Created by tanitia.dooley
almost 11 years ago
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Question | Answer |
What are the three co-receptors in B cells? | CD19, CD21, CD81 |
What is the role of Csk and CD45 in controlling Src kinase activity? | Csk phosphorylates the COOH proximate tyrosine allowing it to bind the SH2 domain= inactive. CD45 is a phosphatase which removes the phosphate from the inhibitory tyrosine allowing the NH2 tyrosine to be phosphorylates=activated |
Which of the co-receptors of B cells is a tetraspan molecule? | CD81 |
What is the role of CD28? | It is a co-stimulatory molecule for T cells, it cross-links and binds B7 family members on APCs which induces tyrosine phosphorylation allowing interaction with Grb-2 and Pi3-Kinase |
What are the co-receptors in T cells? How do they lead to the activation of ZAP-70?? | CD4 and CD8. Lck kinase associates with CD4-it is brought closer to TCR when it binds MHC Class II. It can then phosphorylate CD3ζ ITAMs allowing ZAP70 to bind. Lck also associates with CD8 and CD8 is brought close to TCR when it binds MHC class I etc |
What is the role of CTLA-4? | In T cells- binds B7 family after activation of T cell. If B7 low, CTLA-4 binda prevents CD28/B7 interaction. Also recruits SHP-2 & PP2A pho sphatases-oppose action of kinases |
How do the co-receptors of B cells work? | Ag, Ab and complement bind CD21 and BCR= phosphorylation of tyrosines in CD19= src kinases recruited eg PI3K and Vav=auguement signalling |
Describe how B cell signalling is negatively regulated? | CD22 and FcyRIIb have ITIM motifs. Cross linking of FcyRIIb with BCR=phosphorylation of ITIM by src kinase- recruits SHIP (which is a phosphatase which inhibits PLY-y activation) and SHP-2 |
How does CD22 negatively regulate B cells? | It has 3 ITIMS which when phosphorylated bind SHP-1 which reverses the actions of src kinases |
What is the difference between ITIMs and ITAMS? | ITIMs only have on phosphorylatable tyrosine, ITAMs have 2 |
What is the role of ITIMs in NK cells? | KIR have ITIM motifs which when phosphorylated by Lck when clustered by self MHC-SHP-1 recruited which de-de-phosphorylates ZAP-70 inhibiting activation-prevents killing of own molecules |
How are mast cells regulated with ITIMs? | the co-clustering of IgE receptors with gp49B1 leads to the phosphorylation of its ITIMs- allows recruitment of SHP-1 which opposes action of PTKs recruited by the IgE receptor |
Why do B cells die by apoptosis when there antigen receptors are deleted? | Because antigen receptors send survival signals even in the absence of an antigen |
How can antigen receptors signal cell death? | If immature B cells encounter an antigen they can either be signalled to undergo apoptosis or receptor editing to avoid self reactivity |
What is the role of SLP-76? | It activates Vav-Rac-Mekk-Jnkk-Jnk |
What is the role of LAT? | Activates PLC which cleaves PIP2 into DAG and IP3 and also activates Grb-2 and SOS to activate the Ras pathway-Raf-Mek-Erk |
What is CD16? | An Fc receptor present on macrophages, neutrophils and NK cells. Signals delivered via FcRy which contains ITAM motif (related to CD3ζ) |
What is the link between FcεR1 and ITAM motifs? | FcεR1 is an IgE receptor present on mast cells and basophils-used homodimer y containing ITAM to activate degranulation |
What is KAR? | Killer activatory receptor found on NK cells and triggers killing via the ITAM molecule DAP12 |
Which src kinases do B cells express? | fyn, lyn, blk |
Which src kinases do T cells express? | fyn, lck |
What are ITAM motifs? | Motifs with two tyrosine's seperated by 13 residues |
What is the syk family of kinases? | It contains to SH2 domains which allow binding to phosphorylated ITAM motifs |
How are the txn factors NFAT and NFkB activated? | Btk phosphorylates and activates phospholipase C which cleaves PIP2 into IP3 and DAG. IP3 opens pores in men for Ca2+ to move in-activates calcineurin which activates NFAT. DAG activates PTK which activates NFkB |
How does Ras become activated? | Grb-2 is recruited to BLNK and binds to proline rich motifs on SOS. SOS displaces GDP from SOS allowing GTP to bind and activate RAS |
What happens once Ras is activated? | activates MAPK cascade- activates serine/threonine residues of Raf- Raf phosphorylates + activates Mek- Mek phosphorylates and tyrosine & serine/threonine redidues of Erk. Erk phosphorylates and activates txn factor Elk |
What two linker proteins does ZAP-70 activate in T cells? | LAT and SLP-76 |
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