Exam 3: Cytotoxic T Cells (CTL) Flashcards
T/F naive CDL’s also require costimulation like naive T cells.
False; CTL’s don’t have B7
What 3 things happen upon differentiation into CTL?
Production of cytotoxic lytic granules
Acquisition of killing activity
IFN-gamma secretion
What do CD8+ T cells require to become CTL?
licensing of APC dendritic cell
What are the 2 ways to license APC
- once activated by TH1 cell –> cells expres CD40L and produce IFN gamma–> induce high level of costim molecules on dendritic cells
- If dendritic cells get a strong TLC signal
What APC activates CTL’s
DENTRITIC; must have CD4 and CD8 ligand
What happens in viruses that do not infect dendritic cells and thus cannot activate CTL.
cross-presentation needed for activation;
Difference in differentiation of CD4+ T cells and CD8?
CD4 exhibit autocrine signaling via IL-2; CD8+ need helper T cell help (IL-2) to be activated
What two stages to CTL need help
- Licensing
2. CD4 help (IL-2)
What is the difference in activation of memory CD8 + CTL-Pand naive CTL
Don’t require licensing; exhibit costim molecules CD8; memory also show autocrine IL-2 signaling upon activation
What are the main weapons seen in CTLs
LYTIC GRANULES
What are lytic granues
modified lysosomes that hold effector molecules
WHen are lytic granules released
Ca2+ induced by TCR signaling causes release of granules toward target cells
How do lytic granules kill target cells?
Induce Apoptosis
Difference between apoptosis and necrosis
Apoptosis does not die and spill their toxic contents like necrosis.
Apoptosis is programmed while necrosis is not.
Apoptotic cells express signals for rapid phagocytosis
Why is it important that apoptosis does not cause release of cell contents.
- It would cause more inflammation
2. Cellular proteins in cells that aren’t expressed on T cells could induce autoimmune rxns (lupus)
What is the specific signal for death
activation of cysteine proteases (caspases)
What are some features of apoptosis?
- Nucleus condenses
- Membrane blebbing
- DNA fragmentation into nucleosomes (~200 bp pieces)
- Degradation of cellular components
- Exposure of phosphatidylserine on outer membrane leaflet (usually on inner leaflet)
Can CTL’s kill multiple ttarget cells?
Yes
Describe process of CTL action.
- CTL binds to target cell
- CTL-Target cell complex made
- CTL cytoplasmic rearrangement
- Granule release (exocytosis)
- CTL dissociates from apoptotic cell
- CTL recycles and rearms itself to kill other target cells.
T/F CTLs need CD4 help to kill like they fo for activation
F
What are the 3 major compoents of the lytic granules?
- PERFORIN
- GRANZYMES
- Granulysin
What is the action of perforin?
Forms pore in target membrane, allows ions and water to flow into cell and induce osmotic stress. However, this is inefficient
Action of granzymes?
enter through perforin pore activate apoptosis by initationg caspase signaling cascade via caspase activation
ACtion of granulysin?
Induce apoptosis
What is FasL and what does it do?
It’s a membrane bound TNF (on CTL) family member that binds Fas receptor on target cell
Steps of granule release (perforin)
- Ca 2+ influx into CTL
- Granules move to CTl membrane
- Perforin monomers released into target cells
- perforin monomers polymerize and on target cell and make a pore
Steps of granzyme release
AFTER PERFORIN RELEASE
- granzymes move in through pores
- Granzymes activate Caspase-8
- Caspase-8 activates Caspase-3
- Caspase 3 activates apoptosis effectors
T/F Cells neighboring apoptotic cells also die
F
T/F Cytoskeleton rearrangement occurs after specific recognition and binding between CTL and target cell
T
