Download Document

Part IV
The adaptive
immune response
Chapter 9
T Cell-Mediated Immunity
1
APC
2
Each with different Ag specificity
Low frequency
Naïve
Periphery
Ag-specific T cell response
Ag
Clonal expansion
Effector
Activated
Ag-specific T
3
Effector T cells in CMI and humoral immunity
Effector T subsets
4
CD4 T cell
differentiation
Th17
Treg
CMI: CD8 T
Humoral response
Promote
local
inflammation
From inflammatory site
Entry of APC and naïve T cells into
peripheral lymphoid organs
Priming of naïve T cells by DC
Effector T cell response
6
Professional APC
7
DC subsets
cDC (CD11chi)
pDC
Viral infection
8
Entry of DC
9
Licensing
10
DC maturation / differentiation / migration
Lymphocyte entry into LN from blood
HEV
11
Adhesion molecules
Adhesion molecules
Lymphocyte entry into LN from blood
CCR7
CCL21
T zone: CCL21, CCL19
SLC: Secondary lymphoid tissue chemokine
12
Entry of APC (DC) and naïve T cells
into peripheral lymphoid organs
Priming of naïve T cells by DC
Priming
The activation
and differentiation
of naïve T cells
Signal 1, 2, 3
Clonal expansion
& differentiation
13
Ag specificity
Naïve T cell
activation
in peripheral
lymphoid
organs
Naïve
Activated
Effector
14
Each with different Ag specificity
Low frequency
Naïve
Circulation
Periphery
Ag-specific T cell response
Ag
Clonal expansion
Effector
Activated
Lymph nodes
Ag-specific T
15
Activation of LFA1
Signal 1
16
Three signals
in naïve T cell
activation
Signal 2: proliferation
17
T cell activation
Amount of Ag expression
T-APC
Avidity
Supramolecular activation compolex (SMAC)
18
Signal 1+2
CD28-dependent clonal expansion of CD4 T cells
IL2
CD25
19
IL2 autocrine
for CD4 T
clonal
expansion
Signal 1+2
20
Ag specificity
Naïve T cell
activation
in peripheral
lymphoid
organs
Naïve
21
Activation of LFA1
Signal 1
22
Regulation of
signal 2
23
Signal 1 alone
in LN?
Clonal deletion
Clonal anergy
Self tolerance
24
Type of
Ag-specific
effector
25
Signal 3: differentiation
26
Adaptive Treg
Transcription factor
CD4 T-dependent CD8 T cell activation
IL2
DC (APC) activation
CD40L-CD40
CD8 T
Colgate Immunology (and Virology) Blog
27
Ag
28
Ag capture and preservation by
subcapsular sinus macrophage
CXCR5
Low phagocytosis
CXCL13
CCL21
Ag –nonspecific
B cells
29
Ag-specific
stimulation
CCR7
induction
B cell as APC
Ag-specific
B-T cell
interaction
30
CD4 T activation
Within LN
Egress
31
Egress
S1P R
Plasma:
Sphingosine 1-phosphate
(S1P)
32
Sphingosine-1-phosphate (S1P)
The AOCS Lipid Library
A ceramide-derived phospholipid
An important cellular
metabolite in animal cells
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
Signal 1, 2, 3
Clonal expansion
& differentiation
Egress
35
Homing
Migration of
effector T cells to
inflammatory site
36
Entry of APC and naïve T cells into
peripheral lymphoid organs
Priming of naïve T cells by DC
Effector T cell response
Homing
CD8 T cytotoxic response
CD4 T effector & Macrophage activation
37
Homing
Addressin
Guiding lymphocytes to tissues
Ig domain
38
Vascular addressin (VA)
Ag-specific recognition of CD8 T cells
39
Requirement of signal 2
for effector function?
No signal 2
is required
40
Cytotoxic mechanisms of CD8 T cells
Microtubule-organizing center
41
Cytotoxic granules
Membrane
effector
molecule
CTL
42
Effector
molecules
Membrane molecules
Soluble mediators
43
APC
Professional APC
Macrophage activation & CD4 T activation
Macrophages
activation by Th1
46
Reciprocal
activation
47
Th1 effectors
tissue
Effector T cells
recruitment
49
Signal 1-3
Lymphocyte activation
Innate
immunity
Effector
response
50
Apoptosis of effectors