EM DISEASE

Question 1

What is osteogenesis imperfecta?

Answer 1

(brittle bone disease)
Causes:
- mutation in the gene for collagen type 1
- affects the collagen fibres
- disassembly/unwinding of the fibrils lead to decrease strength
Symptoms:
- have fragile long bones
- increase tendency of fractures

Question 2

What is the structure of collagen?

Answer 2

• Precursors alpha chain gets assembled into a triple helical chain called pro-collagen
• Has frayed ends
• Cleavage of lose ends by enzyme pro-collagen peptidase
• Helices are assembled into a collagen fibril, overlapping
• Collagen fibril is bundled up into a collagen fibre
• What gives collagen its strength (rope like structure)

Question 3

What is Alport’s syndrome?

Answer 3

• Collagen disorder
• mutation in collagen IV
• X-linked and autosomal recessive
• defective collagen IV assembly leads to impaired filtration of urine and kidney functions

Question 4

What are the principal components of the basal lamina?

Answer 4

• collagen (type IV), nidogen, laminin and proteoglycan

- glycoproteins

Question 5

What is the use of the basal lamina in the kidney glomerulus?

Answer 5

• acting as a substrate for both cells to be in contact with:
  Lining the collecting duct is a sheet of epithelial cells = Attached to the basal lamina
  Lining the capillaries is endothelial cells = Close contact to the basal lamina as well
• ‘molecular filter’ preventing passage of macromolecules from the blood to the urine

Question 6

Why are elastic fibres needed?

Answer 6

• to function correctly, many tissues need to be both strong and elastic
• strength comes from collagen but the elastic fibres give tissues their elasticity
• to stretch and relax

Question 7

How are elastin fibres created?

Answer 7

Elastin (a hydrophobic protein) cross links to form a network of elastic fibres
- giving it elastic properties

Question 8

What is the importance of fibrillin?

Answer 8

Fibrillin prevents the over-stretching of elastic fibres.

- without, if they over-stretch, they are unable to relax back to the original shape

Question 9

How does fibrillin work?

Answer 9

Fibrillin fibres microfibrils form a scaffold surrounding the elastin

Question 10

What is fibrillin?

Answer 10

fibres of extracellular matrix protein

Question 11

What is Marfan’s syndrome?

Answer 11

Syndrome where you have long limbs & fingers and are very tall
- can cause aortic aneurysms (and die from these)
Cause:
- mutations in FBN1 gene that encodes Fibrillin

Question 12

What is Leukocyte Adhesion Deficiency (LAD)?

Answer 12

Rare autosomal recessive disease where there are very high levels of circulating neutrophils and impaired neutrophil function causing premature death.
Cause:
- mutation that affects the cell adhesion molecules
TYPE I LAD = integrin β2 is not expressed
TYPE II LAD = integrin β2 is expressed but impaired ligand binding

Question 13

What is the function of β2 integrin?

Answer 13

cell-cell adhesion and immune response

Question 14

Which β2 integrin are involved in LAD?

Answer 14

• αM β2 binds to ICAM-1

- αL β2 binds to ICAM-2

Question 15

What are ICAM’s?

Answer 15

transmembrane intercellular adhesion molecules

• members of immunoglobulin superfamily
• single transmembrane domain
• ICAM1&2 interact reversibly with integrins on opposing cells

Question 16

Are LAD patients neutropenic?

Answer 16

life threatening- lack of neutrophils

- no, LAD patients have plenty of circulating neutrophils but none at sites of infection

Question 17

Why do LAD patients have circulating neutrophils but none at sites of infection?

Answer 17

• The leaving of the cell cannot happen if it has not been rolling and captured
• Capture and stopping of the neutrophil is function of integrins interacting with respective ICAMs in their endothelium cell walls
• If mutation present:
  If doesn’t bind to ICAM’s properly - then response will not occur (the rolling and capture)
  If integrin does not have alpha beta formation then will not be in the membrane of the neutrophil

Question 18

How do neutrophils enter the tissue needed?

Answer 18

• neutrophils receive signal to migrate to site of infection
• Neutrophils will associate with the wall of the capillary (endothelial cells)
  1) Capture and adhesion and rolling
• Will then come to a halt
• Strong adhesion point
• Dependent on selectins
  2) Migrate / leave the blood vessel
• By moving between the endothelial cells into the tissue
• Dependent on integrins