What are immature and mature dendritic cells?
These include immature and mature dendritic cells. In the body, immature dendritic cells (which differentiate from monocytes) can be found in the peripheral tissues. Here, they engulf different types of pathogen/antigens through a process known as nonselective actin-mediated phagocytosis.
Where are dendritic cells found?
Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood.
How do dendritic cells travel through the blood stream?
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.
How do you generate dendritic cells from monocytes?
Alternatively, dendritic cells can be generated from monocytes by culture with the appropriate cytokines (see Basic Protocol 2). In addition, a negative selection approach may be employed to generate cell preparations that have been depleted of dendritic cells (see Basic Protocol 3) to be used for comparison in functional studies.
What stimulates dendritic cell maturation?
Pathogen recognition by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation and the initiation of adaptive immunity. Recent studies have shown that innate lymphocytes--natural killer (NK), natural killer T (NKT), and gammadelta T cells--also trigger DC maturation.
How do immature dendritic cells become mature?
Migration rates of immature and mature DCs Once immature DCs phagocytize foreign molecules and become matured, the phenotypically and functionally mature DCs start to migrate in response to chemokines that are secreted from the lymph nodes, where the mature DCs then interact with naive T cells.
How does a DC mature?
During the development of maturity, DCs go through phenotypic and functional alterations. MHC molecules are moved from endocytic compartments to the surface of the DC during maturation. The uptake of antigens is downregulated, and there is an increase in costimulatory molecules expressed on the cell surface.
Where do dendritic cells mature and circulate?
Once they have come into contact with a presentable antigen, they become activated into mature dendritic cells and begin to migrate to a lymph node.
How are dendritic cells activated?
DCs are activated directly by conserved pathogen molecules and indirectly by inflammatory mediators produced by other cell types that recognise such molecules. In addition, it is likely that DCs are activated by poorly characterised cellular stress molecules and by disturbances in the internal milieu.
Do dendritic cells Phagocytose?
Like macrophages and neutrophils, dendritic cells (DCs) are considered professional phagocytes.
How do dendritic cells linking innate and adaptive immunity?
Dendritic cells (DCs) represent a heterogeneous family of immune cells that link innate and adaptive immunity. The main function of these innate cells is to capture, process, and present antigens to adaptive immune cells and mediate their polarization into effector cells (1).
How do dendritic cells capture and present protein antigens?
Thus, although mature DCs markedly down-regulate their capacity for macropinocytosis, they continue to capture, process, and present antigens internalized via endocytic receptors, suggesting that they may continuously initiate responses to newly encountered antigens during the course of an infection.
Can immature dendritic cells present antigen?
Immature DCs and apoptotic DCs can present antigens, but in the absence of amplification by co-stimulation and cytokine secretion they promote Th2 response, induce anergy or inhibit T cell proliferation that lead to tumour immune evasion.
Do dendritic cells divide?
Initial reports suggested that monocyte-derived dendritic cells (MoDCs) arise from a proliferating precursor and several groups subsequently reported successful retroviral transduction of these cells, again implying that cell division occurs.
How do dendritic cells migrate to lymph nodes?
Dendritic cells (DCs) travel through lymphatic vessels to transport antigens and present them to T cells in lymph nodes. DCs move directionally toward lymphatics by virtue of their CCR7 and a CCL21 chemotactic gradient.
How do dendritic cells activate B cells?
Dendritic cells (DC) are thought to initiate Ab synthesis by activation of T cells, which then provide cytokine and cell-bound “help” to B cells. Here, we provide evidence that DC can capture and retain unprocessed Ag in vitro and in vivo, and can transfer this Ag to naive B cells to initiate a specific Ab response.
What is the function of dendritic cells?
Dendritic cells in a mature age. A common view supposes that dendritic cells (DCs) exist in two basic functional states: immature DCs induce tolerance to self, whereas mature DCs induce immunity to foreign antigens.
What is the difference between a mature and immature DC?
A common view supposes that dendritic cells (DCs) exist in two basic functional states: immature DCs induce tolerance to self, whereas mature DCs induce immunity to foreign antigens. However, the term 'mature' is often used not only functionally to designate immunogenic DCs but also as a phenotypic ….
Where are dendritic cells found?
Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood.
What is the function of dendritic cells?
Their 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 the adaptive immune systems .
What are the three types of DCs in blood?
Three types of DCs have been defined in human blood: the CD1c+ myeloid DCs, the CD141 + myeloid DCs and the CD303 + plasmacytoid DCs. This represents the nomenclature proposed by the nomenclature committee of the International Union of Immunological Societies. 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).
What differentiates iDCs into dendritic cells?
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. These are primarily tolerogenic plasmacytoid dendritic cells.
What is the ultimate consequence of dendritic cell priming and activation?
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.
How far does a dendritic cell drag a conidium?
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.
How does HIV bind to dendritic cells?
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 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). 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. This infection of dendritic cells by HIV explains one mechanism by which the virus could persist after prolonged HAART.
What are dendritic cells? What are their functions?
Dendritic cells (DCs), named for their probing, ‘tree-like’ or dendritic shapes, are responsible for the initiation of adaptive immune responses and hence function as the ‘sentinels’ of the immune system. Paul Langerhans first described DCs in human skin in 1868 but thought they were cutaneous nerve cells. DCs are bone marrow ( BM) -derived leukocytes and are the most potent type of antigen-presenting cells. They can also be propagated in vitro from BM and blood using various combinations of growth factors, such as granulocyte macrophage-colony stimulating factor ( GM-CSF) and Flt3 ligand. DCs are specialised to capture and process antigens, converting proteins to peptides that are presented on major histocompatibility complex (MHC) molecules recognised by T cells. DCs are heterogeneous, e.g. myeloid and plasmacytoid DCs; although all DCs are capable of antigen uptake, processing and presentation to naive T cells, the DC subtypes have distinct markers and differ in location, migratory pathways, detailed immunological function and dependence on infections or inflammatory stimuli for their generation. During the development of an adaptive immune response, the phenotype and function of DCs play an extremely important role in initiating tolerance, memory, and polarised T-helper 1 (Th1), Th2 and Th17 differentiation.
How many T cells are stimulated by DC?
T cells, natural killer cells, neutrophils, epithelial cells etc. For instance, experimentally, only one mature DC ( mDC) is required to stimulate 100–3000 T cells.
Where do DC precursors migrate?
DC precursors migrate from the BM through the blood stream to almost every non-lymphoid tissue, where they reside in an immature state ( iDC ), continuously sampling their environment by endocytosis , macropinocytosis, and phagocytosis.
Where are dendritic cells found?
Dendritic cells (DCs) (see footnote) can be found in three types of location within the body. They are present as ‘immature’ cells in peripheral tissues, especially tissues that are exposed to the external environment, including the skin, lungs and intestine. They are also present in lymphoid tissues, including the lymph nodes and spleen.
What is the role of mature DCs in the immune system?
These mature DCs play a central role in the initiation of T and B cell immune responses, and are therefore extremely important for defence against pathogens, and for the generation of immunological memory.
What is migration of DCs?
Migration of DCs in inflammation. When the immune system is activated, by an infection or other inflammatory stimulus, the functions of DCs change. Additional DCs are driven to migrate from the blood and tissues, and the DCs undergo a process of ‘maturation’.
Where do DCs migrate?
Migration of DCs in the steady state. In the absence of inflammation many DCs migrate via the blood, as precursors, directly to the spleen and lymph nodes. The DC precursors can also migrate to peripheral tissues, where they may reside for many days, before travelling via the lymph to the local lymph nodes ( Figure 1 ).
Do DCs migrate out of the lymph nodes?
In the lymphoid tissues DCs may exist in either the immature state, or as mature cells. Unlike T- or B cells , very few DCs migrate out of lymph nodes or the spleen; the vast majority of DCs die in the lymphoid tissues within a few days of their arrival.
Where do dendritic cells migrate?
As APCs, mature dendritic cells migrate to the lymph nodes and present their captured antigens to T lymphocytes there. Dendritic cells have an important function in the innate immune system where they carry out surveillance duties, looking for antigens in the form of endogenous toxins and exogenous foreign substances.
What are dendritic cells?
Dendritic cells are formed from precursor cells in the bone marrow and lymph tissue and are one of three types of antigen-presenting cells.
What is the role of dendritic cells in the immune system?
They are bone marrow and lymph -derived leukocytes or white blood cells. Dendritic cells play a primary role in immune responses. The ease with which they can be grown in laboratories together with their strong antigen-killing features makes them a promising anti-cancer agent.
How do cytokines affect cell growth?
Cytokines stimulate or inhibit cell growth, cell death, inflammation, cell differentiation, and cell migration. They affect their own cell as autocrine messengers, neighboring cells as paracrine messengers, and travel through the bloodstream to affect more distant targets.
Where do plasmacytoid cells originate?
Plasmacytoid Dendritic Cells. Plasmacytoid dendritic cells originate in the lymphoid organs (lymph nodes, thymus, spleen, and tonsils) and the bone marrow. Lymph vessels and nodes (green) follow the same routes as our blood vessels (blue and red). Lymph – circulatory system of immunity.
Where are epidermal dendritic cells found?
Epidermal Dendritic Cells. Epidermal or dermal dendritic cells are found in different forms on and within the skin. All epidermal dendritic cells activate T-cells on or in the epidermis and dermis. One example is the Langerhans cell (LC).
Which cells scavenge and destroy harmful or foreign particles and release chemicals that attract more white blood cells?
Macrophages and neutrophils scavenge and destroy harmful or foreign particles and release chemicals that attract more white blood cells. Dendritic cells perform phagocytosis and preserve information from ingested particles that can kick-start adaptive (acquired) immune responses. Cytokines are signaling molecules.
Why are mature dendritic cells adapted to move from one site to another?
Because of these differences, mature dendritic cells, using extensions on their surface, are well adapted for movement from one site to another. This characteristic allows them to migrate and activate naive T cells. Immature cells are well suited for phagocytosis, a process that allows them to process antigen material.
Where are dendritic cells found?
Derived from precursors in the bone marrow, dendritic cells (DC) are professional antigen-presenting cells typically found in the mucosa, skin, and lymphoid tissues. As antigen-presenting cells, these cells are primarily involved in processing antigen before presenting them to T cells in order to activate immune response.
What differentiates to produce plasmacytoid dendritic cells?
In turn, the MDP-like progenitor (or CDP-like progenitors) differentiates to produce the plasmacytoid dendritic cell and pre-dendritic cells that ultimately give rise to plasmacytoid dendritic cells and classical dendritic cells respectively.
What do macrophage-dendritic cells produce?
These cells, also known as macrophage-dendritic cell precursors divide to produce the common monocyte progenitors as well as common dendritic cell progenitors (cDPs) with the common dendritic progenitors ultimately giving rise to pre-dendritic cells and plasmacytoid dendritic cells. In turn, these cells migrate to the lymphoid (as well as ...
Why are dendritic cells unable to activate naive T cells?
Apart from difference in morphology, there are also differences in the types of molecules produced. Because immature dendritic cells produce low levels of co-stimulatory molecules (e.g. CD83) as well as limited amounts of immunostimulatory cytokines, they are unable directly activate naive T cells.
What is the role of dendritic cells in autoimmune disease?
While dendritic cells play a central role in the activation of naive T cells and associated immunological responses, they also promote immune tolerance towards self-antigens thus preventing the occurrence of autoimmune disease.
Where do plasmacytoid dendritic cells come from?
Like classical/conventional dendritic cells, plasmacytoid dendritic cells originate from hematopoietic stem cells located in the bone marrow and makeup about 0.05 percent of the total peripheral blood mononuclear cells.
Contents
Introduction
Antigen Uptake
- DCs are derived from hematopoietic stem cells in the bone marrow and are widely distributed as immature cells within all tissues, particularly those that interface with the environment (e.g. skin, mucosal surfaces) and in lymphoid organs. Immature DCs are recruited to sites of inflammation in peripheral tissues following pathogen invasion. Internalization of foreign antigens can subseq…
Antigen Presentation
- DCs are capable of processing both exogenous and endogenous antigens and present peptide in the context of either MHC class I or II molecules (see Figure 1, panel A and B). As DCs mature, they acquire the properties necessary to form and transport peptide-loaded MHC class II complexes to the cell surface.4 Antigen transport to the cell surface coincides with increased ex…
Migration to Lymphoid Organs
- Following antigen exposure and activation, DCs migrate into T cell areas of lymphoid organs, a process regulated by chemokine/chemokine receptor interaction and aided by a variety of proteases and corresponding receptors [e.g. urokinase plasminogen activator (uPA)/uPAR system51]. Mature DCs lose responsiveness to MIP-3 alpha/CCL20, RANTES/CCL5 and ...
Interaction with T Cells
- Cell surface receptors not only facilitate antigen uptake, but also mediate physical contact between DCs and T cells (see Table 1). DC-specific intercellular adhesion molecule (ICAM)-3 grabbing non-integrin (DC-SIGN), a calcium-dependent, type II C-type lectin, is a DC-specific ligand for ICAM-3 expressed on naïve T cells. DC-SIGN can promote a transient clustering between a D…
Summary
- DCs are unique APCs as they can both initiate and modulate immune responses. Even small numbers of DCs and low levels of antigen can elicit strong immune responses. Maturation stage, antigen concentration and route of entry, as well as the cytokine microenvironment all influence DC effector functions. Further studies are necessary to fully elucidate the role DC maturation pla…
References
- Banchereau, J. & R.M. Steinman (1998) Nature 392:245.
- Steinman, R.M. (1991) Annu. Rev. Immunol. 9:271.
- Thery, C. & S. Amigorena (2001) Curr. Opin. Immunol. 13:45.
- Cella, M. et al. (1997) Curr. Opin. Immunol. 9:10.
Overview
Dendritic cells (DCs) are antigen-presenting cells (also known as accessory cells) of the mammalian immune system. Their 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 the adaptive immune systems.
Dendritic cells are present in those tissues that are in contact with the externa…
Development and life cycle
Dendritic cells are derived from hematopoietic bone marrow progenitor cells (HSC). 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. This is done through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs). TLRs recogniz…
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. For discovering the central role of dendritic cells in the adaptive immune response, Steinman was awarded the Albert Lasker Award for Basic Medical Research in 2007 and the Nobel Prize in Physiology or Medicine in 2011.
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.
The most common division of dendritic cells is conventional dendritic cells (a.k.a. myeloid dendritic cells) vs. plasmacytoid dendritic cell (most likely of lym…
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.
Disease
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. This presentation may be accompanied by cPC infiltrations into other tissues to result in swollen lymph nodes, enlarged liv…
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 be…
Media
• 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.