Immunology test 3merlin123
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
· 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.
· 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)
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