T cell polarisation and biomarkers Flashcards
What cells give rise to most cells in the IS?
Progenitors
What do lymphocytes look like?
Small cells with relatively large nuclei
Key features of T cells
Develop in the thymus
Bear an antigen specific receptor - TCR
Interact with APCs to see antigen
What is a common feature of all T cells?
All bear an antigen specific receptor TCR
What happens to T cells upon interactions with APCs bearing antigens?
The T cells proliferate if they recognise the antigen
Make large population of clones
Release cytokines
What is a thymocyte?
An early T cell that is developing in the thymus
What is the major feature of naive alpha beta T cells when they leave the thymus?
They comit to expressing only either CD4 or CD8 proteins on their surface
What is the difference between alpha beta T cells and gamma delta T cells?
Alpha beta T cells express CD4 or CD8 proteins on their surface
Gamma delta T cells don’t express either CD4/CD8
What class of MHC molecules do CD 4 T cells bind to?
MHC II
How do CD 4 T cells recognise antigens?
Presented on MHC II on APCs
What is the role of CD 4 T cells?
Make cytokines - provide help to other immune cells
Instruct and orchestrate the immune response
What is the common name for CD 4 T cells?
T helper cells
What class of MHC proteins do CD 8 T cells bind to?
MHC I
How do CD 8 T cells recognise antigens?
Bind to MHC I on infected cells
On which cells are MHC I molecules found?
On all somatic nucleated cells of vertebrates
What is the role of CD 8 T cells?
Kill target cells - virally infected and tumour cells
Make cytokines
What is the common name for CD 8 T cells?
Cytotoxic T cells
What is CD 3?
Name given to a collection of molecules that all T cells express on their surface
Coreceptors needed for T cells to perform normal function
On which T cells are TCRs expressed?
On all T cells
What are the two regions of the TCR?
Constant region - doesn’t vary much
Variable region - unique to each T cell
What does the high variability of the TCR variable region allow T cells to do?
Allows them to recognise different MHC combinations
What is the source of the large repertoire of T cells?
Large variety TCRs produced by the body
The functional population of T cells is as large as the potential repertoire
TRUE or FALSE
FALSE
The functional population of T cells is not as large as the potential repertoire
Number of different TCRs made by the thymus is bigger than the total lymphocyte count
What do CD 4 and CD 8 molecules bind to?
Non-polymorphic residues on MHC I or II
What does thymic selection do to the bond between MHC and TCR?
Strengthens it
The TCRs with the highest affinity are selected
Why do we need the CD 4/8 to bind to MHC molecules?
TCR has a relatively week biochemical binding
If the only interaction between APCs and T cells was between TCRs and MHC the cells would come apart before anything could happen
What does binding between TCR and MHC do to intracellular environment of the T cell?
Recruits signaling molecules to the immunological patch
Drives cytoskeletal movements in the T cells
CD 4 cells can be subdivided depending on the cytokines produced
TRUE or FALSE
TRUE
What are the different sub types of CD 4 T cells?
Th1
Th2
Th17
Regulatory T cells
T follicular helper cells
Which cytokines do Th1 cells release?
Gamma interferon and IL-2
Which cytokines do Th2 cells release?
IL-4, IL-5, IL-6, IL-10 and IL-13
Strongly associated to immunity to worms, parasites and helminths
Which cytokines do Th17 cells release?
IL - 17
Pro-inflammatory
What is the function of Th2 cells?
Immunity to worms, parasites and helminths
What is the function of Th17 cells?
Pro-inflammatory cells
What is the function of regulatory T cells?
Main funciton is to dampen down the immune system
What is the function of T follicular helper cells?
Critical to drive the cells inside the lymoh nodes
Can polarisation be changed in a T cell?
Yes
Who discovered the Th1/ Th2 division?
Mossman and Coffman in 1986
Mossman and Coffman belived the Th1 and Th2 were completely separate developmental pathways
Can’t switch between the two polarisations
TRUE or FALSE
TRUE
This is a false belief though - Th1 and Th2 polarisation is interchangeable
What is the role of Th1 cells?
Protect against viruses, TB and intracellular parasites
What do the cytokines released by Th1 cells signal through?
STAT 4
What is the main transcription factor in Th1 cells that drive its formation?
T bet
What is the role of Th2 cells?
Protect against extracellular pathogens
What do the cytokines released by Th2 cells signal through?
STAT 6
What is the main transcription factor that drives Th2 molecule formation?
GATA-3
Cytokines released by Th1/2 inhibit each other
TRUE or FALSE
TRUE
Th1 and Th2 cells cross-regulate each other
How do you differentiate between Th1 and Th2 cells?
By the chemokine receptors they express on CSM
What chemokine receptor is expressed on Th1 cells?
CXCR3
What chemokine receptor is expressed on Th2 cells?
CCR3
Summary of characteristics of Th1 cells
Cytokines: IL-2 and gamma interferon
Cytokines signal through STAT4
Chemokine receptor = CXCR3
Transcription factor T bet important for formation of molecule
Summary of characterisitics of Th2 cells
Cytokines: IL-4, IL-5, IL-6, IL-10, IL-13
Cytokines signal through STAT6
Chemokine receptor = CCR3
Transcription factor GATA-3 important for formation of molecule
How is MS linked to Th cells?
Mice with no STAT4 or Tbet were protected against MS
Therefore Th1 cells important in the pathogenesis of the disease
Mice with gamma interferon should have been protected too - got worsening disease
How is arthritis linked to Th cells?
Drugs that block Th17 are used to treat arthritis
Th17 are therefore important in the pathogenesis of the disease
What is meant by the term plasticity in context to Th cells?
T cells in their specific polarisation/ phenotype are plastic
What is an example of Th cells showing plasticity?
Th17 cells removed from synovial fluid of juvenile arthritis sufferers
In high concentration in these patients
Placing these cells in a petri dish makes them switch
What is the biomarker for Th 17 cells?
CCR 6
How can you tell Th cells have switched polarisation?
Th17 cells that switched to Th1 still expressed markers of Th17
Express both IL-17 and IFN = hybrid
Why is it difficult for Th1 cells to switch to Th17?
Energy difference
Th17 is less stable
Are T regulatory cells strongly polarised?
Yes
What is an important molecule for Tregs?
CTLA-4
Mice lacking = huge lymph nodes - too many effector T cells produced
What is IPEX?
X-linked genetic abnormality
Can’t make Tregs - require bone marrow transplant
What is the biomarker for T reg cells?
CD25 receptor
What gene codes for CD25?
IL-2 RA
What is the master transcription factor of Treg cells?
Foxp3
How do Tregs inhibit the function of effector T cells?
IL-2 is an important cytokine for effector cells
Tregs outcompete effector cells for this cytokine
Which cells produce IL-2?
Not Tregs
Other cells at wound site
What can Th17 cells convert to apart from Th1 cells?
Treg cells
Why is it relatively easy for Treg cells to change polarisation into Th17 cells and viseversa?
Both express the same homing receptors - CCR4 and CCR6
Develop under the production of the same cytokine - TGFb
What does conversion between these two phenotypes depend on?
Cytokines
Environment
Infection
What is the role of Th17?
Pro-inflammatory
What is CD161+?
A hybrid of Treg and Th17 cells
Express Th17 (CD161) molecules and Treg (CD4, Foxp3 and CD25) molecules
What on Treg cells binds to IL-2?
CD 25
