Dendritic cell

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This article is about the immune cell. For component of the neuron, see dendrite.

Dendritic cell
ion abrasion scanning electron microscopy, a new[when?] technology the NIH has been developing and applying for 3D cellular imaging.
Details
SystemImmune system
Identifiers
Latincellula dendritiformis
MeSHD003713
THH1.00.01.0.00038
FMA83036
Anatomical terminology]

A dendritic cell (DC) is an antigen-presenting cell (also known as an accessory cell) of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and adaptive immune systems.[1]

Dendritic cells are present in tissues that are in contact with the body's external environment, such as the

intestines. They can also be found in an immature and mature state in the blood. Once activated, they migrate to the lymph nodes, 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 (δένδρον or déndron being Greek for 'tree'). While similar in appearance to the dendrites of neurons, these are structures distinct from them. Immature dendritic cells are also called veiled cells, as they possess large cytoplasmic 'veils' rather than dendrites.[citation needed
]

History

Dendritic cells were first described by Paul Langerhans (hence Langerhans cells) in the late nineteenth century. The term dendritic cells was coined in 1973 by Ralph M. Steinman and Zanvil A. Cohn.[2] For discovering the central role of dendritic cells in the adaptive immune response,[3] Steinman was awarded the Albert Lasker Award for Basic Medical Research in 2007[4] and the Nobel Prize in Physiology or Medicine in 2011.[5]

Types

The morphology of dendritic cells results in a very large surface-to-volume ratio. That is, the dendritic cell has a very large surface area compared to the overall cell volume.

In vivo – primate

Main article: Plasmacytoid dendritic cell

The most common division of dendritic cells is conventional dendritic cells (a.k.a. myeloid dendritic cells) vs. plasmacytoid dendritic cell (most likely of lymphoid lineage) as described in the table below:

Name Description Secretion Toll-like receptors [6]
Conventional dendritic cell (cDC)
(previously called myeloid dendritic cell (mDC)) 		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 cytotoxic T cells
  2. the extremely rare mDC-2, which stimulates helper T cells
 Interleukin 12 (IL-12), Interleukin 6 (IL-6), TNF, chemokines
TLR 4
Plasmacytoid dendritic cell (pDC) Look like plasma cells, but have certain characteristics similar to myeloid dendritic cells.[7] Can produce high amounts of interferon-α[8] and were previously called interferon-producing cells.[9]
TLR 9

The markers

BDCA-4 can be used to discriminate among the types.[10]

Follicular dendritic cells
have round nuclei, centrally located nucleoli, bland and dispersed chromatin, and flattening of adjacent nuclear membrane.

Lymphoid and myeloid DCs evolve from lymphoid and myeloid precursors, respectively, and thus are of

hematopoietic origin and do not express MHC class II
, but are so named because they are located in lymphoid follicles and have long "dendritic" processes.

In blood

The blood DCs are typically identified and enumerated in

CD303+ plasmacytoid DCs. This represents the nomenclature proposed by the nomenclature committee of the International Union of Immunological Societies.[11]
Dendritic cells that circulate in blood do not have all the typical features of their counterparts in tissue, i.e. they are less mature and have no dendrites. Still, they can perform complex functions including chemokine-production (in CD1c+ myeloid DCs), cross-presentation (in CD141+ myeloid DCs), and IFNalpha production (in CD303+ plasmacytoid DCs).

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 monocytes.[12]
  • HP-DC refers to cells derived from
    hematopoietic progenitor cells
    .

Development and life cycle

Formation of immature cells and their maturation

Diagram of hematopoiesis from HSC, showing a separate dendritic cell lineage via CDP (Common Dendritic-cell Progenitor).

Dendritic cells are derived from

B-cells by presenting them with antigens derived from the pathogen, alongside non-antigen specific costimulatory signals. Dendritic cells can also induce T-cell tolerance (unresponsiveness). Certain C-type lectin receptors (CLRs) on the surface of dendritic cells, some functioning as PRRs, help instruct dendritic cells as to when it is appropriate to induce immune tolerance rather than lymphocyte activation.[13]

Every helper T-cell is specific to one particular antigen. Only professional

helper T cells.[14] This help from CD4+ T cells additionally activates the matured dendritic cells and licenses (empowers) them to efficiently induce CD8+ memory T cells, which are also able to be expanded a second time.[14][15] For this activation of CD8+, concurrent interaction of all three cell types, namely CD4+ T helper cells, CD8+ T cells and dendritic cells, seems to be required.[15]

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 cell (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 (TNF) further differentiates the iDCs into mature dendritic cells. Monocytes can be induced to differentiate into dendritic cells by a self-peptide Ep1.B derived from apolipoprotein E.[16] These are primarily tolerogenic plasmacytoid dendritic cells.[17]

Life span

In mice, it has been estimated that dendritic cells are replenished from the blood at a rate of 4000 cells per hour, and undergo a limited number of divisions during their residence in the spleen over 10 to 14 days.[18]

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[when?], 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.[citation needed]

Cytokines

The dendritic cells are constantly in communication with other cells in the body. This communication can take the form of direct cell–cell contact based on the interaction of cell-surface proteins. An example of this includes the interaction of the membrane proteins of the B7 family of the dendritic cell with CD28 present on the lymphocyte. However, the cell–cell interaction can also take place at a distance via cytokines.[citation needed]

For example, stimulating dendritic cells in vivo with microbial extracts causes the dendritic cells to rapidly begin producing

type-1 IFNs, which recruit more activated macrophages to allow phagocytosis.[20]

Disease

Blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm is a rare type of

myeloid cancer in which malignant pDCs infiltrate the skin, bone marrow, central nervous system, and other tissues. Typically, the disease presents with skin lesions (e.g. nodules, tumors, papules, bruise-like patches, and/or ulcers) that most often occur on the head, face, and upper torso.[21] This presentation may be accompanied by cPC infiltrations into other tissues to result in swollen lymph nodes, enlarged liver, enlarged spleen, symptoms of central nervous system dysfunction, and similar abnormalities in breasts, eyes, kidneys, lungs, gastrointestinal tract, bone, sinuses, ears, and/or testes.[22] The disease may also present as a pDC leukemia, i.e. increased levels of malignant pDC in blood (i.e. >2% of nucleated cells) and bone marrow and evidence (i.e. cytopenias) of bone marrow failure.[22] Blastic plasmacytoid dendritic cell neoplasm has a high rate of recurrence following initial treatments with various chemotherapy regimens. In consequence, the disease has a poor overall prognosis and newer chemotherapeutic and novel non-chemotherapeutic drug regimens to improve the situation are under study.[23]

Viral infection

HAART.[citation needed
]

Many other viruses, such as the SARS virus, seem to use DC-SIGN to 'hitchhike' to its target cells.[25] 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.

Cancer

Dendritic cells are usually not abundant at tumor sites, but increased densities of populations of dendritic cells have been associated with better clinical outcome, suggesting that these cells can participate in controlling cancer progression.

tumor growth. In experimental models, dendritic cells have also been shown to contribute to the success of cancer immunotherapies, for example with the immune checkpoint blocker anti-PD-1.[29][30]

Autoimmunity

Altered function of dendritic cells is also known to play a major or even key role in allergy and autoimmune diseases like lupus erythematosus and inflammatory bowel diseases (Crohn's disease and ulcerative colitis).[31][32][33]

Other animals

The above applies to humans. In other organisms, the function of dendritic cells can differ slightly. 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.[34] 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.

Dendritic cells have also been found in turtles.[35]

Dendritic cells have been found in rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio) but their role is still not fully understood [36]

Media

  • A dendritic cell
    A dendritic cell
  • 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.
  • A single dendritic cell can be seen here efficiently taking up at least four conidia in its vicinity.

See also

References

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  36. ^ Salinas, I., & Parra, D. (2015). Fish mucosal immunity: Intestine. In Mucosal Health in Aquaculture. Elsevier Inc. https://doi.org/10.1016/B978-0-12-417186-2.00006-6

External links

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