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56 Cards in this Set
- Front
- Back
What is the effector function of T cells?
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Cell mediated immunity(CMI)
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What do T cells defend against?
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Microbes that replicate within phagocytes and nonphag cells
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What initiates effector phase of CMI?
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recognition of antigens by T cells
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What is the difference in the pathogens that each of these respond to: Th1, Th2 and CTL's
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TH1 respond to microbes in phagocytic cells
TH2 respond to helminthic parasites and various allergens CTLs respond to microbes in various other cells |
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What does a defect in CMI cause susceptibility to?
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Intracellular parasites
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What is DiGeorge syndrome?
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Deletion of portion of chromosome 22 that causes absence of thymus and parathyroids, also cardiac and facial abnormalities
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What are the Sx of DiGeorge syndrome?
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Tetany(hypocalcemia)
Variable T cell counts Decreased response to skin test antigens Suscebtable to opportunistic infection |
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What are the function of Th cells and Tc cells?
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Th: activation of B lymphocytes, phagocytic cell activation, inflammation
Tc: lysis of target pathogen |
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What are the cell surface molecules on T cells that are involved in signal transduction? Functions?
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CD3 and ζ
CD4 or CD8= Th or Tc CD28=Co-stimulation CTLA-4=inhibitory |
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What is the cell surface molecules on T cells that is involved in adhesion?
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Integrins: LFA1 and VLA-4
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Where does T cells activation occur?
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Secondary lymphoid tissue
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What are the 2 signals needed for T cell activation?
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1)Bind of TCR complex to MHC on APC, if TCR bind MHC+antigen the CD8 or 4 will bind MHC
2)Binding of B7 with CD28 on T cell |
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What is the function of CD28 binding B7 on APC?
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initiate intracellular signall transduction pathway
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Why are dendritic cell the APC that activates naive T cells?
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They don't require cytokines (IFN) to be activated
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Where are macrophages most actively stimulating T cells?
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At site of infection after effector t cells have been activated in 2ndary lymphoid tissue
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What is anergy? Cause?
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state of unresponsiveness. Lack of second signal to activate T cells(B7-CD28)
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What do activated APCs express that unactivated ones don't that allows them to activate T cells?
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costimulator-B7 and IL-2
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What are the Transcription factors that are released as a result of the 2 APC activation signals?
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NFAT, NF-KB, AP-1
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What is the function of the 3 transcription factors activated by the 2 APC activation signals?
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expression of the IL-2 gene
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Where are each of the activation transcription factors activated in the T cell?
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Aggregated signalling motifs activate, NFAT and NF-kB in the cytosol and AP1 is activated in the cytosol
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How is T cell proliferation activated?
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activation signals cause expression of IL2 and HIGH AFFINITY IL2R. When IL2 binds IL2R is activates Jak\Stat pathway which increases transcription of CYCLINS
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How is T cell proliferation regulated?
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After several rounds of proliferation the T cells begin to express NTLA-4 which binds to CD28 and inhibits proliferation and limits number of T cells produced
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How can IL-2 be used to fight cancer?
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T cells from cancer are isolated=TIL(tumor infiltrating lymphycytes), TIL's are given IL-2 exogenously and allowed to proliferate, cells put back into patient to fight cancer
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What are 2 drugs that inhibit T cell activation? Action?
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Cyclosporin and Tacrolimus, bind calcinerurin and prevent NFAT activation so no IL2 production
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Which T cells are responsible for primary immune response and secondary immune response?
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Th and Tc are primary IS
Memory T are 2ndary IS |
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T\F effector T cells circulate for long periods of time?
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False short lived
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T\F Memory T cells live a long time and generate a hightened sensitivity to antigens?
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True
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What are the 3 types of T helper cells, their function and specific cytokines expressed
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Th1-controll CMI, IFN-γ
Th2-control humoral reactions, IL-4,IL 5, IL 13 Th17-inflamatory disorders and microbial defense, IL17 |
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What are the Types of antigen that each subset of Th cells responds to and the cytokines that cause differentiation to the 3 types? Where do Cytokines come from?
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TH1-Bacterial fungal and viral
IL-12, IFN-γ TH2-Parasites and Allergens IL4 TH17-unknown IL-6 and TGF-β |
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Where does IL- 12 come from? what causes secretion
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Activated macrophages and dendritic cells
Secreted in response to phag of microb or intracellular microbe infection |
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Where is IFN-γ secreted from to cause Th cell differentiation? Why do they secrete these?
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NK and TH1 cells
NK secretes IFNγ in response to IL-12, TH1 secrete it to increase cell development |
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What is another function of IFNγ?
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augments phagocyte killing mechanisms and antigen presentation
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What are the 2 places that IL-4 is secreted to stimulate differentiation of TH to TH2 cells?
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Mast cells and TH2 cells(autocrine)
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Why do mast cells secrete IL12?
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Inresponse to parasites and allergens activation of mast cells
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What are the functions of IL-6 and TGF β outside of TH17 differentiation?
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IL6= inflamatory cytokine
TGFβ=immunoreglatroy cytokine(often at mucosal surfaces) |
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What are the 2 things that IL-6 and TGFB do to stimulate TH17 cell differentiation and proliferation?
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incudes synthesis of IL-21 which is an autocrine for TH17 differentiation
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Where does Th cell differentiation take place?
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Secondary lymphoid tissue. Enter circulation after differentiation
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The 3 cytokines secreted by Effector Th1 cells?
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IL-2, IFNγ, TNF
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What are the 3 functions of TH1 effector cells?
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cytokine secretion inresponse to intracellular infections and tumor antigens, regulation of CMI responses
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What are the CMI regulatory functions of TH1 cells?
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Activation of PMNs(neutrophils), macrophages, NK and Tc cells, stimulation of B cell production of opsonizing antibodies
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What is the function of IFNγ and CD40L secreted by TH1 cells regarding macrophages?
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aupment APC and phagocytic functions of macrophages
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What is the function of IFN γ on B cells? Antibody class?
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stimulate production of opsonizing antibodies, IgG's
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Why would a TH1 cell be required to activate a Tc cell? What activates Tc
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Because APC lacks both stimulation signal(B7 and MHC), TH1 secretes IL-2 and IFNγ
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What is the function of TNF secreted by THI cells?
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increase expression of CAMs and production of chemokines, increases extravasation
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What are primary functions of TH2 effector cells?
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humoral response to parasites and allergens: stimulate B cells to make non-opsonizing ab's and stimulate mast and basophils during helminthic infections, inhibition of macrophages
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What can the balance between TH1 and TH2 cells tell you about the outcome of infection?
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B\c TH2 inhibits macrophages it tells you how well u will respond
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What is the hypothesized function of Th17 cells?
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Help with massive inflammatory responses that overcome TH1 and TH2 cells
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What do the 3 cytokines that TH17 cells secrete do?
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IL 17, IL 21, IL 22 stimulate inflammatory responses: acute phase protein synthesis, chemokine secretion, stim. production of inflamatory cytokines
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What are the functions of Effector Tc(CTL's)?
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-recognize infected or tumor cells via TCR-MHC interaction(recog triggers killing)
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What is required for a CTL to kill target? What are the 2 mechanisms?
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Cell to Cell contact
Degranulation and Fas-FasL interaction |
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How does the degranulation mechanism of CTL killing work?
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Cells release Granzymes(serine esterase, activate apoptosis via caspase act.) and perforin(perforating protein, insert and polymerize)
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How does the mechanism of Fas-FasL interaction of CTL killing work?
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All nucleated cells express Fas, only CD8 cells express Fas L. When CTL binds MHC is allow enough time for Fas-FasL interaction and caspase activation=apoptosis
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How many subsets of memory cells exist for each type of T cell? What are they?
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2, central memory(Tcm) and Effector memory(Tem)
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What is the function of Tcm cells?
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home to 2ndary lymphoid tissue and generate many effector T cells and memory cells
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What is the function of Tem cells?
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go to peripheral tissues(esp mucosal), secrete cytokines
*not much proliferation just provide initial rapid response |
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What is required for a prolonged response of Tem cells?
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cytokine dependent, IL-7, proliferation is still low
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