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© Garland Science 2009

Chapter 8:

T Cell-Mediated Immunity

Activation of naive T cells on encounter with

antigen

•  T cell activation (priming)

•  T cell effector functions

Chapter 8

© Garland Science 2009

T Cell-Mediated Immunity

Activation of naive T cells on encounter with

antigen •  Immature dendritic cells capture antigen and

migrate to secondary lymphoid tissue (T cell regions of the cortex) where they become mature/activated dendritic cells

•  Macrophages (role in defense and repair of damaged tissue) are resident in tissues

Chapter 8

© Garland Science 2009

T Cell-Mediated Immunity

Dendritic cells carry antigens from sites of infection to secondary lymphoid tissues

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Dendritic cells are adept and versatile at processing antigens from pathogens

yellow = endocytic vesicles red = lysosomal protein green= MHC class II activation induces CCR7, the receptor for CCL21, which chemokine is made in secondary lymphoid tissue (results in migration to lymph node and stops further processing as a consequence dendritic cell focusses on T cell activation)

Dendritic cells use various pathways to process and present protein antigens

Activation of naive T cells on encounter with

antigen •  Naive T cells first encounter antigen presented by

dendritic cells in secondary lymphoid tissues •  dendritic cells enter via afferent lymp (drains from

the site of infection •  Naive T cells enter the lymph node by a) squeezing through blood capillaries (high endothelial venules) and enter the cortecal region b) through the lymph from an upstream lymp node (efferent lymp)

Chapter 8

© Garland Science 2009

T Cell-Mediated Immunity Naive T cells (blue

and green dendritic/macrophage sniffing T cell that do not encounter their specific antigen leave (green) whereas the ones that do, are activated, proliferate and differentiate into effector cells

Naive T cells encounter antigen in the secondary lymphoid organs

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How the lymph network works

In any given infection only 1 in 104 to 1 in 106 of the total pool of circulating T cells is activated.

Homing of naive T cells

to secondary lymphoid tissues is determined by chemokines and cell-adhesion molecules

Chapter 8

© Garland Science 2009

T Cell-Mediated Immunity

Naive T and B cells circulate in the blood and enter lymph nodes by crossing high endothelial venules

chemokine = CCL21 and 19 which binds to CCR7 receptor on Naive T cell

More about lymphocyte adhesion to professional antigen-presenting cells (APC)

DC-SIGN a lectin unique to activated DC

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Transient adhesive interactions between T cells and DC are stablized by specific Ag-recognition Activation of naive T cells requires a co-stimulatory signal

delivered by a professional antigen-presenting cell

signal 1 induces clonal expansion but only when signal 2 is delivered

B7.1 and 7.2 are known as costimulatory molecules

CTLA4 is expressed only on activated T cells, is similar to CD28 but binds much stronger to its ligand B7 and works as an atagonist

Activation of naive T cells on encounter with

antigen

•  There is a concentration gradient of (sphingosine 1-phosfate (S1P) from the lymp/blood to the secondary lymphoid tissues

•  T cells activated by Ag suppress the expression of S1P receptors for several days (makes them stay in the lymph node while they differentiate into effector cells). Later they are drawn away by the gradient of S1P

Chapter 8

© Garland Science 2009

T Cell-Mediated Immunity

Secondary lymphoid tissues contain three kinds of professional antigen-presenting cells which populate distinct areas

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The immunological synaps (T cell synaps)

ITAM = immune receptor tyrosine-based motif

Activated T cells secrete and respond to IL-2 (part I)

Activated T cells secrete and respond to IL-2 (part I)

cyclosporine-A, tacrolimus (FK506), and rapamycine are immunosuppressive drugs that inhibit IL-2 production or signalling from the IL-2 receptor

Ag recognition by a naive T cell in the absence of co-stimulation leads to anergy

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On activation, CD4 T cells acquire distinctive helper functions

Different cytokine profiles drive the differentiation of CD4 positive T cells that produce different cytokines and possess distinct functions

cell mediated immunity (TH1) humoral immunity (TH2)

Naive CD8 T cells are activated to become cytotoxic effector cells in several different ways

Effector T-cell responses to infection do not depend on co-stimulatory signals

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The three types of effector T cell produce distinct sets of effector molecules Kiss of death

LG lytic granules MTOC microtubule organizing center

Cytotoxic CD8 T cells are selective and serial killers of target cells at sites of infection

Cytotoxic T cells kill their target cells by inducing apoptosis or programmed cell death

Two pathways; 1 by granzymes, perforin and granulysin 2 Fas ligand

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TH1 CD4 cells activate macrophages to become highly microbicidal

conjugate pair, activation requires two signals

TH1 cells coordinate the host response to pathogens that live in macrophages

Granuloma’s form when an intracellular pathogen or its constituents resist elimination (MT)

The properties and functions of effector T

cells

•  CD4 Th2 cells activate only those B cells that recognize the same antigen as they do

•  Regulatory CD4 T cells (Tregs) limit the activities of effector CD4 and CD8 T cells

Chapter 8

© Garland Science 2009

T Cell-Mediated Immunity

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CD4 TH2 cells activate only those B cells that recognize the same antigen as they do

molecular components recognized both by B and T cells make effective vaccines

The adaptive T cell response has two distinct stages