T Cell Subsets Flashcards
where does activation of T cells occur and why
in the nearest lymph node in order to concentrate APCs
where do T cells proliferate and differentiate
in the lymph node organ
what 3 signals do APCs present to a naive T cell in order to activate it
MHC-TCR activation
survival signal sent between CD28 coreceptors
differentiation signal mediated by cytokines e.g. IL6, 12 and TGFb
which cells express CD8
cytotoxic T cells
what percentage of T cells are cytotoxic
30
which MHC class molecule do CD8+ cells bind to
MHCI
Why are CD8+ cells mostly activated by professional APCs
because they have a very high activation threshold so Dcs are the only cells which express sufficient B7 co receptors to bind to CD28
How do non-professional APCs activate CD8+ T cells?
They require help from Th2 cells which express the CD40 ligand which increases the APCs ability to produce B7 as well as inducing IL2 production which drives CD8 proliferation
what percentage of T cells in circulation are CD4+
70%
what are the 5 subsets of Th cells
Th1, Th2, Th17, Tfh and Treg
which form of T cells does HIV target
T helper cells
How are Th cells stimulated to differentiate to Th1 cells
once DCs have engulfed a pathogen they release IL12. This promotes differentiation to Th1
after stimulation, what is the action of Th1 cells
Th1 secrete IFNg and CD40 ligand. this hyperactivates macrophages to increase expression of enzymes and H2O2 improving its killing capabilities.
in addition cytokine release causes vasodilation to increase blood flow and access of immune cells. Il2 release promotes proliferation and IL3 instructs the bone marrow to make more cells. finally TNFa release causes macrophages to accumulate at the site of infection
which circumstances elicit a Th2 response
parasite infection- humoural response
how are Th2 cells stimulated
DCs release IL4
what is the action of Th2 cells
Il4 release optimises IgE class switching in B cells to activate macrophages.
IL5 mobilises, matures and recruits eosinophils
IL13 induces goblet cell differentiation and mucous production
what are the 2 types of leprosy and which Th response is responsible for each
Th1 response leads to tuberculoid leprosy (milder) whilst Th2 response leads to the lempromatus leprosy which has a high mortality rate
give an example of an autoimmune disease associated with inappropriate Th1 response
Arthritis/Diabetes
give an example of an autoimmune disease associated with inappropriate Th2 response
systemic lupus erythromatus
what is the role of Tfh cells
B cells depend upon these to produce antibodies
where are Tfh cells predominantly found
lymph nodes - upon activation the migrate to different region of lymph node where B cells are found
what is the action of Tfh cells
migrate to B cell region of lymph node and find B cells which recognises same pathogen. It then produces cytokines to allow B cell to produce antibodies
how are Th17 cells activated
Docs release IL6 and TGFb . Th17 cells reinforce this by releasing IL21 in an autocrine manner
what is the action of Th17 cells
they secrete Il17 to attract neutrophils as well as cause keratinocytes of the endothelium to release b defensins and IL21 to activate Nk cells
which sort of response is IL17 linked to
inflammatory
what sort of infections do Th17 cells fight against
extracellular bacteria and fungal infection
which auto inflammatory diseases are linked to Th17 response
rheumatoid arthritis, MS, IBS and psoriasis
how is Th17 response linked to auto inflammatory disease
increase in Il6,8 and TNFa are potent inflammatory cytokines
what is the cause of Hyper IgE syndrome
an impaired response to IL6 which prevents Th17 differentiation resulting in recurrent infection but the absence of fever
what is the role of Treg cells
suppress immune response
how does Treg suppress T cell proliferation
CD25 receptor on Treg is an IL2 receptor also. Treg cells sequester IL2 which is a major proliferation signal for other T cells. - cytokine consumption hypothesis.
They also actively secrete anti-inflammatory cytokines such as Il10 and TGFb.
They have cell surface receptors such as CTLA 4 which represses APC activation level upon interaction.
Finally cytolysis kills other T cells and APCs
which transcription factor is essential for Treg cell differentiation
Foxp3
what is the cause of IPEX disease
polymorphisms in Foxp3 preventing Treg differentiation
