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  • Review Article
  • Published:

Immune surveillance in the skin: mechanisms and clinical consequences

Nature Reviews Immunology volume 4, pages 211–222 (2004)Cite this article

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.

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Figure 1: Immune-response elements in non-inflamed skin.
Figure 2: Innate immune mechanisms in the skin.
Figure 3: Adaptive immune responses in the skin.
Figure 4: Immune-surveillance mechanisms in the skin.

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Acknowledgements

This work is supported by the National Institutes of Health.

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Authors and Affiliations

  1. Department of Dermatology, Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, 02115, Massachusetts, USA

    Thomas S. Kupper & Robert C. Fuhlbrigge

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  1. Thomas S. Kupper
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  2. Robert C. Fuhlbrigge
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Correspondence to Robert C. Fuhlbrigge.

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The authors declare no competing financial interests.

Related links

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DATABASES

LocusLink

CCL17

CCL22

CCL27

CCR4

CCR6

CCR7

CCR10

CD62L

CD80

CD86

CTLA4

CXCL9

CXCL10

CXCL11

CXCR3

E-selectin

GM-CSF

ICAM1

IFN-γ

IL-1α

IL-1β

IL-4

IL-5

IL-6

IL-10

IL-13

LFA1

P-selectin

TNF

VCAM1

FURTHER INFORMATION

Harvard Skin Research Center

Brigham and Women's Hospital Dermatology Clinic

Glossary

DANGER SIGNALS

Cell-wall components and other products of pathogens that alert the innate immune system to the presence of potentially harmful invaders, usually by interacting with Toll-like receptors and other pattern-recognition receptors that are expressed by tissue cells and dendritic cells, for example.

LANGERHANS CELLS

Immature bone-marrow-derived dendritic cells that reside for long periods of time in the epidermis. They contain Langerin and Birbeck granules, express E-cadherin and bind to contiguous keratinocytes. Stimulation through Toll-like receptors or other danger-signal receptors causes them to migrate to the draining lymph node and mature into highly efficient antigen-presenting cells.

ANTIMICROBIAL PEPTIDES

Evolutionarily conserved peptides that directly bind to and interact with cell surfaces of bacteria and fungi, usually inducing the formation of pores, leading to the death of target cells.

PROSTANOID

A member of the broad family of arachidonic-acid-derived inflammatory mediators.

GRAFT-VERSUS-HOST DISEASE

(GVHD). Tissue damage in a recipient of allogeneic transplanted tissue (usually a bone-marrow transplant) that results from the activity of donor cytotoxic T lymphocytes that recognize the recipient's tissue as foreign. GVHD varies markedly in severity, but can be life threatening in severe cases. Typically, damage to the skin and gut mucosa leads to clinical manifestations.

REGULATORY T CELL

A type of T cell that can inhibit effector-T-cell activation in an antigen-specific manner.

T HELPER 1 CELL

(TH1). A type of T cell that, through the production of interferon-γ, interleukin-10 and other cytokines, can stimulate cellular immunity against viral and bacterial pathogens.

T HELPER 2 CELL

(TH2). A type of T cell that, through the production of interleukin-4 (IL-4), IL-13 and other cytokines, can help B cells to produce IgE and other antibodies and, through the secretion of IL-5, IL-3 and others, can promote increased numbers of eosinophils, basophils and mast cells.

DELAYED-TYPE HYPERSENSITIVITY

A cellular immune response to antigen that develops over 24–72 hours with the infiltration of T cells and monocytes, and depends on the production of T helper-1-specific cytokines.

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Kupper, T., Fuhlbrigge, R. Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 4, 211–222 (2004). https://doi.org/10.1038/nri1310

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