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