DC Maturation Process
Figure 1: The above diagram shows the process of maturation of DCs
DC progenitors that carry sensing pathogens travel from bone marrow to lymphoid and non lymphoid tissues. The ‘maturation/danger’ signal together with components of pathogens, cytokines and other molecules from the inflamed or damaged tissues are being released. Upon getting the signal, the immature DCs transform to mature DCs. In order to respond productively with T-cells, the mature DCs have higher peptide-loaded MHC class II, CD80 and CD86.
Dendritic Cells (DCs), are strong antigen presenting cells (APCs). Due to their natural properties, they are able to set off primary immune responses and tolerogenic functions. Therefore, DCs have been developed for immunotherapies for cancer, chronic infections, autoimmune disease and induction of transplant tolerance.
Process of Maturation of DCs
The purpose of maturation of DCs is to stimulate naïve T-Cell. The immature DCs, like the skin Langherhans cells, have the receptors to absorb antigen for uptake and processing. However, the mature DCs, which are located in the secondary lymphoid tissues, like lymph nodes and spleen have the ability to produce antigen and stimulate T-Cell. However, they have lower abilities to absorb antigen.
The maturation of DCs reflects the changing roles of functional cells. The process starts when 'maturation/danger' signal is being triggered. From bone marrow, DC progenitors that carry sensing pathogens, may flow to all lymphoid and non lymphoid tissues, like skin and lung, due to cytokine gradient in the inflamed area. The 'maturation/danger' signal integrates with the components of pathogens, cytokines and other molecules from the inflamed or damaged tissues.
In the process of receiving the signal, the immature DCs respond to certain chemokines. Hence, the maturing DCs switch the patterns of chemokine receptor and adhesion molecule expression in order to travel to secondary lymphoid organs as maturation process.
In order to respond to T-cells, the mature DCs may increase the cell surface expression of peptide-loaded MHC class II and co-stimulatory molecules like CD80 and CD86, which are co-stimulated by CD28 route. In contrast, T-cells respond to DCs and produce cytokines like IL-12 through CD40-CD40L interaction. Therefore, through proper maturation process, DCs are able to stimulate and induce immune response to T-cells.
DCs Multipurpose function in Immunity
DCs have been in the limelight as strong forerunners in immunity. They also play an essential role as regulatories to secrete cytokines which can develop Th1 or Th2 effector cells that respond to immune system and also provide link in between innate and adaptive community. DCs also respond to 'danger' signal and act as inducers to T-cells response. By activating macrophages, natural killer (NK) cells, NK-T cells and eosinophils, DCs can respond to attack infectious agents. The major source of Interferon (IFN) -a and -b, such as plasmacytoid DCs (P-DCs), also being found to respond to certain viruses.
Different State of Dendritic Cells
The differences in origin, morphology, localization, maturation state, phenotype and functions, also show differences in the types of DCs and DC precursors. For example, like human and mouse models are two different species in terms of cell surface phenotype, which also have two types of DCs, being found to have different lineages: plasmacytoid (P-DCs) and myeloid DCs (M-DCs). The functional differences in P-DCs and M-DCs are the appearance in Toll-like receptors, the usage of chemokine receptors and the pattern of cytokine secretion. Therefore, different lineages or DCs subset may also contribute to regulate the results in T-cells.
In short, there are numerous factors like different lineages and maturation stages of DCs, can influence T-Cells responses. Therefore, more research activities and enhancement of knowledge in physiological and pathological of DC biology are necessarily required. Figure 1 above shows the process of maturation of DCs.
DC progenitors that carry sensing pathogens travel from bone marrow to lymphoid and non lymphoid tissues. The 'maturation/danger' signal together with components of pathogens, cytokines and other molecules from the inflamed or damaged tissues are being released. Upon getting the signal, the immature DCs transform to mature DCs. In order to respond productively with T-cells, the mature DCs have higher peptide-loaded MHC class II, CD80 and CD86.
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