The mammalian immune system consists of both innate and adaptive components, which work together to protect against microbial infections. The innate immune system, composed of functionally distinct modules, senses pathogens through pattern-recognition receptors (PRRs) and triggers antimicrobial defenses and adaptive immune responses. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. Recent progress has brought us closer to an integrated view of the immune system and its function in host defense. Infectious diseases are a leading cause of morbidity and mortality worldwide, and improving sanitary conditions, clean water supplies, and vector control are effective measures to reduce their incidence. However, the development of vaccines and therapeutics remains crucial, and understanding the host immune system is essential. Recent advancements have been made in discovering the mechanisms of microbial pathogenesis and host-microbe symbiosis, but challenges remain, particularly in effective vaccine development. The host-microbe interactions are complex, with hosts providing various niches colonized by microorganisms. The effects of microbial colonization on host fitness depend on the microbial adaptation strategy, which can be positive or detrimental. Virulence factors enable pathogens to adapt to specific host niches and promote transmission, leading to varying degrees of tissue damage. The recognition of microorganisms by the immune system is mediated by PRRs in the innate system and antigen receptors in the adaptive system. PRRs have broad specificity and can bind to conserved microbial structures, while antigen receptors are diverse and specific. The innate immune system deals with molecular diversity through pattern recognition, while the adaptive system uses antigen-specific recognition. The innate immune system includes modules such as mucosal epithelia, phagocytes, acute-phase proteins, complement, inflammasomes, natural killer (NK) cells, type I interferons (IFNs), and eosinophils, basophils, and mast cells. These modules evolved at different stages of phylogeny and are co-induced by infections, often co-regulated by cytokines. The adaptive immune system involves T-cell and B-cell responses, which are activated by the innate immune system. T cells can differentiate into effector lineages (T(H)1, T(H)2, and T(H)17 cells) based on the infecting pathogen, each producing distinct sets of cytokines. B cells can also be activated directly or indirectly by the innate immune system to produce protective antibodies. Understanding the balance between immunopathology and protection against infection is crucial for developing appropriate therapeutic strategies. Protecting against infection requires an immune response of the correct effector class directed at specific antigens, and understanding these principles is vital for vaccine development.The mammalian immune system consists of both innate and adaptive components, which work together to protect against microbial infections. The innate immune system, composed of functionally distinct modules, senses pathogens through pattern-recognition receptors (PRRs) and triggers antimicrobial defenses and adaptive immune responses. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. Recent progress has brought us closer to an integrated view of the immune system and its function in host defense. Infectious diseases are a leading cause of morbidity and mortality worldwide, and improving sanitary conditions, clean water supplies, and vector control are effective measures to reduce their incidence. However, the development of vaccines and therapeutics remains crucial, and understanding the host immune system is essential. Recent advancements have been made in discovering the mechanisms of microbial pathogenesis and host-microbe symbiosis, but challenges remain, particularly in effective vaccine development. The host-microbe interactions are complex, with hosts providing various niches colonized by microorganisms. The effects of microbial colonization on host fitness depend on the microbial adaptation strategy, which can be positive or detrimental. Virulence factors enable pathogens to adapt to specific host niches and promote transmission, leading to varying degrees of tissue damage. The recognition of microorganisms by the immune system is mediated by PRRs in the innate system and antigen receptors in the adaptive system. PRRs have broad specificity and can bind to conserved microbial structures, while antigen receptors are diverse and specific. The innate immune system deals with molecular diversity through pattern recognition, while the adaptive system uses antigen-specific recognition. The innate immune system includes modules such as mucosal epithelia, phagocytes, acute-phase proteins, complement, inflammasomes, natural killer (NK) cells, type I interferons (IFNs), and eosinophils, basophils, and mast cells. These modules evolved at different stages of phylogeny and are co-induced by infections, often co-regulated by cytokines. The adaptive immune system involves T-cell and B-cell responses, which are activated by the innate immune system. T cells can differentiate into effector lineages (T(H)1, T(H)2, and T(H)17 cells) based on the infecting pathogen, each producing distinct sets of cytokines. B cells can also be activated directly or indirectly by the innate immune system to produce protective antibodies. Understanding the balance between immunopathology and protection against infection is crucial for developing appropriate therapeutic strategies. Protecting against infection requires an immune response of the correct effector class directed at specific antigens, and understanding these principles is vital for vaccine development.