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