The chapter discusses the reciprocal interactions between the intestinal microbiota and the immune system, highlighting the coevolution of these two systems. The adaptive immune system, characterized by specificity and memory, has evolved to efficiently tailor responses to diverse microbes, promoting mutualism or host defense. However, this system also carries the risk of immune-mediated diseases linked to the intestinal microbiota. The chapter emphasizes the importance of understanding how the adaptive immune system copes with the vast number and diversity of microbes in the digestive tract and integrates with innate immune mechanisms to maintain homeostasis. The introduction explains how the human body transitions from a germ-free state at birth to colonization by a diverse microbiota, which is crucial for the development of the immune system. The complex, dynamic interaction between the microbiota and the host is shaped by nearly half a billion years of coevolution, resulting in a mutualistic relationship where the microbiota benefits from a nutrient-rich environment, and the host benefits from metabolic and nutritional advantages. The chapter also explores the role of maternal transmission in shaping the neonatal microbiome and immune system, the development of the intestinal mucosa and its lymphoid tissues, and the mechanisms by which the host senses and restrains the microbiota. It details the reciprocal interactions between the intestinal epithelium and the microbiota, including the production of mucus, antimicrobial peptides, and cytokines, and the role of innate immune cells such as Paneth cells and ILCs in maintaining homeostasis. The chapter further examines the adaptive immune response to the microbiota, focusing on the roles of regulatory T cells (Tregs) and effector T cells (Th17 cells). Tregs play a critical role in maintaining mutualism, while Th17 cells contribute to mucosal barrier defenses and can be both protective and pathogenic depending on the context. The chapter concludes by discussing the balance between regulatory and effector responses to the microbiota, emphasizing the importance of these interactions in maintaining immune homeostasis.The chapter discusses the reciprocal interactions between the intestinal microbiota and the immune system, highlighting the coevolution of these two systems. The adaptive immune system, characterized by specificity and memory, has evolved to efficiently tailor responses to diverse microbes, promoting mutualism or host defense. However, this system also carries the risk of immune-mediated diseases linked to the intestinal microbiota. The chapter emphasizes the importance of understanding how the adaptive immune system copes with the vast number and diversity of microbes in the digestive tract and integrates with innate immune mechanisms to maintain homeostasis. The introduction explains how the human body transitions from a germ-free state at birth to colonization by a diverse microbiota, which is crucial for the development of the immune system. The complex, dynamic interaction between the microbiota and the host is shaped by nearly half a billion years of coevolution, resulting in a mutualistic relationship where the microbiota benefits from a nutrient-rich environment, and the host benefits from metabolic and nutritional advantages. The chapter also explores the role of maternal transmission in shaping the neonatal microbiome and immune system, the development of the intestinal mucosa and its lymphoid tissues, and the mechanisms by which the host senses and restrains the microbiota. It details the reciprocal interactions between the intestinal epithelium and the microbiota, including the production of mucus, antimicrobial peptides, and cytokines, and the role of innate immune cells such as Paneth cells and ILCs in maintaining homeostasis. The chapter further examines the adaptive immune response to the microbiota, focusing on the roles of regulatory T cells (Tregs) and effector T cells (Th17 cells). Tregs play a critical role in maintaining mutualism, while Th17 cells contribute to mucosal barrier defenses and can be both protective and pathogenic depending on the context. The chapter concludes by discussing the balance between regulatory and effector responses to the microbiota, emphasizing the importance of these interactions in maintaining immune homeostasis.