This chapter provides a brief introduction to the most relevant parts of the immune system and the mechanisms by which the immune system responds to bacteria, with particular focus on probiotic bacteria. It discusses the knowledge and evidence for an effect of probiotics on the immune system and which mechanisms may be involved. The cells and physiological conditions in the gastrointestinal tract are of relevance for the way by which probiotic bacteria may interact with and influence the immune system. Beneath the epithelial cell layer, immune cells in high numbers are scattered in the lamina propria. The presence of microorganisms at the surface is imperative in order to stimulate the epithelial production of mucins and antimicrobial proteins (AMPs) and recruit immune cells to the mucosal sites. The transcription of inflammasome proteins and the assembly of the inflammasome is required for an appropriate recruitment of immune cells to the lamina propria, as well as for production of AMPs and mucus.