Dendritic cell

From Academic Kids

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. They have long spiky arms, called dendrites, hence the name. (Neurons also have dendrites, but dendritic cells have nothing to do with neurons. 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'.

Unfortunately, there are at least two different types of cells involved with immunity that are called dendritic cells. Most of the time, dendritic cell refers to myeloid dendritic cells (MDC) that arise from monocytes. Then there are plasmacytoid dendritic cells (PDC) which appear to be another kind of myeloid cell that 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. (There are also follicular dendritic cells that are probably not of hematopoietic origin, but simply look similar to 'true' dendritic cells.) Additionally, MDC at least are made up of at least two subsets, the more common MDC-1 and the extremely rare MDC-2, which may have a function in fighting wound infection. Mo-DC refers to cells matured in vitro from monocytes, HP-DC to cells derived from hematopoietic progenitor cells. In some respects, they 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.

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 viruses and bacteria. 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, 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.

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.

HIV, which causes AIDS, is attracted by one particular kind of dendritic cell, namely those that express the cell surface antigen DC-SIGN (usually MDC subset 1, but other subsets under certain conditions); when these get infected and then travel to lymph nodes, 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 targetted by a therapy. This infection of dendritic cells by HIV explains why the virus will persist even when the supply of helper T-cells is exhausted, e.g. after prolonged HAART. Also, the SARS virus seems to use DC-SIGN to 'hitchhike' to its target cells.

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.

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 'library' or 'encyclopedia' of the immune system.

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)de:Dendritische Zelle

ja:樹状細胞

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