Dendritic cells are antigen-representing immune cells capable of T-cell activation. Thus, they trigger a specific immune response. Because of their sentinel position in the immune system, they have historically been implicated as therapeutic agents for diseases such as cancer and multiple sclerosis.
What is the dendritic cell?
Dendritic cells are part of the immune system. Along with monocytes, B lymphocytes, and macrophages, they are among the antigen-presenting cells in the immune system. The group includes several immune cell types, between which there is distant relationship. On the basis of shape and surface features, two main forms are differentiated: myeloid and plasmacytoid dendritic cells. Sometimes the cell group is also subdivided into follicular dendritic reticulum cells, interdigitating dendritic reticulum cells and so-called Langerhans cells. That they are included in a common group is due to their common tasks, which include in particular the activation of T cells. Dendritic cells develop from monocytes or precursor stages of B and T cells. Each dendritic cell recognizes and represents specific antigens. Because of their ability to activate T cells, dendrites are the only immune cells that can elicit a primary immune response. This distinguishes them from other antigen representatives, which are only capable of uptake, replication, and representation. Colloquially, dendritic cells are known as the sentinels of the immune system.
Anatomy and structure
Immature dendrites in peripheral tissues are star-shaped. They are equipped with cytoplasmic extensions more than ten µm long that can serve to radiate in all directions. Living dendritic cells keep their dendrites permanently in motion and thus trap pathogens and antigens. Immature dendritic cells also contain endocytotic vesicles of stainable and lysosomal proteins. In this phenotypic form, the cells have few MHC proteins and no B7 molecules at all. During their migration to the lymphoid sink organs, the dendritic cells change their anatomy. The dendrites of the cells become membrane protrusions and the cells are no longer capable of phagocytosis or antigen processing. Mature dendritic cells express MHC class II complexes loaded with peptides. They additionally take up co-stimulatory B7 molecules. The cells interact with T cell receptors via the peptide MHC elements. Through the co-stimulatory B7 molecules, they bind CD28 antigens on naive T cells.
Function and Tasks
Dendritic cells are present in nearly all peripheral tissues of the human body. As part of the defense against pathogens, dendritic cells perform a sentinel function. They permanently control their environment. They take up extracellular components by phagocytosis. Phagocytosing cells flow around the foreign bodies and guide the individual particles of the foreign bodies through the invaginations and constrictions of their cell membrane into the cell. This forms large vesicles, also known as phagosomes, which confluence with lysosomes to form phagolysosomes. In these phagolysosomes, the absorbed particles of the foreign bodies are enzymatically degraded. Thus, with phagocytosis, the dendritic cells process foreign bodies and subsequently represent them in the form of peptides on in their MHC complex on the surface. Once they have come into contact with a foreign body, the dendritic cells migrate out of the affected tissue and embark on a journey to the nearest lymph node. In the lymph nodes, they encounter 100 to 3000 T cells with which they interact. By coming into direct contact with a T cell, the dendritic cells in the lymph nodes trigger a specific immune response that is precisely tailored to the antigen they present. Thus, as immune mediators, dendritic cells have two main functions: as immature cells, they take up antigens and process them. In the process, they become mature cells and, after migrating to lymphoid tissue, stimulate T and B cells. Thus, they have a controlling function in the cellular immune response. They also contribute to the protection against autoimmune reactions, because they induce tolerance to the so-called self-antigens. Apoptotic cells are constantly accumulating in the organism and are a source of self-antigens.This makes the maintenance of immunological self-tolerance difficult. In this context, dendritic cells are involved in the elimination of self-reactive T cells.
Diseases
Dendritic cells are thought to play a role in autoimmune diseases as well as allergies and cancer. Cancer cells, for example, evade the body’s own defense mechanisms and have an immunosuppressive effect, so to speak. In this context, a reduced function of the dendritic cells is a possible cause. In autoimmune diseases and allergies, on the other hand, the opposite mechanism is present: the dendritic cells overreact in both cases. These connections have made scientists think of dendritic cells in the past in the context of various therapeutic approaches. For example, the use of dendritic cells was mentioned when considering cancer vaccination. Specific and autologous antigen-presenting cells should thus trigger an immune response in which the activated T lymphocytes act against the tumor cells. Immunotherapies have been used for years as secondary therapies for various cancers. In the context of autoimmune diseases, a reduction of dendritic cells was discussed as a therapeutic pathway. Surprisingly, however, studies have shown that the intensity of autoimmune diseases actually increases after a reduction of dendritic cells. Consequently, it is not the reduction but the increase of the cells that could provide an improvement in these diseases.
