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DR.HIMANI TANDON
PG 1ST YEAR
M.D. DERMATOLOGY
RMCH
DERMO-EPIDERMAL JUNCTION
AND DERMIS
1
DERMO-EPIDERMAL JUNCTION
2
DERMO-EPIDERMAL JUNCTION
 DEJ forms an extensive interface between the lower
part of the epidermis and the top layer of dermis
3
FUNCTIONS OF DEJ
4
 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
ULTRASTRUCTURE OF DEJ
6
 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
LAYERS OF BMZ
 BMZ of the skin is divided into 4 regions:
1. Plasma membrane of basal keratinocytes and
hemidesmosomes.
2. Lamina lucida
3. Lamina densa/ Basal Lamina
4. Lamina fibroreticularis
8
9
10
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
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 β4 INTEGRIN SUBUNIT POLYPEPTIDE
HD4 180-kDa BULLOUS PEMPHIGOID ANTIGEN
HD5 α6 INTEGRIN PEMPHIGOID ANTIGEN
12
STRUCTURE OF HEMIDESMOSOME
 Inner plaque
 Outer plaque
 Sub basal dense plaque
13
SECOND LAYER/ LAMINA LUCIDA
 Less electron dense, directly abuts plasma
membrane of basal keratinocytes.
COMPONENTS
ANCHORING
FILAMENTS
α6β4
INTEGRIN
ECTODOMAIN
OF 180-kDa
ANTIGEN
14
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 α6β4 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
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 (α6β4 in BMZ).
16
 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 α6β4 : JEB with pyloric
atresia.
17
18
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
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
Transmemb
erane
component
•Ehlers
Danlos
Syndrome
•Alport
Syndrome
•Good-
Pasture
Syndrome
•Ehlers
Danlos
Syndrome
(AD)
•Muscular
Dystrophy
•Dystrophi
c
Epidermol
ysis
Bullosa
•Junctional
epidermoly
sis bullosa
•Bullous
Pemphigoid
20
TYPE IV COLLAGEN
 Heterogenous group of macromolecules consists of six
genetically distinct but structurally related α-chains. α1 & α2
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 α5 and α6 chain leads to subepidermal
blistering.
21
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
23
DISORDERS OF THE DEJ
24
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
 Based level of cleavage they are classified into following:
1. 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
2. JUNCTIONAL EB: blistering occurs in lamina lucida
3. DYSTROPHIC EB: cleavage occurs immediately below
lamina densa, in region of anchoring fibrils.
4. MIXED EB/ KINDLER SYNDROME: cleavge plane is
variable, maybe at level of basal keratinocytes, lamina lucida
or sub lamina densa.
26
27
28
DERMIS
29
DERMIS
 Layer beneath the epidermis and the DEJ
 Demarcated on the top - lamina densa
on the bottom – subcutis
 Richly supplied by
1. Connective tissue 6. macrophages
2. Blood vessels 7. mast cells
3. Sweat glands 8. fibroblast
4. Sebaceous glands
5. nerve endings
 15-20% of total body weight
30
FUNCTIONS OF DERMIS
31
 Provides pliability, elasticity and tensile strength
 Protects the body from mechanical injury
 Aids thermal regulation
 Receptors for sensory stimuli
32
STRUCTURE OF DERMIS
33
LAYERS OF DERMIS
PAPILLARY
SUBPAPPILARY
PLEXUS
RETICULAR
34
35
PAPILLARY DERMIS
36
 Outer 1/5th 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
RETICULAR DERMIS
37
 Inner (deep)4/5th 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
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
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
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
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)
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
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
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)
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
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
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)
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.
49
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 -
51
52
53
 APPLIED
- Immediate type hypersensitivity reactions
- Subacute and Chronic inflammation
- Mastocytosis : hyperplastic Mast cells
54

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Dermo epidermal junction

  • 1. DR.HIMANI TANDON PG 1ST YEAR M.D. DERMATOLOGY RMCH DERMO-EPIDERMAL JUNCTION AND DERMIS 1
  • 3. DERMO-EPIDERMAL JUNCTION  DEJ forms an extensive interface between the lower part of the epidermis and the top layer of dermis 3
  • 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
  • 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: 1. Plasma membrane of basal keratinocytes and hemidesmosomes. 2. Lamina lucida 3. Lamina densa/ Basal Lamina 4. Lamina fibroreticularis 8
  • 9. 9
  • 10. 10
  • 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 β4 INTEGRIN SUBUNIT POLYPEPTIDE HD4 180-kDa BULLOUS PEMPHIGOID ANTIGEN HD5 α6 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. COMPONENTS ANCHORING FILAMENTS α6β4 INTEGRIN ECTODOMAIN OF 180-kDa ANTIGEN 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 α6β4 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 (α6β4 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 α6β4 : JEB with pyloric atresia. 17
  • 18. 18
  • 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
  • 21. TYPE IV COLLAGEN  Heterogenous group of macromolecules consists of six genetically distinct but structurally related α-chains. α1 & α2 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 α5 and α6 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
  • 23. 23
  • 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: 1. 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 2. JUNCTIONAL EB: blistering occurs in lamina lucida 3. DYSTROPHIC EB: cleavage occurs immediately below lamina densa, in region of anchoring fibrils. 4. MIXED EB/ KINDLER SYNDROME: cleavge plane is variable, maybe at level of basal keratinocytes, lamina lucida or sub lamina densa. 26
  • 27. 27
  • 28. 28
  • 30. DERMIS  Layer beneath the epidermis and the DEJ  Demarcated on the top - lamina densa on the bottom – subcutis  Richly supplied by 1. Connective tissue 6. macrophages 2. Blood vessels 7. mast cells 3. Sweat glands 8. fibroblast 4. Sebaceous glands 5. nerve endings  15-20% of total body weight 30
  • 32.  Provides pliability, elasticity and tensile strength  Protects the body from mechanical injury  Aids thermal regulation  Receptors for sensory stimuli 32
  • 35. 35
  • 36. PAPILLARY DERMIS 36  Outer 1/5th 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)4/5th 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.
  • 49. 49
  • 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 -
  • 51. 51
  • 52. 52
  • 53. 53  APPLIED - Immediate type hypersensitivity reactions - Subacute and Chronic inflammation - Mastocytosis : hyperplastic Mast cells
  • 54. 54