Dendritic cells (DCs) are a multifunctional group of cells that serve as sentinels of the immune system and thus regulate many immune functions. DCs play a central role in initiating adaptive immune responses to pathogens and initiating antitumor immune responses. DC 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, DCs can both induce T-cell proliferation (activation) or lack of activation (tolerance). In this way, DCs 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.
Acronyms and Abbreviations
CD, cluster of differentiation; CMV, cytomegalovirus; DC, dendritic cell; cDC, classical 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; pDC, plasmacytoid dendritic cell; Th, T helper; TLR, toll-like receptor; TNF, tumor necrosis factor; Tr, T regulatory.
FUNCTIONS OF DENDRITIC CELLS
Host defence is mediated by innate and adaptive immune responses, and dendritic cells (DCs) play essential roles in linking together innate and adaptive immunity.1–4 The innate immune response provides rapid resistance to pathogens, but the potency of innate responses does not increase after initial exposure (Table 21–1). Adaptive responses, mediated by B and T lymphocytes, generate immune memory, resulting in more rapid and more potent responses following antigen reexposure (Table 21–2).
TABLE 21–1.Some Innate Mechanisms of Host Resistance ||Download (.pdf) TABLE 21–1. Some Innate Mechanisms of Host Resistance
|Phagocytic cells: granulocytes and macrophages |
|Innate lymphocytes: natural killer (NK) cells, NK T cells, γδ T cells |
|Mast cells |
|Microbial-binding lectins and pentraxins |
|Cytokines, including interferons |
|Chemokines and antimicrobial peptides |
TABLE 21–2.Some Features of Adaptive Immunity by B and T Lymphocytes ||Download (.pdf) TABLE 21–2. Some Features of Adaptive Immunity by B and T Lymphocytes
|Diversity and specificity: somatically rearranged immunoglobulin receptors |
|Tolerance: specific silencing to self and harmless environmental antigens |
|Clonal expansion and its regulation: increased, then decreased, numbers of antigen-specific lymphocytes during an immune response |
|Appropriateness: pathogen-relevant, differentiation of lymphocytes |
|Memory: long-lived capacity for improved function upon reexposure to antigen |
DENDRITIC CELLS AND INNATE IMMUNITY
DCs provide innate immune resistance through production of cytokines, including interleukin (IL)-12 and type I interferons (INFs), and by activating other innate lymphocytes such as natural killer (NK) cells, NKT cells, and γδ T cells (Table 21–3).3 Innate responses are most often initiated by “pattern recognition receptors,” which respond to evolutionarily conserved molecules found in microbes, parasites, and viruses. ...