The skin is one of the human body's largest organs, with a surface area m2 and a thickness that commonly varies between 0.5 and 4 mm (Kerr, 1999). Many of the specialized physiological functions of the skin are made possible by its unique, stratified structure (Fig. 2). The two major components of the skin are the epidermis and dermis. The primary architecture of the epidermis is formed through the division of keratinocytes, the predominant epidermal cell type, in the basal (bottom) layer of the epidermis followed by a process of differentiation and upward migration to the skin's surface forming the upper layers of the viable epidermis. The most superficial layer of the skin, the stratum corneum, is composed of lipids and corneocytes which are dead, enucleated cells in the final stage of differentiation (Madison, 2003). Differentiation of keratinocytes gives rise to the following histologically distinct strata in the epidermis: stratum basale (single row of mitotically active basal cells), stratum spinosum (about five rows of cells having spines, or desmo-somes), stratum granulosum (about five rows of cells having cytoplasmic keratohyalin granules), stratum lucidum (present in thick skin and containing dead cells with abundant keratin proteins), and stratum corneum (lipids and a dead, anucleated, keratin-containing cell layer ranging in thickness from 10 to a few hundred cells). Although estimates can vary substantially, it is thought that the time interval between division of a keratinocyte in the stratum basale and the appearance of this newly formed cell as a corneocyte in the stratum corneum (i.e., the minimal transit time) is about 14 days and that complete replacement of the epidermis occurs in 52-75 days (Hoath and Leahy, 2003). In addition to keratinocytes, other types of cells are present in the epidermis and perform critical physiological functions. Melanocytes, which are typically located between every 5 and 10 basal keratinocytes and synthesize melanin, play a critical role in the protective function of the skin against sunlight.
FIGURE 2. Major structural components of the skin.
Langerhans cells, found in the lower epidermis, are an integral part of the skin's immunological defenses serving as antigen-presenting cells. Merkel cells, which are specialized sensory cells, are found adjacent to basal cells, particularly in the epidermis of the fingers, lips, and around hair follicles (Kerr, 1999).
The dermis is the lower layer of the skin and in large part serves to sustain and support the epidermis. The dermis interfaces with the epidermis through a layer of upward protrusions of dermal papillae (Fig. 2), also called rete pegs, which provide a firm anchor to physically connect the dermis with the epidermis. In addition, the papillary dermis contains a network of capillaries. Since the epidermis contains no blood vessels, all of the metabolic needs of the epidermis are met through diffusion of nutrients and waste products between the epidermis and capillaries in the dermis. The lower portion of the dermis, known as the reticular dermis, is less profusely vascularized. Dermal fibroblasts, the primary cell type in the dermis, are a heterogeneous population of cells whose subpopulations are unique to the dermal layer (Sorrell and Caplan, 2004). An important role of dermal fibro-blasts is synthesis of the various components that constitute the extracellular matrix of the dermis. These proteins include collagens (mainly type I), elastin, and glycosaminoglycans. Dermal fibroblasts also produce matrix metalloproteinases (MMPs) that provide for a dynamic turnover of extracellular matrix proteins and also are important in wound healing (Pilcher et al., 1999). These MMPs include collagenase-1 (MMP-1), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). A balance between synthesis and enzymatic degradation of extracellular matrix proteins is required for homeostasis in the dermis. In aging skin, the synthesis of matrix proteins slows, while expression of MMPs is increased (West, 1994). These biochemical changes in the dermis can result in the sagging and wrinkles commonly observed in aged skin. Chronic exposure to sunlight can further exacerbate these biochemical changes in the dermis (Wlaschek et al., 2001).
The unique structure of the skin allows it to perform a number of specialized functions. One fundamental function of the skin, in particular the stratum corneum, is to provide an essential barrier to penetration of environmental chemicals by limiting their diffusion into the skin (Madison, 2003; Monteiro-Riviere, 2004). In addition, cells in the viable epidermis are able to metabolize compounds that penetrate the stratum corneum and thereby moderate toxicity (Bronaugh et al., 1994; Steinstrasser and Merkle, 1995). The skin also presents a barrier to penetration of sunlight (Kornhauser et al., 2004). About 60% of incident sunlight in the damaging UVB (290-320 nm) region of the spectrum is reflected at the skin's surface or absorbed in the stratum corneum. Light that enters the viable epidermis is further attenuated by scattering and through absorption by epidermal chromophores such as melanin, proteins, and urocanic acid. Because of the constant exposure of skin to a diverse set of antigenic pathogens and environmental chemicals, the skin also provides a unique immune defense. Streilein (1983) proposed that skin-associated lym-phoid tissues (SALT) provide immune surveillance in the skin. Components of SALT include epidermal Langerhans cells, with the capacity for antigen presentation, keratinocytes, which release cytokines and other mediators, infiltrating immunocompetent lymphocytes and strategically placed lymph nodes that accept signals derived from the skin. In addition to protection from environmental insults, the skin performs other important physiological functions such as thermoregulation and synthesis of vitamin D (Anderson and Parrish, 1981; Holick et al., 1982).
Was this article helpful?