The role of T cells in mediating resistance and susceptibility to the parasitic gastrointestinal nematode Trichuris muris has been well defined. This is due to the existence of strains of mice which are resistant and susceptible to the parasite and early observations of polarized T helper responses in these strains. The importance of the thymus as a source of T cells was confirmed by careful observation of congentially athymic nude mice on a resistant background. Adoptive transfer of lymphocytes restored resistance in athymic mice. T cells fall into two categories based on their expression markers CD4 and CD8. CD4+ T cell association with T. muris had already been identified, depletion of CD4+ T cells led to a susceptible phenotype. Seminal work was carried out by Mosmann et al., in which two distinct CD4+ T cell subsets were identified by differentiated secretion of cytokines and this has enhanced our understanding of resistance to nematode infections. CD4+ T cells were separated in to Th1 and Th2 cells. The T helper type 1 (Th1) cells produce type 1 cytokines IFN-γ, lymphotoxin and IL-2 stimulating immunoglobulin (Ig)G2a population and cell mediated effector responses. Type 2 cytokines produce IL-4, IL-5, IL-6, IL-9 and IL-13 are secreted by Th2 cells in absence of type 1 cytokines and promote mastocytosis, eosinophillia and production of IgE and IgG1. This classification of cytokines is a simplified model. It is however excellent to characterize the cellular and molecular regulation of immunity of nematodes. This difference is important in order to understand the immunity of Trichuris muris. Some strains of BALB/c mouse produced Th2 associated cytokines when infected with Trichuris muris which caused clearance of worms. On the other hand other strains like B10.BR and AKR developed chronic adult infection associated with a Th1 response and production of IFN-γ and IL-12. An Association of Th2 with human whipworm has also been suggested. It can be said that host immune responses dramatically influenced resistance to T. muris and to an extent the parasite itself influences its own survival.-you need to explain this sentence if you are putting it in.
B cells and other antibodies
Relatively little is known about the role of B cells in immune responses to Trichuris muris. Changes do occur in B cells within MLN during infection. Increased numbers of B cells were seen during worm expulsion and in mice that harbor a chronic infection. B cells in MLN have proved to play an important role in the production of anti-T. muris antibody. Blackwell and Else in 2001 showed that μMT mice were unable to make B cells and they do not expel T. muris efficiently. Chronic infection in these mice showed increased IFN-γ production. Reconstitution of µMT mice with CD4 cells from infected C57BL/6 wild type mice showed increase in production of Th2 cytokines. B cells may also be important in the generation of effective CD4+ T cell responses, which subsequently led to worm expulsion.
NK cells which are natural killer cells have the natural ability to kill tumour cells without prior activation. These cells have the innate ability to produce IFN-γ without transcription factor binding and chromatin remodeling of the IFN-γ gene. NK cells are identified by their expression of the markers DX5 or NK 1.1. Many subsets of NK cells exist including NK-T cell which are restricted via the CD1d molecule like T cells and can also express CD3 although these do not constitute majority of DX5+ NK cells. Growing evidence supports? the hypothesis that these cells play an important role in parasitic infection. Recent data have shown that NK cells can also express type 2 cytokines including IL-4 and IL-13 suggesting these may play a role in type 2 immune responses against helminths. An expansion of both DX5+ CD3- and DX5+ CD3+ NK cells was observed in the pleural cavity of mice infected with Litomosoides sigmodontis which helped in clearing of parasite. NK cells produced IL-13 in absence of IFN- γ in response to IL-2 stimulation. DX-5+ TCR NK cells were thought to contribute to immune responses against Trichuris muris in absence of IL-4 and IFN- γ by producing IL-13. Thus NK cells may provide alternative source of cytokines to aid expulsion of gastrointestinal helminths.
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