Adaptive Immune Response to Intra-cellular pathogens - Steiner/Jones

Question 1

How are Natural Killer cells activated?

Answer 1

When it binds with a virus, the inhibitory receptor is not engaged, (Class I MHC expression is inhibited) which activates the NK cell. *A normal autologous cell would engage the inhibitory receptor as well as the Activating receptor.

Question 2

Activation of NK cells lead to what?

Answer 2

Degranulation, which kills the infected cell.

Question 3

How do CD4+ and CD8+ T cells eradicate intracellular pathogens?

Answer 3

CD4+ help by marking pathogens

CD8+ kill pathogens directly

Question 4

Interactions with ______ are necessary to activate Naive T cells.

Answer 4

Antigen Presenting Cells (APC’s)

*Naive T cells come in contact with APC’s in lymphodes

Question 5

T cell Activation requires 2 steps, what are they?

Answer 5

1. TCR recognition of peptide: MHC on APC

2. Co-stiumlatory molecule binding.

Question 6

What is the Function of L-selectin receptor/ligand pair?

Answer 6

Adhesion of the native T cell to high endothelial venue in lymph nodes.

Question 7

What is the function of the E and P selectin receptor/ligand pair?

Answer 7

Initial, weak adhesion to effector and memory T cells to cytokine-activated endothelium at peripheral site of infection.

Question 8

What is the Function of the LFA-1/VLA-4 (Receptor) and ICAM/VCAM (Ligand) relationship?

Answer 8

Stable arrest on cytokine-activated endothelium at peripheral site of infection.

Question 9

True or false, Activated T cells must migrate to site of infection to eradicate virally infected cells.

Answer 9

True

Question 10

Macrophages _______ and T cells _________.

Answer 10

Macrophages kill, and T cells Protect.

Question 11

How are Macrophages activated by T cells?

Answer 11

CD4+ T cell Transfers IFN-Gamma to IFN-gamma receptor on Macophages.

Question 12

Describe the Corporation between CD4 and CD8…

Answer 12

CD4 marks vesicles in the cytoplasm that contained phagocytosed microbes (Essential infected cells) and marks them with IFN-gamma, which trigger the CD8 to kill the cell.

Question 13

________ kill targets that express the same class I-assoctiaed antigen that triggered the proliferation and differentiation of naive CD8 T cells to become Cytotoxic lymphocytes (CTL’s)

Answer 13

CTL’s

Question 14

What are the three main kinases that activate CD8+ T cells to differentiate into CTL’s?

Answer 14

MAP kinase (AP-1)
Protein Kinase C
Calcineurin (NFAT)

Question 15

What are the 5 steps of CTL-mediated lysis of target cells?

Answer 15

1. Antigen recognition & conjugate formation
2. CTL Activation
3. Granule exocytosis
4. Detachement of CDL
5. Target cell death

Question 16

How does CTL lyse the target cell?

Answer 16

• Lytic granules

- Fas-fasL

Question 17

What are the 3 proteins in lytic granules of cytotoxic T cells, and what does watch do?

Answer 17

1. Perforin = Polymerizes to form a pore in target membrane
2. Granzymes = serine proteases, which activates apoptosis once in the cytoplasm of the target cell.
3. Granulysin = Induces apoptosis

Question 18

True or False, Mechanisms of CTL mediated lysis and NK cell mechanism are the same.

Answer 18

True they are.
They use:
Granule exocytosis —> entry of granzymes —> activation of capsases —> apoptosis of target cell.

Question 19

How do Granzymes enter the target cell?

Answer 19

Through Polyperforin pore, or via CI-MPR

Question 20

How does granzyme B induce apoptosis?

Answer 20

• By activating 3 specific caspases
• Caspase activation will lead to capsize-activated DNAse (CAD)
• CAD causes DNA fragmentation and thus apoptosis.
• Granzyme B can also directly activate CAD

Question 21

_____ destroyed the integrity of the mitochondrial outer membrane (induces formation of BAD/BAX channel).

Answer 21

BID

Question 22

___________ will activated caspase 9 and endonuclease G (ENDOG) which cleaves DNA.

Answer 22

Cytochrome C

Question 23

How do Fas:FasL interactions eradicate cells infected with an intracellular pathogen?

Answer 23

FasL on CTL interacts with FAS on target cell and induces apoptosis of target cell.

• Fas receptor trimerization activates the death domain.
• Death Domain (FAFF) leads to signaling cascades that activate caspase 8.
• Caspase 8 can activate caspase 3

Question 24

_______ activates Caspase 3 & BID.

Answer 24

Caspase 8

Question 25

Describe Fas (CD95)….

Answer 25

• member of the TNF family
• Initiates a signaling cascade which results in apoptosis to the target cell.
• Death pathway is initiated upon the binding of Fas to Fas ligand expressed on T cells.

Question 26

Why is Fas-mediated killing important?

Answer 26

for the maintenance of T cell self tolerance.

Question 27

Why are CD4+ T cells important? (3)

Answer 27

1. They produce IFN-gamma to activate Macrophages.
2. They produce cytokines to provide co-stimulation for CD8+ T cell activation.
3. They produce cytokines to enhance the activity of APC’s.

Question 28

How do Intracellular pathogens try to thwart the immune system? (5 ways)

Answer 28

• Inhibition of proteasomal activity
• Block MHC synthesis and or ER retention.
• Block TAP transport
• Removal of class I from ER
• Interference with Ctl recognition by “decoy” viral class I-like molecules.