dendritic cells

Dendritic cells and their immature counterparts, Langerhans cells (LC), are highly specialized, professional antigen-presenting cells (APC) located in the skin, mucosa, and lymphoid tissues.

adhesion : APC activities : clonal expansion B cells : cytokines : DC types : disorders : ectopic FDC-formation : follicular dendritic cells (FDC) : FDC networks : generating germinal centers : germinal centers : immature dendritic cells : immune regulators : immunological synapse : interferon producing cells : lymphoid dendritic cells : maturation : morphology : myeloid dendritic cells : pDC : plasmacytoid dendritic cells (PDC, IPC) : precursor dendritic cells : regulators : Th1 and Th2 stimulation : TLRs : types of DC : veiled cells

Immune dendritic cells are named for their morphology (long surface projections), and bear no relationship to neurons. Immature dendritic cells are also called 'veiled cells' because they display large cytoplasmic 'veils' rather than dendrites. DC and LC play a key role in the induction phase of contact allergenicity.

As key regulators of immune responses, dendritic cells (DC) stimulate lymphocytes to perform cell-mediated and humoral immune responses against pathogens and tumor cells. DCs can also educate T cells to tolerate self-antigens, thereby minimizing autoimmune reactions.

Types of dendritic cell
follicular dendritic cells (origin?) – FDC
lymphoid dendritic cells (lymphopoiesis) –
myeloid dendritic cells (monocytopoiesis) – MDC1, MDC2
plasmacytoid dendritic cells – PDC, IPC – the major producers of type I interferon (IFN)

Immature, precursor dendritic cells (pDC) circulate throughout the body, migrating to lymphocyte rich tissues (such as spleen and lymph nodes) upon stimulating encounter with antigen. The dendritic cells internalize the antigen, then digest, and externalize the fragmented antigen that they present to lymphocytes in MHC-peptide complexes, expressing markers that stimulate lymphocyte activation. Dendritic cells are the most effective antigen presenting cells. Follicular dendritic cells stimulate differentiation of B cells, monocytopoietic lineages (pDC1) stimulate differentiation of Th1 cells, lymphopoietic dendritic cells (pDC2) induce differentiation of Th2 cells. Plasmacytoid cells produce type 1 interferon (IFN-α, β, Ω) and can mature into dendritic cells that link innate and adaptive immune responses.

A variety of factors operate in antigen recognition and processing by immature (precursor) dendritic cells and in the maturation of immature cells. Toll-like receptors on the surfaces of precurson dendritic cells recognize microbial components and induce the differentiation of dendritic cell precursors. GM-CSF and IL-4 stimulate the maturation of monocytopoietic pDC1, while IL-3 stimulates the differentiation of pDC2. The transition to mature dendritic cells down-regulates those factors that were involved in antigen internalization, while up-regulating the expression of MHC, costimulatory molecules that participate in lymphocyte activation, adhesion molecules, and specific cytokines and chemokines.

Adhesion molecules enhance direct interactions between T cells and dendritic cells (immunological synapse). Dendritic cell stimulation of formation of Th1 and Th2 cells appears to be regulated by negative feedback. Th1 production of interferon-γ blocks the further stimulation of Th1 differentiation by DC1 cells. Th2 production of IL-4 kills the dendritic cell precursors that contribute to Th2 cell creation. Thus, although IL-4 stimulates Th2 differentiation, the promotion of Th2 cell formation by DC2 cells does not appear to involve IL-4. Costimulatory receptors CD80 and CD86 expressed by mature dendritic cells activate T cells in concert with the recognition of antigen/MHC by the T cell receptor. The secretion of IL-12 by dendritic cells stimulates T cell responses, in particular the differentiation of Th1 cells, which produce interferon-γ and other inflammatory cytokines.

Follicular dendritic cells are stromal cells unique to primary and secondary lymphoid follicles. FDCs express all three types of complement receptors as well as Ig-Fc receptors, through which antigen-antibody immune complexes are retained. FDCs present native antigens to potential memory B cells, of which only those coated with high affinity B cell receptors (BCR) are able to bind.

Recirculating resting B cells migrate through the FDC networks. Antigen-activated B cells undergo clonal expansion within the FDC networks in a T cell-dependent fashion, generating germinal centers. Evidence suggests the presence of two types of dendritic cells within human germinal centers: (i) the classic FDCs that express DRC-1, KiM4, and 7D6 antigens represent stromal cells; and (ii) the newly identified CD3-CD4-CD11c- germinal center dendritic cells (GCDC) represent hematopoietic cells that may be analogous to antigen-transporting cells of mice.

Within germinal centers, B cells undergo somatic hypermutation, positive and negative clonal selection, isotype switching and differentiation into high-affinity plasma cells and memory B cells. Adhesion between FDCs and B cells is mediated by ICAM-1 (CD54)-LFA-1(CD11a) and VCAM-VLA-4. T cells may interact with FDCs in a CD40/CD40-ligand-dependent fashion.

Ectopic FDC-formation is found in a number of autoimmune diseases and/or chronic inflammatory situations, suggesting that FDC development is not restricted to secondary lymphoid organs, but rather that local conditions drives a precursor cell type into FDC-maturation. The precursor of FDCs has presently not been identified, but data suggests a close relation to fibroblast-like cells. [s] It was initially believed that all DCs were of myeloid origin until several recent studies demonstrated that some DCs could also be efficiently generated from lymphoid-restricted precursors. FDCs appear to be involved in the growth of follicular lymphomas and in the pathogenesis of HIV infection.[pm]

Lymphoid dendritic cells are of lymphopoietic origin, and IL-3 stimulates the differentiation of pDC2 cells into DC2 cells, which stimulates differentiation of Th2 cells, which secrete the lymphokine interleukins 4, 5, 10, and 13. (IL-4, IL-5, IL-10, IL-13)

Myeloid dendritic cells are of monocytopoietic origin, and the maturation of precursor cells (pDC1) is stimulated by GM-CSF, and IL-4. Mature DC1 cells secrete interleukin 12 (IL-12), which acts through the JAK-STAT pathway to induce Th1 cells to secrete TNF-β (lymphotoxin) and IFN-γ. MDC-1 is the more common subtype, and is a major stimulator of Th1 cell differentiation. MDC-2 is rare, and may function in response to wound infection.

Plasmacytoid dendritic cells (pDC=IPC) are the major producers of type I interferon (IFN) and exhibit the unique ability to link innate and adaptive immune responses, by differentiating into DC capable of stimulating naive T cells and modulating the adaptive immune response. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively.

Plasmacytoid dendritic cell precursors (pDC) are type 1 interferon-(α, β, Ω)-producing cells (IPCs) that comprise 0.2%-0.8% of peripheral blood mononuclear cells (humans, mice). IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and rapidly secrete massive amounts of type 1 interferon following viral stimulation. IPCs promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons (IFN) during an antiviral immune response. Later in viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. [s, ] [fft]

images [] sem dendritic cell and T cell [] micrograph Langerhans cells [] PKC bII signaling in dendritic cells [] micrograph gallery dendritic cells [] photomicrograph dendritic cells interacting with yeast (lilac) [] photomicrograph Human Dendritic cell (labelled with anti MHC class-I FITC) presenting Influenza antigens to T-lymphocytes.
videos Џ Nature video library index Q Џ

ф activation ф affinity maturation ф anergy ф antibodies ф antigen ф APCs ф autoimmunity ф B cells ф bloodbone marrow ф CD ф cellular response ф class-switch recombination ф clonal selection ф complement system ф costimulation ф helper T cell ф hematopoiesis ф humoral immunity ф immune cytokines ф immune response ф immune tolerance ф inflammatory response ф interferons ф isotype switching ф killer T cells ф lymphocytes ф lymphokines ф lymphoid system ф lymphopoiesis ф macrophages ф MHC ф monocytopoiesis ф pattern-recognition receptors ф phagocyte ф plasma cells ф receptors ф signaling ф somatic hypermutation ф surface receptors ф T cells ф thymus

Tables  Complement Receptors  Cytokines  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors

IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. [Annu Rev Immunol. 2005]
Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9. [Springer Semin Immunopathol. 2005] PMID: 15592841 [Free Full Text]
Natural type I interferon-producing cells as a link between innate and adaptive immunity. [Hum Immunol. 2002] PMID: 12480256
Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. [Blood. 2004] PMID: 14670916
Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. [J Exp Med. 2003] PMID: 12515817
Roles of toll-like receptors in natural interferon-producing cells as sensors in immune surveillance. [Hum Immunol. 2002]


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