Flashcards in Chapter 29 - The Biology of the Basement Membrane Zone Deck (30):
From which primitive germ layer (i.e. ectoderm, mesoderm, or endoderm) are keratinocytes derived? Dermal fibroblasts?
- Keratinocytes are derived from ectoderm
- Dermal fibroblasts are derived from mesoderm
If a patient has a mutation in the gene that codes for plectin, what disease do they most likely have?
Epidermolysis bullosa simplex with limb-girdle muscular dystrophy
True or false: both plectin and BP1 are members of the plakin family of proteins.
True or false: BP1 is found only within the cytosol of the basal keratinocytes (i.e. it has no extracellular domains).
What diseases have BP2 as an autoimmune target? List four.
Bullous pemphigoid, pemphigoid gestationis, cicatricial pemphigoid, and linear IgA bullous dermatosis
*Note: the precise autoimmune target location on BP2 differs for these conditions.
True or false: integrin ligand binding is divalent cation-dependent.
True (e.g. Ca2+, Mg2+, Mn2+)
What are the preferred ligands for alpha6-beta4 integrins?
Laminin 1 and 5
What disease will a patient have if they have a mutation in either their alpha6 or beta4 integrin genes?
Junctional EB associated with pyloric atresia
True or false: in one form of cicatricial alopecia, patients develop autoantibodies to integrin subunit beta4.
True or false: integrins are heterodimeric transmembrane receptors.
True or false: CD151 is a tetraspan molecule associated with hemidesmosomes (specifically alpha6-beta4).
Collagen molecules are made up of repeating G-X-Y amino acid residues. What does the "G" stand for?
True or false: both Alport syndrome and Goodpasture syndrome are related to problems with collagen IV.
*Note: Alport syndrome is caused by a mutation in collagen IV, while Goodpasture syndrome is caused by an autoantibody to collagen IV.
True or false: perlecan is an example of a heparan sulfate proteoglycan found in the basement membrane.
In a patient with epidermolysis bullosa acquisita (EBA), what molecule is targeted by autoantibodies?
Name the layers of ultrastructures of the BM top to bottom.
1. Cytoskeleton, hemidesmosome and plasma membrane (of keratinocytes), 2. lamina lucida, 3. lamina densa/BM proper, 4. sublamina densa
Name the adhesion proteins of the keratinocyte cytoskeleton.
Keratin 5, 14
Name the adhesion proteins of the hemidesmosome anchoring filament complexes.
BPAg1, BPAg2, plectin, integrin subunits (alpha 6, beta 4), tetraspan CD151, laminin 5
Name the adhesion proteins of the lamina densa.
Laminin 5, 6, 10, type IV collagen, nidogen, heparan sulfate proteoglycans
Name the adhesion proteins of the sublamina densa.
Type VII, IV, III, I collagen, elastin, fibulins, fibrillins, linkin, latent TFG beta binding proteins
What is the gene involved in junctional EB, the non-Herlitz subtype?
COL17A1. They present with skin fragility, subepidermal blister, alopecia, dystrophic nails, dental enamel hypoplasia
Which integrin subunit is involved in junctional EB with pyloric atresia?
Alpha 6 or beta 4. They present with subepidermal blister of skin, oral and respiratory mucosa
Which laminins are present in the epidermal BM in the greatest amounts?
Laminin 5, 6, 10
What genes are involved in laminin 5 defect?
LAMA3, LAMB3, LAMC2. They present with subepidermal blister, epidermal detachment, eg. EB-Herlitz, antiepiligrin/laminin 5 cicatricial pemphigoid
What gene is involved in Alport syndrome?
COL4A5. They present with hematuria, progressive renal failure, sensorineural hearing loss, +/- ocular abnormalities
What is the pathology in Goodpasture syndrome?
AutoAb against the non collagenous 1 (NC1) domain of alpha 3 type IV collagen, aka tumstatin. They present with pulmonary hemorrhage, glomerulonephritis
Which immunobullous disease localize where on indirect IF microscopy studies of salt split skin?
IgG deposits on epidermal/above lamina densa (BP, PG, LABD, CP) vs. dermal/below lamina densa (AECP, EBA, BSLE)
Which genes and proteins are affected in EB simplex?
KRT5, KRT14, PLEC1, keratin 5, 14, plectin
Which genes and proteins are affected in junctional EB?
COL17A1, ITGB4, LAMA3, LAMB3, LAMC2, ITGA6, BPAG2, beta 4 integrin, laminin 5, alpha 6 integrin