03/06c T Cells Flashcards
What four events are required for T cell priming?
1) Antigen capture by dendritic cells
2) Activation of dendritic cells
3) Co-localization of dendritic cells and naive T cells at lymphoid tissues
4) Cross-talk and activation signals between dendritic cells and T cells
What are the three components of activating cross-talk between DCs and T cells?
Antigen presentation (signal 1)
Co-stimulatory molecules (signal 2)
Cytokines
How are newly-activated T cells retained in the lymph node?
Activated T cell downregulate expression of S1P receptors
S1P is a chemotactic lipid that normally promote T cell egress from the lymph node
It takes several days for the trapped antigen-specific T cell to proliferate, differentiate, and re-express S1P receptors
What molecules mediate initial binding of a T cell with an APC? What is their mechanism of action?
T cell adhesion molecules LFA-1 and CD2
Form an initial low-affinity binding, long enough for TCRs to interact with peptide-MHC complexes
When TCRs become activated, this signals a conformational change in LFA-1 and promotes a longer binding
If the TCR is NOT activated, the T cell will let go and continue sampling other APCs
What is the Immunologic Synapse?
Interaction between LFA-1 and ICAM-1, and TCRs with MHC-peptide complexes
What is Signal 1?
Binding of TCRs to MHC-peptide complexes
What is Signal 2?
Stimulation of CD28 on T cells by B7-1 and B7-2, which promotes T cell activation, proliferation, and survival via IL-2
What is IL-2?
Major T cell growth factor - necessary for growth, proliferation, and differentiation of T cells to become effector cells
Produced mainly by CD4 T cells
Also used therapeutically in chemotherapeutics and immunosuppressive drugs
What are the effects of Signals 1 and 2?
Stimulate the expression of IL-2 and IL-2 receptors
Stimulate the survival, proliferation, and differentiation of T cells
What happens if a naive T cell sees Signal 1, but not Signal 2?
Leads to tolerance induction or anergy - important for maintaining peripheral tolerance of the host
What is the function of CTLA-4?
Induced on activated T cells and binds to B7 more avidly than CD28
Delivers inhibitory signals to activated T cells to help terminate the T cell response
In what applications is CTLA-4 used therapeutically?
Treatment of rheumatoid arthritis
To extend graft survival
Treatment of melanoma
What are the helper activities of CD4 cells?
Express cytokines that allow them to activate other cells
Major example - CD40 ligand binds CD40 on APCs - makes them more potent by increasing their expression of B7 molecules, cytokines, and other activators
What are the effector functions of Th1 cells?
Stimulate macrophages through production of IFN to make them more efficient at phagocytosis and destruction of virus-infected cells
What are the effector functions of Th2 cells?
Drive IgE production and mobilize eosinophils from the bone marrow to destroy helminths
What are the effector functions of Th17 cells?
Secrete IL-17 and recruit lots of neutrophils to clear extracellular bacteria and fungal infections