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Dendritic cells

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Dendritic cells (DCs) are antigen-presenting cells of the mammalian immune system. 

 

Dendritic cells can also be found in an immature state in the blood. 

Dendritic cells (DCs) are a heterogeneous leukocyte (white blood cell) population in healthy peripheral tissues are in an immature state.

The cells are capable of sensing microbes as well as antigen capture and processing capabilities.

Activated dendritic cells migrate to the lymph nodes where they interact with T cells and B cells to initiate the adaptive immune response. 

 

With subsequent developmental stages they grow branched projections.

DCs main function is to process antigen material and present it on the cell surface to the T cells of the immune system. 

 

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

 

Antigen-presenting cells (APCs: macrophages, B lymphocytes, and dendritic cells) are able to activate a resting helper T-cell when the matching antigen is presented. 

 

 

Dendritic cells can activate both memory and naive T cells, and are the most potent of all the antigen-presenting cells (APCs).

Dendritic cells (DCs) are classified into two populations—myeloid DCs (mDCs) and plasmacytoid DCs (pDCs)—according to their morphology, cell surface markers and their functions. 

In the lymph node and secondary lymphoid organs, all three APCs can activate naive T cells. 

Mature dendritic cells are able to activate antigen-specific naive CD8+ T cells.

 

The formation of CD8+ memory T cells requires the interaction of dendritic cells with CD4+ helper T cells.

 

CD4+ T cells additionally activates the matured dendritic cells and empowers them to efficiently induce CD8+ memory T cells.

 

For 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.

 

 

The dendritic cells communicate  with other cells in the body, by direct cell–cell contact based on the interaction of cell-surface proteins: interaction of the membrane proteins of the B7 family of the dendritic cell with CD28 present on the lymphocyte. 

 

In non-lymphoid organs, macrophages and B cells can only activate memory T cells

 

Dendritic cells have a very large surface-to-volume ratio, a very large surface area compared to the overall cell volume.

Dendritic cells are divided into myeloid versus plasmacytoid cells.

 

DCs act as messengers between the innate and the adaptive immune systems.

 

Dendritic cells are present in tissues that in contact with the external environment: such as the skin, the inner lining of the nose, lungs, stomach and intestines. 

 

The skin has specialized dendritic cell type called the Langerhans cell.

 

Conventional dendritic cells are similar to monocytes. 

 

Myeloid dendritic cells (mDCs) made up of at least two subsets:

the more common mDC-1, which is a major stimulator of T cells

the extremely rare mDC-2, which may have a function in fighting wound infection.

 

 

mDC probably arise from monocytes, and 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).  Co

 

Plasmacytoid dendritic cells look  like plasma cells, but have certain characteristics similar to myeloid dendritic cells.

 

Plasmacytoid dentritic cells have the ability to produce huge amounts of type-1 IFNs, which recruit more activated macrophages to allow phagocytosis.

 

Blastic plasmacytoid dendritic cell neoplasm is a rare type of myeloid cancer in which malignant plasmacytoid dentritic cells infiltrate the skin, bone marrow, central nervous system, and other tissues. 

 

DCs can produce high amounts of interferon.

 

Lymphoid and myeloid DCs evolve from lymphoid and myeloid precursors,and thus are of hematopoietic origin. 

 

The blood DCs are typically identified by flow cytometry. 

 

Three types of DCs have been defined in blood: the CD1c+ myeloid DCs, the CD141+ myeloid DCs and the CD303+ plasmacytoid DCs. 

 

Circulating dendritic cells do not have all the typical features of their counterparts in tissue: less mature and have no dendrites. 

 

Dendritic cells are derived from hematopoietic bone marrow progenitor cells, as immature dendritic cells. 

 

Activated T cells that bear the correct receptor for antigens they have internalized.

Heterogeneous group of non-lymphoid, nonphagocytic immune accessory cells present in lymphoid and non-lymphoid organs.

25% of skin is covered with dentritic cells, a antigen presenting cell that can recognize foreign microbes and initiate an immune response.

Integrate incoming signals and helps arrange immune responses.

Cell–cell interaction can also take place at a distance by cytokines: causing  the dendritic cells to produce  IL-12 that helps send naive CD4 T cells towards a Th1 phenotype. 

 

The antigens present on the dendritic surface result in the activation of the immune system against those antigens.

 

Different cytokines are produced by  the type of dendritic cell. 

Bidirectional interaction between dendritic cells and antigen-experienced T cells initiate immunogenic or a tolerogenic pathway and involve autoimmune disease and transplantation medicine.

The most potent antigen presenting cells.

Key antigen-presenting cells and initiators of the immune response.

Ability of cells to initiate immune responses or induce tolerance depends on their maturation state or subsets.

Immature cells deficient of costimulatory molecules can induce T

cell anergy, generate T (Treg) cells and promote alloantigen tolerance.

Dendritic cells can also induce T-cell tolerance or unresponsiveness

 

Certain C-type lectin receptors (CLRs) on the surface of dendritic cells,

 

help instruct dendritic cells as to when it is appropriate to induce immune tolerance rather than lymphocyte activation.

Immature dendritic cells have high endocytic activity and low T-cell activation potential. 

 

Immature dendritic cells assay the surrounding environment for pathogens such as viruses and bacteria. 

 

Immature dendritic cells have pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) that recognize specific chemical signatures found on subsets of pathogens. 

 

Immature dendritic cells come into contact with a presentable antigen, they then become activated into mature dendritic cells and begin to migrate to a 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. 

 

With maturation 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. 

 

 

Mature dendritic cells 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. 

 

 

In the spleen or lymph nodes mature dendritic cells 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. 

Several types have been found the have negative regulatory functions.

GM-CSF promotes growth and maturation of dendritic cells.

Are attracted to tumor environments.

Professional antigen-presenting cells of myeloid origin and are essential for primary T cell response via crosspriming allowing transfer of antigens from neoplastic cells and their presentation through major histocompatibility complex class II molecules (Banchereau J et al).

Function depends upon their ontogenetic origin, stage of maturation and are influenced by tumor cell signals, stromal tissue, and T cells.

As dendritic cells mature they change their mobility, present MHC molecules on the cell surface, increase expression of CD80 and CD86 and interact with lymphocytes.

Defects in immunological functions of dendritic function in myeloma, with lack of CD80 and CD86 molecules, defective antigen presentation, and accumulation of immature and inactivated dendritic cells.

Chronic activation of plasmacytoid dendritic cells by circulating immune complexes triggers autoimmunity in SLE.

Immune complexes cause plasmacytoid dendritic cells to secrete type I interferons.

A single plasmacytoid dendritic can synthesize about 1 billion interferon-alpha molecules in a 12 hour., 200-to 1000 times as many is the other cell types (Obermoser G, Pascual V).

Four types of DCs exist in lymph nodes: Follicular, interdigitating, Langerhans and fibroblastic cells.

Dendritic tumors are rare, representing less than 1% of all lymph node tumors.

Dendritic tumors of lymph nodes were previously classified as lymphomas, sarcomas, or histiocytic neoplasms.

HIV, can bind to dendritic cells via various receptors expressed on the cell, and when the dendritic cell takes up HIV and then travels to the lymph node, the virus can be transferred to helper CD4+ T-cells, contributing to the developing infection. 

 

 

The infection of dendritic cells by HIV is one mechanism by which the virus could persist after prolonged HAART.

 

Many other viruses, such as the SARS virus, seem to use dentritic cell binding to gain access to its target cells.

 

Increased densities of dendritic cells have been associated with better clinical outcome in cancers, suggesting that these cells can participate in controlling cancer progression.

 

Some dendritic cell subsets can activate CD4+ helper T cells and CD8+ cytotoxic T cells, which are immune cells that can also suppress tumor growth. 

 

Dendritic cells contribute to the success of cancer immunotherapies: immune checkpoint blocker anti-PD-1.

Dendritic cells play a major role in allergy and autoimmune diseases like lupus erythematosus and inflammatory bowel diseases.

The  principal function of dendritic cells as known to date is always to act as an immune sentinel, surveying the body and collecting  information relevant to the immune system.

Dendritic cells  to instruct and direct the adaptive arms to respond to challenges.

 

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