Dermal immunopathology: from genetics to effector mechanisms.

The immune system represents highly sophisticated defense mechanisms by which the body is protected against invasion by various infectious microbes and against the resulting tissue destruction. The concept of “immune” was introduced originally to explain a mysterious phenomenon in which those individuals who had survived an epidemic disease became resistant to the same disease. This concept was subsequently validated by the striking efficacy of vaccination against infectious pathogens. The underlying mechanisms, however, had remained almost unknown for many years. We now know many cellular and molecular components of the immune system. Different leukocyte subsets, which possess distinct functional properties, work together in a concerted manner to form multiple layers of defense lines. They include T lymphocytes, B lymphocytes, monocytes, macrophages, dendritic cells, natural killer cells, neutrophils, basophils, eosinophils, and mast cells. These leukocytes communicate with each other by secreting various soluble factors (e.g., cytokines, chemokines, antibodies, and antimicrobial peptides) and by signaling through cell surface molecules (e.g., receptors for the soluble factors, major histocompatibility complex class I and class II molecules, adhesion molecules, and costimulatory molecules). Impairment of the individual components or their communication may result in failure of the body’s defense (immune deficiency). Although the immune system is important for the host defense, its dysfunction may cause various forms of diseases, such as overreactions to environmental antigens (i.e., hypersensitivity reactions) and inappropriate responsiveness to self-antigens (i.e., autoimmunity). As an organ separating the body from external insults, the skin is well equipped with most, if not all, of the above immune components. The skin has long served as a test site to assess the immune responsiveness to infectious microbes and environmental antigens. In fact, physicians were almost totally dependent on various skin reactions or skin tests for measuring the magnitude, type, and antigen specificity of patients’ immunity until more sophisticated in vitro immunological assays became available. Owing to the marked progress in genetic, molecular, cellular, and clinical immunology, we now appreciate that the skin acts as an immunological organ as a whole (i.e., skin immune system) and that its dysfunction may result in a wide variety of immunological skin diseases. The purpose of this issue ofClinical Reviews of Allergy and Immunology is to provide an overview of several prototypic immunological skin diseases. Because the issue is not meant to include all the autoimmune and allergic skin disorders, we have decided to cover selected diseases representing various forms of skin manifestation and invited experts from the corresponding fields. Because of the space limitation, each article can highlight only certain aspects of recent developments. The first two articles describe the skin immune system from different angles. Michael Girardi focuses on the adaptive immunity, and Heidi Goodarzi, Janet Trowbridge, and Richard Gallo place a special emphasis on the innate immunity. Recent efforts in basic and translational research have unveiled immunological bases of several common inflammatory skin disorders, such as allergic contact dermatitis, atopic dermatitis, and psoriasis. Dendritic cells are special Clinic Rev Allerg Immunol (2007) 33:1–3 DOI 10.1007/s12016-007-0035-6