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
What is the last step in post TCR signalling
- Differentiate into effector or memory T cells
What induces T cell polarisation into the different subsets
- The polarising cytokines
- These are generated by the
stimulating APC
What does the produced cytokine depend on
- The cellular origin of the APC
- The maturation and activation status of the APC
- Which pathogens or inflammatory
mediators were encountered by the APC - In which tissue environment the encounter takes place
What are the main functions of Treg cells and what cytokines are involved
- IL-10, TGF-Beta
- Regulation, and suppression of immune and inflammatory response
What are the main functions of Th17 cells and what cytokines are involved
- IL-17A, IL-17F, IL-22
- Inflammation
What are the main functions of Th2 cells and what cytokines are involved
- IL-4, IL-5, IL-13
- Allergic and anti-helminth responses
What are the main functions of Tfh cells and what cytokines are involved
- IL-4, IL-21
- B cell help in germinal centersWhat are the main functions of Treg cells and what cytokines are involved
What are the main functions of Th1 cells and what cytokines are involved
- IFN-y, TNF
- Cell-mediated immunity, macrophage activation and inflammation
Describe the development of Th1 cells
TH1 polarisation occurs in response to the presence of intracellular pathogens such as viruses and bacteria that are ingested by and destroyed by phagocytes.
* Master transcription factor that controls differentiation - T-bet
What are the main functions of Th1 cells
- They produce IFNg
- Help to activate macrophages to ingest and destroy microbes
- Induce antibody class switching to IgG (opsonization).
- All helpful response in eliminating an intracellular pathogen
Describe Th2 cell development
- TH2 polarization occurs in response to phagocyte independent immune responses.
- TH2 polarizing cytokine is IL-4
- Dendritic cells do not make IL-4
- Eosinophils, basophils and mast cells produce IL-4. ILCs also produce IL-4
- Transcription factors: IL-4
activates STAT6 which promotes expression of GATA 3 - GATA 3 is a transcriptional activator of IL-4 and IL-13 genes
Describe the main function of Th2 cells
- TH2 cells produce IL-4, IL-5 and IL-13, effector cytokines that help eliminate extracellular parasitic infections such as worms
- Promote class switching to IgE, which causes inflammatory cytokines to be released by eosinophils and mast cells.
- They also increase intestinal movement and mucus production.
- IgE also mediates allergy
