DiscussionIntense exposure to microorganisms and parasites changes the immunological landscape. Using mass cytometry, which allows the characterization of the peripheral blood mononuclear cells by more than 35 antibodies, it has been possible to show that not only large differences exist in the adaptive immune system but also the innate immune cells are affected profoundly in rural areas of the developing world. The consequences of such differences in "normal immunological profile" that is seen in areas where exposure to microorganisms and parasites is high is thought to result in lower prevalence of disorders such as allergies and diabetes, but at the same time might contribute to poorer responses to certain vaccines. Focusing on helminth infections, which skew immune responses towards Th2 and lead to increase in regulatory immune cells, it has been possible to show a negative association between helminths and allergic response to environmental allergens. More recently, elegant studies in murine models have indicated that Th2 and regulatory responses are important for control of insulin sensitivity and helminth infected animals are protected against the development of insulin resistance. Population studies and clinical trials conducted in areas where helminth infections are highly prevalent have shown a negative association between helminths and insulin resistance. Currently, helminth derived antigens are being identified that can replicate the effect seen by the whole parasite on glucose metabolism. Such compounds, acting via the immune system or directly on tissues can form the basis of novel therapeutics for a number of inflammatory disease. However, the specificity of their effect will have to be engineered so that detrimental effects such as attenuation of vaccine responses are circumvented.