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Chapter: Clinical Dermatology: The function and structure of the skin

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Some cellular components of the skin immune system

Their prime role is to make the protective horny layer and to support to the outermost epithelium of the body but they also have immunological func-tions in their own right.

Some cellular components of the skin immune system

Keratinocytes

Their prime role is to make the protective horny layer  and to support to the outermost epithelium of the body but they also have immunological func-tions in their own right. Keratinocytes produce large numbers of cytokines (see Table 2.2), and can be induced by γ-interferon to express HLA-DR. They can also produce α-melanocyte-stimulating hormone, which is immunosuppressive. Keratinocytes play a central part in healing after epidermal injury (Fig. 2.11).




Langerhans cells

These dendritic cells come from the bone marrow and circulate through the epidermis, the dermis, lymphatics (as ‘veiled cells’), and also through the T-cell area of the lymph nodes where they are called ‘dendritic’ or ‘interdigitating’ cells. They can be identified in tissue sections by demonstrating their characteristic surface markers (e.g. CD1a antigen, MHC Class II antigens, adenosine triphosphatase) or S-100 protein in their cytoplasm (also found in melanocytes). Langerhans cells have a key role in antigen presentation.

Dermal dendritic cells

These poorly characterized cells are found around the tiny blood vessels of the papillary dermis. They bear MHC Class II antigens on their surface and, like Langerhans cells, probably function as antigen-presenting cells.

T lymphocytes

These develop and acquire their antigen receptors (T-cell receptors, TCR) in the thymus. They differentiate into subpopulations, recognizable by their different surface molecules (cluster of differentiation markers), which are functionally distinct.

T-helper (TH)/inducer cells

These help B cells to produce antibody and also induce cytotoxic T cells to recognize and kill virally infected cells and allogeneic grafts. TH cells recognize antigen in association with MHC Class II molecules (Fig. 2.12) and, when triggered by antigen, release cytokines that attract and activate other inflammatory cells (see Fig. 2.18). They are CD4+.Helper T cells are divided into type 1 (TH-1) and type 2 lymphocytes (TH-2) according to the main cytokines that they produce (Fig. 2.13). Some skin diseases dis-play a predominantly TH-1 response (e.g. psoriasis), others a mainly TH-2 response (e.g. atopic dermatitis).




T-cytotoxic (TC) cells

These lymphocytes are capable of destroying allogeneic and virally infected cells, which they recognize by the MHC Class I molecules on their surface. They are CD8+.

T-cell receptor and T-cell gene receptor rearrangements

Most T-cell receptors are composed of an α and β chain, each with a variable (antigen binding) and a constant domain, which are associated with the CD3 cell surface molecules (Fig. 2.12). Many different com-binations of separate gene segments, termed V, D and J, code for the variable domains of the receptor. An analysis of rearrangements of the gene for the recep-tor is used to determine whether a T-cell infiltrate is likely to be malignant or reactive. The identification of a specific band, on analysis of DNA from the lesion, which is not matched by the patient’s DNA from other sites, indicates monoclonal T-cell proliferation, and suggests either malignancy or a T-cell response to a single antigen.

L cells/null (non-T, non-B) cells

These leucocytes have properties between those of T and myelomonocytic cells. Most have receptors for FcIgG. This subpopulation contains natural killer (NK) and killer (K) cells.

Natural killer cells

These are large granular leucocytes that can kill virally infected cells, or tumour cells that have not previously been sensitized with antibody.

Killer cells

These are not a separate cell type, but rather cytotoxic T cells, NK cells or monocytic leucocytes that can kill target cells sensitized with antibody. In antibody-mediated cellular cytotoxicity, antibody binds to anti-gen on the surface of the target cell: the K cell binds to the antibody at its other (Fc) end by its Fc receptor and the target cell is then lysed.

Mast cells

These are present in most connective tissues, pre-dominantly around blood vessels. Their numerous granules contain inflammatory mediators (see Fig. 8.1). In rodentsaand probably in humansathere are two distinct populations of mast cells, connective tissue and mucosal, which differ in their staining properties, content of inflammatory mediators and proteolytic enzymes. Skin mast cells play a central part in the pathogenesis of urticaria.

 


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