Dermo epidermal junction

dermo epidermal junction and dermis

1. DR.HIMANI TANDON PG 1 st YEAR M.D. DERMATOLOGY RMCH DERMO-EPIDERMAL JUNCTION AND DERMIS 1

2. DERMO-EPIDERMAL JUNCTION 2

3. DERMO-EPIDERMAL JUNCTION DEJ forms an extensive interface between the lower part of the epidermis and the top layer of dermis 3

4. FUNCTIONS OF DEJ 4

5. Plays a key role in epidermal and dermal interactions Acts as vehicle for cellular attachment of cells. A matrix for cellular migration. Acts as gatekeeper for cellular and macromolecule transit. As moderator of cellular activities ranging from differentiation to apoptosis 5

6. ULTRASTRUCTURE OF DEJ 6

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

8. LAYERS OF BMZ BMZ of the skin is divided into 4 regions: Plasma membrane of basal keratinocytes and hemidesmosomes. Lamina lucida Lamina densa / Basal Lamina Lamina fibroreticularis 8

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11. FIRST LAYER The basal plasma memberane of basal keratinocytes comprises of 1. Tonofilaments /keratin intermediate filaments : which comprises of keratin 5, keratin 14.They course through the basal cells and are inserted into the hemidesmosomes 2. Hemidesmosomes : electron dense attachment complexes extending from basal keratinocytes to the lamina lucida . Attach to the kif within the basal keratinocytes and to the anchoring filaments in the lamina lucida ,the unit is termed as hemidesmosome -anchoring filament complex 11

12. HEMIDESMOSOMES Initially 5 major components of hemidesmosomes were recognized namely HD1 to HD5 They were later renamed as: HD 1 PLECTIN HD2 230-kDa BULLOUS PEMPHIGOID ANTIGEN HD3 β 4 INTEGRIN SUBUNIT POLYPEPTIDE HD4 180-kDa BULLOUS PEMPHIGOID ANTIGEN HD5 α 6 INTEGRIN PEMPHIGOID ANTIGEN 12

13. STRUCTURE OF HEMIDESMOSOME Inner plaque Outer plaque Sub basal dense plaque 13

14. SECOND LAYER/ LAMINA LUCIDA Less electron dense, directly abuts plasma membrane of basal keratinocytes . 14

15. Anchoring Filaments Fine, thread like structures , 3-4 nm in diameter Traverse through the lamina lucida and connects the hemidesmosomes to the lamina densa . Major anchoring filament antigen is LAMININ 322 which binds to the α 6 β 4 integrin in the hemidesmosome and to the type VII collagen in the anchoring fibrils. Other anchoring filament antigens include 125-kDa, 19-DEJ-1, 105 kDa , LAD-1. 15

16. LAMININ Out of 16 different laminin identified, atleast 4 of them are present in skin. STRUCTURE: cruciform structure with three short polypetide subunits α , β and ϒ chains. Cell binding of laminin is mediated by integrins ( α 6 β 4 in BMZ). 16

17. FUNCTIONS: interaction with extra cellular matrix molecules ( HDs & type VII collagen) Providing Integrity to BMZ Cell attachment and spreading neurite outgrowth. Cellular differentiation. APPLIED ANATOMY: Genetic mutation in any polypeptide of laminin 332: junctional form of EB with profound fragility of skin. Mutation in polypeptide of integrin α 6 β 4 : JEB with pyloric atresia . 17

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19. THIRD LAYER/ LAMINA DENSA electron dense layer, interacts with mesenchymal matrix of upper dermis. Major biochemical component is type IV collagen Other components include laminin 5, laminin 6, laminin 10, nidogen , perlecan , heparin sulphate proteoglycan 19

20. COLLAGEN COLLAGEN I &III COLLAGEN IV COLLAGEN V COLLAGEN VI COLLAGEN VII COLLAGEN XVII Main interstitial dermal collagen Major component of basement membrane zone Most connective tissues Minor collagen Major component of anchoring fibrils BPAG2 Transmemberane component Ehlers Danlos Syndrome Alport Syndrome Good-Pasture Syndrome Ehlers Danlos Syndrome (AD) Muscular Dystrophy Dystrophic Epidermolysis Bullosa Junctional epidermolysis bullosa Bullous Pemphigoid 20

21. TYPE IV COLLAGEN Heterogenous group of macromolecules consists of six genetically distinct but structurally related α -chains. α 1 & α 2 chains being main components of BMZ, other α chains subunit are also present in lower quantities. These collagen molecules arrange themselves in lattice like structure to increase the fexibility of BMZ, this arrangement also allows interaction with other collagenous and non collagenous components. Consists of triple helical domain(7-S) and globular domain.(amino-NC1 , carboxyl- NC2) Autoantibodies against α 5 and α 6 chain leads to subepidermal blistering. 21

22. FOURTH LAYER/ LAMINA FIBRORETICULARIS The major component of the lamina fibroreticularis is the ANCHORING FIBRILS., microfibrils , anchoring plaques. Anchoring fibrils are short, U-shaped structures that extend from the lower part of the lamina densa to the upper reticular dermis. Main component is type VII collagen ., synthesized by both dermal fibroblast and epidermal kerationocytes Secures the adhesion of DEJ to the dermis. MICROFIBRILS make up the elastic fibres that enmesh with the microfibrillar system of the dermis. Many of them insert their distal ends into electron dense structures k/a ANCHORING PLAQUES. 22

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24. DISORDERS OF THE DEJ 24

25. EPIDERMOLYSIS BULLOSA GROUP OF INHERITED MECHANOBULLOUS DISORDERS characterized by development of blisters over the skin and mucous membranes following minor frictional trauma. Diagnosis of EB is mainly clinical, skin biopsy can be done to confirm the subtype of EB. TREATMENT of all forms of EB is supportive and multidisciplinary approach is needed for effective management. 25

26. Based level of cleavage they are classified into following: EB SIMPLEX : level of separation is within epidermis. A. Basal form- cytolysis of infranuclear portion of basal keratinocytes B. Suprabasal form- blister appear in suprabasal epidermis JUNCTIONAL EB : blistering occurs in lamina lucida DYSTROPHIC EB : cleavage occurs immediately below lamina densa , in region of anchoring fibrils. MIXED EB/ KINDLER SYNDROME : cleavge plane is variable, maybe at level of basal keratinocytes , lamina lucida or sub lamina densa . 26

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29. DERMIS 29

30. DERMIS Layer beneath the epidermis and the DEJ Demarcated on the top - lamina densa on the bottom – subcutis Richly supplied by Connective tissue 6. macrophages Blood vessels 7. mast cells Sweat glands 8. fibroblast Sebaceous glands nerve endings 15-20% of total body weight 30

31. FUNCTIONS OF DERMIS 31

32. Provides pliability, elasticity and tensile strength Protects the body from mechanical injury Aids thermal regulation Receptors for sensory stimuli 32

33. STRUCTURE OF DERMIS 33

34. LAYERS OF DERMIS 34 DERMIS

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36. PAPILLARY DERMIS 36 Outer 1/5 th part of the dermis that interdigitates with the ridges on the undersurface of the epidermis. Upward waves- Dermal Papilla Downward extensions- Epidermal ridges Contains collagen fibrils and elastic fibres

37. RETICULAR DERMIS 37 Inner (deep)4/5 th layer Contains dense, irregular, collagen and mature elastic fibres Hair follicles, sweat glands Divided into: 1. upper zone- intermediate sized collagen fibre bundles 2. lower zone- in contact with the subcutaneous fatty tissue

38. INTERSTITIAL COMPONENTS 38 Four major classes of interstitial components: 1. Collagen Fibers 2. Elastic Structures 3. Non Collagenous Glycoproteins ( fibrillins , fibulins , integrins ) 4. Proteoglycans / Glycosaminoglycans

39. COLLAGEN 39 Major component of the dermis 75 % dry wieght of the dermis Soft and flexible but tough and inelastic Charz . Triple helical conformation TYPE I 80-90% LARGER AND COARSE TYPE III 08-10% SMALL FIBRILS, FINE NETWORK TYPE V <05% POLYMORPHIC

40. ELASTIC FIBRES 40 2-4% of dry weight of dermis Forms a continuous network throughout the dermis Maintain the normal configuration of the skin Central core- ELASTIN(major protien ) Peripheral part- fibrillin 1&2, MAGP-1&2, MFAP-1&3, lysyl oxidase , collagen VI

41. PROTEOGLYCANS/ GAGs 41 0.2% of dry weight of dermis Binds a large amount of water , influencing dermal volume and compressibility Major PGs- chondroitin sulfate/ dermatan sulfate - heparan / heparan sulphate pg - chondroitin-6 sulfate pg Major GAGs- fibronectin ( involved in cell proliferation, differentiation and wound healing.) - hyaluronic acid (has expansive water binding capacity, hydration)

42. APPLIED 42 Elastic fibres - loss ( cutix lata ) - decr . No and length( wrinkling skin syndrome) - localised loss ( anetoderma ) - loss in mid dermis( mid dermal elastolysis ) Fibrillin molecule abnormal- marfan syndrome Collagen abnormality- Ehlers Danlos Syndrome(skin fragility), osteogenesis imperfecta Collagen synthesis and degradation- scleroderma, keloid , hypertrophic scar

43. CELLULAR COMPONENTS 43 Cells residing in the dermis are: 1. Fibroblasts 2. Monocytes , Macrophages 3. Dendrocytes 4. Mast Cells Mostly present in the papilary dermis

44. FIBROBLASTS 44 M.C cells found in the dermis Derived from mesenchymal tissues Produce collagen fibres , elastic fibres and GAGs Appear as bipolar spindle Cells with elongated ovoid Nucleus. Cytoplasm has RER and Golgi complexes(active)

45. MONOCYTES, MACROPHAGES 45 Monocytes from the blood migrate into the dermis Differentiate into macrophages Similar to fibroblasts Contains lysosomes and phagocytic vacuoles Phagocytuc in nature Helps in processing and presentation of antigen

46. MONOCYTES, MACROPHAGEGS 46 Monocytes from the blood migrate to the dermis and differentiate into macrophages. Morphologically similar to fibroblats but contains lysosomes and phagocytic vacuoles

47. DENDROCYTES 47 Fixed connective tissue cells Stellate , dendritic and occ. Spindle shaped Highly phagocytic Involved in dermal Ag presentation Immunocompetent cells Marker for factor XII APPLIED Bening fibrotic proliferative conditions ( dermatofibromas , fibroxanthomas )

48. MAST CELLS 48 Bone marrow derived cells In papillary dermis Oval to spindle shape, oval nuclei Contain histamin , neutrophil , eosinophil chemotactic factors Release LTB4, platelet activating factor, PGD2. Surface has glycoprotein receptor sites for IgE .

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50. TYPE OF MAST CELLS 50 TYPE I TYPE II Connective tissue mast cells Mucosal mast cells Dermis and submucosa Bowel and Respiratory Tract Granules with poorly formed scrolls Granules with well formed scrolls Tryptase +, Chymase + Tryptase +, Chymase -

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53. 53 APPLIED Immediate type hypersensitivity reactions Subacute and Chronic inflammation Mastocytosis : hyperplastic Mast cells

54. 54 THANK YOU