Lecture 7 - Effector CD4 T cells Flashcards
What is a ‘primed’ effector cell?
cell that is getting ready to respond
What is a ‘effector’ cell?
cell that has been induced to differentiate into a form and ready to function
What is the process of T cell activation?
1) Niave T cells differentiate into ‘primed’ effector T cell when interact with APC presenting peptide/MHC complex, CD28 with CD80/CD86 - signal the T cell to get ready to be activated
2) Rearrangement of the cytoskeleton leads to concentration of key molecules required for activation creating a central ‘cap’ - immunological synapse
3) The IS tells T cells to become activated through the recruitment of kinases. Signal i (MHC/peptide complex) and signal 2 (costimulation CD28 and CD80/CD86) triggers phosphorylation of TCR receptors, changes protein from inactive to active
4) IL-2 growth hormone produced
When is IL-2 produced?
1) T cells activated
2) when T cell binds to APC releases small amopunt of IL-2, needs larger signal to survive and proliferate
- uses feedback loop to initiate proliferation and expansion of T cell
Where does priming take place and how long does it take?
Priming takes place in the lymph nodes and take 2-3 days
What is the importance of differentiation of activated primed T cells?
To supply the best immune response to deal with the type of threat presented e.g. parasites need IgE
Which signal governs differentiation in T cells?
Signal 3
- surface molecules CD40
- cytokines
What are cytokines?
- small proteins (hormones) that allow communication between immune and non-immune cells
- widespread thoughout body
- act locally between APC and T cell
- bind to specific receptors
What are two subclasses of cytokines?
- Interleukins (IL) e.g. IL-2, IL-4
- Interferons (IFN) e.g. IFNy
What are the four types of effector CD4 T cells and what cytokines are they characterised by?
-Th1 (T helper 1) interferon gamma (IFNy)
-Th2 (T helper 2) interleukin… (IL-4, IL-5, IL-13)
-Th17 (T helper 17) interleukin 17 (IL-17)
Treg (Regulatory T)transforming growth factor beta (TGFb) interleukin 10 (IL-10)
What are features of the four types of effector CD4 T cells?
- each T cell cannot produce the cytokines other T cells produce
- cannot undifferentiate T cells into different type
What are the functions of cytokines?
1) induce differentiation of an activated CD4 T cell into correct subtype
2) Differentiated T cell subtype produces cytokines to deal with pathogenic threat
TO
-enable macrophages to destroy intracellular bacteria
-enable B cells to transform into plasma cells and secrete antibodies
How do cytokines induce differentiation of activated CD4 T cells into appropriate sub type?
cytokines can control what TF/promoter combination are brought together
1) Th1 production of IFNy controlled by TF T-bet binds to IFNy promotor upstream of the IFNy gene
2) Th2 production of IL-4 controlled by TF GATA-3 binding to IL-4 promoter upstream of IL-4 gene
3) Th17 production of IL-17 controlled by TF RoRyT binding to promoter upstream of IL-17 gene
What cytokines are produced by APC to induce the appropraite TF for each type of T CD4 cell?
1) Th1 = IL-12 induces T-bet
2)Th2 = IL-4 induces GATA-3 (feedback loop)
3) Th17 = TGFb and IL-6 induce RoRyT
4) Treg TGFb and IL-2 induce Foxp3
cytokines that T cell recieves determine which TF is activated and which subset differentiate in to
How cytokines induce transcription
1) cytokine receptors are not in active form
2) binding of cytokine to receptor causes change in cytokine intracellular region, recruits kinases
3) kinases phosphorylate cytokine receptor which activates signal-transducing activator or transcription (STAT)
4) STAT interacts with and transports the transcription factors to the promotor
5) induces cytokine production
