Dermo epidermal junction

dermoepidermal junction is the main interconnecting supporting strucure binding the Epidermis and Dermis together

1. DERMO-EPIDERMAL JUNCTION By Dr. RANJAN DASH

2. DERMATOLOGY GREAT SAYING :

3. HEADS TO BE HIGHLIGHTED DEFINITION ORIGIN AND DEVELOPMENT FUNCTION ULTRASTRUCTURE UBIQUITUOUS COMPONENTS OF DEJ APPLIED ASPECTS RECENT ADVANCES

4. DEFINITION of DERMO-EPIDERMAL JUNCTION / DEJ “ A highly complex form of basement membrane that underlies the basal keratinocytes of epidermis and extend into the upper layer of dermis ”. A critical interface/junction between the overlying epidermis and underlying dermis. It is continuous along the epidermis and skin appendages .

5. GROSS VIEW OF DEJ IN A SKIN SECTION

6. ULTRASTRUCTURE OF DEJ

7. The BMZ can be recognized histologically by positive labelling with Periodic AcidSchiff Stain. Electron microscopy is an essential technique to reveal the ultrastructure morphology of basement memberane zone.

8. ORIGIN & DEVELOPMENT Structures of basal lamina ( lucida & densa ) : ectodermal origin Structures of sub-basal-lamina( fibroreticular lamina): mesodermal origin. As early as 8 weeks EGA ,a simple Basement membrane separates the epidermis from dermis,comprising of all basic ubiquituous components : Laminin 111,collagen IV,Heparan sulfate and Nidogen . Components of hemidesmosomes and anchoring filaments and fibrils develop around the start of early embryonic period(3-5m).

9. ZONE 1 : LAMINA LUCIDA AND ITS COMPONENTS Tonofilaments : keratin intermediate filaments, keratin 5,14 that course through basal keratinocytes into the hemidesmosomes . Hemidesmosomes : are anchoring junctional proteins, extend from the intracellular compartment of the basal keratinocytes to the lamina lucida inthe upper portion of the dermal–epidermal basement membrane.

10. Hemidesmosomes cont . Also constitute the hemidesmosome –anchoring filament complex. HD1 to HD5 with molecular masses of approximately 500, 230, 200, 180 and 120 kD , respectively. HD 1 corresponds to plectin , a large intracytoplasmic adhesion molecule. HD2 and HD4 as the 230 and 180 kDa bullous pemphigoid antigens (BPAG1 and BPAG2). HD 3 & HD 5 corresponds to α 6 and β 4 chain of integrin molecule . BPAG 2 also known as type XVII collagen, interacts with α6β4 integrin and extends from the intracellular compartment of basal cells to the extracellular space, thus stabilizing the association of basal keratinocytes to the underlying basement membrane .

11. Lamina lucida components cont. Anchoring filaments : are thread ‐ like structures that complex with hemidesmosomes.laminin 332 may be the major component of the anchoring filaments. The cell binding of laminins is mediated by

12. LAMININS High MW glycoproteins (400-900). Important part of basal lamina that help in cell adhesion,cell differentiation and migration. Structurally ,a trimer of 3 polypeptide chains with varying orientation. Nomenclature as per constituent chains ex : laminin 511 contains α5 , β1 and γ1 chains. Laminins are associated with typeIV collagen via entactin and perlecan . Also bind to cell membranes via Integrin receptors. and muscle membrane via dystroglycan molecules.

13. DISTRIBUTION OF LAMININ As many as 16 different laminins have been identified thus far and at least four of them are physiologically present in the skin in significant quantities. Type of laminin P olypeptide Distribution 111 α1β1γ1 Blood vessels, LD 311 α3β1γ1 LL/LD 511 α5β1γ1 LL/LD 332 α 3 β 3 γ 2 Interface of LL/LD

14. INTEGRIN Transmembrane glycoproteins that attach cell-cell or cells to extracellular matrix. Bind to ligands such as fibronectin,vitronectin,collagen and laminin . Structurally heterodimers of α and β peptide chains.

15. INTEGRIN LIGAND DISTRIBUTION α 5 β 1 fibronectin ubiquitous α 6 β 1 laminin ubiquitous α 7 β 1 , laminin muscle α 1 β 2   Ig superfamily white blood cell α 2 β 3 fibrinogen platelet α 6 β 4 laminin hemidesmosome

16. Components of lamina densa COLLAGEN Type IV A heterotrimer of three α polypeptide chains . Each of these chain contain 3 distinct domains : 1) N- terminalcysteine -rich 7-s domain 2) a central triple-helical domain and 3) a C-terminal globular domain (NC-1) . Covalent interactions among 7-s region form specialised network forms esp. a four-legged Spider form ** α 1 and α 2 are ubiquitous but the third chain can be α 3 or α 4 or α 5 in different basement membranes .

17. NIDOGEN/ENTACTIN ARE SMALL glycoprotein MOLECULES EXPRESSED AS NIDOGEN 1 AND NIDOGEN 2 CONNECTING LINK BETWEEN COLLAGEN IV AND LAMININ , FURTHER IT INTEGRATE OTHER COMPONENTS OF BASEMENT MEMBRANE SUCH AS PERLECAN, FIBULIN .

18. HEPARAN SULFATE proteoglycan Three major types present in vascular and epithelial basement membrane: 1) perlecan 2) agrin 3) collagenxviii Perlecan in basement membrane of myocardium and skin, Agrin in neuro muscular junction and renal tubular basement membrane. Collagen xviii : considerd a hybrid collagen- proteoglycan present over glomeluar basement membrane allowing selective permeability.

19. COMPONENTS OF SUBLAMINA DENSA Anchoring fibrils : condensed filamentous aggregate of type VII collagen . proximal end (NC-1 domain) insert into basal lamina- laminin 332 distal end integrate into fibrous network of dermis or electron dense amorphous anchoring plaques(TYPE IV COLLAGEN) Anchoring fibrils form a scaffold that entraps large number of dermal fibrils Bind them with covalent crosslinking between collagen vii and collagen 1 ,securing the lamina densa to the subjacent dermis .

20. ANCHORING FIBRILS

21. APPLIED ASPECTS BIOPSY : Evaluation of inflammation and change in tissue architecture at the level of dermoepithelial junction. SPLIT SKIN METHOD : splitting of skin through lamina lucida,so as to distinguish the distribution of immune deposits at epidermal & dermal level .methods used are : 1) enzymatic via Trypsin , dispase 2)NACL Splitting: incubation in 1 M NS at for 24-48 hr. TRANSMISSION ELECTRON MICROSCOPY : to ascertain the architectural details of epidermis ,DEJ and dermis . DIF(DIRECT IMMUNOFLUOROSCENCE) and IF (INDIRECT IMMUNOFLUOROSCENCE ) study : to determine the type of immune deposits and the sites of distribution ,i.e. at epidermal,subepidermal /BMZ or at upper dermis.

22. DEJ/BMZ TARGETS IN SKIN DISEASE STRUCTURAL LEVEL COMPONENT MOLECULES AUTOIMMUNE TARGET GENETIC TARGET TONOFILAMENT KERATIN 5,14 EBS HD PLAQUE BPAG 1 PLECTIN BP BP,CP EBS EBS-MD,JEB-PA HD TRANS- MEMBRANE PROTEI N COLLAGEN XVII α 6 β 4 BP,CP,LAD,PG BP ,CP JEB-non- Herlitz JEB- PA ANCHORING FILAMENT LAMININ332 ECTODOMAIN OF COLLAGEN XVII CP BP, LAD JEB- Herlitz JEB-nonlethal ANCHORING FIBRILS COLLAGEN VII EBA DEB

23. THAN K YOU