Mucosal surfaces represent the main sites in which environmental microorganisms and antigens interact with the host. In particular the intestinal mucosal surfaces are in continuous contact with a heterogeneous population of microorganisms of the endogenous flora and are exposed to food and microbes. As a result, the immune system of the host has to discriminate between pathogenic and commensal microorganisms. This article reviews the types of sentinel cells that continuously sense the environment and coordinate immune defenses as well as the mechanisms of the innate and adaptive immune systems that are activated by bacterial and viral molecular patterns leading to inflammatory, allergic, or regulatory immune response with special emphasis on probiotic bacteria.