Apoptosis: Mechanisms, Causes, and Recognition by Macrophages

Apoptosis APOPTOSIS 00:10 Programmed cell death Activation of intrinsic enzymes by programming to form fagmented cells called Apoptotic Body Apoptotic Bodies are engulfed by macrophages CAUSES of APOPTOSIS 02:15 Physiological During embryogenesis Cells during organogenesis. Hormonal withdrawal Endometrial cell breakdown during . menustrual cycle Removal of self reactive lymphocytes menopause In thymus (Central tolerance) Post inflammatory responce excess inflammatory cells are removed.

Pathological DNA Damaged by Radiotherapy, Chemotherapy, Hypoxia Accumulation of misfolded protein Cell death in viral infection. Eg : HIV, Hepatitis virus. In organ due to ductal obstruction Eg:- Parotid gland Pancreas. MECHANISM of APOPTOSIS 10:15 Intrinsic pathway Extrinsic pathway (Mitochondria) (Death /FAS Receptor) Cell suicide Programmed cell murder Cell injury :- FIRST APOPTOTIC SIGNAL Growth Factor withdrawal Radiation FAS (TNF-R or CD95) Interact Protein misfolding FAS Ligand (TNF) Sensed by FADD Apoptotic sensors BH3 only proteins Fas associated death domain [Have 3rd BH Domain protein) + BIM, BID, BAD, NOXA, PUMA Caspase 8 Antiapoptotic gene Proapoptotic gene

Antiapoptotic gene Proapoptotic gene Caspase 8 (Have 4BH domain) (Have 3 BH domains) BCL- - 1,2 BCL- XL BAX MCL BAK L= Long life mitochondrial permeability Initiator Cytochrome C comes out Caspase Apoptosome activates Caspase D Cytochrome C APAR-1 Apoptosis acti. Factor 1 Initiator Caspase (Caspase 8&9) Activate Executional caspase 3,6 + Endonuclease Cytoskeleton Protein breakdown Apoptotic Body Apoptotic Body seperates from main cell Removed by macrophage

Cell Injury FAS FAS Ligand Caspase 8 BH3 Caspase 9 anti- apoptotic Proapop + gene totic gene >poptosome Caspase 36 BLC 1,2 BAX BLC XL MCL BAK Endonuclease Cytoskeleton (Nucleus) Breakdown Macrophage Bleb Phosphatidy) serire Nuclear frag ments Apoptotic Body Organelles RECOGNITION OF APOPTOTIC BODY BY MACROPHAGE Through EAT ME Signal Fliping out of Phosphatidyl Serine on membrane of apoptotic body. Phosphatidy) Serine is recognised by Phagocyte-Receptor Through Antibody / Thrombospondin coating the apoptotic body Engulfed by macrophages

Necrosis Apoptosis Pathological Physiological > Pathological MORPHOLOGY Cell Size Cell Swelling Cell Shrinkage (AB) Chromatin Pyknosis Pyknosis Karyorrhesis Karyolysis Plasma membrane Disintegrated Intact Neutrophils + e (Acute inflammation)