gamma delta T cells Flashcards
(29 cards)
Which cells split off ‘earlier’ from aB T cells? yD or iNKT /MAIT cells?
yD cells!
Where are the unconventional T cells localised too? And yD T cells in particular?
Unlike aB T cells, don’t circulate through SLOs. Instead they are found in peripheral tissues (and treat SLOs like my other tissue)
Localisation of iNKT cells?
Lots in vasculature and some in the liver.
Localisation of MAIT cells?
Large abundance in the liver, also largely in mucosal surfaces and (also everywhere else).
Localisation of yD T cells?
In peripheral tissues, especially concentrated at epithelial sites (intra-epithelial lymphocytes) and tissues, also in SLO (spleen) and blood. and thymus.
Are yD cells evolutionarily conserved?
Yes, found in all jawed vertebrates and express the two ancient cytokines IL-17 (repair and resolution) and IFN-y killing.
In mice, what are the skin intra-epithelial lymphocytes called?
The dendritic epidermal T cells (DETC)
yD T cells aren’t motile like aB cells, what does this mean?
They normally stay localised in the tissue.
what rearrangement occurs in the gamma chain of TCR?
Just normal V-J recombination.
What is special about the TCR delta locus?
it is within the TCR a locus and is normally excised out.
you can also get tow diversity regions added in to make delta chain with VDDJ recombination.
Why is the restriction of the yD TCR repertoire especially odd?
Because theoretically they are the most diverse TCR and immune recepotr.
What TCR restricition do you see in yD T cells of the skin in mouse and humans?
In mice, mostly Vy5 TCRs.
In human Vdelta 1 in epithelial tissues.
What TCR restriciton of yD t cells in blood and Lymphoid tissues?
Vy9Vdelta2
Are ab or yd T cells produced in thymus first in development?
yd T cells produced before brith and aB T cells, they are produced in waves of TCR restriction, which are localised to body surfaces.
What stage before do yD T cell have to come from in thymus?
Before the double positive stage.
yD or aB lineage depends on which recetpro expressed first and low (aB) or higher (yD) signalling.
Is there a negative selection of yD T cells?
no evidence found of this, Becuase they do not under rapid expansion and production of or inflammatory cytokines following activation that could be pathogenic.
Is there positve selection of yD T cells?
In mice, 17. D1 antibody recognises the surface of Vy5vdelta1 heterodimer in skin.
In vy5 knockout, reduced number of yD T cells in skin. But Vy1Vdelata1 were found that were also recognised by 17.D1 antibody.
Positively selected to enter tissues?
What are the four broad categories of protection that yD T cells have?
- Unique responses to microbial infeciton
- Immunosurveillance ‘sensing stressed/ potential tumour cells.
- Immunoregulatory functions ‘of conventional T cells)
- Protective in very young animals.
What antigens do Vy9Vdelta 2 cells of the blood respond to?
HMBPP
Where does HMBPP come from?
Comes from isoprenoid synthesis in microbes. In humans, the MVA pathway used. Whereas in microbes the MEP pathway used. HMBPP is a derivative of the microbial MEP pathway.
How many microbes use the MEP pathway and produce HMBPP?
LOooads, includes TB.
Why is it odd that yD TCR would bind the phosphoantigen HMBPP?
because it is very very small compared to the normal peptides that TCRs would bind.
Evidence that yD cells have a role in immunosurveillance?
What cells under higher surveillance?
In tumour models, yD- deficient mice had greater incidence of tumour formation. (synergised with aB- T cell deficiency).
Shows yD t cells detect early stages of stress that could be sign of tumours, especially in epithelial cells.
carcinomas (cancer of epithelial cells) accounts for most human cancers.
How may yD T cells recognise tumours?
Via NK like recpotrs that detect molecules that are upregulated in response to stress?
May include phophoantigens that stimulate the yD TCR too.
