Exam 3: Cytotoxic T Cells (CTL)

Question 1

T/F naive CDL’s also require costimulation like naive T cells.

Answer 1

False; CTL’s don’t have B7

Question 2

What 3 things happen upon differentiation into CTL?

Answer 2

Production of cytotoxic lytic granules
Acquisition of killing activity
IFN-gamma secretion

Question 3

What do CD8+ T cells require to become CTL?

Answer 3

licensing of APC dendritic cell

Question 4

What are the 2 ways to license APC

Answer 4

1. once activated by TH1 cell –> cells expres CD40L and produce IFN gamma–> induce high level of costim molecules on dendritic cells
2. If dendritic cells get a strong TLC signal

Question 5

What APC activates CTL’s

Answer 5

DENTRITIC; must have CD4 and CD8 ligand

Question 6

What happens in viruses that do not infect dendritic cells and thus cannot activate CTL.

Answer 6

cross-presentation needed for activation;

Question 7

Difference in differentiation of CD4+ T cells and CD8?

Answer 7

CD4 exhibit autocrine signaling via IL-2; CD8+ need helper T cell help (IL-2) to be activated

Question 8

What two stages to CTL need help

Answer 8

1. Licensing

2. CD4 help (IL-2)

Question 9

What is the difference in activation of memory CD8 + CTL-Pand naive CTL

Answer 9

Don’t require licensing; exhibit costim molecules CD8; memory also show autocrine IL-2 signaling upon activation

Question 10

What are the main weapons seen in CTLs

Answer 10

LYTIC GRANULES

Question 11

What are lytic granues

Answer 11

modified lysosomes that hold effector molecules

Question 12

WHen are lytic granules released

Answer 12

Ca2+ induced by TCR signaling causes release of granules toward target cells

Question 13

How do lytic granules kill target cells?

Answer 13

Induce Apoptosis

Question 14

Difference between apoptosis and necrosis

Answer 14

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

Question 15

Why is it important that apoptosis does not cause release of cell contents.

Answer 15

1. It would cause more inflammation

2. Cellular proteins in cells that aren’t expressed on T cells could induce autoimmune rxns (lupus)

Question 16

What is the specific signal for death

Answer 16

activation of cysteine proteases (caspases)

Question 17

What are some features of apoptosis?

Answer 17

1. Nucleus condenses
2. Membrane blebbing
3. DNA fragmentation into nucleosomes (~200 bp pieces)
4. Degradation of cellular components
5. Exposure of phosphatidylserine on outer membrane leaflet (usually on inner leaflet)

Question 18

Can CTL’s kill multiple ttarget cells?

Answer 18

Yes

Question 19

Describe process of CTL action.

Answer 19

1. CTL binds to target cell
2. CTL-Target cell complex made
3. CTL cytoplasmic rearrangement
4. Granule release (exocytosis)
5. CTL dissociates from apoptotic cell
6. CTL recycles and rearms itself to kill other target cells.

Question 20

T/F CTLs need CD4 help to kill like they fo for activation

Answer 20

F

Question 21

What are the 3 major compoents of the lytic granules?

Answer 21

1. PERFORIN
2. GRANZYMES
3. Granulysin

Question 22

What is the action of perforin?

Answer 22

Forms pore in target membrane, allows ions and water to flow into cell and induce osmotic stress. However, this is inefficient

Question 23

Action of granzymes?

Answer 23

enter through perforin pore activate apoptosis by initationg caspase signaling cascade via caspase activation

Question 24

ACtion of granulysin?

Answer 24

Induce apoptosis

Question 25

What is FasL and what does it do?

Answer 25

It’s a membrane bound TNF (on CTL) family member that binds Fas receptor on target cell

Question 26

Steps of granule release (perforin)

Answer 26

1. Ca 2+ influx into CTL
2. Granules move to CTl membrane
3. Perforin monomers released into target cells
4. perforin monomers polymerize and on target cell and make a pore

Question 27

Steps of granzyme release

Answer 27

AFTER PERFORIN RELEASE

1. granzymes move in through pores
2. Granzymes activate Caspase-8
3. Caspase-8 activates Caspase-3
4. Caspase 3 activates apoptosis effectors

Question 28

T/F Cells neighboring apoptotic cells also die

Answer 28

F

Question 29

T/F Cytoskeleton rearrangement occurs after specific recognition and binding between CTL and target cell

Answer 29

T