Lecture 10: Adaptive Immunity to Infectionstreaming.einstein.yu.edu/docs/conferences/...Cellular and Molecular Immunology. TH1 vs. TH2 Differentiation Mediated by IL-12 vs. IL- 4 is

Lecture 10: Adaptive Immunity to Infection

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?

Response to Divergent Pathogens Requires Different Immune Responses

CD4 + T Cells Differentiate Along Two Distinct Pathways That Modulate the Immune Response Differently

CD4 + T Cells Differentiate Along Distinct Pathways That Modulate the Immune Response Differently

Divergent Function of TH1 T Cells is Due to Differential Cytokine Production

Divergent Function of Treg T Cells is Due to Differential Cytokine Production

Divergent Function of Helper T Cells is Due to Differential Cytokine Production

Uncontrolled Mycobacteria leprae Leads to Lepromatous Leprosy

Inhibition of Mycobacteria leprae Leads to Tuberculoid Leprosy

Development of TH1 vs. TH2 Response Determines Clinical Outcome of Leprosy

TH1 Cells Induce Cell Mediated Immune Responses Directed to Intracellular Pathogens

Abbas- Cellular and Molecular Immunology

Activated CD4 TH1 Cells Produce a Broad Range of Cytokines With Diverse Functions

TH2 Cells Induce Cell Mediated Immune Responses Directed at Extracellular Pathogens


TH1 vs. TH2 Differentiation is Mediated by IL-12 vs. IL-4 Secretion

TH1 vs. TH2 Differentiation is Mediated by Monocyte vs. B Cell Antigen Presentation

THreg vs. TH17 Differentiation is Mediated by TGF

vs. IL-6 Production

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) - ?


TH1 vs. TH2 vs. TH17 Differentiation is Suppressed by IL-10 vs. IFN-

vs. TGF

Production

The T Cell Response Involves Activation, Proliferation and Differentiation Into Effector Cells

Cytokine Receptors are Predominantly Heterodimeric Membrane Proteins

IL-2 Binds to the Interleukin 2 Receptor and is the Major T Cell Growth Factor

Differential Expression of Multichain IL-2 Receptor Permits Variable IL-2 Receptor Affinity

Signal Transduction by Heterodimeric Cytokine Receptors is Mediated by JAK/STAT Pathway

TH1 vs. TH2 Differentation Mediated by IL-12 vs. IL-4 is Transduced by STAT4 vs. STAT6


TH1 vs. TH2 Differentiation Mediated by IL-12 vs. IL- 4 is Transduced by STAT4 vs. STAT6


Temporal Course of Immune Response to Infection

Some Effector T Cells Become Memory T Cells

Adaptive Immune Response Markedly Inhibits Subsequent Infections

CCR7 vs. CCR3/5 Expression Distinguishes Central From Effector Memory Cells

Original Antigenic Sin

M Cells Provide a Portal for Selective Mucosal Antigen Uptake

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

Lecture 10: Adaptive Immunity to Infectionstreaming.einstein.yu.edu/docs/conferences/...Cellular and Molecular Immunology. TH1 vs. TH2 Differentiation Mediated by IL-12 vs. IL- 4 is

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