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Circulating T cells
Agin the
Inflammatorytissue
Ch 9 T Cell-Mediated ImmunityCh 9 T Cell-Mediated ImmunityAg-specific T cell response
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
Egress 2
Entry of DC into draining LN
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Inflammation
Immature DC:Ag uptake
CCR7
Ag presentation (signal 1)B7 (signal 2)
Mature DC(T cell zone)
CCL21
Naïve T cell activation in peripheral lymphoid organs
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NaïveActivatedEffector
500 T cells/hr for 1 DC
Naïve T: CCR7
T-APC interaction: activation of LFA1
Signal 1
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Ag specificity
Three signals in naïve T cell priming
Signal 2: proliferation6
IL2 autocrine
Signal 1+2
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CD28-dependent clonal expansion of CD4 T cells
Signal 3: differentiation
Adaptive Treg
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Transcription factor
Effector T subsets
Induced Treg
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Colgate Immunology (and Virology) Blog
CD40L-CD40
2. IL2
CD4 Th1-dependent CD8 T cell activation
CD8 T
1. DC (APC) activation
DC
CD8TAPC
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TRA: Tissue restricted antigen
mTEC: AIRE transcription factor
2011, 32: 188
Thymic negative selection : Self tolerance
Effector T cell response
CD8 T cytotoxic response
CD4 T effector & Macrophage activation
Homing
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Ch 9 T Cell-Mediated ImmunityCh 9 T Cell-Mediated Immunity
Entry of APC and naïve T cells into
peripheral lymphoid organsPriming of naïve T cells
by DC
HomingEffector response
CD4 Th1/ Th2CD8 TcB cells
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Where to go ?
CD4 T activation
Within LN
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Ig domain
AddressinGuiding lymphocytes to tissuesHoming
Vascular addressin (VA)16
Ag-specific recognition of CD8 T cells
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Microtubule-organizing center
Cytotoxic mechanisms of CD8 T cells (NK)
Membrane effector molecule
CTL
Cytotoxic granules
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Membrane molecules Effector molecules
Soluble mediators
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APC
Inflammatory site
Macrophage activation by Th1
Reciprocal activation
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Th1 coordinates a macrophage response
22Collaboration of adaptive and innate immunity
tissue
Systemic
The course of immune response to infection
Immunological memory
Ch 11
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Innate immunity
Humoral immunity
CMI
Sequential activation and
regulation of T cell subsets
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Amplifier of acute inflammation
(local site, BM)
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TH17
Neutrophils
Activation of macrophages
Antimicrobial peptides
Ubiquitous expression of IL17R on tissue cells: fibroblasts, epithelial cells, keratinocytes, etc.
Cytokines: G-CSF, GM-CSF
No IL4, IFNg, IL12)
Chemokines: CXCL8, CXCL2
Proinflammatory cytokine
Antimicrobial peptides PhagocytosisInflammed site
Signal 1+2
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Adaptive Treg
TH17
Rapid response to
infectionPreventing anti-selfresponse
Inhibition of proliferation & differentiation
TH17
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In the later stages of infectionPolarization
IL12 – Th1 IL4 – Th2
Intracellular infection Extracellular infection
Regulation among CD4 T subsets
Cytokine pattern of the dominant response
Inhibition of early Th17 response
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IL4
Th1
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Th1
CMI
Intracellular infection: Virus Intracellular bacteria Protozoa
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Th2
Humoral response
Mast cells
Extracellular infection: Helminths Parasites Protozoa Bacteria
Neutralizing Ab IL10
Early IL4 & Th2 polarization
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Natural/adaptive Treg
Sequential activation and regulation of T cell subsets
Survival and sequential activation
of B cell subsets
T/B cell activation & differentiation
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Barrier immunity
Professional APC
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Induction of antibody response in LN
(Th2) B cell response B cell as APC
Ag-specific
5 days
Isotype switchingSomatic hypermutation36
Ab response are sustained in medullary cords and BM
In situ 2-3 days, 6-7 cell divisions
Plasma cells
Life span: 2-4 days
Germinal center
BM
Plasmablasts
Life span: months - years
Plasma cells
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Adhesion molecules Homing R / addressin
Chemokine & R
Migration of immune cells
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Sequential activation and regulation
CD5 B cells
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CD5 B cells
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Early blockingReinfection
Effector response
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The course of immune response to infection
Immunological memory
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Two types of memory T cells
Central memory T
Effector memory T
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Maintenance of memory T cells
TCR, IL7, IL15
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Homeostasis
The role of IL7 in memory response
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CD4 T-dependent CD8 T cell memory response
Promote efficient effector activityMaintain memory T cell numbers
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Memory T cells
Balance of cell proliferation and death
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Long-lived
Memory B cell response
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Somatic hypermutation
Isotype switching
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Barrier immunity
Regulation of signal 2
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Effector T cells
recruitment
Apoptosis of effectors
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Continuous regulation of the expansion and
effector activity
in inflammatory sites
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Protective immunity & time
Apoptosis of effectors
Long-lived
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Stages of infection and immune response
Local inflammation
Macrophage activation
Activation of APC
Activation of lymphocytes
Homing of effectors
Endothelial cells
Collaboration with innate and tissue cells
Endothelial cells Endothelial cells 58
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