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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