Epithelial surfaces are those directly exposed to the surrounding environment, and they include the skin, respiratory tract, gastrointestinal (GI) tract, and urogenital tract. Considering the skin and GI tract, in particular, allergic and autoimmune disease commonly affect these surfaces (see right aside) and are, in toto, prevalent, debilitating, and costly. In each of these diseases, allergen-specific and/or autoantigen-specific acquired immune response(s) appear to contribute to tissue inflammation. Thus, controlling these inflammatory immune responses in an antigen-specific manner would likely prove to be therapeutically beneficial. To understand this further, it should be instructive to consider some of the pertinent disease-driving factors and key cell types.