Skin is a “Grenzorgan” equipped with the capacity to mount and execute immune responses.
The cutaneous immune system disposes of an innate and adaptive arm to exert these functions.
Molecular constituents of the cutaneous immune system include pattern recognition receptors and effector molecules.
Tissue homeostasis requires the prevention of exaggerated responses to innocuous substances and the occurrence of host-defense reactions at a subclinical level, ie, in the absence of inflammation.
Under pathological conditions, danger signals or other disease-eliciting/-promoting factors in the skin elicit a coordinated (host defense) reaction of its cellular and molecular elements.
The skin is a border organ (“Grenzorgan”) separating the host’s structural constituents from the environment and, at the same time, allowing the communication between the inside and the outside world. This dual role of the skin is commonly referred to as “skin barrier function.” Its major task is to secure and maintain tissue homeostasis and, thus, to preserve host integrity. In case of a major danger signal such as the overwhelming assault of pathogenic microorganisms, it must allow for the rapid generation and mobilization of effective host defense reactions leading to the neutralization of the pathogen. To fulfill these obligations, the skin contains a variety of structural, cellular, and molecular elements, which confer physical, chemical, and immunological protection. The immunological barrier consists of the different constituents of both the innate and active immune response, which, dependent on the situation, are either productive and—at the expense of tissue destruction—protective or nonproductive and downregulating, thus preventing overreaction to an otherwise innocuous substance. This chapter describes the basic structural elements of the cutaneous innate and adaptive immune system and, based on this information, develops a concept of its functionality under physiologic and pathologic conditions.
In 1905, the pediatricians Clemens von Pirquet and Béla Schick published their monography named “Die Serumkrankheit” (“serum sickness”) and meticulously described the clinical symptoms of children that had received sera of horses previously vaccinated with Corynebacterium diphtheriae (Fig. 10-1).1 This serum treatment was quite successful in mitigating or even abrogating the diphtherial infection, but, as a complication, the children later developed a transitory disease attack consisting of fever, arthritis, nephritis, encephalitis, and, very notably, a skin rash. Because the intensity of the symptoms directly correlated with the amount of serum administered, Pirquet and Schick correctly speculated that serum sickness is an undesired (immunological?) host reaction against animal proteins. The validity of this assumption was not confirmed until the 1950s when investigators at the Scripps Research Institute showed that rabbits immunized with foreign proteins would develop a clinical disease complex similar to that of serum-injected children and, microscopically and serologically, characterized by the occurrence of immune complexes.2,3 It is very likely that the skin rash in serum sickness was the first demonstration of the skin being a target of immune responses. Despite this, most dermatologists would date the actual beginning ...