Skin as a protection against environmental threats.PPT

Skin as a protection against environmental threats Antti Lauerma, M.D., Ph.D. Chief Medical Officer FIOH Dermatology Figures: copyright Blackwell (Rook, Textbook of Dermatology) SKIN AS ORGAN Surface area 1.5 - 2 m2 Weight ~10% of body weight Purpose: To protect body against: Mechanical stress Physical damage Pathogens Foreign biologic material Foreign nonbiologic material SKIN: THREE LEVELS OF PROTECTION Mechanical barrier (stratum corneum) Innate immunity Acquired immunity STRATUM CORNEUM The outer-most layer of skin Approximately 10 cell layers thick Consists of corneocytes and extracellular matrix Protective layer against water loss from body STRATUM CORNEUM DAMAGE EXOGENOUS DAMAGE excess washing (toxic hand dermatitis) ENDOGENOUS DAMAGE inflammation STRUCTURAL DAMAGE atopic skin STRATUM CORNEUM REPAIR Lipid synthesis in corneocytes Lipid synthesis in keratinocytes Basal keratinocyte proliferation STRATUM CORNEUM REPAIR (2) Ointment/cream application UV light therapy Systemic retinoid use??? Coombs-Gell I Mast cells release histamine Vasodilatation Leakage of water to skin Intense pruritus 15 min - 2 hours (immediate hypersensitivity) Coombs-Gell II Cytotoxic response Macrophage-mediated killing of unfit cells 24 hours Erythema multiforme Coombs-Gell III Antibody-antigen complexes Complexes trapped at capillaries Exanthema 8-24 hours Coombs-Gell IV APC presents antigen T-cell mediated cellular inflammation Allergic contact dermatitis 24-48 hours (delayed hypersensitivity) INNATE IMMUNITY IN SKIN - START Damage - danger signal Preformed IL-1a released from KC IL-1a stimulates KC to produce IL-1b, IL-6, TNFa and more IL-1a TOLL receptors have same effect as IL-1a, sharing NF-kappa-beta signalling Arrival of Granulocytes Larger vessel - lower speed Attachment via P- and E-selectins Movement to dermis through CXC -chemokine gradient Proteases enable movement through ECM Entrance to epidermis, movement through epidermis (”zipper movement”) Granulocytes in e