T cell activation Flashcards
Generally describe the T cell immune resonse
1) naive T cells are activated via dendritic cells MHC-pathogen antigen and TCR.
2) rapid clonal expansion, proliferation and differentiation cause the specific TCR on effector T cells. Lymph nodes expand
3) apoptosis of T cells
4) Memory T cells aquired with specific TCR.
Describe the large cell contact between TCR/T cell and APC
There are lots of receptors in this interaction causing lots of signalling via tyrosine kinases.
- TCR: triggers interaction
- CD4+/CD8+
- integrins: cell adhesin
- co-stimultors
Describe the T cell response to activation
1) Changes migration patter in order to move to the site of infection
2) proliferate and clonally expand
3) Induce expression of genes for cytokines, cytokine receptors
4) Upregulate growth and protein synthesis so there is rapid cell division and cytokine making.
5) Differentiate into killer or helper so there is the correct immune response.
What is transmigration? Describe T cell migration in body.
circulating T cells receptors allow for transmigrate to secondary lymphoid tissue (spleen, lymph nodes) through the blood vessel wall.
Here T cells can find pathogen presented. If there is activation, they differentiate but then exit tissue to site of infection
If no activation, T cell goes to Lymphatic fluid where the are drained back into the blood.
Repeats
Describe the T cell response to activation caused by the TCR.
1) Changes migration patter in order to move to the site of infection
2) proliferate and clonally expand
3) Induce expression of genes for cytokines, cytokine receptors
4) Upregulate growth and protein synthesis so there is rapid cell division and cytokine making.
5) Differentiate into killer or helper so there is the correct immune response.
Describe the T cell response to activation caused by the TCR.
1) Changes migration patter in order to move to the site of infection
2) proliferate and clonally expand (Effector cells are larger, granular)
3) Induce expression of genes for cytokines, cytokine receptors
4) Upregulate growth and protein synthesis so there is rapid cell division and cytokine making.
5) Differentiate into killer or helper so there is the correct immune response.
What is Transcriptional reprogramming?
Number of Gene expressed changes after TCR activation up and down regulated
List some genes that are regulated by activation of T cells; transcriptional reprogramming
- Cytokine gene (IFN-gamma, IL2, TNF-alpha)
- Cytokine receptor gene
- Cell cycle regulator gene
- Nutrient transporter genes (amino acid, glucose, transferin) so T cells can match their metabolism to what is needed
- Chemokine receptors and adhesion molecules
What is the difference between the metabolism of naive unactivated T cells and effector cells (Cytotoxic)?
Naive:
Uses oxidative phosphorylation to make ATP. (These cells have low rates of glucose uptake, so it has to be efficient in producing glucose)
Cytotoxic:
High number of glucose and aa transporters.
The make alot of effector cytokines and protein synthesis which needs alot of ATP.
Become Glycolytic= They switch on aerobic glycolysis where they have excess to oxygen but use glycolysis instead
Using Glycolytic pathway, glucose can be broken down into lots of intermediates for RNA/DNA synthesis used in proliferation of the T cells.
What is the difference between the metabolism of naive unactivated T cells and effector cells (Cytotoxic)?
Naive:
Uses oxidative phosphorylation to make ATP. (These cells have low rates of glucose uptake, so it has to be efficient in producing glucose)
Cytotoxic:
High number of glucose and aa transporters.
The make alot of effector cytokines and protein synthesis which needs alot of ATP.
Become Glycolytic= They switch on aerobic glycolysis where they have excess to oxygen but use glycolysis instead
Using Glycolytic pathway, glucose can be broken down into lots of intermediates for RNA/DNA synthesis used in proliferation of the T cells.
What is the difference between the motility of naive unactivated T cells and effector cells (Cytotoxic)?
Naive:
They express chemokine receptor CCR7 and adhesion molecule CD62L.
This allows recirculation constantly blood.
Effector:
Downregulates CCR7/ CD62L and switch on expression of chemokine receptor CxCr3.
Stops cells migrating to lymphoid tissue and instead redirects them to peripheral tissues to mediate effector function.
What is the difference between the inflammatory cytokines of naive unactivated T cells and effector cells (Cytotoxic)?
Naive: IL7 receptor (from epithelial cells in lymph/bone) which enables cells to survive in lymphoid/bone.
Effector:
downregulates IL7 receptor and switches on inflammatory cytokine receptors IL2, IL12 which
What is the difference between the inflammatory cytokines of naive unactivated T cells and effector cells (Cytotoxic)?
Naive: IL7 receptor (from epithelial cells in lymph/bone) which enables cells to survive in lymphoid/bone.
Effector:
downregulates IL7 receptor and switches on inflammatory cytokine receptors IL2, IL12 which are sensitive to the cytokines from APC cell.
How does the activated T cell make a cytokine?
The expression of cytokine genes is regulated by combinations of different transcription factors.
How does the activated T cell make a cytokine?
The expression of cytokine genes is regulated by combinations of different transcription factors.
Non activated T cells: NFAT transcription factor is sitting in cytosol phosphorylated. No expression of genes
TCR activated, TF gets dephosphorylated and travels to nucleus.
It forms partnerships with other TF in nucleus. The complex binds to promoters of cytokine genes and causes IL2 production.
What is NFAT?
A transcription factor called Nuclear Factor of Activated T cells.
There are 5 NFAT genes and splice variants.
