20090528-6

Des Tobin MD

Department of Biomedical Sciences at the University of Bradford

 Professor of Cell Biology.

By Desmond J. Tobin MD, University of Bradford, UK  —  Adult human skin extends to approximately 2 m2 in area, is around 2.5 mm thick on average and has an average density of 1.1. Together these provide for a 5-6 kg mass value for skin or to put it another way skin constitutes an impressive 6% of our total body weight. As such the skin exceeds all other organs in total mass, if we exclude the muscle, bone, adipose and blood systems from this limited definition of organ.’ The skin invests the body to provide a vast physical barrier at the interface with the external environment and is designed to protect us against a range of insults including: desiccant (temperature, electrolyte/fluid balance), mechanical, chemical and microbial. Further protection is provided by the ultraviolet radiation (UVR)-absorbing pigmentation system and the complex immuno-regulatory sentinel networks, which sense tissue micro-environments for foreign or abnormally expressed components. It is only by thinking of the skin in holistic terms can we accommodate, and then tackle, the difficulties in modern clinical dermatology, dermato-pathology, and dermato-pharmacology that will hopefully guide us to development of targets for therapeutic intervention.

Conventionally, the skin is described as consisting of two broad tissue types; the epidermis – an external stratified, non-vascularized, epithelium of between 75 and 150 µm (up to 600 µm thick on palms/soles), and an underlying connective tissue called the dermis – consisting of mixture of fibroblasts producing dense fibrous/elastic components and the erroneously termed ground substance. The dermis may be up to 4 mm thick (e.g. adult back) but is usually less than 2 mm and houses many of the skin’s business centers including; its vascular, neural and lymphatic systems and its multiple accessory appendages. The latter include its excretory and secretary glands (Sebaceous, Eccrine and Apocrine glands), its keratinizing structures (Hair follicles and Nails), and its sensory nerve receptors of Meissner’s corpuscles (touch), Pacinian corpuscles (pressure), Pilo-Ruffini corpuscles (mechanoreceptors), free terminals, hair follicle endings etc. There is considerable variation in the presence and density of these appendages between different body sites. Finally, anatomists include a third skin layer, the sub-cutis or hypodermis consisting of fatty connective tissue that connects the dermis to underlying skeletal components. Interested readers keen on learning more about the cell biology and physiology of skin can consult specialized texts.

20090528-7

Fig. 1 High-resolution light microscopy view of a portion of normal

human skin showing epidermis and dermis (D). SC, S. corneum;

SG, S. granulosum; SS, S. spinosum; SB, S. basale.

Scale bar = 30 µM.

20090528-8

Fig. 2 Cartoon of normal human skin showing epidermis (E), dermis (D), subcutaneous fat layer (SCFL), and skin appendages including hair follicle (HF) with hair shaft (HS), sebaceous gland (SG), eccrine sweat gland (ESG), Meissner’s corpuscle (MC), Pacinian corpuscle (PC), blood vessels (BV), sweat gland pore (P), nerve fiber (NF), free nerve ending (FNe). 

By Des Tobin MD, University of Bradford, UK  —  It is only appropriate that the immune function should be strongly represented in the organ that is most directly responsible for separating physically the self from the non-self. However, the skin not only provides immune protection for itself, but also helps protect the whole body. More stimulation of the immune system is likely to occur at this biological interface (between you and your external environment) than any other area of your body. Biological aggressors like bacteria, viruses, mould, yeast, fungus and chemical insults that threaten our health can gain entry to our bodies via the skin and its numerous ports of entry (e.g. hair follicle canals, sweat gland pores etc.) However, unless the skin itself is damaged (e.g. wounds, abrasions or disease) or the host is compromised (e.g. immuno-suppressed), most of these threats are repelled by our skin.

Immunodermatology, the study of the skin immune system (SIS), has grown enormously over the last couple of decades and we have made great strides in the dissection of the skin immunological networks involved in both physiologic and pathologic circumstances.45 The make up of the SIS can be most simply described in terms of its components, i.e. cellular and humoral components or alternately whether we are looking at its innate (pre-existing) or adaptive (subsequent to prior exposure to an immune response generating stimulus) immunity. In the last few years it has become clear that practically all cell types residing in and transiting through skin can exhibit immune functionality. The better characterized cellular components include keratinocytes, lymphocytes (various subpopulations in skin), Langerhans cells (and other skin dendritic cells), monocytes and macrophages, endothelial cells of blood and lymphatic vessels, mast cells (containing a battery of mediators of both immune and neuroendocrine responses), neutrophils, eosinophils, and basophils. Innate components include free radicals, anti-microbial peptides including defensins and cathelicidins, cytokines, chemokines, neuropeptides, adhesion molecules and a wide range of pro- and anti-inflammatory mediators. Immunoglobulins or antibodies are additional potent proteins that are secreted from activated B-lympocytes and can neutralize threats to the body. Given the surface location of skin, it is not surprising that the physiology and pathology of skin can be affected by ultraviolet sunlight and so the sub-field of photo-immunology has yielded several important findings. Prominent among these is the general immuno-suppressive effect of sunlight with its associate killing of Langerhans cells or altering their function. Our increasing longevity will require us to depend even more on the skin immune system immuno-surveillance function to prevent and limit tumor growth etc.

There are also may congenital and acquired disorders with associated skin manifestations, as well as immune or autoimmune related disorders. Examples, of the latter include so-called immunobullous or blistering diseases, Lichen planus and graft-versus-host disease, Lupus erythematosus, psoriasis etc. Moreover, how the skin handles xenobiotics also involves immunological mechanisms, and the degree to which individuals may exhibit an allergic or atopic tendency will determine whether they will develop atopic dermatitis, allergic contact dermatitis etc. The last decade or so has witnessed the development of new immuno-modulatory drugs (both biologics and chemicals) for manipulating skin immune response and so managing treatment of skin disease.

The hair follicle has its own unique immune system principally characterized by its so-called immune privileged status, where its lower regions are immuno-silent during parts of the hair growth cycle. This appears to be an adaptation to protect this critical mini-organ during its hair cycle-dependent dramatic tissue remodeling events.

To read this entire paper, go to the following website of the Royal Society of Chemistry:

http://www.rsc.org/delivery/_ArticleLinking/DisplayHTMLArticleforfree.cfm?JournalCode=CS&Year=2006&ManuscriptID=b505793k&Iss=1

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