Apoptosis

Question 1

Compare and contrast necrosis and apoptosis

Answer 1

Stimuli - pathological vs patho and/or physiological
Histology - inflammatory reaction etc
DNA breakdown mechanism
Tissue reaction

Question 2

What sort of signals and receptors in apoptic cells?

Answer 2

sugars on protines
TSP binding
PS
LDL-like

Question 3

What sort of interactions can occur between MP and apoptic cells?

Answer 3

Sanitation analogy:
MP picks up garbage
MP induce or stimulate garbage - MP tells you what is garbage
MP help strengthen the apoptotic signalls - MP assisted suicide
Epithelial cells can change temporarily to a phagocyte when exposed to eat-me signals - Neighbour takes on garbage collector functions

Question 4

What other functiosn do MP have in apoptosis?

Answer 4

removeal of cell corpses
prevention of leakage of contents from dying cells
suppression of inflammation (inc TGFbeta 1, inc PGE2, dec TNFalpha)
modulation of cell killing (decr NO, Incr CD95L)
reulgation of immune response (via class I MHC)

Question 5

How does Trypansoma cruzi cause T cell apopotisi?

Answer 5

Organism ingestion diminishes NO levels and increases PGE2 levels thus diminishing the host inflammatory response. When aspirin is given, this counters the PG release and thus decrease parasitemia.

Question 6

How do caspases function?

Answer 6

DREDD analogy- one of the caspases (formerly ICE proteases)
cysteins proteases that cleave Asp-XXX bonds
selectively chop up a restricted set of target proteins - selective
targets: NDA nucleases, nuclear lamins, cytoskeletal proteins, PAK2

Question 7

What are the different types of caspases?

Answer 7

Initiator caspases - Caspases 8-10, 1, 2, 4, 5,11, 12

Effector caspases - Caspases 3

Question 8

What is the apoptosome and its function?

Answer 8

Form in cytoplasm
Initiator Caspase 9 is bound by Apaf1 which is later activated by cytochrome c from the mitochondria.
Lies inactive until the activator is available.

Question 9

What are the two pathways of apoptosis?

Answer 9

Intrinsic - mitochondrial dependent
-use of cytochrome C, AIF, procaspases 2,3 and 9)
Extrinsic - mitochonidrla independent

Question 10

What is the function IAP and what proteins can inhibit them?

Answer 10

Inhibitors of apoptosis proteins - inhibit caspases
eg. survivin
These can be broken down by Smac (second mitochondrial activators of caspases) / DIABLO (Direct IAP binding protein with low pI) –> these can then remove the IAP and thus allowing apoptosis

Question 11

What are RING domains and how do they contribute to apoptosis?

Answer 11

IAPs contain a conserved RING domain. The RING proteins represent the largest class of E3 ubiquitin ligases. THe IAPs use their RING domains to ubiquinate to target cell components to cause cell death or target caspases to cause cell survival.

Question 12

Bcl2 family members (dBORG1 and dBORG2 - pro-death; BUFFY - pro-life) has three groups, waht are they?

Answer 12

1 - anti apopotic (Bcl2, BclXl)
Groups 2 and 3 have pro apopticic function (Bax, Bad, Bid, Bik)
Pro and anti- can form heterodimers

Question 13

What is the major mechanisms for chemoresistance in FL?

Answer 13

Inhibition of apoptosis such as overexpression of Bcl2 and Bcl-XL.

Question 14

Applications of seeing apoptosis

Answer 14

GVHD
apoptoic colopathy
MMF toxicity
apoptic index for tumour
Minor predictor of MICA of Cervix

Question 15

How are death receptor functions modulated?

Answer 15

All these receptors share common death domain
Receptors modulate apoptosis pathways include members such as TNF - Fas and TRAIL
Functions modulated by decoy receptors such as FLASH and SADS - inactivating and by C-FLIP/Usurupin dominant negative inhibitor of extrisic pathway apoptosis

Question 16

What is anoikis?

Answer 16

Detachment-induced apoptosis. Components of the matrix have not been specified but include Hormones, soluble cytokines, integrins, synaptic connections, ECM, C adherin.