Dendritic cell
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Dendritic cells (DC) are immune cells and form part of the mammal immune system. They are present at a low frequency in those tissues which are in contact with the environment: in the skin (where they are often called Langerhans cells) and the lining of nose, lungs, stomach and intestines. Especially in immature state, they can also be found in blood. Once activated, they migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and shape the immune response. In certain stages they have long spiky arms, called dendrites, from which their name is derived. While neurons also have dendrites, they are not related to DCs. In both types of cell, the dendrites seem to serve the same purpose: to enable a single cell to contact a large number of other cells at one time (the dendrites confer a high surface-to-volume ratio.) The name veiled cells refers to immature or maturing dendritic cells; these cells do not yet possess the dendrites, but rather larger cytoplasmic 'veils'. Dendritic cells were discovered in 1973 by Ralph M. Steinman and Zanvil A. Cohn.
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Types of dendritic cells
Unfortunately, there are at least two different types of cells involved with immunity that are called dendritic cells. The exact relationship of these types to each other, as well as the identity of their parent cells in vivo, remains controversial.
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.
In vivo
- Myeloid dendritic cells (MDC) are most similar to monocytes. MDC are made up of at least two subsets:
- the more common MDC-1
- the extremely rare MDC-2, which may have a function in fighting wound infection
- Plasmacytoid dendritic cells (PDC) look like plasma cells, but have certain characteristics similar to myeloid dendritic cells. They can produce high amounts of interferon-alpha and have thus become known as IPC (interferon-producing cells) before their dendritic cell nature was revealed.
- Follicular dendritic cells (FDC) that 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 behavior or capability as dendritic cells isolated ex vitro, but they are often used for research, as they are still much more readily available than genuine DCs.
- Mo-DC refers to cells matured from monocytes
- HP-DC refers to cells derived from hematopoietic progenitor cells.
Life cycle
Dendritic cells start out as immature dendritic cells. These cells are characterized by high endocytic activity and low T-cell activation potential. Dendritic cells constantly sample the surroundings 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. Once they have come into contact with such a pathogen, they become activated into mature dendritic cells. Immature dendritic cells phagocytose pathogens and degrade its 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 and CD86, 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 helper T-cell which has never encountered its antigen before. Dendritic cells are the most potent of all the antigen-presenting cells.
As mentioned above, MDC probably form from monocytes, white blood cells which circulate in the body and, depending on the right signal, can turn into either dendritic cells or macrophages. 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 unactivated state for much longer. The monocytes in turn are formed from stem cells in the bone marrow. However, 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, in combination, are unique to DCs.
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 other subsets under certain conditions; since not all dendritic cell subsets expresss 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 mechanisms 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. 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. Allergy is a pathologically overblown reaction to an outside allergen, autoimmune diseases are erroneous immune reactions to self-antigen.
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 strong killer cell-like activity. However, the principal function of dendritic cells as known to date is always to act as the generals or an "central encyclopedia" of the immune response, collecting and storing immunological knowledge, enabling them to instruct the adaptive arms to respond invading pathogens and telling the adaptive immune system what the most effective type of response is.
External links
References
- Jacques Banchereau: The Long Arm of the Immune System, Scientific American Vol. 287, No. 5 (November 2002), pp. 52 - 59 (summary of dendritic cell knowledge)
- A. Dzionek et al.: BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood, J. Immunol. Vol. 165, No. 11 (December 2000), pp. 6037 - 6046 (detailed description of MDC-1, MDC-2, PDC phenotypes)
- Kelli McKenna et al.: Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity, J. Virol. Vol. 79 No. 1 (January 2005), pp. 17–27 (summary of current knowledge about dendritic cells and PDC in particular)
- Zhi-Yong Yang et al.: 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. Vol. 78, No. 11 (June 2004), pp. 5642 – 5650 (dendritic cells in SARS)
- Ralph M. Steinman; Zanvil A. Cohn. Identification of a novel cell type in peripheral lymphoid organs of mice: I. Morphology, quantitation, tissue distribution, J. Exp. Med. Vol. 137 No. 5 (May 1973), pp. 1142-1162 (First publication).
es:Célula dendrítica fr:Cellule dendritique ko:수지상 세포 he:תא דנדריטי ja:樹状細胞 ur:شجری خلیہ vi:Tế bào tua