Chapter 3 - Apoptosis - To be continued... Flashcards
T or F: Apoptosis is ATP-dependent process
TRUE
Apoptotic changes of a cell:
Cell shrinkage
Chromatin condensation
Membrane blebbing
Morphologic features of apoptosis:
Eosinophilic cytoplasm and basophilic nucleus
Pyknosis and karyorrhexis
In Apoptosis, the cell membrane typically remains…
Intact, without significant inflammation
Sensitive indicator of apoptosis:
DNA laddering (fragments in multiples of 180 bp)
Under what conditions does intrinsic (or mitochondrial) apoptosis occur?
Tissue remodeling during embryogenesis and exposure to noxious stimuli (eg, radiation, toxins, hypoxia)
Intrinsic Apoptosis Pathway: BAX and BAK are…
Proapoptotic
Intrinsic Apoptosis Pathway: Bcl-2 and Bcl-xL are…
Antiapoptotic
BAX and BAK: mechanism
Pores in the mitochondrial membrane → release of cytochrome C → activation of caspases
Bcl-2: mechanism
Keeps mitochondrial membrane impermeable
Bcl-2 overexpression results in…
Tumorigenesis
Example of Bcl-2 overexpression
Follicular lymphoma - t[14; 18]
Extrinsec Apoptosis Pathway: 2 ways
- FasL - Fas (CD95) OR TNF-α - receptor
2. T cytotoxic releasing Perforin and Granzyme B
Fas-FasL interaction: example
Thymic medullary negative selection
Defective Fas-FasL interactions cause…
Autoimmune lymphoproliferative syndrome
What is the final common target of the intrinsic and extrinsic pathways of apoptosis?✅
Activation of caspases (cytosolic proteases)
What might be seen on DNA gel electrophoresis of a sample containing genetic material from apoptotic cells?✅
Fragments in multiples of 180 bp (DNA laddering)
Differentiate between pyknosis and karyorrhexis✅
Pyknosis is nuclear shrinkage; karyorrhexis is nuclear fragmentation by endonuclease action at internucleosomal regions
What steps result in the formation of apoptotic bodies after caspase activation?✅
Cellular shrinkage, chromatin condensation, nuclear fragmentation, cytoskeletal dispersion → cytoplasmic bleb → attached with ligands for macrophage cell receptors → apoptotic bodies
What is the consequence of Fas mutation in regard to negative selection in the thymus?✅
Increased number of self-reacting lymphocytes due to failure of clonal deletion
A decrease in IL-2 after a completed immunologic reaction causes apoptosis of proliferating effector cells through the…
Intrinsic pathway