WK 3- T CELL ONTOGENY AND EFFECTOR FUNCTIONS Flashcards
What is the structure of a T cell
Has an alpha and a beta chain
-alpha chain resembles the light chain, the beta chain resembles the heavy chain
What are complexed to the TCR on the T cells
CD3
What immunological memory
T cells can be plasma cells or memory cells- these cells are long lived and respond rapidly to antigens. After exposure to the familiar antigens the memory cell will differentiate into effector cells
What immunological memory
T cells can be plasma cells or memory cells- these cells are long lived and respond rapidly to antigens. After exposure to the familiar antigens the memory cell will differentiate into effector cells
What is T cell anergy
antigen recognition in the absence of co-stimulation results in T cell anergy (unresponsiveness)
What is the function of a CD8 T cell
These are cytotoxic cells that kill virus infected cells- when a MHC1 binds to the CD8 receptor and TCR receptor it will trigger the release of TNF/IL-1/IL-6 which will kill the cell
What are the 3 signals required for T cell activation
- Binding of antigen to MHC complex-> kickstarts activation of T cell
- Binding of B7:CD28 triggers T cell to enter the cell cycle and cause production of IL-2
- Cytokines released by the APC determine the function/differentiation of the T cell
Describe signal transduction in a T cell
- antigen peptide on MHC will bind to TCR
- Binding causes a signal to move through the alpha and beta chain causing phosphorylation of the signalling proteins-> downstream signals are sent to nucleus
What drives CD4 T cell differentiation
Cytokines released in signal 3 drive differentiation
What are the 2 minority chains of a T cell
gamma (γ) and delta (δ)
What is the function of the gamma (γ) and delta (δ) chains
Gamma (γ) and delta (δ) cells behave like cells of the innate immune system and are found in lymphoid tissue /skin /intestines /reproductive tract
True or false; T cells recognise whole antigens
False: T cells only recognise antigen peptides attached to an MHC molecule
Describe the development of T cells
Common lymphoid progenitor (double negative) cells start to populate the thymus early in embryogenesis→ the progenitor cells sit in the cortex of the thymus and as they mature they move through the cortex in the direction of the medulla and become exposed to stromal cells and antigen presenting cells
Describe the maturation of T cells
Exposure to stromal cells/thymic epithelial cells stimulates the VDJ recombination →
1) The lymphoid precursor is a DN1 cell (double negative in stage 1→ does not have CD4 or CD8 receptors)
2) The cell will then progress to form a precursor T cell in DN2 → (double negative 2→ is destined to become a T cell from here and slowly expresses TCR and CD3)
3) Precursor t cell will turn into a thymocyte and is in DN3 (has no CD8 or CD4 receptors but has expressed the TCR)
4) When thymocyte moves into the DN4 stage it will begin to proliferate
5) Cytokines will cause the cell to move from DN4 to a DP stage and the T cell will express both CD4 and CD8 receptors along with the existing TCR
6) The DP thymocyte can then interact with a thymic epithelial cell/dendritic cell/macrophage which have MHC’s attached→ the MHC will either express MHC1 or MHC2 and be presenting a self-antigen→ depending on which MHC molecule the thymocyte will interact with will determine whether it becomes a CD4 (will interact with MHC2) or a CD8 cell (will interact with MHC1)
7) Those that interact with the presenting cells undergo positive selection→Thymocytes that do not recognise the MCH or attach to it too strongly are apoptosed
8) Once the cell becomes either a CD8 or a CD4 it will become a single positive thymocyte→ aka naïve T cell
9) The naiive T cell will move into the medulla of the thymus where it will be presented with self-antigens→ if it reacts too strongly with the peptides on the MHC molecule it will undergo apoptosis→ negative selection
10) The remaining mature naïve T cells will migrate from the thymus to the secondary lymphoid tissue
Describe T cell activation
- T cells enter the secondary lymph tissues by either:
Spleen→ Afferent splenic artery
Lymph node→ HEVS (high endothelial venules) → Recruited by chemokines
2.Once in the secondary lymphoid tissue they encounter antigens (presented as a peptide by MHC on APC- dendritic cell). If antigen is not recognised in that node, it will continue to flow to another lymph node - Antigens deliver 3 types of signals to T cells
- T cell differentiation is dependent on the cytokines released in the third signal
