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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:

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skin as a protection against environmental threats

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
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
SKIN: THREE LEVELS OF PROTECTION
  • Mechanical barrier (stratum corneum)
  • Innate immunity
  • Acquired immunity
stratum corneum
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
STRATUM CORNEUM DAMAGE
  • EXOGENOUS DAMAGE
    • excess washing (toxic hand dermatitis)
  • ENDOGENOUS DAMAGE
    • inflammation
  • STRUCTURAL DAMAGE
    • atopic skin
stratum corneum repair
STRATUM CORNEUM REPAIR
  • Lipid synthesis in corneocytes
  • Lipid synthesis in keratinocytes
  • Basal keratinocyte proliferation
stratum corneum repair 2
STRATUM CORNEUM REPAIR (2)
  • Ointment/cream application
  • UV light therapy
  • Systemic retinoid use???
coombs gell i
Coombs-Gell I
  • Mast cells release histamine
  • Vasodilatation
  • Leakage of water to skin
  • Intense pruritus
  • 15 min - 2 hours (immediate hypersensitivity)
coombs gell ii
Coombs-Gell II
  • Cytotoxic response
  • Macrophage-mediated killing of unfit cells
  • 24 hours
  • Erythema multiforme
coombs gell iii
Coombs-Gell III
  • Antibody-antigen complexes
  • Complexes trapped at capillaries
  • Exanthema
  • 8-24 hours
coombs gell iv
Coombs-Gell IV
  • APC presents antigen
  • T-cell mediated cellular inflammation
  • Allergic contact dermatitis
  • 24-48 hours (delayed hypersensitivity)
innate immunity in skin start
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
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 epidermis
Granulocytes in epidermis
  • Presence of IL-1, IL-6, TNF-a, GM-CSF, IFNg induce a respiratory burst in granulocytes
  • C3R, FCg receptors bind to microbes with opsonins (part of complement) to microbes
  • 1 bacteria/min, total over 50 bacteria per granulocyte
turn off the inflammation or call in the lymphocytes
Turn off the inflammation or call in the lymphocytes?
  • Keratinocytes produce IL-10, IL1ra, aMSH.
  • FB, MF, Lymphocytes produce TGF-beta:
    • IFN down
    • T cell anergy
    • Endoth. Cell Chk, adh mol down
turn off the inflammation or call in the lymphocytes21
Turn off the inflammation or call in the lymphocytes?
  • Inflammation over 24-35 hours starts acquired immunity
  • Endothelial cells produce ICAM, VCAM
  • T cells adhere to endothelial cells and enter skin via chemokine (CC, not CXC) gradient
lymphocytes in the skin
Lymphocytes in the skin
  • Professional APC present antigen in the context of MHC II and B7.1/B7.2 to T cells.
  • (If keratinocytes present antigen, anergy results (no B 7.1/7.2))
  • IFNg, IFNa, TNFa, and LPS, bacterial cell wall, CpG induce MF and DC to produce IL-12
  • IL-12 favors Th1 response
  • Th1 T cells produce more IFNg that keeps up production of CC-chemokines
what if danger persists
What if ”danger” persists???
  • Inflammatory area will be isolated from surrounding tissue
  • IL-4 and IL-10 induce giant cells from MF
  • TGF beta stimulates action of giant cells and FB
  • Granulomatous inflammation