Immunology of the skin

Professional antigen presenting cells

The Langerhans cells (epidermis) and dermal dendritic cells are the outermost sentinels of the cellular immune system (Fig. 1). They are dendritic, bone marrow-derived cells. Langerhans cells are characterized ultrastructurally by a unique cytoplasmic organelle known as the Birbeck granule. Recent work has shown the important role ultraviolet radiation plays in inducing photoimmunosuppression, which is mediated by effects on the skin dendritic cell population.

Fig. 1 Langerhans cell.

The dendritic Langerhans cells form a network in the epidermis. In this section, the Langerhans cells have been stained with a monoclonal antibody to HLA-DR.

T lymphocytes

T cells are defined by expression of the T cell receptor (TCR), the structure of which determines the foreign antigens the T cell will recognize. Consequently, TCR specificity is closely regulated to prevent circulation of T cells strongly recognizing self-proteins. The TCR recognizes the antigen as presented by the major histocompatibility complex (MHC) and this interaction is stabilized by CD8⁺ (MHC class I) or CD4⁺ (MHC class II) molecules.

T lymphocyte circulation through normal skin for immunosurveillance is regulated by lymphocyte surface molecules that promote ‘skin homing’, including cutaneous leucocyte antigen (CLA), CCR4, CCR6 and CCR10. Epithelial danger signals induced by infection and inflammation increase cutaneous and endothelial expression of skin homing receptor ligands thereby enhancing the influx of lymphocytes into the cutaneous compartment.

Different types of T cell with differing functions are recognized in the skin, for example:

Fig. 2 CD4⁺ T cell subsets.

The cytokine/function polarization of CD4⁺ T cells, which was until recently limited to the Th1/Th2 paradigm, has been expanded. Cytokines that are critical to lineage development are indicated in the arrow boxes. Below the cells are the effector or regulatory cytokine repertoires of each cell type (nTreg are contact dependent) and their abbreviated names.