PCD Flashcards
(26 cards)
PCD v Necrosis
PCD: mediated, controlled, regulated, cell suicide. Orderly controlled dissolution of cell components
Necrosis: forced, accidental, no control
Morphological changes during apoptosis
Cell shrinks
Membrane blebs
Pyknosis
Karyorrhexis
Morphological changes during necrosis
Cell swells Membrane Ruptures Pyknosis Karyorrhexis Karyolysis
Apoptotic process v necrotic process
A: programmed, caspase signalling, non-lytic, non-inflam
N: accidental, non-caspase, lytic, inflam
Physiological apoptosis processes
Sculpting stuctures (lose interdigital webbing) Deletion of structures (larva-adult fly/ persistant mullerian duct syndrome) Regulating cell no. (Embryo neurones & oocytes, hormone resp eg prostate/mammary)
Disease causes of apoptosis
Cancer
Pathogen infection
What is a caspase
Enzymes (proteases)
Synthesised as inactive pro-caspase then (auto)cleaved just after aspartate residue.
Form cascades activating next in line
Can also be involved in inflam and differentiation
Initiator and executioner
Initiator caspase
Inactive monomer - dimerise - active dimer
8&9, have 3 domains
Can self cleave
Found early in pathway- needed to activate executioner caspase
V specific (only a few substrates)
Can self cleave
Executioner caspase
3&7
Inactive dimer - active dimer via active initiator caspase
2 domains
Occur downstream from initiator
Less specific (many substrates) cause cellular changes seen in apoptosis
Intrinsic pathway
Dna damage - BAK/BAX activation - act on mitochondria - cause MOMP - cytochrome c leak out - bind APAF1 - bind procaspase 9 (in apoptosome) - activate caspase 3&7 - cause apoptosis
Extrinsic pathway
Signal eg necrosis factor - activate death rec - activate caspase 8 (can x talk and affect BAK & BAX) - activate caspase 3&7 - cause apoptosis
Engulfment process
Sensing of apoptotic cell (find me)
Recognition of ap cell (eat me)
Internalisation of ap cell
Digestion of ap cell
Which cells carry out engulfment
Macrophages or dendritic cells
Describe the eat me signal
Phosphatidylserine externalisation
A phospholipid normally found on the inner leaflet that is flipped due to an apoptotic signal
Antiapoptotic proteins
AA BCL-2 proteins
Inhibitors of apoptosis proteins (IAPs)
AA BCL-2 fx
Interfere with BAK/BAX activation
IAP fx
Interfere with caspase 3&7 activation
Interfere with procaspase 9 activation to caspase 9 amd so apoptosome formation
Cellular changes during apoptosis
Caspase activation and protein cleavage
Phosphatidylserine externalisation
Chromosome DNA cleavage into internucleosomal fragments
Factors promoting apoptosis inhibition
GFs
Androgens
Some viral pros
How does Vaccinia virus inhibit apoptosis
Pros N1 and F1 have similar structure to AA BCL-2 so bind BAX and BAK so prevent them from altering the MOMP so prevent apoptosis
How does African Swine Fever prevent apoptosis
Pro A24L is similar to cellular IAP pros so binds casp 3 and so prevent apoptosis
Describe autophagy
PCD type in response to lack of nutrients or damaged cell components (eg misfolded pro response)
Recycles its own organelles and macromolecules by forming autophagosomes. Creates vacuolated cytoplasm. Reversible up to a point
Can occur in the same cell at the same time as apoptosis and is a back up cell death method
Describe pyroptosis
Uses casp 1 Inflammatory and lytic Mechanism of overcoming IC survival by some pathogens Chromatin condense but no karyorrhexis Half way between apoptosis and necrosis
Cells that carry out pyroptosis
Only macrophages and dendritic cells
