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  • Human immune system consists broadly of innate vs adaptive immune responses.

  • Innate immune system has multiple different cellular subsets that have in common rapid response to infection and injury but are restricted in their ability to recognize and respond to all pathogens, instead relying on germline encoded pattern recognition receptors and danger signals.

  • Adaptive immune system is a slower but more adaptive arm of the immune system that can respond to near limitless range of pathogens.

  • Recently identified immune cells, such as innate lymphoid cells and unconventional T cells, span the spectrum between the innate and the adaptive immune system.


Apart from being one of the largest organs in the human body, the skin acts as a protective barrier between the internal and external environments. Although the epidermis acts as a physical and physiologic barrier to the entry of commensals and pathogens, the near constant exposure to an array of both benign and harmful microorganisms and other stressors in the skin has promoted the evolution of a complex cellular immune network, involving both the innate and adaptive parts of the immune system. This ensures adequate responses against pathogens as well as mechanisms to promote homeostasis and control excessive inflammatory response. This network in the skin has been named the skin immune system and consists of a large number of specialized skin-resident immune cells as well as circulating lymphocytes constantly recirculating between the skin, skin-draining lymph nodes, and the peripheral circulation.1 The cellular constituents of the skin immune system involve multiple cell types, subtypes of immune cells, and often involve participation of parenchymal cells including keratinocytes, endothelial cells and fibroblasts (Fig. 11-1). The interactions between these are highly complex, with each cell type often having both specific and redundant roles in immune responses.

Figure 11-1

Components of the cellular immune system in healthy skin. Multiple different immune cell populations are present in healthy skin. Langerhans cells and resident memory T cells, primarily CD8+, reside in the epidermal layer, whereas CD4+ and γδ T cells are found in the upper dermis. Innate lymphoid cells (ILCs) are found in proximity to the dermal-epidermal junction, whereas mast cells are often in proximity to dermal blood vessels. Dermal dendritic cells and macrophages are found in the dermis. Other cells may contribute to immune responses in skin such as fibroblasts, lymphatic blood vessels, nerves (not shown), and melanocytes (not shown).


The skin immune system includes components of both the innate and adaptive immune components (Fig. 11-2). The innate immune system recognizes specific motifs, such as proteins, lipids, nucleotides, and other metabolites, associated with broad classes of pathogens, and with the receptors for these encoded in germline DNA. In contrast, the adaptive ...

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