Mucosal immunity in the gastrointestinal (GI) tract is composed of physical factors and non-immune molecules, plus non-immune and immune cells of the mucosal epithelium and Peyer's patches. The mucosal epithelium with its tight junctions forms an effective physical barrier that normally functions as a perfect barrier. The mucosa-associated lymphoid tissue is used to describe all the mucosal lymphoid tissues in the body. Non-lymphoid cells include the intestinal epithelial cells that form a continuous monolayer separating the outside world from the human body. Peyer's patches consist of mucosal lymphoid aggregates that functionally perform the important role of initiating the local immune system. Specialized epithelial cells designated membranous or microfold cell provides access to Peyer's patches. Reoviruses enter the body through the very mechanism that protects and initiates an immune response against infections agents—demonstrating the imperfect barrier function of Peyer's patches. The gut microbiome has been shown to influence the outcome of cancer immunotherapy in patients by modulating the immune response.