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INTRODUCTION

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SUMMARY

Dendritic cells are a multifunctional group of cells that serve as sentinels of the immune system and thus regulate many immune functions.* Dendritic cells play a central role in initiating adaptive immune responses to pathogens and initiating antitumor immune responses. Dendritic cell receptors sense environmental stimuli and can respond rapidly to both foreign pathogens and danger signals derived from tissue damage or immune complexes. Through their capacity to present antigen to T cells in immune-activating or immune-dampening contexts, dendritic cells can both induce T-cell proliferation (activation) or lack of activation (tolerance). In this way, dendritic cells help regulate immune responses mediated by T cells and B cells of the adaptive immune system. This chapter describes the varied types and functions of this important class of cells.

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Acronyms and Abbreviations:

CD, cluster of differentiation; CMV, cytomegalovirus; DC, dendritic cell; GM-CSF, granulocyte-monocyte colony-stimulating factor; GVHD, graft-versus-host disease; GVL, graft-versus-leukemia; Ig, immunoglobulin; IL, interleukin; M-CSF, monocyte colony-stimulating factor; MHC, major histocompatibility complex; NK, natural killer; Th, T helper; TLR, toll-like receptor; TNF, tumor necrosis factor; Tr, T regulatory.

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*Deceased. Substantial portions of his contribution have been retained in the current version of this chapter.

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FUNCTIONS OF DENDRITIC CELLS

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Host defense is mediated by innate and adaptive immune responses, and dendritic cells (DCs) play essential roles in linking together innate and adaptive immunity.1,2,3 The innate immune response provides rapid resistance to pathogens, but the potency of innate responses does not increase following initial exposure. Adaptive responses, mediated by B and T lymphocytes, generate immune memory, resulting in more rapid and more potent responses following antigen reexposure (Chaps. 75 and 76).

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DENDRITIC CELLS AND INNATE IMMUNITY

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DCs provide innate immune resistance through production of cytokines, including interleukin (IL)-12 and type I interferons, and by activating other innate lymphocytes such as natural killer (NK) cells, NKT cells, and γδ T cells (Chap. 75). Innate responses are most often initiated by “pattern recognition receptors” (Chap. 20), which respond to evolutionarily conserved molecules found in microbes, parasites and viruses.4,5 Pattern recognition receptors include toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors, retinoic acid-inducible gene 1-like receptors, and numerous C-type lectins. Pattern recognition receptors recognize a wide array of ligands, such as single- or double-stranded RNA, lipopolysaccharides, and other microbial constituents. DCs express pattern recognition receptors and respond to pattern recognition receptor agonists by becoming potent immunostimulatory cells and by presenting captured antigens to T cells in the context of major histocompatibility antigens. Pattern recognition receptors on DCs can also be activated via noninfectious stimuli induced by tissue damage and malignant cells, including uric acid crystals and heat shock and chromatin proteins. Such pathways are likely important for activating DCs toward tumor-associated antigens following transplantation or in disease states such as cancer or ...

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