بسم الله الرحمن الرحيم. Epidermis as an immune organ. By Doaa Hegab Ass. Lecturer of Dermatology & Venereology. Cutaneous immune responses involve the coordinated actions of epidermal and dermal cells along with the network of cytokines.
Ass. Lecturer of Dermatology & Venereology
(Immune-Competent epithelial Cells)
(Epidermal Antigen-Presenting Cells)
(Dendritic Epidernal T Cells-Specialized Resident Epithelial T Cells)+ (Epidermotropic T Lymphocytes-Circulating T Cells That Home to the Epidermis)
(Epidermal Pigment Cells With Immune Properties)
ʘ Keratinocytes play a role in innate immune responses in the skin
ʘ Keratinocytes may play a role in initiating adaptive immune responses in the skin by releasing cytokines and expressing cellular adhesion molecules to facilitate the movement of immunecompetent cells.
Immunomodulatory and inflammatory role of keratinocyte is played through its
Exposure to noxious stimuli
(hypoxia, trauma, radiation, Haptens, microbes, toxins)
Production and release of many cytokines
Bacteria, viruses, fungi, parasites
Attack cell membrane
Damage numerous intracellular structures
(Pro Opio Melano Cortin)
(Stimulated by UVR, IL-1, Tumour promoters)
Release of IL-10 with anti-inflammatory & immunosuppressive effect
Hydrogen peroxide (H2O2)
Nitric oxide (NO)
Hydroxy radical (HO)
Host defense via pro-inflammatory & immunomodulatory function
Keratinocytes as inducers of immune response & as immunologic target cells
Target for CD8 (cytotoxic T cells)
MHC I/CD8 mediated cell death occurs in:
Infiltrating T cells IFNɣ
Tolerance to subsequent stimulation.
MHC II bearing keratinocytes provide signals that specifically inhibit cell-mediated immune responses in the skin
* Binding & killing by MHC II restricted T cells (CD4)
*Activate memory and effector T cells.
Infiltrating T cells IFNɣ & TNFα
LFA-1-ICAM-1 conjugate formation with T cells.
Recruiting and moving immune cells to the point of antigenic stimulation or skin injury.
-Allergic contact hypersenstivity -Psoriasis
Toll like receptors on keratinocytes & LC
B cells Ab
Ag presentation to naïve T cells
IL1 & IL18
Auto inflamation &autoimmunity
Ps Vitiligo SLE RA
TLR/Nod receptor engagement of microbe-derived moieties
IL-1αandβ, GMCSF, TNFα
Maturation of LC
*upregulation of MHC II
*upregulation of T cell co-stimulatory molecules, such as ICAM1, CD86, CD40 and CD11c
*upregulation of LN homing CCR7
Differentiation and activation of LC
enhanced capacity to take up, process & present antigen
Proliferation & differentiation signals
alpha(E)beta(7) of memory cells
E-cadherin on keratinocytes
IL-l, -3, and -6, GMCSF, TNFα, and TGFβ
After exposure to specific cytokines or neuropeptides
increase the production of these cytokines and secrete IL-8 and monocyte chemotactic and activating factor.