Immune surveillance in the skin: mechanisms and clinical consequences

Key Points

• The skin, together with other epithelial-cell interfaces with a hostile environment, supports a range of passive and active immune defence mechanisms.

• Cutaneous immune responses serve as a model for the study of interactions between innate and acquired immune mechanisms.

• Adaptive immune surveillance addresses the logistical challenge of targeting naive, effector and memory T cells to their respective sites of function by using distinct homing mechanisms at different stages of the immune response, termed primary, secondary and tertiary immune surveillance.

• Primary immune surveillance involves the process by which tissue dendritic cells are induced to engulf foreign particles, undergo maturation and emigrate through the afferent lymphatics to the local draining lymph node, where they encounter naive T cells recruited from the peripheral circulation. This greatly increases the efficiency with which naive T cells are exposed to antigens presented by professional antigen-presenting cells.

• Secondary immune surveillance involves the production and distribution of antigen-specific effector memory T cells that express homing receptors that direct their migration back to the tissue draining the lymph node where activation occurred and their participation in tissue-based immune responses. The persistence of memory T cells with both antigen and tissue specificity also protects against possible future encounters with the same pathogen, by providing a population of antigen-specific effector cells pre-targeted to the site where exposure to that pathogen might most probably recur.

• Tertiary immune surveillance involves the production of central memory and effector cells potentially directed to lymph nodes and tissues other than the site of primary exposure, providing broad coverage in the event that the pathogen is encountered through a different route.

• These concepts have implications for the understanding of both inflammatory skin disorders and the development of antitumour and antipathogen vaccine strategies.

Abstract

The skin, as the primary interface between the body and the environment, provides the first line of defence against a broad array of microbial pathogens and trauma. In addition to its properties as a physical barrier, the skin has many active defence mechanisms. In this review, we discuss the interaction between the innate and adaptive immune systems in the skin as a model for immune function at epithelial-cell interfaces with the environment. How these mechanisms account for the robust nature of cutaneous immune surveillance and how their dysregulation drives the pathogenesis of inflammatory skin disorders and skin-based tumours are the subjects of this review.