SummaryBeginning with the physical barrier presented by the epithelium, infectious agents such as viruses and bacteria encounter an array of cellular and molecular countermeasures that evolved within the host to resist them. Host immune responses are of two types, termed innate and adaptive. Immediate defensive responses, which include inflammation, phagocytosis of pathogens, and recruitment of a variety of immune cells, are employed against all classes of microbe, irrespective of prior exposure, and are collectively termed the innate immune response. Innate immunity is evolutionarily ancient, and selected mechanisms are known to be conserved from plants to humans. In contrast, the adaptive immune response is mobilized over a more protracted timescale, is influenced by prior exposure, and, by virtue of antigen-specific receptors generated through somatic DNA recombination within lymphoid clones, is highly specific at the molecular level, often to the point of specificity for a particular microbial species. Adaptive immunity evolved relatively recently and exists only in vertebrates. In mammals, the immune response encompasses the innate and adaptive responses, and, although cross-talk occurs between them, each can be carried out independently by distinct cellular and molecular mechanisms.