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A dendritic cell
A dendritic cell

Dendritic cells (DCs) are immune cells and form part of the mammalian immune system. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor 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. See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed

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. The skin is the outer covering of living tissue of an animal (or plant Not to be confused with the Beta cells making up the Islets of Langerhans. Anatomically a nose is a protuberance in Vertebrates that houses the Nostrils or nares which admit and expel air for respiration in conjunction with the lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists They can also be found in an immature state in the blood. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products 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. Dendrites (from Greek δένδρον déndron, “tree” are the branched projections of a Neuron that act to conduct the electrochemical However, these do not have any special relation with neurons, which also possess similar appendages. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Immature dendritic cells are also called veiled cells, in which case they possess large cytoplasmic 'veils' rather than dendrites.

Contents

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. Ralph Marvin Steinman, MD is an Immunologist and Cell biologist at Rockefeller University, who coined the term Dendritic cells together with Cohn. [1]. In 2007 Steinman was awarded the Albert Lasker Award for Basic Medical Research for his discovery. The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for the understanding diagnosis prevention treatment

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. The term myeloid suggests an origin in the Bone marrow or Spinal cord, or a resemblance to the marrow or spinal cord "plasmacytoid" (or "lymphoid"):

Name Description Secretion Toll-like receptors[2]
Myeloid dendritic cells (mDC) are most similar to monocytes. Plasma cells (also called plasma B cells or plasmocytes) are cells of the Immune system that secrete large amounts of antibodies. The lymphatic system in Vertebrates is a network of conduits that carry a clear fluid called Lymph. Toll-like receptors ( TLRs) are a class of single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from Microbes Monocyte is a type of Leukocyte, part of the Human body 's Immune system. 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. For Il-12 see also Ilyushin Il-12 Interleukin 12 ( IL-12) is an Interleukin that is naturally produced by Dendritic TLR-2 is a Biomolecule, which plays a role in the human Immune system. Toll-like receptor 4, also known as TLR4, is a human Gene. TLR 4 is a Toll-like receptor. Plasma cells (also called plasma B cells or plasmocytes) are cells of the Immune system that secrete large amounts of antibodies. [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. Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents [4] TLR 7, TLR 9

The markers BDCA-2, BDCA-3, and BDCA-4 can be used to discriminate among the types. Toll-like receptor 7, also known as TLR7, is an immune Gene possessed by humans and other mammals and additionally in avian species TLR 9 is a Toll-like receptor. It recognizes unmethylated CpG sites on DNA molecules CLEC4C is a Dendritic cell marker Thrombomodulin, CD 141 or BDCA-3 is an Integral membrane protein expressed on the surface of endothelial cells Neuropilin is a Protein receptor active in Neurons. Overview There are two forms of Neuropilins NRP-1 and NRP-2 [5]

Lymphoid and myeloid DCs evolve from lymphoid or myeloid precursors respectively and thus are of haematopoietic origin. Haematopoiesis (from Ancient Greek haima blood poiesis to make (or hematopoiesis in the United States sometimes also haemopoiesis or By contrast, follicular dendritic cells (FDC) are probably not of hematopoietic origin, but simply look similar to true dendritic cells. Follicular dendritic cells (FDC are cells of the Immune system found in Lymph follicles They are probably not of Hematopoietic origin but simply look Haematopoiesis (from Ancient Greek haima blood poiesis to make (or hematopoiesis in the United States sometimes also haemopoiesis or

In vitro

In some respects, dendritic cells cultured in vitro do not show the same behaviour or capability as dendritic cells isolated ex vivo. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism Nonetheless, they are often used for research as they are still much more readily available than genuine DCs.

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. The Rhesus Macaque ( Macaca mulatta) often called the Rhesus Monkey, is one of the best known species of Old World monkeys Adult males measure A mouse (plural mice) is a small Animal that belongs to one

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. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have This is done through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs). Pattern recognition receptors, or PRR s are Proteins expressed by cells of the Immune system to identify molecules associated with microbial Pathogens Toll-like receptors ( TLRs) are a class of single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from Microbes 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. A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. 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. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region Simultaneously, they upregulate cell-surface receptors that act as co-receptors in T-cell activation such as CD80, CD86, and CD40 greatly enhancing their ability to activate T-cells. The protein CD80 ( C luster of D ifferentiation The protein CD86 ( C luster of D ifferentiation 86) is a molecule expressed on antigen-presenting cells that provide costimulatory signals necessary for CD40 is a costimulatory protein found on Antigen presenting cells and is required for their activation 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. Chemokine receptors are Cytokine receptors found on the surface of certain cells which interact with a type of Cytokine called a Chemokine. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red The lymphatic system in Vertebrates is a network of conduits that carry a clear fluid called Lymph. A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. 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. See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or A cytotoxic T cell (also known as TC, CTL T-Killer cell cytolytic T cell CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes B cells are Lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by

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. See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed 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. Memory T cells are a specific type of Infection -fighting T cell (also known as a T lymphocyte) that can recognize foreign invaders such as Bacteria A naive T cell or Th0 cell is a T cell that has differentiated in Bone marrow, and successfully undergone the positive and negative processes of central

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. Monocyte is a type of Leukocyte, part of the Human body 's Immune system. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that The monocytes in turn are formed from stem cells in the bone marrow. Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of 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. CD40 is a costimulatory protein found on Antigen presenting cells and is required for their activation CD154, also called CD40 ligand or CD40L is a protein that is primarily expressed on activated T cells and is a member of the TNF family of molecules A lymphocyte is a type of White blood cell in the Vertebrate Immune system. However, the cell-cell interaction can also take place at a distance via cytokines. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular

For example, stimulating dendritic cells in vivo with microbial extracts causes the dendritic cells to rapidly begin producing IL-12. For Il-12 see also Ilyushin Il-12 Interleukin 12 ( IL-12) is an Interleukin that is naturally produced by Dendritic [7] IL-12 is a signal that helps send naive CD4 T cells towards a Th1 phenotype. For Il-12 see also Ilyushin Il-12 Interleukin 12 ( IL-12) is an Interleukin that is naturally produced by Dendritic CD4 ( Cluster of differentiation 4 is a Glycoprotein expressed on the surface of T helper cells, Regulatory T cells, Monocytes, T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or 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. Human type I Interferons comprise a vast and growing group of IFN proteins [8]

Relationship to HIV, allergy, and autoimmune diseases

HIV, which causes AIDS, can bind to dendritic cells via various receptors expressed on the cell. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome 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). DC-SIGN or CD 209 is a C-type Lectin receptor present on both Macrophages and Dendritic cells. 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. Allergy is a disorder of the Immune system often also referred to as Atopy. Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming

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 lifespan. 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

See also

External links

References

  1. ^ Steinman RM, Cohn ZA (1973). The following is a list of human clusters of differentiation (or CD) molecules The protein CD80 ( C luster of D ifferentiation The protein CD86 ( C luster of D ifferentiation 86) is a molecule expressed on antigen-presenting cells that provide costimulatory signals necessary for Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books "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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 4573839.  
  2. ^ Sallusto F, Lanzavecchia A (2002). "The instructive role of dendritic cells on T-cell responses". Arthritis Res. 4 Suppl 3: S127-32. PMID 12110131.  
  3. ^ McKenna K, Beignon A, Bhardwaj N (2005). "Plasmacytoid dendritic cells: linking innate and adaptive immunity". J. Virol. 79 (1): 17-27. The Journal of Virology is an academic journal that covers research concerning Viruses using cross-disciplinary approaches including Biochemistry, PMID 15596797.  
  4. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15771572.  
  5. ^ 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.  
  6. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16959355.  
  7. ^ 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.  
  8. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  9. ^ 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. The Journal of Virology is an academic journal that covers research concerning Viruses using cross-disciplinary approaches including Biochemistry, PMID 15140961.  
  10. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  

Dictionary

dendritic cell

-noun

  1. (biology) Any cell, having branching processes, that forms part of the mammalian immune system
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