The Skin Immune System
Pathogens will usually first
be encountered at body surfaces, either the skin or the mucosae and these are
therefore endowed with a variety of barriers against infection (see Figure
1.6). The outer surface of the skin is composed of keratinocytes which
constitute a strong physical barrier against microorganisms.
In addition, keratinocytes
express many types of pattern recognition receptors, including
TLRs, NOD‐like receptors, RIG‐1‐like receptors, and C‐type lectins. Upon
detectionof pathogens, these receptors trigger the keratinocytes to produce microbicidal
compounds such as β‐defensins as well as a variety of cytokines (including
chemokines, a family of molecules with chemotactic and other
functions). In a normal, non‐inflamed state the epidermis contains
resident Langerhans cells and both αβ and γδ T‐cells (Figure
6.2). The Langerhans cells can promote Th17 responses against extracellular
pathogens and may also regulate the development of tolerance against
nonpathogenic antigens.
The underlying dermis contains
dendritic cells, macrophages, T‐cells (again
both αβ and γδ), NK cells, and mast cells. About
10% of human CD4+ T‐cells in
the skin express Foxp3, indicating that these cells may function as regulatory
T‐cells. There is a continuous migration of leukocytes into the dermis from the
blood vessels. T‐cells that are directed to migrate to the skin upregulate a
number of adhesion molecules, including cutaneous leukocyte antigen (CLA),
CD43, and CD44, all three of which bind to E‐selectin on the blood vessel
endothelium in the skin. LFA‐1 and Mac‐1 bindingto ICAM‐1, and VLA‐4 binding to
VCAM‐1, as well as CCR4 on the T‐cell binding to CCL17 on the blood vessel
endothelium, are also involved in this process (Figure 6.3). The T‐cells can
subsequently return to the circulation via the draining lymphatics and the
lymph nodes. Should a pathogen provoke an inflammatory reaction in the skin,
then other cells of the
immune system will fairly
rapidly appear on the scene, including neutrophils, monocytes,
and eosinophils. In diseases such as atopic eczema the number of leukocytes in the skin increases substantially.
