Immunology T4

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  • Created by: Kavita :)
  • Created on: 19-02-15 15:01
Where are CD4+ and CD8+ T cells produced?
Thymus
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What are the compartments of the thymus and where are WBCs located in it?
1) Cortex - immature thymocytes + macrophages 2) Medulla - mature thymocytes with dendritic cells, positive and negative selection
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What are the stages of thymocyte differentiation?
DN1 > DN2 > DN3 > DN4 - Immature double - thymocytes > Immature double + thymocytes > Mature CD8+4- and CD4+8- thymocytes
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Which chain rearranges first in T cell development?
Beta Chain (DN3 B chain protein produced) DN4 rapid cell prolifieration until co-receptor proteins CD8/4 are produced
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Why are multiple alpha chain gene rearrangements useful?
To rescue non-productive V-J joins and multiple rounds of rearrangements occur to generate a functional alpha chain
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When is the γδ T cells produced?
Early development and has limited antigen specificity and becomes established in specific tissue locations
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What does positive selection ensure?
Ensures all T cell bearing cells can interact with self MHC I (CD8+) or MHC II (CD4+)
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Where does selection take place?
thymic cortical epithelial cells
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Where does -ve selection take place?
Thymic cortex + medulla
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What are the 3 features of -ve selection?
1) Driven by APCs 2) T cells with TCRs which react strongly with ubiquitous self antigens are deleted in thymus - prevents autoimmunity. 3) T cells that interact strongly with self MHC molecules are deleted - preventing inappropriate activation
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What are the 5 major types of T-cells and their functions?
1) CD8 Tc cells - kill virus infected cells 2) CD4 TH1 - activate infected macrophages - help to B cells 3) CD4 TH17 - enhane neutrophil response, promote barrier integrity 4)TFH cells - B cell isotypes switching, antibody 5) CD4 Treg - suppression
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Where do naive T cells encounter antigen?
Recirculation through secondary lymphoid organs
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How do T cells enter lymph node cortex?
Enter from blood via high endothelial venules (HEVs) Regulated by adhesion molecules, chemokines. ROLLING (L-selectins) > ACTIVATION (chemokines) > ADHESION (integrins) > DIAPEDESIS (chemokines)
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How do T cells exit the lymph node?
Via cortical sinuses
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What is the role of L-selectin?
Recognise carbohydrate motifs and is expressed on all T-cells. Addressins on epithelial surface bind L-selectins and bind T-cells weakly to endothelial surface
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What is the role of Integrins?
Stabalise binding to APCs, HEVs or endothelia. Bind to adhesion molecules that are important immunoglobulin superfamily
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What allows the rolling interaction of T cells when entering lymph node
Binding of L-selectin to GlyCAM-1 and CD34. LFA-1 is activated by chemokines and then binds to ICAM-1 (adhesion molecule). Lymphocyte migrates into lymph node by diapedesis
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What are the 5 routes of antigen processing and presentation by dendritic cells?
1) Receptor mediated phagocytosis (MHC II) 2) Macro-pinocytosis (MHC II) 3) Viral Infection (MHC I) 4) Cross-presentation after phagocytic uptake (MHC I) 5) Transfer from incoming dendritic
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Name 3 cell adhesion molecules?
ICAM-1 + 2, CD58
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Name the 3 signal naive T cells need to become activated?
1) A specific interaction between TCR + MHC + Antigen peptide 2) co-stimulatory interaction which provides a survival & proliferation signal (CD28:B7) 3) A differentiation signal provided by a secreted cytokine
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What does the co-stimulatory signal CD28:B7 stimulate?
The production of high affinity IL-2 receptor on activated T cell
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Which signal 1, 2 or 3 results in naive CD4+ T cells acquiring different effector functions?
Signal 3
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What are the different effector T cells and what do they do?
Treg (TGF-B) - produced when pathogen absent, TFH (IL-6) - found in lymphoid follicals involved in B cell Ab stimulation, TH17 (TGF + IL-6) - early in infection, produce IL-17 recruits neutrophils, TH1 (IL-12, IFN-y) - B cell help, TH2 (IL4) - Bchelp
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What does partial signalling result in?
Functional inactivation (anergy) or deleted of T cell. Decreased TCR signalling of GRAIL
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How does CD4+ T cell help CD8+ T cell?
Production of CD40L and IL-2 when CD4 interacts with APC. CD40L binds CD40 on APC, APC increases level of B7 and produces 4-IBBL which binds to 4-IBB on CD8+ T cell and B7 binds to CD28 (co-stim), production of IL-2 (growth factor promote CD8+ diff)
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Which two proteins from T cells kill the cell?
Granzymes target proteins that regulate apoptosis, Pertorin
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What are the compartments of the thymus and where are WBCs located in it?

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1) Cortex - immature thymocytes + macrophages 2) Medulla - mature thymocytes with dendritic cells, positive and negative selection

Card 3

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What are the stages of thymocyte differentiation?

Back

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Card 4

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Which chain rearranges first in T cell development?

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Card 5

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Why are multiple alpha chain gene rearrangements useful?

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