091614 basement membrane Flashcards
structure of basement membrane zone
hemidesmosome
lamina lucida
lamina densa
sublamina densa
in pts with inherited blistering diseases, what is the basis?
genes encoding some structural proteins of the basement membrane zone are mutated
BP 230
bullous phemphigoid antigen 1
from the plakin family of proteins
cytoplasmic localization
important for cytoskeletal organization
BP 180
bullous pemphigoid antigen 2
also known as type XVII collagen
transmembrane protein that connects basal keratinocytes through BP 230 to the cytoskeleton and through laminin 332 to dermal collagen VII
bullous pemphigoid (BP)
tense blisters (fluid could be clear or hemorrhagic)
antibody binding to BP antigens causes subepidermal separation
BP is the most common
autoimmune bullous dermatosis
BP occurs primarily in whom
elderly
stages of BP
early: highly pruritic urticaria w/o blistering
later: tense blisters with serous or rarely hemorrhagic content (very stable blisters in contrast to pemphigus groups of diseases)
antibodies in BP are directed against what?
BP 230 and BP 180
generalized atrophic benign epidermolysis bullosa
mutated BP 180 protein
synonyms are collen type XVII and bullous pemphigoid antigen 2
clinical presentation of generalized atrophic benign epidermolysis bullosa
blisters
loss of hair
lamina lucida
immediately underlies hemidesmosomes
LL may be an artifact of tissue prep and dehydration
lamina densa
composed mostly of type IV collagen (one of the most abundant collagens of the BMZ) and laminins
key laminin is laminin 332 (prev known as laminin 5)
what makes up more than 1/2 of the mass of the BMZ
type IV collagen
what does laminin 332 do?
laminin 332 binds to hemidesmosomal protein integrin alpha6beta4 on the basal keratiocytes and to type VII collagen in the dermis, providing adhesion
mucous membrane pemphigoid predominantly affects whom
older ppl
mucous membrane pemphigoid
recurrent blistering of mucous membranes (also skin)
development of scars, strictures, synchiae(iris sticks to lens or cornea), and blindness
majority of pts have Ig against BP 180 (some have Ig against BP230, integrin beta4, laminin 332)
what subtype of MMP has an association with malignancies?
anti-laminin 332 pemphigoid
Herlitz junctional EB
defect in laminin 332
laminin 332
prev known as laminin 5
sublamina densa
type VII is composed of 3 identical alpha chains
type VII collagen is important for what?
to maintain epidermal dermal cohesion, b/c it binds to both type I and type IV collagens
epidermolysis bullosa acquisita
autoantibodies against type VII collagen
rare autoimmune bullous dermatosis
slight trauma elicits blistering and erosions of skin
often there’s involvement of oral mucosa-hemorrhagic erosions
where does epidermolysis bullosa acquisita affect most?
mechanically stressed areas
inherited epidermolysis bullosa
mutations in genes encoding BMZ proteins
skin fragility
erosions after minimal trauma
types of inherited epidermolysis bullosa
EB simplex (keratin 5, 14) junctional EB (laminin, BP180, integrins) dystrophic EB (type VII collagen) kindler syndrome (kindlin 1)
direct immunofluorescence
detects Ig and C3
samples are from pt perilesional skin
antibodies are against human Ig or complement
indirect immunofluorescence
detects circulating Ig against BMZ in the pt’s serum
serum is applied to foreign substrate such as normal human skin, monkey esophagus, rodent bladder
