T Cell Activation And Generation Of Effector T Cells Flashcards
Where are naive T cells activated?
In secondary lymphoid organs
Spleen and LNs
describe what occurs to naive T cells up to treating infection
Naive T cels circulate through the lymph nodes and find antigens on APC
Activation of naive T cells in lymph node, development of effector cells
Activation of effector T cells at site of infection: eradicate of microbe
What types of cells activate naive T cells?
Dendritic cell
Macrophage
B lymphocyte
ONLY ACTIVATED APCs EXPRESS HIGH LEVELS OF MHC CLASS 2
What 3 signals does a T cell need to be fully activated and differentiated into effector or memory T cells?
Signal 1: Antigenn recognition
Signal 2: Co-stimulation
Signal 3: Cytokines
What is signal 1 - Antigen recognition?
Is the signal that initiates the immune response so that the immune response is antigen specific
TCR recognises the antigen in context of MHC
CD4 - MHC2
CD8 - MHC1
What is the co-stimulators signal of APC?
Most commonly on dendritic cells
But may also be provided by macrophages or B cells
Are REQUIRED for naive cel activation
What happens in signal 2 (only provided when APC is activated)?
Activated APCs have increased expression of co stimulators, secretion of cytokines
B7 is present on the surface of activated APCs
IL—12 is secreted by activated APCs and cause naive T cell to express IL-2
This will induce the proliferation and differentiation of effector cells
How can T cells activate APCs via CD40?
- T cells recognise antigen (activated/non activated) causing expression of CD40L on T cells
- CD40L binds to CD40 on Dendritic cells
- leads to DC expression of B7 and the secretion of cytokines
- Activated DCs simulate T cell proliferation and differention
How can co stimulation be negative?
They inhibit the downstream effector processes initiated by TCR/MHC peptide interaction
Used to reduce inflammation after the infection has been cleared
These are not expressed by naive T cells, there are induced upon activation
Mainly expressed in T cells in peripheral tissues
Where is Cytotoxic T Lymphocytes Antigen 4: CTLA-4?
CTLA-4 is expressed approx 2-3 days post stimulation
Has high affinity for CD8 but opposing effects to CD28
It’s most expressed nT cells in secondary lymphoid organs
Peak levels of expression lower than CD28 but avidity of interaction is much higher.
Describe the 3rd signal; cytokines, induction of T cell polarisation.
The dendritic cell can release specific cytokines which can drive the T cell into the type of cell it becomes.
The dendritic cell also does cell signalling by binding to receptors on the T cell
What are the different cytokines that stimulate T cell proliferation?
TGF-beta : Treg cell
IL-6; B cells
IL-4: GATA3 - helper T cell
Why are there different forms of signal 3?
Various forms of signal 3 induce the differentiation of naive CD4 T cells down distinct effector pathways
Each effector T cells expresses a master transcription factor
This transcription factor controls the expression of effector cytokines
What are the steps that occur in signal 3?
- TCR signalling
- Costimulatory interaction
- Cytokine signalling
- Gene expression
What signal is. Important for cell proliferation?
IL-2 bind to T cells and trigger proliferation
How is T cell proliferation regulated?
This process is regulated by regulatory T cells which can suppress IL-2 using its receptors
Why is it important for T cells to express different receptors on their surface?
CD69 expression allows for retention in the lymph node - long enough for them to be fully activated and receive all the signals
IL-2 expression allows for proliferation
CD40L expression activation of dendritic cells, macrophages, B cells
CTLA-4 expression control of response
What are the consequences of this interaction between T cell receptors?
Activation of macrophages, B cells other cells, inflammation
Killing of infected cells, macrophage activation
Describe the steps that happen post TCR signalling
- Modify the expression of surface molecules
- Upregulate cytokine production
- Undergo active rounds of proliferation (expression of pro survival genes and IL-2)
- Differentiate into effector or memory cells
What induces T cell polarisation into the different subsets?
The polarising cytokines, which are generated by the stimulating APC
What factors determine what cytokines are produced by APC?
Cellular origin of the APC
Maturation and activation status of the APC
What pathogens were encountered by the APC
Tissue environment the encounter takes place
What are he different types of effector T cell?
Th1 cells
Th2 cells
Th17 cells
Tfh cells
Treg cells
What is the function off Induced Treg cells?
Regulation, suppression of immune and inflammatory responses
What is the function of Th17 cells?
Inflammation
What is the function of Th2 cell?
Allergic and anti-helminth responses
Produce IL-4, IL-5 an IL-13 that help eliminate extracellular parasite infections such as worms
promote class switching to IgE, which causes inflammatory cytokines to be release by eosinophils and mast cells.
Increase intestinal movement and mucus secretion
What is the function of Tfh cells?
B cell help in germinal centres
What is the function of Th1 cells?
- produce IFNg
- Cell mediated immunity
- Macrophage activation (activate macrophages)
- Inflammation
- (opozonisation) antibody class switching to igG
Transcription factor that causes differentiation: T-bet
When are Th1 cells polarised?
In the presence of intracellular pathogens
When are Th2 polarised?
In response to Phagocyte - independent immune responses
Polarising cytokine - IL-4
Transcription factors - IL-4 activated STAT6 which promotes expression oof GATA 3
GATA-3 activates expression of IL-4 and IL-13 genes
