Part IV The adaptive immune response Part IV The adaptive immune response Chapter 9 T Cell-Mediated...
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Transcript of Part IV The adaptive immune response Part IV The adaptive immune response Chapter 9 T Cell-Mediated...
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Part IV
The adaptive
immune response
Part IV
The adaptive
immune response
Chapter 9T Cell-Mediated Immunity
Chapter 9T Cell-Mediated Immunity
11
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APC
22
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33
Effector
Each with different Ag specificity
Periphery
Ag-specific T
Ag
Activated
Naïve
Ag-specific T cell response
Low frequency
Clonal expansion
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Effector T cells in CMI and humoral immunity
Effector T subsets 44
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CD4 T cell differentiation
CMI: CD8 T Humoral response
Th17
Promote local inflammation
Treg
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Entry of APC and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Effector T cell response
66
From inflammatory site
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Professional APC
77
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DC subsets
cDC (CD11chi) pDC
Viral infection 88
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Entry of DC
99
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Licensing
DC maturation / differentiation / migration
1010
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Lymphocyte entry into LN from blood
Adhesion moleculesAdhesion molecules
HEVHEV
1111
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Lymphocyte entry into LN from blood
SLC: Secondary lymphoid tissue chemokine
CCL21
CCR7
T zone: CCL21, CCL19
1212
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Entry of APC (DC) and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Clonal expansion & differentiation
Signal 1, 2, 3PrimingThe activation
and differentiationof naïve T cells
1313
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Naïve T cell activation in peripheral lymphoid organs
1414
NaïveActivatedEffector
Ag specificity
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1515
Effector
Each with different Ag specificity
Periphery
Ag-specific T
Ag
Activated
Naïve
Ag-specific T cell response
Low frequency
Clonal expansion
Circulation
Lymph nodes
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Activation of LFA1
Signal 1
1616
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Three signals in naïve T cell activation
Signal 2: proliferation1717
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Supramolecular activation compolex (SMAC)Avidity
T-APC
T cell activation
Amount of Ag expression
1818
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CD28-dependent clonal expansion of CD4 T cellsSignal 1+2
CD25
IL2
1919
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IL2 autocrine for CD4 T clonal expansion
Signal 1+2
2020
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Naïve T cell activation in peripheral lymphoid organs
2121
Naïve
Ag specificity
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Activation of LFA1
Signal 1
2222
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Regulation of signal 2
2323
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Self tolerance
Clonal anergy
Signal 1 alone in LN?
Clonal deletion
2424
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Type of Ag-specific effector
2525
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Signal 3: differentiation
Adaptive Treg
2626Transcription factor
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2727
Colgate Immunology (and Virology) Blog
CD40L-CD40
IL2
CD4 T-dependent CD8 T cell activation
CD8 T
DC (APC) activation
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2828
Ag
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2929
Ag capture and preservation by subcapsular sinus macrophage
Low phagocytosis
Ag –nonspecific B cells
CCL21
CXCL13
CXCR5
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3030
CCR7 induction
Ag-specific stimulation
B cell as APC
Ag-specific B-T cell
interaction
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CD4 T activation
Within LN3131
Egress
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Plasma:Sphingosine 1-phosphate (S1P)
Egress
S1P R
3232
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Sphingosine-1-phosphate (S1P)
The AOCS Lipid Library
An important cellular metabolite in animal cells
A ceramide-derived phospholipid
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S1P producer: Blood mononuclear cells, Neutrophils,Erythrocytes.
Efficiently phosphorylate exogenously added sphingosine and discharge S1P into the medium, which suggests a general contribution of hematopoietic cells in maintaining plasma S1P levels.
It is relatively insoluble in aqueous solution.Most of the plasma S1P is bound to carriers such as albumin.
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Entry of APC (DC) and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Clonal expansion & differentiation
Signal 1, 2, 3
Egress3535
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Migration of effector T cells to inflammatory site
Homing
3636
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Entry of APC and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Effector T cell response
CD8 T cytotoxic response
CD4 T effector & Macrophage activation
Homing
3737
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Ig domain
AddressinGuiding lymphocytes to tissuesHoming
Vascular addressin (VA)
3838
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Ag-specific recognition of CD8 T cells
3939
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No signal 2 is required
Requirement of signal 2 for effector function?
4040
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Cytotoxic granules
Microtubule-organizing center
Cytotoxic mechanisms of CD8 T cells
4141
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Membrane effector molecule
CTL
4242
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Membrane molecules Effector molecules
Soluble mediators
4343
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Professional APC
APC
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Macrophage activation & CD4 T activation
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Macrophages activation by Th1
4646
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Reciprocal activation
4747
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Th1 effectors
tissue
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Effector T cells
recruitment 4949
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Effector response
Innate immunity
Lymphocyte activation
Signal 1-3
50Apoptosis of
effectors