Immunology test 3

The Immune System Fourth Edition 2015 - Chapter 8: T Cell-Mediated Immunity

Activation of naïve mature T cells:

· Mature T cells Circulate from: blood secondary lymphoid organs lymph blood

· While in the T cell zone of the lymph node (or other secondary lymphoid organ) they have the opportunity to encounter antigen.

· Dendritic cells as antigen presenting cells (APCs)

· Primary activators of naïve T cells.

· (Fig. 8.1 and 8.4) Dendritic cells take up antigens at a site of infection and bring them to the closest secondary lymphoid tissue

· Examples:

· Blood infections stimulate T-cell response in spleen.

· Skin infections stimulate T cell response in draining lymph nodes.

· Intestinal infections stimulate T cell response in the GALT

· DC’s are considered immature before recognizing and processing antigen. A mature DC has processed antigen and is displaying it on its surface in a molecule of MHC. It also has defined dendrites and cell surface receptors that allow it to easily interact with T-cells.

· (Fig. 8.3) Dendritic cells use several pathways to process and present protein antigens.

· Macrophages B cells as antigen presenting cells (APCs)

· Can aid in a T cell response, but are considered to be a secondary activator of a T-cell (DCs would be the primary activator)

· Filter antigens from lymph entering a lymph node

· Help to clean up the mess left by apoptosed B and T cells in lymph node.

· Regardless of what cell type activates a T cell. Activation of a naïve CD8 or CD4 T cell requires an antigen-specific signal and a co-stimulatory signal.

· T-cell Anergy - If three binding events do not occur the cell is considered to have bound self-antigen and will become anergic. (Fig. 8.13) *This is only true for initial naïve T cell activation in the secondary lymphoid tissues.

· If this anergic cell recognizes and binds to self antigen again it can receive a co-stimulatory signal but will still remain anergic

· T-cell Activation – Three things need to bind! (Fig. 8.8) 1st TCR – MHC, 2nd Co-receptor (CD4 or CD8) – ligand on MHC, and 3rd Co-stimulatory receptor (CD28) – Co-stimulatory ligand (B7)

· The binding of the TCR-MHC and the Co-receptor-ligand initiates a signaling pathway inside the T cell that leads to ZAP-70 activation. (Fig. 8.10)

· Activated ZAP-70 leads to activation of transcription factors (for example: nuclear factor of activated T cells (NFAT), AP-1 and NFκB) that initiate gene expression of molecules needed for T-cell proliferation, differentiation, and effector function.

· The binding of the Co-stimulatory receptor (CD28) – Co-stimulatory ligand (B7)

· Is needed in addition to TCR-MHC and the Co-receptor-ligand binding for a T-cell to divide and survive.

· CD28 receptor on T cell interacts with its ligand B7 on DC

· When a T cell is activated by binding antigen and a co-stimulator, a signal will be sent from the activator cell (APC) to the T cell or from the T cell to itself.

· This signal is in the form of cytokines.

· These cytokine signals can be autocrine or paracrine.

· The cytokines produced can vary based on the type of infection.

· Examples:

· IL-12

· produced by APCs and acts on T cells (paracrine signal).

· Works as a paracrine signal.

· Induces the differentiation of a CD4 T cell to become a TH1 (CD4) cell

· IL-2 (Fig. 8.12)

· Produced by an activated T cell and acts on that T cell (autocrine signal).

· Drives the proliferation and differentiation of all T cell subtypes.

· The types of cytokines secreted from the activator cell will determine the differentiation of the activated T cell into one specific type of effector T cell.

· The cytokine signal is determined by the innate immune response at the site of infection and the APCs and antigen processing that occurs in secondary lymphoid tissue.

Activated effector T cells:

· Once a T cell is activated and becomes an effector T cell, as described above, it leaves the secondary lymphoid tissue and travels to the site of infection. Here it will carry out its effector function to fight infection.

· Once at the site of infection it still needs to recognize antigen but no longer needs a co-stimulatory signal (Co-stimulatory receptor CD28 – Co-stimulatory ligand B7) to carry out its effector function. It only needs binding of the TCR-MHC and the Co-receptor-ligand. (Fig. 8.20)

· At the site of infection effector T cells are activated by antigen to produce more activated effector T cells and memory T cells.

· Five types of effector T cells that a CD4 T cell can become. (Fig. 8.14 and 8.21-focus on type and function in the tables) The most common is T helper cells (TH1 and TH2)

1. TH1 (Fig. 8.27)

2. TH2

3. TH17

4. TFH (Fig. 8.28)

5. Treg (Fig. 7.19)

· One type of effector T cell that a CD8 T cell can become. (Fig. 8.21, 8.23 and 8.24)

1. cytotoxic T cell