoptosis : Mechanism of apoptosis Signalling-
A) An intrinsic programmed event-eg.-lack of growth factor, specific ligand –receptor interactions, release of enzymes from T cells or selected injurious agent
B) These signals may either suppress preexisting death programs or initiate a death cascade
Slide 6 : Control and integration- Done by specific proteins that connect the original death signals to the final execution programme
There are two broad pathways
1) signals by specific adapter proteins
2) regulation of mitochondrial permeability by the members of BCL-2 family of proteins ( controlled by BAD, BAX & BID genes)
Slide 7 : Receptor-CD95 + Signal (Ligand) = Specific adapter protein
Procuspase 8
Cuspase 3----Death inducing signal
Activates cleavage of DNA or other substitutes