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ergogenic22
Bortezomib does not directly activate perforin. It directly inhibits the proteasome which → enables CD8+ T cells to initiate apoptosis → via perforin release (in essence a downstream effect).
+4
drzed
Exactly, it triggers the cells to undergo apoptosis which means that it can either be cell mediated (perforin and granzyme via FAS/FASL) OR it could also be through the intrinsic pathway (e.g. mitochondrial; cytochrome c)
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powerhouseofthecell
Question: But how do CD8 cells have a role in this process exactly in the vignette? Is it saying that when the proteins build up, only then do CD8 cells come and instead of MHC I presenting to proteasomes, they present it to CD8 to initiate apoptosis?
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flexatronn
@powerhouseofthecell
so it all goes back to basic immuno (i got this wrong and put apoptosis as well) but after reviewing relevant anki cards, i now get it.
So proteasomes break down tagged proteins within the cell (endogenous). The breakdown products get taken up by transport associated with antigen processing (TAP) and brought to the rough ER. The breakdown products are then loaded onto MHC I molecules and brought to the surface of the cell. When thinking about MHC I, think about CD8+ T cells (FA MHC 1 x 8 = CD8.
Now to summarize, when using a proteasome inhibitor, you're blocking that tagging and MHC I loading process. As stated before, CD8 recognizes MHC I (which won't happen when using these drugs)
+3
Why would perforins be the wrong answer? Wouldnt accumulation of toxic proteins cause the cell to undergo apoptosis ?