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The innate immune system provides immediate protection against infection and serves an essential antigen-presenting role that allows the adaptive immune response to occur during the days and weeks that follow. The sensory apparatus that allows detection of infectious microbes has been deciphered in large part, and it is now known that toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I–like helicases (RLHs) permit recognition of specific molecules of microbial origin. Much has also been learned of the biochemical events that follow activation of these sensors. Susceptibility to infection in humans is strongly heritable, and among the many loci that influence it, those that encode proteins vital to the innate immune response are of central importance. Moreover, autoinflammatory and autoimmune diseases are dependent upon the activation of innate immune signaling pathways.

Acronyms and Abbreviations

Abbreviations and acronyms that appear in this chapter include: AD, acidic activation domain; BIR, baculovirus inhibitor of apoptosis repeat; CARD, caspase activation and recruitment domain; CD, cluster of differentiation; CMV, cytomegalovirus; CTLA, cytotoxic T lymphocyte antigen; DAI, DNA-dependent activator of IRFs; ERK, extracellular signal-regulated kinase; FADD, Fas-associated death domain; FIIND, F-interacting domain; IFN, interferon; IFN-β promoter stimulator 1; I-κB, inhibitor of κB; IKK, I-κB kinase; IL, interleukin; IPAF, ice-protease activating factor; IPS-1, IRAK, interleukin-1 receptor-associated kinase; IRF, interferon response factor; JAK, Janus-associated kinase; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide; LRR, leucine-rich repeat; MAL, MyD88 adaptor-like; MCMV, mouse cytomegalovirus; MDA5, melanoma differentiation-associated gene 5; MDP, muramyl dipeptide; MyD88, myeloid differentiation 88; NACHT, a nucleotide-binding domain present in NAIP, CIITA, HET-E, and TP-1; NAD, NACHT-associated domain; NADPH, nicotinamide adenine dinucleotide phosphate; NBS, nucleotide binding sequence; NEMO, NF-κB essential modulator; NF-κB, nuclear factor-κB; NK, natural killer; NLR, NOD-like receptor; NOD, nucleotide-binding oligomerization domain; PAR-2, proteinase-activated G-protein-coupled receptor; PRAT4A, protein associated with TLR4; PYD, pyrin domain; RIG-I, retinoic acid inducible gene I; RIP, receptor-interacting protein; RLH, RIG-I like helicase; SARM, sterile-alpha and armadillo motif; SOCS-1, suppressor of cytokine synthesis 1; STAT, signal transducer and activator of transcription; STING, stimulator of interferon genes; TAK-1, transforming growth factor B activating kinase 1; TBK1, TANK-binding kinase 1; TIR, toll/interleukin-1 receptor/resistance; TLR, toll-like receptor; TNF, tumor necrosis factor; Tpl2, tumor progression locus 2; TRAF, tumor necrosis factor receptor-associated factor; TRAM, TRIF-related adaptor molecule; TRIF, toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-β; UCM, upregulation of costimulatory molecules.

In humans, as in all mammals, resistance to microbial infection is based partly upon lymphocytes, which yield highly specific responses to microbial antigens: either the production of antibodies or the expansion of T-cell cell clones that are directly cytotoxic to infected cells (see Chaps. 77 and 78). This, the adaptive immune response, is a recent fixture in evolution, witnessed only in vertebrates and traceable to the development of a mechanism for recombination of genomic DNA that arose approximately 450 million years ago. A more fundamental type of immunity, known as innate immunity, is represented in one form or another in all multicellular organisms. For ...

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