Adaptive Immune Response to Intra-cellular pathogens - Steiner/Jones Flashcards
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?
- 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.
True
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)
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?
- Antigen recognition & conjugate formation
- CTL Activation
- Granule exocytosis
- Detachement of CDL
- 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?
- Perforin = Polymerizes to form a pore in target membrane
- Granzymes = serine proteases, which activates apoptosis once in the cytoplasm of the target cell.
- 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).
BID
___________ 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)
- They produce IFN-gamma to activate Macrophages.
- They produce cytokines to provide co-stimulation for CD8+ T cell activation.
- 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.
