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//DENDRITIC CELLS

DENDRITIC CELLS

There are two distinct groups of dendritic cell, myeloid dendritic cells (also known as conventional dendritic cells) and plasmacytoid dendritic cells. Both groups of cells are derived from haematopoietic stem cells. Until recently it was thought that plasmacytoid dendritic cells were derived from the lymphoid precursor cells, while the myeloid dendritic cells were derived from the myeloid progenitor cell. However, it is now apparent that these cells can be derived from either lineage, possibly from a common stem cell indicating considerable plasticity in their developmental pathways. Both cells are involved in antigen presentation, though have somewhat different functional roles in controlling both the adaptive and innate immune system. The myeloid dendritic cells are professional antigen-presenting cells (APC), which are able to process and present antigen to T lymphocytes, including naïve T cells. They are present as immature dendritic cells in the epidermis of the skin (Fig. 4.14) and other stratified squamous epithelia, e.g. the oral mucosa (Langerhans cells), and in the dermis and most other tissues (interstitial dendritic cells), where they are concerned with immune surveillance. Immature dendritic cells have an antigen-capturing function. They respond to chemotactic signals, for example defensins released by epithelial cells in the small intestine and they express pattern recognition receptors (e.g. Toll-like receptors) on their surface. Binding of bacterial molecules (e.g. carbohydrate or DNA) to these receptors stimulates the dendritic cells to migrate via the lymphatics to nearby secondary lymphoid tissues where they mature and acquire an antigen-presenting function. Mature dendritic cells are known as veiled cells when in the afferent lymphatics and the subcapsular sinuses of lymph nodes, and as interdigitating dendritic cells once they are within the lymphoid tissue proper. Their function within the secondary lymphoid tissue is to present their processed antigen to T lymphocytes, and thus to initiate and stimulate the immune response. For a review of recent research on dendritic cell function, see Colonna et al (2006).

Langerhans cells

Langerhans cells (Fig. 4.14) are one of the most well-studied types of immature dendritic cell (reviewed in Berger et al 2006). They are present throughout the epidermis of skin, where they were first described, but are most clearly identifiable in the stratum spinosum (see Ch. 7). They have an irregular nucleus and a clear cytoplasm, and contain characteristic elongated membranous vesicles (Birbeck granules). Langerhans cells endocytose and process antigens, undergoing a process of maturation from antigen-capturing to antigen-presenting cells which express high levels of MHC class I and II molecules, co-stimulatory molecules and adhesion molecules. They migrate to lymph nodes to activate T lymphocytes.

Interdigitating dendritic cells

Immature dendritic cells are found all over the body, including peripheral blood, and function in antigen-processing and immune surveillance. Mature dendritic cells are present in T cell-rich areas of secondary lymphoid tissue (paracortical areas of lymph nodes, interfollicular areas of MALT, periarteriolar sheaths of splenic white pulp), where they are frequently referred to as interdigitating dendritic cells. Within the secondary lymphoid tissues, they are involved in the presentation to T lymphocytes of antigens associated with either MHC class I (CD8 T cells) or MHC class II (CD4 T cells) molecules. Naïve T cells can only respond to antigen presented by dendritic cells. The T cells are stimulated not only by recognition of the antigen-MHC complex by the TcR, but also by interaction with co-stimulatory molecules expressed by the dendritic cells, and by cytokines secreted by the cells. These cytokines not only help activate the T cell but can also direct the nature of the T-cell response (e.g. Th1 or Th2). Appropriate T cells are thus activated to proliferate and are primed for carrying out their immunological functions. Once primed, T cells can then be stimulated by any APC, including macrophages and B cells.

Follicular dendritic cells

Follicular dendritic cells, FDCs (Fig. 4.15), are a non-migratory population of cells found in the follicles of secondary lymphoid tissues, where they attract and interact with B cells. Unlike other dendritic cells, FDCs are not haemopoietic in origin, but are probably derived from the stromal cells of lymphoid tissues. They are unable to endocytose and process antigen, and they lack MHC class II molecules. However, Fc receptors and complement receptors CD21 and CD35 on FDCs allow the cells to bind immune complexes to their surface for subsequent presentation, as unprocessed antigen, to germinal centre B cells. Interactions between B cells, CD4 helper T cells and FDCs in the germinal centres are important in the selection of high affinity B cells and their maturation to either plasma cells or memory B lymphocytes.

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