Cell Death Flashcards
what are the different types of necrosis?
\+ coagulative \+ colliquative \+ caseous \+ gangrenous \+ fibrinoid \+ fat necrosis
features of coagulative necrosis?
+ in most tissues
+ firm, pale area
+ ghost outlines on microscopy
features of colliquative necrosis?
+ in brain
+ dead area liquified
features of caseous necrosis?
+ TB
+ pale yellow, semi-solid material
features of gangrenous necrosis?
+ with putrefaction
+ follows vascular occlusion or certain infections
+ black
features of fibrinoid necrosis?
microscopic feature in arterioles in malignant hypertension
features of fat necrosis?
+ follow trauma, cause a mass
+ follow pancreatitis visible as multiple white spots
what is apoptosis?
+ programmed cell death
+ usually involves DNA fragmentation
+ recognition by macrophages and non-professional phagocytes
what are extrinsic causes/pathways for cell death?
+ receptors
+ T cells
what are intrinsic causes/pathways for cell death?
+ stress (intracellular)
+ DNA damage and p53
what are key features of T cell mediated cell death?
+ perforin and granzymes
+ cytoplasmic activation
what are key features of intrinsic cell death?
+ endogenous activation
+ mitochondrial involvement
what are key features of extrinsic cell death?
+ reception interaction
+ cytoplasmic signals
+ caspase cascade
what are examples of extrinsic causes of cell death?
+ TNF family
+ Fas CD95
+ inflammation
what is a key step in the early stages of apoptosis?
release of cytochrome c - 2 step process
what is the role of the Bcl2 family?
controls apoptosis - dimerisation
what are the anti-apoptotic members of the Bcl2 family?
Bcl-2 and Bcl-XL (Bcl2 proteins)
how do anti-apoptotic members halt apoptosis?
+ sequestering proforms of death-driving cysteine proteases called caspases (a complex called the apoptosome)
or
+ by preventing the release of mitochondrial apoptogenic factors such as cytochrome c and AIF (apoptosis-inducing factor) into the cytoplasm
what are the pro-apoptotic members of the Bcl2 family?
+ Bax and Bak (BH123 proteins)
+ Bad, Bim, Bid, Puma, Noxa
BH3-only protein
how do pro-apoptotic members halt apoptosis?
+ trigger the release of caspases via heterodimerization
+ also by inducing release of mitochondrial apoptogenic factors into the cytoplasm via acting on mitochondrial permeability transition pore, thereby leading to caspase activation
what can abnormal Bcl2 expression cause?
cancer
what survival factors can override apoptosis?
+ increased production of anti-apoptotic Bcl2 protein
+ inactivation of pro-apoptotic BH3-only Bcl2 protein
+ inactivation of anti-IAPs
what conditions can occur when apoptosis goes wrong?
+ autoimmune disease
+ cancer
+ neurodegeneration
which pathway components can be drug targets?
+ Bcl2 in lymphoma
+ caspase 3 in Alzheimer’s
+ IAP in cancer
what are IAPs?
Inhibitors of Apoptosis Proteins - regulate caspases
what is pyroptosis?
+ highly inflammatory form of programmed cell death
+ occurs most frequently upon infection with intracellular pathogens
+ likely to form part of the antimicrobial response
what triggers pyroptosis?
microbial trigger e.g. salmonella
what are the pattern recognition receptors for pyroptosis?
NOD like and Toll like receptors
what features of pyroptosis are similar to both necrosis and apoptosis?
+ caspase 1 activation, not caspase 3
+ nuclear fragmentation but not cytoplasmic blebbing
+ pro-inflammatory
what is anoikis?
programmed cell death after losing contact with basement membrane/ECM
what are examples of extrinsic cell death?
- TNF family
- Fas CD95
- inflammation
what are examples of T cell mediated death?
- viral infection
- transplantation rejection
caspases: cleave ICAD
destroy genetic information
caspases: cleave PARP
prevent DNA repair
caspases: cleave lamin
break down nuclear architecture
caspases: cleave keratin
break down cytoplasmic architecture
