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

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Flashcards in Adaptive Immune Response to Intra-cellular pathogens - Steiner/Jones Deck (28)
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How are Natural Killer cells activated?

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.


Activation of NK cells lead to what?

Degranulation, which kills the infected cell.


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

CD4+ help by marking pathogens

CD8+ kill pathogens directly


Interactions with ______ are necessary to activate Naive T cells.

Antigen Presenting Cells (APC's)
*Naive T cells come in contact with APC's in lymphodes


T cell Activation requires 2 steps, what are they?

1. TCR recognition of peptide: MHC on APC
2. Co-stiumlatory molecule binding.


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

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


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

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


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

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


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



Macrophages _______ and T cells _________.

Macrophages kill, and T cells Protect.


How are Macrophages activated by T cells?

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


Describe the Corporation between CD4 and CD8...

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.


________ 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)



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

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


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

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


How does CTL lyse the target cell?

- Lytic granules
- Fas-fasL


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

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


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

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


How do Granzymes enter the target cell?

Through Polyperforin pore, or via CI-MPR


How does granzyme B induce apoptosis?

- 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


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



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

Cytochrome C


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

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


_______ activates Caspase 3 & BID.

Caspase 8


Describe Fas (CD95)....

- 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.


Why is Fas-mediated killing important?

for the maintenance of T cell self tolerance.


Why are CD4+ T cells important? (3)

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.


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

- 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.