Resistance mechanisms of the innate and adaptive immune responses prevent the colonization of foreign organisms in unwanted anatomical sites and participate in tissue repair and restoration of homeostasis after damage induced either by the invasion of pathogenic microbes or by the organism's response to them. The intensity of the response is controlled and limited by positive and negative feedback circuits that aim at preventing collateral tissue damage. In this Review we will discuss the protective and pathogenic effects of host–commensal microbiota mutualism on the immune response and illustrate some examples of collateral tissue and systemic damage caused by immunity to pathogens.