The article by Akiko Iwasaki and Ruslan Medzhitov discusses the regulation of adaptive immunity by the innate immune system. It highlights the role of pattern recognition receptors (PRRs) in detecting microbial pathogens and their subsequent signaling pathways that control the generation of T and B-lymphocyte-mediated immune responses. The authors address several fundamental questions, including how pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury. The article categorizes PRRs into secreted, transmembrane, and cytosolic classes, each with distinct functions. Secreted PRRs, such as collectins, ficolins, and pentraxins, bind to microbial cell surfaces and activate the complement system. Transmembrane PRRs, including the Toll-like receptor (TLR) family and C-type lectins, recognize conserved microbial patterns on the cell surface or within endosomes. Cytosolic PRRs, such as RIG-I-like receptors (RLRs) and nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs), detect viral nucleic acids and microbial products. The authors explore the relative contributions of different PRRs to specific arms of adaptive immune responses and the mechanisms by which they activate these responses. They also discuss the distinction between cell intrinsic and cell extrinsic innate immune recognition, and how these mechanisms establish the origin of antigens for T cell responses. Additionally, they examine the role of pathogen recognition by antigen-presenting cells (APCs) versus infected cells in generating adaptive immune responses. The article further investigates the differences between microbial and endogenous ligands of TLRs, suggesting that microbial ligands trigger distinct responses from endogenous ligands. Microbial ligands activate inflammatory, tissue repair, and adaptive immune responses, while endogenous ligands primarily induce inflammatory and tissue repair responses. The authors conclude by emphasizing the ongoing discovery of new mechanisms of immune recognition and the need for further research to understand the complex interactions between the innate and adaptive immune systems.The article by Akiko Iwasaki and Ruslan Medzhitov discusses the regulation of adaptive immunity by the innate immune system. It highlights the role of pattern recognition receptors (PRRs) in detecting microbial pathogens and their subsequent signaling pathways that control the generation of T and B-lymphocyte-mediated immune responses. The authors address several fundamental questions, including how pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury. The article categorizes PRRs into secreted, transmembrane, and cytosolic classes, each with distinct functions. Secreted PRRs, such as collectins, ficolins, and pentraxins, bind to microbial cell surfaces and activate the complement system. Transmembrane PRRs, including the Toll-like receptor (TLR) family and C-type lectins, recognize conserved microbial patterns on the cell surface or within endosomes. Cytosolic PRRs, such as RIG-I-like receptors (RLRs) and nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs), detect viral nucleic acids and microbial products. The authors explore the relative contributions of different PRRs to specific arms of adaptive immune responses and the mechanisms by which they activate these responses. They also discuss the distinction between cell intrinsic and cell extrinsic innate immune recognition, and how these mechanisms establish the origin of antigens for T cell responses. Additionally, they examine the role of pathogen recognition by antigen-presenting cells (APCs) versus infected cells in generating adaptive immune responses. The article further investigates the differences between microbial and endogenous ligands of TLRs, suggesting that microbial ligands trigger distinct responses from endogenous ligands. Microbial ligands activate inflammatory, tissue repair, and adaptive immune responses, while endogenous ligands primarily induce inflammatory and tissue repair responses. The authors conclude by emphasizing the ongoing discovery of new mechanisms of immune recognition and the need for further research to understand the complex interactions between the innate and adaptive immune systems.