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       The Skin as an Immune Organ

       Domenico Santoro and Megan Boyd

      KEY POINTS

      The skin is the largest organ in the body. It has long been known as the primary physical barrier between an organism and its environment, but since the early 1980s the skin has been recognized as an active immune organ with its own skin‐associated immune system. The skin’s defense system consists of physical, chemical, immunologic, and microbiologic components that protect the body against trauma, chemicals, toxins, and microorganisms.

      The physical barrier represents the first line of defense against invaders. It is composed of keratinocytes tightly bonded together by a lipid‐rich mortar in the stratum corneum (top layers) and keratinocytes joined together by tight cell‐to‐cell junctions in the lower layers. The chemical barrier consists of compounds with active antimicrobial activity, including fatty acids and antimicrobial or host defense peptides secreted by sebaceous glands and keratinocytes. If the physical and chemical defenses of the skin are overcome by invaders, components of the innate and active immune system along with beneficial microorganisms in the skin microbiome become important. Beneficial microorganisms compete for the same niche as pathogens and actively secrete antimicrobial peptides (AMPs) that inhibit the proliferation of pathogenic competitors.

When pathogenic microorganisms breach the physical and chemical defenses of the skin, they activate the skin‐associated lymphoid tissue (SALT) (Table 1.1). SALT includes dendritic cells, mast cells, lymphocytes, and keratinocytes, and forms part of the innate immune system (Figure 1.1). Innate immunity, which is considered the most ancient branch of the body’s immune defenses, is characterized by a rapid onset of action (minutes to hours), a lack of specificity (it recognizes common microbial structures as opposed to specific organisms), and a lack of memory, which means the response does not improve with each exposure. Cells of the innate immune system include macrophages, dendritic cells, neutrophils, natural killer (NK) cells, mast cells, and keratinocytes. When innate immunity is overwhelmed, the adaptive branch of the immune system (Figure 1.2), primarily made of T and B lymphocytes, is activated. The adaptive immune response is characterized by a slow onset of action (days to weeks), high specificity (recognizes unique antigens), and memory, which means the speed and magnitude of the response improve with each exposure. The innate and adaptive branches of the immune system are highly interconnected. When cells of the innate immune system are activated, they secrete numerous inflammatory cytokines and chemokines that prime and direct the adaptive immune system’s response.

Table 1.1 Cells of the innate and adaptive immune system discussed in this chapter.