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Inflammation, immunity and the skin
Inflammatory responses are central to biological homeostasis. Inflammation is mediated by molecular signalling between resident skin cells and specialized immunological cells which results in specific cellular interactions, or by release of soluble mediators. In the skin, strong inflammatory reactions are important for defence against infection (e.g. redness and exudate in impetigo), but in immunocompromised individuals, the risk of infection is increased (e.g. viral warts). As well as defence against infection, it is increasingly recognised that immunological responses are important in host defence against skin cancer, and that immunosuppression results in increased risk of all skin cancers, including squamous cell carcinoma and malignant melanoma. However, immune responses in the skin can also be detrimental to the host and when dysregulated, result in inappropriate responses against self-proteins (autoimmune diseases) or benign environmental antigens (allergic responses).
The immunological components of skin are similar to other epithelia and can be separated into innate and adaptive immune systems. Innate immunity is a key inflammatory immune response by cells sensing ‘danger’, and is principally mediated by keratinocytes. Equally, the generous blood and lymphatic supplies to the dermis are important channels through which immune cells can pass to or from, which are required for adaptive immunity that requires immunological priming and delivers immunological memory.
Microbiome
On the surface of the skin lies a complex population of bacteria and fungi which make up the skin microbiome. The density and proportions of different species differ per body site, and are more similar at the same site between individuals, than at different sites in the same individual, which emphasises the important environmental niches created by differences such as sweatiness, sebaceous secretions, flexural locations and hair-bearing sites. In each square centimetre of skin, it is estimated that one billion bacteria exist, but most do not penetrate the epidermal barrier. These microbes provide important stimuli for innate immunity, and in the steady state, these are important for maintaining skin barrier function.
Immunologically functional cells in the skin
Keratinocytes
Keratinocytes synthesize antimicrobial peptides, produce proinflammatory cytokines (especially IL-1) and express immune reactive molecules such as major histocompatibility complex (MHC) class I and II molecules on their surface. They signal to cutaneous dendritic cells and have been shown to be able to induce specific dendritic cell: T-cell functional outcomes. For example, keratinocyte production of thymic stromal lymphopoietin (TSLP) induces dendritic cells to drive T cells towards an inflammatory Th2 phenotype.
Professional antigen presenting cells
The Langerhans cells (epidermis) and populations of dermal dendritic cells are the outermost sentinels of the cellular immune system ( Fig. 5.1 ). Langerhans cells are dendritic and 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.
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