Effector T cells (ch 8)
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What is the result of positive selection in T cells? Negative selection?
1) Self-restricted pool of T cells (can interact with MHC class I or II molecules) which become single positive, either CD4 or CD8 T cells 2) self-tolerant pool of T cells( i.e. not reactive to self Ag)
Describe the process in which naive T cells encounter their antigen in the secondary lymphoid tissues. What is the role of dendritic cells in this process? How does the dendritic cell change its function (before, during and after contact with antigen).
Dendritic cells capture Ag and present them to Tcells in SLT. T cells can enter LN via HEVS or afferent lymph. If TCR is specific for the Ag:MHC the T cell will proliferate and differentiate into an effetor T cell. The dendritic cell's function changes from phagocytosis, to presentation upon entering the LN cortex and becoming a mature DC.
What determines if a T or B cell will enter the secondary lymphoid tissues?
The concentration of chemokines leading to the HEVs
Describe the interaction of APCs and T cells when they have encountered their specific antigen.
TCR must binde peptide:MHC complex. If costimulatory signal (B7) on APC is also present it binds CD28 on Tcell. If both signals are present the T cell is activated and begins to upregulate CTLa4 which binds B7 more tightly (leads to downreg of T cell and less prolif).
What is the importance of the co-stimulatory signal between a T cell and an APC?
The costimulatory signal is necessary for T cell activation by APCs.
Describe the similarities and differences of the three types of APCs: macrophage, dendritic cell and B cell.
Location in LN: DC - Tcell areas. Mac- paracortical and medulla Bcell - follicles. Antigen Uptake: DC - macropinocytosis and phagocytosis Mac- Phagocytosis Bcell- Ig MHC uptake: DC - Low in tissue, high in lt Mac - induced by bacteria Bcell-increases on activation.
What is the importance of IL-2 during T cell activation? Typically where is it coming from?
IL-2 binds to IL-2 receptors on the surface of activated T cells to drive clonal expansion of the activated cell.
What happens to a T cell which is interacting with an APC if there is no co-stimulatory signal? ... if there is no antigen specific signal? Why do we have such a check and balance system concerning the activation of T cells?..
1) It becomes anergic 2)No effect on T cell. 3) To avoid overproduction of T cells which lead to icreased inflammation and immune response and possible autoimmune disease.
What determines if a Th1 or a Th2 will predominate during an infectious process?
Th1 (cell mediated) or TH2 (humoral) depends on the local environment in slt. IFN-g and CD12 = TH1. IL-4 = TH2
Using fig.8.22 describe the three ways that a CD 8 T cell can be activated. ( In each instance, note which type of APC is present.)
1) Virus infected DC expresses B7 and activates CD8 T 2) APC stimulates CD4T, CD4T activates APC, APC expresses B7, Stimulates CD8T 3) APC activates CD4T, CD4T makes IL-2, activates CD8T
Is a costimulatory signal necessary for Effector T cells to respond to antigen?
No, most human cells never express the costimulatory molecule.
What happens to LFA-1 of the T cell when the T cell receptor of an effector T cell binds its antigen?
The LFA-1 changes it's conformation and strengthens the adhesion between the two cells.
Why don�t T effector cells recirculate through the lymph nodes? What�s the role of VLA-4 on the T effector cell?
They do not express L-selectin and therefor can not re-enter through the HEV. They express VLA-4 which binds to VCAM-1 on endothelial cells of blood vessels in infected tissue.
Distinguish cytokines from cytotoxins.
cytokines alter the behavior of an infected cell, cytotoxins kill
Describe the �life history � of the chemicals stored in the lytic granules of an effector T cell.
Lytic granules are produced and packaged seperately at the beginning of an infection then released onto the surface of an infected cell upon binding with a T cell.
How would you describe the release of granules onto a target cell? (Fig.8.29)
Focused release of granule contents onto the target cell.
What is required to activate a macrophage? What is the role of interferon gamma in the process? Which cells could supply the IFN gamma?
AR of TH1 binds to Ag on macrophage MHC 2, forms a tightly bound conjugate pair. MHC:Peptide:TCR. Need IFN-g from TH1 cells and CD40 on macrophage binds to CD40 ligand on T cell
Describe how the effector CD 8 cell induces apoptosis in its target. What are the two pathways that result in apoptosis?
1) Cytotoxic granules with serine proteases. 2)FAS liand on T cell binds FAS on target cell and signals apoptosis -- used for unwanted lymphocytes.
Autoimmune Lymphoproliferative Syndrome (ALPS)
Caused by lack of FAS molecules. Body can't clear lymphocytes -- swollen lymph nodes.
What�s the relationship between perforin, granulysin and granzyme?
Serglycin on target cell binds perforin and granulysin on CD8T cell to form a pore in target cell mem, granzymes enter pore and initiate proteolysis and apoptosis.
In order for macrophage activation to occur by the Th1 cell, what components must interact? What are the two signals that are required?
CD40 and Cd40 ligand. Signal 1) IFN-g Signal 2) CD40
What are four effects of macrophage activation?
1)Phagosomes more efficiently fuse with lysosomes. 2) Increased synthesis of ROIs and RNIs. 3) Increased MHC2 and B7, can activate more naive Ts 4) maintains an increased number of macs in infected tissues
Why must a CD 4 Th1 cell be required to maintain contact with the macrophage for several hours? Are the effector molecules of a CD4 cell preformed as in a CD8 cell?
It takes several hours for the T cell to produce effector cytokines and cell surface molecules to activate mac. NO.
Describe in histological terms what a granuloma looks like? Why did it arise?
Form when an intracellular pathogen or its constituents resist elimination by macrophage. Multinucleated giant cell surrounded by mac epithelialoid cells and helper Ts.
What is linked recognition or cognate interaction? How is this knowledge utilized to produce vaccines against polysaccharides in infants? Why is it difficult to vaccinate infants against polysaccharides? Give two examples of vaccines that use this strategy in order to successfully vaccinate children
CD4 TH2 cells activate only the B cells that recognize the same antigens that they do. Knowledge of cognate recognition has helped improve the immune response to certain vaccines. they must use the conjugate in children because children do not mount an adequate IR to carbohydrate antigens
Describe regulatory CD 4 T cells. What is their role?
- Produce high levels of CD25, alpha chain of IL 2 receptor, FOX P3, and inhibitory cytokines such as TGF beta, IL4, & IL10.
- Two ways CD4 T reg can suppress the IR
- 1. direct contact the DCs that are initiating IR
- 2. direct contact with effector T cells
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