lecture 10: adaptive immunity to infectionstreaming.einstein.yu.edu/docs/conferences/...cellular and...
TRANSCRIPT
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Lecture 10: Adaptive Immunity to Infection
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Questions to Consider
How do CD4 + T cells orchestrate responses appropriate to the infecting pathogen?
How do CD4+ T cells differentiate appropriately- TH1 vs Th2?
How do diverse cytokines transmit signals that mediate divergent responses?
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Response to Divergent Pathogens Requires Different Immune Responses
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CD4 + T Cells Differentiate Along Two Distinct Pathways That Modulate the Immune Response Differently
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CD4 + T Cells Differentiate Along Distinct Pathways That Modulate the Immune Response Differently
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Divergent Function of TH1 T Cells is Due to Differential Cytokine Production
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Divergent Function of TH2 T Cells is Due to Differential Cytokine Production
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Divergent Function of Treg T Cells is Due to Differential Cytokine Production
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Divergent Function of TH17 T Cells is Due to Differential Cytokine Production
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Divergent Function of Helper T Cells is Due to Differential Cytokine Production
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Uncontrolled Mycobacteria leprae Leads to Lepromatous Leprosy
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Inhibition of Mycobacteria leprae Leads to Tuberculoid Leprosy
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Development of TH1 vs. TH2 Response Determines Clinical Outcome of Leprosy
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TH1 Cells Induce Cell Mediated Immune Responses Directed to Intracellular Pathogens
Abbas- Cellular and Molecular Immunology
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Activated CD4 TH1 Cells Produce a Broad Range of Cytokines With Diverse Functions
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TH2 Cells Induce Cell Mediated Immune Responses Directed at Extracellular Pathogens
Abbas- Cellular and Molecular Immunology
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TH1 vs. TH2 Differentiation is Mediated by IL-12 vs. IL-4 Secretion
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TH1 vs. TH2 Differentiation is Mediated by Monocyte vs. B Cell Antigen Presentation
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THreg vs. TH17 Differentiation is Mediated by TGF
vs. IL-6 Production
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Differential activation of Nuclear Factor of Activated T cells (NF-AT) Regulates TH1 vs. TH2
Induces cytokine and membrane receptor genes when coupled with AP-1
Translocated from the cytoplasm into the nucleus after dephosphorylation by calcineurin
Four members of the family (70% homology):
NF-ATc1(NF-ATc) - mediatesIL-4/TH2 responses
NF-ATc2 (NF-ATp) - mediates IFN-
/TH1 responses
NF-ATc3(NF-AT4) - no effect on TH2/TH2 responses
NF-ATc4 (NF-AT3) - ?
Abbas- Cellular and Molecular Immunology
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TH1 vs. TH2 vs. TH17 Differentiation is Suppressed by IL-10 vs. IFN-
vs. TGF
Production
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The T Cell Response Involves Activation, Proliferation and Differentiation Into Effector Cells
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Cytokine Receptors are Predominantly Heterodimeric Membrane Proteins
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IL-2 Binds to the Interleukin 2 Receptor and is the Major T Cell Growth Factor
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Differential Expression of Multichain IL-2 Receptor Permits Variable IL-2 Receptor Affinity
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Signal Transduction by Heterodimeric Cytokine Receptors is Mediated by JAK/STAT Pathway
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TH1 vs. TH2 Differentation Mediated by IL-12 vs. IL-4 is Transduced by STAT4 vs. STAT6
Abbas- Cellular and Molecular Immunology
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TH1 vs. TH2 Differentiation Mediated by IL-12 vs. IL- 4 is Transduced by STAT4 vs. STAT6
Abbas- Cellular and Molecular Immunology
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Temporal Course of Immune Response to Infection
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Some Effector T Cells Become Memory T Cells
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Adaptive Immune Response Markedly Inhibits Subsequent Infections
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CCR7 vs. CCR3/5 Expression Distinguishes Central From Effector Memory Cells
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Original Antigenic Sin
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M Cells Provide a Portal for Selective Mucosal Antigen Uptake
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Questions to Consider
How do CD4 + T cells orchestrate responses appropriate to the infecting pathogen?
How do CD4+ T cells differentiate appropriately- TH1 vs Th2?
How do diverse cytokines transmit signals that mediate divergent responses?
Slide Number 1Questions to ConsiderResponse to Divergent Pathogens Requires Different Immune Responses CD4 + T Cells Differentiate Along Two Distinct Pathways�That Modulate the Immune Response DifferentlyCD4 + T Cells Differentiate Along Distinct Pathways�That Modulate the Immune Response DifferentlyDivergent Function of TH1 T Cells is�Due to Differential Cytokine ProductionDivergent Function of TH2 T Cells is Due to Differential Cytokine ProductionDivergent Function of Treg T Cells is�Due to Differential Cytokine ProductionDivergent Function of TH17 T Cells is Due to Differential Cytokine ProductionDivergent Function of Helper T Cells is Due to Differential Cytokine ProductionUncontrolled Mycobacteria leprae Leads to Lepromatous LeprosyInhibition of Mycobacteria leprae�Leads to Tuberculoid LeprosyDevelopment of TH1 vs. TH2 Response Determines Clinical Outcome of LeprosyTH1 Cells Induce Cell Mediated Immune Responses Directed to Intracellular PathogensActivated CD4 TH1 Cells Produce a Broad�Range of Cytokines With Diverse FunctionsTH2 Cells Induce Cell Mediated Immune Responses Directed at Extracellular PathogensTH1 vs. TH2 Differentiation is� Mediated by IL-12 vs. IL-4 SecretionTH1 vs. TH2 Differentiation is Mediated by Monocyte vs. B Cell Antigen PresentationTHreg vs. TH17 Differentiation is Mediated by TGF vs. IL-6 ProductionDifferential activation of Nuclear Factor of�Activated T cells (NF-AT) Regulates TH1 vs. TH2TH1 vs. TH2 vs. TH17 Differentiation is �Suppressed by IL-10 vs. IFN-g vs. TGF ProductionThe T Cell Response Involves Activation, Proliferation and Differentiation Into Effector CellsCytokine Receptors are Predominantly Heterodimeric Membrane ProteinsIL-2 Binds to the Interleukin 2 Receptor�and is the Major T Cell Growth FactorDifferential Expression of Multichain IL-2 Receptor Permits Variable IL-2 Receptor AffinitySignal Transduction by Heterodimeric Cytokine Receptors is Mediated by JAK/STAT PathwayTH1 vs. TH2 Differentation Mediated by IL-12 vs. IL-4 is Transduced by STAT4 vs. STAT6TH1 vs. TH2 Differentiation Mediated by IL-12 vs. IL-4 is Transduced by STAT4 vs. STAT6Temporal Course of Immune Response to InfectionSome Effector T Cells Become Memory T CellsAdaptive Immune Response Markedly Inhibits Subsequent InfectionsCCR7 vs. CCR3/5 Expression Distinguishes Central From Effector Memory CellsOriginal Antigenic SinM Cells Provide a Portal for Selective Mucosal Antigen UptakeQuestions to Consider