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The term dendritic cell defines a multifunctional group of cells that serve as sentinels, adjuvants, and controllers of many immune functions. The cells play important roles in both innate and adaptive immune response to invading pathogens and other clinically important situations, such as malignancy. Dendritic cells have receptors for substances found in the environment, providing the cells with the capacity to respond rapidly to pathogens and certain endogenous stimuli, such as antigen-antibody complexes. In this capacity, they can play an important role in activation of innate immune effector mechanisms involved as the first-line defense against infection. In addition, these cells can serve as highly effective antigen-presenting cells that can induce T-cell proliferation (activation) or lack of activation (tolerance) in response to recognition of peptides presented by the dendritic cells’ major histocompatibility complex antigens. As such, the cells help regulate the responses to antigen by the adaptive immune system involving T and B lymphocytes. This chapter describes the varied types and functions of this important class of cells.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: CD, cluster of differentiation; CMV, cytomegalovirus; DC, dendritic cell; GM-CSF, granulocyte-monocyte colony-stimulating factor; Ig, immunoglobulin; IL, interleukin; MHC, major histocompatibility complex; NK, natural killer; TLR, toll-like receptor; TNF, tumor necrosis factor.

Host defense against pathogens, both infectious and neoplastic, is mediated by innate and adaptive responses, often in concert. Innate immune mechanisms act quickly to resist pathogens but do not develop improved function or memory following an initial exposure. Adaptive responses by B and T lymphocytes are acquired over days to months and are capable of memory, that is, improved responses upon pathogen reexposure (see Chaps. 77 and 78). Dendritic cells (DCs) are important mediators of both innate and adaptive immunity and often are responsible for linking together these two forms of resistance.1–3

Dendritic Cells and Innate Immunity

Among the many mechanisms of innate resistance (Table 19–1), DCs participate by producing large amounts of protective cytokines, including interleukin (IL)-12 and type I interferons, and by activating innate lymphocytes such as natural killer (NK) cells, NK T cells, and γδ T cells. The innate response of DCs, particularly cytokine and chemokine production, frequently is mediated by distinct “pattern-recognition receptors” (see Chap. 18). These respond to evolutionarily conserved molecular signatures of microbes, parasites and viruses4–11 and include toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors, retinoic acid-inducible gene 1-like receptors, as well as numerous C-type lectins. Innate pattern recognition receptors do not have the exquisite specificity provided by the antigen receptors for adaptive immunity on B and T cells, but they do recognize specific classes of ligands such as single- or double-stranded RNA, lipopolysaccharides, and other microbial constituents. DCs express these receptors, as do many cell types. Distinctively, DCs respond to agonists for pattern recognition receptors by becoming potent immunostimulatory cells, including the presentation of captured antigens. DCs ...

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