User:Kinkreet/Immunology/Helper T Cells

Helper T cells have minimal cytotoxic effects, its role is to direct and aid other parts of the immune system, and so determine the type of response to activate.

A naive T cell (TH0) can differentiate into a TH1 cell, or a TH2 cell. Generally speaking, TH1 cells respond by increasing cytotoxic T cell and macrophage activity, while TH2 cells produce a humoral response.

When TH0 first become activated, it will differentiate into a TH1 cell, which releases cytokines such as IL-2, IFN-γ and TNF. IL-2 promote the proliferation of cytotoxic T cells and NK cells, which secretes more IL-2 and IFN-γ, to amplify the effects; IFN-γ primes macrophages and increases their MHC expression and antigen presentation; TNF activates primed macrophages and NK cells.

Upon secondary re-stimulation by APCs, it can then differentiate into TH2 cells, secreting other cytokines such as IL-4, IL-5, IL-10 and IL-13, most of which are involved in inducing class switching. IL-4 promotes B cell, thymocyte and mast cell proliferation and along with IL-5, promotes class switching to IgE (best for parasites); IL-5 encourage the class switch to IgA (best for mucosal infections); IL-13 promotes class switch to IgE, but also activates macrophages and mucus production.

The switch to TH1 or TH2 is highly localized, and is done according to which is the best mode of response. Against viruses and bacteria, TH1 response would be the best because it activates cytotoxicity and complement fixation; TH2 response would be best against parasites and mucus infection, as they promote the production of antibodies best suited for the role.

Once the switch has taken place, it has a runaway positive feedback, where IFN-γ will bind to class II receptors and activates Stat1, in turn upregulating the transcription factor T-bet, and lead to the expression of more IFN-γ. T-bet also has an inhibitory effect on the transcription factor GATA-3, the transcription factor for TH2 genes, and also limit the production of IL-4 and IL-5, which promotes TH2 differentiation. The same is true for when IL-4 binds, the binding activates Stat6, which unregulates the expression of GATA-3 transcription factor. GATA-3 has an inhibitory effect on T-Bet. This means that once a cell is committed to a subgroup, it will stay at that group and try to promote neighbouring cells to differentiate to that group also.