Chapter 29 - The Biology of the Basement Membrane Zone

Question 1

From which primitive germ layer (i.e. ectoderm, mesoderm, or endoderm) are keratinocytes derived? Dermal fibroblasts?

Answer 1

• Keratinocytes are derived from ectoderm

- Dermal fibroblasts are derived from mesoderm

Question 2

If a patient has a mutation in the gene that codes for plectin, what disease do they most likely have?

Answer 2

Epidermolysis bullosa simplex with limb-girdle muscular dystrophy

Question 3

True or false: both plectin and BP1 are members of the plakin family of proteins.

Answer 3

True

Question 4

True or false: BP1 is found only within the cytosol of the basal keratinocytes (i.e. it has no extracellular domains).

Answer 4

True

Question 5

What diseases have BP2 as an autoimmune target? List four.

Answer 5

Bullous pemphigoid, pemphigoid gestationis, cicatricial pemphigoid, and linear IgA bullous dermatosis
*Note: the precise autoimmune target location on BP2 differs for these conditions.

Question 6

True or false: integrin ligand binding is divalent cation-dependent.

Answer 6

True (e.g. Ca2+, Mg2+, Mn2+)

Question 7

What are the preferred ligands for alpha6-beta4 integrins?

Answer 7

Laminin 1 and 5

Question 8

What disease will a patient have if they have a mutation in either their alpha6 or beta4 integrin genes?

Answer 8

Junctional EB associated with pyloric atresia

Question 9

True or false: in one form of cicatricial alopecia, patients develop autoantibodies to integrin subunit beta4.

Answer 9

True

Question 10

True or false: integrins are heterodimeric transmembrane receptors.

Answer 10

True

Question 11

True or false: CD151 is a tetraspan molecule associated with hemidesmosomes (specifically alpha6-beta4).

Answer 11

True

Question 12

Collagen molecules are made up of repeating G-X-Y amino acid residues. What does the “G” stand for?

Answer 12

Glycine

Question 13

True or false: both Alport syndrome and Goodpasture syndrome are related to problems with collagen IV.

Answer 13

True
*Note: Alport syndrome is caused by a mutation in collagen IV, while Goodpasture syndrome is caused by an autoantibody to collagen IV.

Question 14

True or false: perlecan is an example of a heparan sulfate proteoglycan found in the basement membrane.

Answer 14

True

Question 15

In a patient with epidermolysis bullosa acquisita (EBA), what molecule is targeted by autoantibodies?

Answer 15

Collagen VII

Question 16

Name the layers of ultrastructures of the BM top to bottom.

Answer 16

1. Cytoskeleton, hemidesmosome and plasma membrane (of keratinocytes), 2. lamina lucida, 3. lamina densa/BM proper, 4. sublamina densa

Question 17

Name the adhesion proteins of the keratinocyte cytoskeleton.

Answer 17

Keratin 5, 14

Question 18

Name the adhesion proteins of the hemidesmosome anchoring filament complexes.

Answer 18

BPAg1, BPAg2, plectin, integrin subunits (alpha 6, beta 4), tetraspan CD151, laminin 5

Question 19

Name the adhesion proteins of the lamina densa.

Answer 19

Laminin 5, 6, 10, type IV collagen, nidogen, heparan sulfate proteoglycans

Question 20

Name the adhesion proteins of the sublamina densa.

Answer 20

Type VII, IV, III, I collagen, elastin, fibulins, fibrillins, linkin, latent TFG beta binding proteins

Question 21

What is the gene involved in junctional EB, the non-Herlitz subtype?

Answer 21

COL17A1. They present with skin fragility, subepidermal blister, alopecia, dystrophic nails, dental enamel hypoplasia

Question 22

Which integrin subunit is involved in junctional EB with pyloric atresia?

Answer 22

Alpha 6 or beta 4. They present with subepidermal blister of skin, oral and respiratory mucosa

Question 23

Which laminins are present in the epidermal BM in the greatest amounts?

Answer 23

Laminin 5, 6, 10

Question 24

What genes are involved in laminin 5 defect?

Answer 24

LAMA3, LAMB3, LAMC2. They present with subepidermal blister, epidermal detachment, eg. EB-Herlitz, antiepiligrin/laminin 5 cicatricial pemphigoid

Question 25

What gene is involved in Alport syndrome?

Answer 25

COL4A5. They present with hematuria, progressive renal failure, sensorineural hearing loss, +/- ocular abnormalities

Question 26

What is the pathology in Goodpasture syndrome?

Answer 26

AutoAb against the non collagenous 1 (NC1) domain of alpha 3 type IV collagen, aka tumstatin. They present with pulmonary hemorrhage, glomerulonephritis

Question 27

Which immunobullous disease localize where on indirect IF microscopy studies of salt split skin?

Answer 27

IgG deposits on epidermal/above lamina densa (BP, PG, LABD, CP) vs. dermal/below lamina densa (AECP, EBA, BSLE)

Question 28

Which genes and proteins are affected in EB simplex?

Answer 28

KRT5, KRT14, PLEC1, keratin 5, 14, plectin

Question 29

Which genes and proteins are affected in junctional EB?

Answer 29

COL17A1, ITGB4, LAMA3, LAMB3, LAMC2, ITGA6, BPAG2, beta 4 integrin, laminin 5, alpha 6 integrin

Question 30

Which genes and proteins are affected in dystrophic EB?

Answer 30

COL7A1, type VII collagen