Abstract

The original hygiene hypothesis proposed that certain diseases derive from low levels of early-life microbial exposure. Since then, the hypothesis has been applied to numerous inflammatory, autoimmune, and allergic conditions. The changes in hygiene linked to these diseases include numerous changes in biotic exposure and lifestyle. To this end, some scholars have called for abandonment of the term or have suggested alternate labels, e.g., the old friends hypothesis. However, neither of these terms encompasses the complexity of plasticity in immune response and host–parasite/commensal interactions that influence these conditions. Here, I review this complexity, with particular regard to the factors affecting immunological strategies, the development of tolerance, immune dysfunction, and ecological interactions among organisms. I discuss the biotic factors that affect immune plasticity and how these interact with abiotic factors such as nutrition, as well as how transgenerational exposures may affect immune plasticity. Finally, I review the general features of diseases linked to biotic exposures.

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