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
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
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
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
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
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
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
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.
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 -