Flashcards
T Cell Activation
Flashcards do conjunto (38)
- 1What are the stages of T cell activation?1. Presentation and subsequent recognition of specific anitgen
2. Activation/early phase initiation of signal transduction cascade (membrane)
3. Activation/intermediate phase initiation of signal transduction cascade (into the cell)
4. Activation/late phase initiation of gene transcription/nuclear events
5. Functional responses effector-cell end-actions - 2How did Gell and Benacerraf prove differences in antigen recognition?It was shown that denatured (boiled protein, usually ovalbumin) antigen can still activate T cells but not B cells
Indicates that T cells do not require an antigen to be in its tertiary structure - 3What is denaturation of a protein?Changes the shape of the protein by collapsing the hydrogen bonds and the 3D shape
It is not broken down - 4Question TextAnswer Text
- 5What is the definition of fixed?Metabolically killed by gamma radiation or formaldehyde but structurally intact
- 6What are the two antigen processing pathways?Cytosolic pathway
Endocytic pathways - 7What is the cytosolic pathway?Endogenous proteins
Makes peptides for MHC class I
CD8/cytotoxic T cells - 8What is the endocytic pathway?Exogenous proteins
Peptides for MHC class II
CD4/T helper cells - 9describe the cytosolic pathway (MHC I)Processes an antigen to yield the antigen on MHC class I molecules
Job is to remodel proteins regardless of what they are/where they came from - 10What are the steps in the cytosolic pathway?A protein in the cytosol, not necessarily from an antigen/pathogen
Proteasomes chop the proteins into random fragments of 8-20 peptides
TAP takes peptide fragments to the ER where there is a preformed MHC class I molecule
These peptides are placed onto a MHC molecule
The MHC class I molecule is packaged and transported to the Golgi - 11How do T cells proliferate?Clonal expansion
- 12What are the steps in the endocytic pathway?An endosome containing protein fuses with a lysosome
The natural process of chopping up the protein by proteolytic enzymes within the lysosome occurs
The lysosome compartment then fuses with the golgi which has a premade MHC class II molecule inside it
CLIP blocks the MHC II
CLIP is cleavedoff which allows the protein fragments to be loaded onto the MHC II molecule - 13Describe the endocytic pathwayProcessing of an antigen via the vesicle pathway to yield antigen on MHC class II molecule
- 14What are the parts of an MHC Class I molecule?Peptide Binding Cleft
Membrane distal Domains (alpha 1 and 2)
Membrane proximal domains (Ig fold structure)
B2 microglobuliin
CD8
Transmembrane segment
Cytoplasmic tail - 15What are the parts of an MHC class II molecule?Peptide binding cleft
Membrane distal domains
Alpha 1 and alpha 2
CD4
Membrane proximal domains
Transmembrane segment
Cytoplasmic tails - 16Describe the peptide binding cleft of a MHC class IPeptide 8-10 amino acids long
- 17Describe the peptide binding cleft of MHC class IIPeptide 15-20 amino acids long, full length of cleft, can hang out the side
- 18What are the parts of the TCR?4 immunoglobulin domains
Constant and variable regions
alpha chain and beta chain
Disulphide bonds
Transmembrane segments
Cytoplasmic tails - 19What is the TCR?T cell receptor which does the recognition and binding it loops like an antibody; it has alpha and beta chains; constant and variable regions
On each T cell the combination is identical, but the combination of amino acids in the variable domain are different
TCR only recognises, it is not a signalling molecule - 20What are the TCR components?Alpha chain
Beta chain
2 Homodimers
CD3 complex
CD4
Lck
CD45 - 21What are the alpha and beta chains?The TCR
- 22What is the CD3 complex?Has four chains and is a cell surface marker for T cells
- 23What is CD4?Receptor for MHC class II molecules
- 24What is lck?A kinase with signalling ability which always associates with CD4; allows lck to access the other proteins
- 25What s CD45?A phosphotase
- 26What is the significance of CD4?MHC II molecule taken to the CD4 which takes the antigen close to the TCR allowing the T cell to test the antigen; also allows clustering
- 27What are SH2/SH3?Src homology regions 2/3
SH2: 100 amino acids/Tyr-P docking
SH3: 60 amino acids, proline rich targets - 28What is an ITAM?Immunoreceptor Tyrosine Activation Motifs
Phosphorylated ITAMs are docking sites for kinases - 29What are the properties of lck kinase?Fatty acids link it to the membrane
Lipid soluble
Inactive when not phosphorylated - 30Describe the tyrosine phosphorylation sequence/signal transductionSignalling following binding of antigen by TCR and the recruitment of lck to the TCR complex when CD4 binds to MHC II on the APC
ITAMs become phosphorylated and subsequently PLC is recruited, activated and hydrolyses PIP2 to yield IP3 and DAG to activate 2 pathways
CD3 are phosphorylated the homodimers are phosphorylated to allow ZAP-70 to dock
PLC generates molecules that are soluble and penetrate into the cell
It takes membrane phospholipids (PIP2) and cleaves it into DAG and IP3
IP3's role is to release calcium; zap-70 is an adaptor protein that allows other proteins to stick to it and create a scaffold DAG is an activator of PKC - 31Explain calcium signals in activated T cellsActivation of calcium release in t cells via the TCR by directly ligating TCR molecules (not requiring antigen) an allowing membrane components to be brought together by using an anti-TCR antibody
This experiment shows directly the increase in intracellular calcium using calcium sensitive dyes - 32What are the three major signal activation pathways?Calcium pathway
PKC pathway
Ras/Rac-GTP pathway - 33Describe the calcium pathwayCalcium binds to calmodulin to activate the enzyme calcineurin
Calcineurin removes the phosphate from NFATc
NFATc remains cytosolic when it has a phosphate attached
NFATc translocates from the cytoplasm to the nucleus
NFATn is a transcription factor for regulating DNA which codes for mRNA - 34Describe the PKC pathwayPKC phosphorylyses the NFkb kinase which causes it to disengage from the Ik-b to allow it to enter the nucleus
Nf-kb is a transcription factor - 35Describe the Ras/Rac-GTP pathwayRas/Rac-GTP activates MAP-k and JNK
MAP-k activates the transcription factor fos and JNK activates the transcription factor jun
Jun and fos are called AP-1 - 36Describe the gene transcription phase1. Immediate genes eg fos-c,c-myc
2. Early genes eg IL-2, IL-2Ra, cytokines (within 2-12 hours)
3. Late genes eg MHC, adhesion molecules, VLA (up to a week) - 37What is CD28's role?One of the proteins on the surface of T cells
it interacts with B7 ligands on antigen surfaces to produce co-stimulation signals
Optimal activation requires its binding - 38What is the role of CTLA-4?A transmembrane protein expressed on CD4 and CD8 t cells
It blocks T cell proliferation by telling the cell to undergo apoptosis
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- 3 BM325 FlashCards sobre T Cell Activation, criado por Caitlin M em 17-11-2017.
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- Caitlin M
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