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Pathology Cellular Pathology 03fc5489

All of the following are true about apoptosis excep:

A
Expression of caspases
B
Internucleosomal cleavage of DNA
C
"Smeared" pattern of DNA fragmentation
D
Expression of phosphatidyl serine
High-Yield Explanation
Ans: c (Smeared pattern of DNA fragmentation) Ref: Robbins, 7th ed, p. 27Smeared pattern of DNA fragmentation is indicative of necrosis and ladder pattern of DNA fragmentation on electrophoresis is indicative of apoptosisMorphological features of apoptosis:1) Cell shrinkage2) Chromatin condensation - most characteristic feature3) Formation of cytoplasmic blebs and apoptotic bodiesApoptotic bodies are round or oval bodies with eosinophilic cytoplasamand dense chromatin fragments4) Phagocytosis of apoptotic cells by macrophagesMechanism of apoptosis:Extrinsic pathway ot ApoptosisFas ligand|Binds with three molecules of FAS|Forms binding site for FAS associated death domain|FADD(Fas associated death domain binds)|Activation of caspases 8( Caspases 10 in humans)|Activation of execution caspases (3,6)|APOPTOSISIntrinsic pathwayWithdrawal of growth hormone/stress or injury|Loss of BCL 2,BCL-XL (antiapoptotic)Accumulation of Bax ,Bim, Bid etc.|Increasing permeability of mitochondrial membrane and leakage of proteins|||cytochrome cApoptosis inducing factor||Activation of caspases 9Neutralisation of inhibitor of Apoptosis|||Activation of execution caspases (3,6)|APOPTOSISDifference between necrosis and apoptosisFeatureNecrosisApoptosisNucleusPyknosis,Karyorrhexis,KaryolysisFragmentation into nucleosomePlasma membraneDisruptedIntactCellular contentsEnzymatic digestion - contents may leak out of cellIntact; released as apoptosisAdjacent inflammationFrequentNilPhysiological/ pathologicalAlways pathologicalOften physiologicImportant points regarding apoptosis:Best known death receptor - TNF 1 receptor (TNFR1) and a related protein called FAS (CD 95)Apoptotic cells express phosphatidyl serine and thrombospondin on their surfaceTumor marker of apoptosis - Annexin 5Intermediate molecule between death receptor andcaspases - SphingolipidceramideBRIDGEPyroptosis: Programmed cell death associated with antimicrobial responses during inflammation. It is studied in the context of Salmonella infected macrophages

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