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23 Cards in this Set
- Front
- Back
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Steps in T Cell Activation
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Antigen/MHC binding to TCR
Co-receptor binds to ligands Activation of of transcriptional factors NFAT, NFkB, AP-1, C-fos, C-jun All have an effect on gene expression of CD40L, IL-2, and IL-2R |
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What is the most important cell in adaptive immune response?
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CD4+ T cell
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What is expressed when the TCR is bound in T cell activation and in what order?
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First there is an increase of c-FOS, then expression of CD40L, IL-2, IL-2R, and then DNA synthesis (via IL-2/IL-2R)
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What are the parts of the TCR and what do they do?
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Alpha and Beta chains: Bind the antigen; NO cytosolic domains
CD3: Business end Weird Symbol (pg.65-2): Mostly cytosolic, have ITAMS |
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ITAMs
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Site for regulator tyrosine phosphorylation: CAN BE BOTH POSITIVE AND NEGATIVE
Present on the cytoplasmic tails of all CD3 proteins |
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PTK
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Phosphorylates tyrpsine residues
Which regulates protein-protein interactions and enzymatic activity 3 important ones: lck, fyn, and ZAP70 |
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Resting T cell surface
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lck is inactive b/c of phosphorylation of tyrosine
CD4 not associated with TCR ITAMs not phorphorylated |
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Activation of ZAP-70
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Once ITAMs are phosphorylated by lck, ZAP70 gets phosphorylated and activated
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Consequence of ZAP70 activation?
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Ras activation
Tyrosine phosphorylation of Phospholipase C (PLC) |
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What happens when PLC is activated
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Catalyses PIP2 to form DAG and IP3
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What does IP3 do
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Raises intracellular Ca2+
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Functions of Calcium
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Co-factor for PKC
Important for calcium dependent protein CALMODULIN |
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What does Calmodulin do with help from Calcium?
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Activates Calcineurin
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What does DAG do
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Activates PKC with the aid of Ca2+ which levels were increased by IP3
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What does Calcineurin do?
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Dephosphorylates the inhibitroy protein of NFAT which activates NFAT
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What inhibits Calcineurin?
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Cyclosporin and Tacrolimus
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Calcineurin and Immunosuppressive Treatment
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Cyclosporin: complexes with cyclophilin
Tacrolimus (FK506): complexes with FKBP Both complexes inhibit Calcineurin |
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When is RAS (G protein)activated?
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when the bound GDP is replaced with GTP
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What intiaties a cascade of MAP kinases?
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Activated RAS binding to RAF which activates RAF
Therefore RAF activates a MAP-K cascade, which is fully activated when phosphorylated on both residues |
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What does the MAP-K cascade activate?
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The transcriptional factor Elk-1
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What does Elk-1 regulate
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The transcription of C-fos which with C-jun make up AP-1
C-fos + C-jun = AP-1 |
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How does C-jun get activated to make the up the other part of Ap-1
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jun is phosphorylated by JNK-1 to get activated
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What forms the complex of AP-1?
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Activated C-jun and C-fos
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