T cell activation and generation of effector T cells Flashcards
Where are T cells activated
- Activated in secondary lymphoid organs
- Spleen and LNs
How can T cells be activated
- Naive T cells circulate through lymph nodes and find antigens
- Activation of naive T cells in Lymph nodes, development of effector cells
- Activation of effector T cells at the site of infection; eradication of microbe
What can activate T cells
- Only activated professional APCs express high levels of
MHC class II - These APCs also express co-stimulatory molecules.
What 3 signals are needed for T cell activation
- Signal 1: Antigen recognition
- Signal 2: Co-stimulation
- Signal 3: Cytokines
Describe the antigen recognition signal for T cell activation
- The signal that initiates the
immune response, so that the immune response is antigen-specific - TCR in T cell recognises the
antigen in the context of MHC - CD4 TCR recognises MHC II/peptide
complex - CD8 TCR recognises MHC I/peptide complex
- But in T cell - APC interactions other molecules participate
Where does the co-stimulatory signal come from
- Commonly from dendritic cells
- May also be provided by macrophages or B cells
Name the co-stimulatory molecules in T-cell activation
B7:CD28:
- CD28 is expressed by the T
cell - B7-1 (CD80) and B7-2
(CD86) molecules are
expressed by the APC
What is the difference between T cell activation without and with the co-stimulatory signal
- Unactivated APC is costimulator-deficient) and fails to activate T-cells to produce a response
- Activated APC’s express a higher level of costimulatorss such as IL-1, and activated T-cells into effector cells
Explain how T cells can provide signals to APCs
- T-cells recognise antigen on APCs causing expression of CD40L on T-cells
- CD40L binds to CD40 on APCs and leads to APC expression of B7 secretion of cytokines
- Activated APCs then stimulate T cell proliferation and differentiation
Describe how can TCR-MHC interactions cause a negative stimulation
- Negative co-stimulatory molecules inhibit processes initiated by TCR-MHC interactions
- Reduces inflammation after the infection has cleared
- Not expressed by naive T cells, they’re induced upon activation
- CTLA-4, PD-1 and LAG3
Describe the effects of CTLA-4
- Expressed approx 2-3 days post-stimulation
- Has a high affinity for CD80 but opposing effects to CD28
- Mostly expressed in T cells in secondary lymphoid organs
- Peak levels of expressions is lower than cd28 but avidity of interaction is higher
- Competes favourably with CD28 for ligation to CD80/86
Explain how cytokine release cause T cell polarisation
- Various forms of signal 3 induce the differentiation of naive CD4 T cells down
distinct effector pathways. - Each effector T cell expresses a master controller transcription factor
- This transcription factor controls the expression of effector cytokines
Describe the actions of IL-2 in T cell activation
- It is a growth, survival and differentiation factor for T cells and Tregs
Describe the changes in expression of surface molecules in T cell activation
- CD69 - Retention in lymph node
- Proliferation - IL-2Ra
- Activation of dendritic cells, macrophages and B cells - CD40L
- Control of response - CTLA-4
What is the difference in function of activated CD4 and CD8 T cells
- CD4 - activation of macrophages, B cells and other cells and causes inflammation
- CD8 - Killing of infected cells and macrophage activation
