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07-SEPTEMBER-2008 03:17:44 - Dendritic cell A dendritic cell A dendritic cell Dendritic cells in skin Dendritic cells in skin Dendritic cells DCs are immune cells and form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells. Dendritic cells are present in small quantities in tissues that are in contact with the external environment, mainly the skin where a specialized dendritic cell type is called Langerhans cells and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the dendrites, that give the cell its name. However, these do not have any special relation with neurons, which also possess similar appendages. Immature dendritic cells are also called veiled cells, in which case they possess large cytoplasmic 'veils' rather than dendrites. Contents 1 History 2 Types of dendritic cells 2.1 In vivo - primate 2.2 In vitro 2.3 Nonprimate 3 Life cycle 3.1 Formation of immature cells 3.2 Life span of dendritic cells 3.3 Research challenges 4 Dendritic cells and cytokines 5 Relationship to HIV, allergy, and autoimmune diseases 6 Dendritic cells in animals other than humans 7 Media 8 See also 9 External links 10 References History Dendritic cells were first described by Paul Langerhans Langerhans cells in the late nineteenth century. It wasn't until 1973, however, that the term dendritic cells was coined by Ralph M. Steinman and Zanvil A. Cohn.1. In 2007 Steinman was awarded the Albert Lasker Award for Basic Medical Research for his discovery. Types of dendritic cells In all dendritic cells, the similar morphology results in a very large contact surface to their surroundings compared to overall cell volume. In vivo - primate The most common division of dendritic cells is myeloid vs. plasmacytoid or lymphoid: Name Description Secretion Toll-like receptors2 Myeloid dendritic cells mDC are most similar to monocytes. mDC are made up of at least two subsets: 1 the more common mDC-1, which is a major stimulator of T cells 2 the extremely rare mDC-2, which may have a function in fighting wound infection IL-12 TLR 2, TLR 4 Plasmacytoid dendritic cells pDC look like plasma cells, but have certain characteristics similar to myeloid dendritic cells.3 They can produce high amounts of interferon-alpha and thus became known as IPC interferon-producing cells before their dendritic cell nature was revealed.4 TLR 7, TLR 9 The markers BDCA-2, BDCA-3, and BDCA-4 can be used to discriminate among the types.5 Lymphoid and myeloid DCs evolve from lymphoid or myeloid precursors respectively and thus are of haematopoietic origin. By contrast, follicular dendritic cells FDC are probably not of hematopoietic origin, but simply look similar to true dendritic cells. In vitro In some respects, dendritic cells cultured in vitro do not show the same behaviour or capability as dendritic cells isolated ex vivo. Nonetheless, they are often used for research as they are still much more readily available than genuine DCs. Mo-DC or MDDC refers to cells matured from monocytes6 HP-DC refers to cells derived from hematopoietic progenitor cells. Nonprimate While humans and non-human primates such as Rhesus macaques appear to have DCs divided into these groups, other species such as the mouse have different subdivisions of DCs. Life cycle Formation of immature cells Dendritic cell Dendritic cell Dendritic cells are derived from hemopoietic bone marrow progenitor cells. These progenitor cells initially transform into immature dendritic cells. These cells are characterized by high endocytic activity and low T-cell activation potential. Immature dendritic cells constantly sample the surrounding environment for pathogens such as viruses and bacteria. This is done through pattern recognition receptors PRRs such as the toll-like receptors TLRs. TLRs recognize specific chemical signatures found on subsets of pathogens. Immature dendritic cells may also phagocytose small quantities of membrane from live own cells, in a process called nibbling. Once they have come into contact with a presentable antigen, they become activated into mature dendritic cells and begin to migrate to the lymph node. Immature dendritic cells phagocytose pathogens and degrade their proteins into small pieces and upon maturation present those fragments at their cell surface using MHC molecules. Simultaneously, they upregulate cell-surface receptors that act as co-receptors in T-cell activation such as CD80 B7.1, CD86 B7.2, and CD40 greatly enhancing their ability to activate T-cells. They also upregulate CCR7, a chemotactic receptor that induces the dendritic cell to travel through the blood stream to the spleen or through the lymphatic system to a lymph node. Here they act as antigen-presenting cells: they activate helper T-cells and killer T-cells as well as B-cells by presenting them with antigens derived from the pathogen, alongside non-antigen specific costimulatory signals. Every helper T-cell is specific to one particular antigen. Only professional antigen-presenting cells macrophages, B lymphocytes, and dendritic cells are able to activate a resting helper T-cell when the matching antigen is presented. However, macrophages and B cells can only activate memory T cells whereas dendritic cells can activate both memory and naive T cells, and are the most potent of all the antigen-presenting cells. As mentioned above, mDC probably arise from monocytes, white blood cells which circulate in the body and, depending on the right signal, can turn into either dendritic cells or macrophages. The monocytes in turn are formed from stem cells in the bone marrow. Monocyte-derived dendritic cells can be generated in vitro from peripheral blood mononuclear cells PBMCs. Plating of PBMCs in a tissue culture flask permits adherence of monocytes. Treatment of these monocytes with interleukin 4 IL-4 and granulocyte-macrophage colony stimulating factor GM-CSF leads to differentiation to immature dendritic cells iDCs in about a week. Subsequent treatment with tumor necrosis factor alpha TNFa further differentiates the iDCs into mature dendritic cells. Life span of dendritic cells Activated macrophages have a lifespan of only a few days. The lifespan of activated dendritic cells, while somewhat varying according to type and origin, is of a similar order of magnitude, but immature dendritic cells seem to be able to exist in an inactivated state for much longer. Research challenges The exact genesis and development of the different types and subsets of dendritic cells and their interrelationship is only marginally understood at the moment, as dendritic cells are so rare and difficult to isolate that only in recent years they have become subject of focused research. Distinct surface antigens that characterize dendritic cells have only become known from 2000 on; before that, researchers had to work with a 'cocktail' of several antigens which, used in combination, result in isolation of cells with characteristics unique to DCs. Dendritic cells and cytokines The dendritic cells are constantly in communication with other cells in the body. This communication can take the form of direct cell-to-cell contact based on the interaction of cell-surface proteins. An example of this includes the interaction of the receptor CD40 of the dendritic cell with CD40L present on the lymphocyte. However, the cell-cell interaction can also take place at a distance via cytokines. For example, stimulating dendritic cells in vivo with microbial extracts causes the dendritic cells to rapidly begin producing IL-12.7 IL-12 is a signal that helps send naive CD4 T cells towards a Th1 phenotype. The ultimate consequence is priming and activation of the immune system for attack against the antigens which the dendritic cell presents on its surface. However, there are differences in the cytokines produced depending on the type of dendritic cell. The lymphoid DC has the ability to produce huge amounts of IFN-a, more than any other blood cell.8 Relationship to HIV, allergy, and autoimmune diseases HIV, which causes AIDS, can bind to dendritic cells via various receptors expressed on the cell. The best studied example is DC-SIGN usually on MDC subset 1, but also on other subsets under certain conditions; since not all dendritic cell subsets express DC-SIGN, its exact role in sexual HIV-1 transmission is not clear. When the dendritic cell takes up HIV and then travels to the lymph node, the virus is able to move to helper T-cells, and this infection of helper T-cells is the major cause of disease. This knowledge has vastly altered our understanding of the infectious cycle of HIV since the mid-1990s, since in the infected dendritic cells, the virus possesses a reservoir which also would have to be targeted by a therapy. This infection of dendritic cells by HIV explains one mechanism by which the virus could persist after prolonged HAART. Many other viruses, such as the SARS virus seems to use DC-SIGN to 'hitchhike' to its target cells.9 However, most work with virus binding to DC-SIGN expressing cells has been conducted using in vitro derived cells such as moDCs. The physiological role of DC-SIGN in vivo is more difficult to ascertain. Altered function of dendritic cells is also known to play a major or even key role in allergy and autoimmune diseases like lupus erythematosus. Dendritic cells in animals other than humans The above applies to humans. In other organisms, the function of dendritic cells can differ slightly. For example, in brown rats but not mice, a subset of dendritic cells exists that displays pronounced killer cell-like activity, apparently through its entire lifespancitation needed. However, the principal function of dendritic cells as known to date is always to act as an immune sentinel. They survey the body and collect information relevant to the immune system, they are then able to instruct and direct the adaptive arms to respond to challenges. In addition, an immediate precursor to myeloid and lymphoid dendritic cells of the spleen has been identified.10 This precursor, termed pre-DC, lacks MHC class II surface expression, and is distinct from monocytes, which primarily give rise to DCs in non-lymphoid tissues. Media S8-Dendritic Cells Dragging Conidia in Collagen.ogg Play video A well-resolved dendritic cell drags a conidium through a distance of up to 9 μm. The conidium, however, is not phagocytosed by the cell. The observation was made over 3 h with one frame every 30 s S6-Dendritic Cells with Conidia in Collagen.ogg Play video A single dendritic cell can be seen here efficiently taking up at least four conidia in its vicinity See also List of human clusters of differentiation for a list of CD molecules as CD80 and CD86 External links MeSH Dendritic+Cells Dendritic cells Presented by the University of Virginia www.dc2007.eu : 5th International Meeting on Dendritic Cell Vaccination and other Strategies to tip the Balance of the Immune System Website of Dr. Ralph M. Steinman at The Rockefeller University contains information on DCs, links to articles, pictures and videos References ^ Steinman RM, Cohn ZA 1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137 5: 1142-62. doi:10.1084/jem.137.5.1142. PMID 4573839. ^ Sallusto F, Lanzavecchia A 2002. The instructive role of dendritic cells on T-cell responses. Arthritis Res. 4 Suppl 3: S127-32. PMID 12110131. ^ McKenna K, Beignon A, Bhardwaj N 2005. Plasmacytoid dendritic cells: linking innate and adaptive immunity. J. Virol. 79 1: 17-27. doi:10.1128/JVI.79.1.17-27.2005. PMID 15596797. ^ Liu YJ 2005. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23: 275-306. doi:10.1146/annurev.immunol.23.021704.115633. PMID 15771572. ^ Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck D, Schmitz J 2000. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol 165 11: 6037-46. PMID 11086035. ^ Ohgimoto K, Ohgimoto S, Ihara T, Mizuta H, Ishido S, Ayata M, Ogura H, Hotta H 2007. Difference in production of infectious wild-type measles and vaccine viruses in monocyte-derived dendritic cells. Virus Res 123 1: 1-8. doi:10.1016/j.virusres.2006.07.006. PMID 16959355. ^ Reis e Sousa C, Hieny S, Scharton-Kersten T, Jankovic D, et al 1997. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J. Exp. Med. 186 11: 1819-29. PMID 9382881. ^ Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, et al 1999 June 11. The nature of the principal type 1 interferon-producing cells in human blood. Science 284 5421: 1835-7. doi:10.1126/science.284.5421.1835. PMID 10364556. ^ Yang, Zhi-Yong et al. 2004. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J. Virol. 78 11: 5642-50. doi:10.1128/JVI.78.11.5642-5650.2004. PMID 15140961. ^ Naik SH, Metcalf D, van Nieuwenhuijze A, et al. 2006 Jun. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nature Immunolgy 7 6: 663-71. doi:10.1038/ni1340. v d e Blood General Plasma - Hematopoietic stem cells Lymphoid - WBC T cells: Cytotoxic CD8+, Helper CD4+/Regulatory, γδ, Natural Killer T cell B cells: Plasma, Memory Natural killer cells Lymphokine-activated killer cell Null cell Myeloid - WBC Monocytes/Macrophages Histiocytes, Kupffer cells, Langhans giant cells, Microglia, Osteoclasts, Epithelioid cells Granulocytes Neutrophil, Eosinophil, Basophil - Mast cell precursors Dendritic cells Langerhans cells, Follicular dendritic cells Megakaryoblast - Megakaryocyte - Platelets Myeloid - RBC Reticulocyte - Normoblast Retrieved from http://en..org/wiki/Dendritic_cell Categories: Mononuclear phagocytes | Human cellsHidden categories: All articles with statements | Articles with statements since February 2007 | Articles containing video clips Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Español Français עברית Bahasa Indonesia Italiano 日本語 í•œêµì–´ Nederlands Polski Português РуÑ?Ñ?кий Tiếng Việt اردو ä¸æ–‡ This page was last modified on 14 August 2008, at 16:52
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