Download Lecture 10: Adaptive Immunity to Infection

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 TH2 T Cells is Due to
Differential Cytokine Production
Divergent Function of Treg T Cells is
Due to Differential Cytokine Production
Divergent Function of TH17 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
Abbas- Cellular and Molecular Immunology
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) - mediates
IL-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
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
Abbas- Cellular and Molecular Immunology
TH1 vs. TH2 Differentiation Mediated by IL-12 vs. IL4 is Transduced by STAT4 vs. STAT6
Abbas- Cellular and Molecular Immunology
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?