Immunology and skin in health and disease

Abstract

The skin is a complex organ that, in addition to providing a strong barrier against external insults, serves as an arena for a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy. A variety of cells collaborate to mount functional immune responses, which are initiated by resident populations and evolve through the recruitment of additional cell populations to the skin. Inflammatory responses are quite diverse, resulting in a wide range of signs and symptoms that depend on the initiating signals, characteristics of the infiltrating cell populations, and cytokines that are produced (cytokines are secreted protein that allows for cell-cell communication; usually refers to communication between immune-immune cells or stromal-immune cells). In this work, we will review the skin architecture and resident and recruited cell populations and discuss how these populations contribute to inflammation using human diseases and treatments when possible to illustrate their importance within a clinical context.

Figure 1.

Immune populations in the skin. (Top) Langerhans cells, dermal dendritic cells, macrophages, other innate cells (mast cells, NK cells, NKT cells, γδ-T cells), and memory T cells comprise the skin-resident immune system under the steady state. Langerhans cells, dermal dendritic cells, macrophages, and γδ-T cells first sense infection or injury and initiate a rapid, innate response that includes the recruitment of effector cells. Innate effectors (NK populations) provide a rapid, antigen-nonspecific response, whereas memory T cells provide a rapid, antigen-specific memory response to previously encountered pathogens. Stromal cell populations, such as keratinocytes, fibroblasts, and endothelial cells, also participate in immune responses by sensing tissue damage and producing inflammatory cytokines. (Bottom) On activation of the skin-resident immune system, additional immune cells are recruited to help contain and fight infection and/or to remove cellular debris to aid in the healing process. These include additional innate cells like neutrophils and eosinophils, as well as adaptive populations like naïve or central memory T cells and B cells.

Figure 2.

Location of immune cells within normal skin architecture. Distinct populations of immune cells inhabit local niches within the skin. The epidermis contains Langerhans cells to provide immune surveillance. Memory T cells are also retained in the epidermis, presumably for early detection and control of re-encountered pathogens. Keratinocytes may sense pathogens or other damage-associated signals and communicate this to the immune system through cytokines. The dermis contains dermal dendritic cells, T cells, and fibroblasts. In this example, we depict a T cell being recruited out of the blood and into the dermis and potentially the epidermis, depending on the site of infection/injury. Recruitment of cells to peripheral tissues requires production of chemoattractants. Endothelial cells, which form the walls of the vasculature, may present chemokines and/or adhesion molecules to immune cells to direct their transmigration into the skin.