236b cell death Flashcards
apoptosis - overview? cell appearance? E required? pathways? final activator? radiation involvement?
programmed cell death without inflammation
red cytoplasm, cell shrinkage, pyknosis, membrane blebbing, apoptotic bodies (engulfed by adjacent cells)
ATP required
intrinsic + extrinsic pathways
both activate cytosolic caspases –> cell breakdown (endonuclease yield 180 bp fragments)
radiation causes apoptosis via free radicals and dsDNA breaks –> rapidly dividing cells (skin, GI mucosa) very susceptible
intrinsic pathway for apoptosis - when does it normally occur? how? factors involved? final step?
tissue remodeling in embryogenesis
regulating factor withdrawn (IL-2 after immuno reaction leads to cell death) OR injury (radiation, toxins, hypoxia)
BAX and BAK –> apoptosis
bcl-2 –I apoptosis (via –I Apaf-1)
increases mito permeability and cytochrome c release
extrinsic pathway for apoptosis - pathways?
2 pathways
1) FasL binds to Fas (CD95) – occurs in thymic medullary negative selection (defect = autoimmune disease) –> forms death domain FADD binding site, FADD activates caspases
2) immune cell (cytotoxic cell release of perforin and granzyme B)
necrosis - overview? test? inflammation? E required?
enzymatic degradation and protein denaturation from exogenous injury
intracellular components leak (tropin, LFTs)
inflammatory process
no E required
irreversible cell injury markers
nuclear pyknosis, karyorrhexis, karyolysis
plasma membrane damage (PL degradation)
lysosomal rupture
mito permeability –> see amorphous densities within mito
reversible cell injury with return on O2
ATP depletion –> membrane bleebing and swelling due to loss of Na/K pump activity -> ribosome detachment –> lower protein synthesis
nuclear chromatin clumping
fatty change
what cytokines mediate systemic inflammation (thus increas ESR via hepatic production of acute phase reactants)?
what makes them?
TNF-a
IL-1
IL-6
from macrophages and neutrophils activation during injury
