Particulates in the micro and nano range, including environmental pollutants, mineral and organic dusts, nanomaterials, nanomedicines, and metabolite crystals, can bio-accumulate in the body and cause a range of pathological conditions. These diseases, which include autoimmune disorders, organ fibrosis, cancer, and allergy, are frequently progressive and refractory to therapy with severe outcomes. Recent research has highlighted critical roles of the immune system in the response to particulates. This symposium discusses the current understanding of immune mechanisms in disease development caused by particulates, with focus on autoimmunity, fibrosis, mast cell function, innate memory, and the idiosyncratic reaction to infusion of nanomedicines.