j. Soc. Cosmet. Chem., 41, 249-257 (July/August) ImmunologyConcepts and skin relationships GEOFFREY BROOKS, Brooks Industries, South Plainfield, NJ, and BERNARD IDSON, Austin, TX 78759. Synopsis The classical concept of the function of skin as a barrier versus the environment is being expanded with the recognition that important metabolic and immunologic processes also occur. The immunological role of skin has been expanded from a simple target of immune injury to an active role in the initiation and regulation of certain skin-associated immune responses. This review presents the fundamentals of mecha- nisms underlying the skin immune system. Included are discussions of antigens, antibodies, allergens, lymphocytes, compliment, macrophages, Langerhans cells, keratinocytes, and interleukins, as well as the roles of antioxidants, UV light, and fatty acids. INTRODUCTION Concepts of the function of skin have changed in the last decade from that of a barrier against microbiologic and chemical invasion to include an important role in immunity. There is increasing recognition that skin could serve as a target organ of immunologic injury and in the initiation and regulation of both local and systemic immune respon- siveness (1). Immunodermatology is primarily directed toward an understanding of immunological mechanisms operating in skin as a complementary line of defense against external assault (2). Classical concepts of the function of skin have focused primarily on its capacity to establish and maintain an effective barrier versus the environment. Stratum corneum, the outermost region of the skin, serves as the most important component of the barrier. Within the last several decades, the barrier concept of epidermal function has been expanded with the recognition that important metabolic and immunologic processes also occur at this interface. Investigators from the clinical and basic sciences first studied the biochemical features of skin, with primary attention to the factors that regulate the function of skin cells such as keratinocytes, melanocytes, and fibroblasts. Other investigators collected data that suggested that many skin disorders possessed features of immunologic relevance. More recently the immunologic role of skin has been expanded from a simple target of immune injury to an active role during the initiation and regulation of certain skin-associated immune responses (3). This review is intended to acquaint cosmetic scientists with the fundamentals of the complex mechanisms underlying the skin immune system (SIS). 249

250 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ANTIGENS, ANTIBODIES, AND ALLERGENS Immunology is concerned with the response of the organism to antigenic challenge. Antigenic stimulation results either in the formation of humoral (fluid-like) antibodies known as immunoglobulins or alters the reactivity or response of certain cells, e.g., lymphocytes, which, when primed with antigen specificity, are referred to as immuno- logically competent cells. Their reaction with antigen is termed a cell-mediated re- sponse. Thus, the term "immunocompetence" refers to the ability or capacity of an organism to develop an immune response (i.e., antibody production and/or cell-me- diated immunity) following antigenic challenge. It has been hypothesized that the lym- phocytes reaching the epidermis may, to a large extent, be noncompetent lymphoid cells that become competent during or shortly after a stay in the epidermis or close to it in the dermis. Antigens that commonly sensitize persons to anaphylactic or to delayed-type hypersen- sitivities are known as allergens. The properties that confer allergenic potential are not definitely known, but molecular size, chemical composition, and the ability to bind to tissue may be important. Certain substances, among which are low-molecular-weight chemicals, are unable to stimulate formation of antibodies unless they are combined with protein. Such substances are known as haptens. When combined with protein they stimulate antibodies specific for the hapten. Haptens are important sensitizing agents in contact dermatitis. Antibodies may render the individual allergic to that antigen. The term allergy desig- nates a specific altered reactivity of the tissues to substances compared with the response to the first exposure to the same substance. In contrast to immune responses that pro- tect the organism from pathogens, allergies are immune responses that produce dam- aging effects on the organism. Cutaneous anaphylactic responses are allergic responses that occur in skin or on mucous membranes. Thus urticaria (hives), allergic rhinitis (hay fever), and some forms of asthma represent localized responses to environmental an- tigens-for example, in food or air. These allergic reactions are rapid, occurring within minutes of exposure to the antigen. LYMPHOCYTES Lymphocytes are the key cells associated with the immune response. They mediate and monitor immunological competence and responses, being the effector cells of delayed- type hypersensitivity and the precursors of plasma cells synthesizing antibody. They are formed from stem cells in the blood marrow and released into the blood, whence some pass to the thymus to proliferate and to become modified in their properties. These are the T-cells (T designating thymus) or thymus-dependent cells. Other lymphocytes are not modified by the thymus, having distinctly different properties, and are known as B-cells or thymus-independent cells. T-cells comprise about 60% of the lymphocytes in the blood of normal adults, and B-cells comprise about 10% (3). T-lymphocyte-specific properties are acquired after stimulation by a thymic hormone, thymosin, present in the thymus gland and the blood. This hormone induces matura- tion of T-precursor cells to T-lymphocytes. T-cells treated with thymosin in vitro, or fetal calf serum that contains thymosin activity, show enhanced mitogenic responses when treated with antigens thus, it is possible that the amount of thymosin formed in