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Home HITV Cancer Therapy What is Cancer Immunotherapy Migration and Maturation of Dendritic Cells

Tuesday22 August 2017

Migration and Maturation of Dendritic Cells

Migration of Dendritic Cells

Migration of Dendritic Cells
[ Image source from Krauthammer Lab, Yale University ]

Before dendritic cells can perform their major function—to initiate the immune response—two events typically need to take place, migration and maturation. Most dendritic cells circulate in the body in an "immature" state and lack many features that lead to a strong T-cell response. Immature dendritic cells are, nonetheless, ideally poised and well equipped to capture microbes and other sources of antigens.

Dendritic cells are present in small quantities in tissues that are in contact with the external environment, mainly the skin (where there is a specialized dendritic cell type called Langerhans cells) and the inner lining of the nose, lungs, stomach and intestines. There, dendritic cells are involved with two of the body's most powerful immune responses, organ transplantation and contact allergy.

Dendritic cells are also located in distinct incoming channels, called lymphatic vessels, which allow cells to move from peripheral tissues to lymphoid organs. There they can encounter immune lymphocytes, selecting those cells that specifically recognize the antigens being carried by the dendritic cells. At this point the immune response begins. The lymphocytes begin to grow vigorously and they start to produce products that will serve to eliminate infections and other sources of antigens.

Maturation of Dendritic Cells

Maturation of Tcell
[ Image source from the National Cancer Institute, US ]
Killer Tcell Immunity
[ Image source from the National Cancer Institute, US ]

The captured infections and other forms of antigens also carry signals that induce the further development or maturation of dendritic cells. This process begins as dendritic cells take up infections by phagocytosis, forming large vesicles to sample these foreign substances, and then converting them into MHC-peptide complexes, or fragmented proteins. These fragments are sent to their cell surface where they can be recognized by receptors on T cells.

Immature dendritic cells have several features that allow them to increase their capacity to convert antigens into MHC-peptide complexes. One feature involves surface receptors, like DEC-205, that increase antigen uptake. Following uptake, the antigens are processed, including a pathway called "cross-presentation" in which dendritic cells take up dead cells from tumors, transplants, and tissues under microbial or autoimmune attack and efficiently extract peptides from them.

Another feature is that maturing dendritic cells proceed to make other products that are used to stimulate lymphocytes and guide the development of the immune response. The type of immune response that the dendritic cell orchestrates depends upon the type of maturation stimulus that the infection provides and upon other factors in the immune microenvironment. Maturation is therefore a pivotal process for initiating immunity.

HITV Lab

HITV Lab is involved in cell-based biotechnology medical applications with special focus on Dendritic Cell-Based Immunotherapy for cancer. HITV Lab is committed to support an international collaboration in the FDA clinical trial of HITV Therapy in late-stage cancer patients led by the University of Maryland, USA.

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