Tutorials 4-5 Flashcards
What can neutralise proteins that are separated due to size in electrophoresis?
SDS - sodium dodecyl sulphate
What mutation causes OI and on what gene?
Single base substitution from GGC to TGC on COL1A1 gene.
What does the OI mutation result in?
Cysteine is formed instead of glycine.
What are the implications of having cysteine present instead of glycine?
Larger amino acid so caused steric hindrance as only amino acid that can fit inside the triple helix is glycine (only hydrogens can fit in the middle). Also causes inappropriate formation of disulphide bridges between the two alpha chains.
What do mutations to proline cause?
Structural problems - collagen may not pack together properly.
Alongside glycine, what amino acids are normally found in collagen?
Modified amino acids - hydroxyproline and hydroxlysine
How many types of collagen are there?
5
Which collagen type is OI linked with?
Collagen I
Why is collagen important?
Important in mechanical and tensile strength of muscle tissue and bones.
How is collagen formed?
- First synthesised on free ribosomes then translocated to the rER
- Recognised as a secretory protein
- Pre-pro collagen is cleaved off to form pro-collagen
- Pro-peptides on ends of each chain are lost after collagen formation
What are the functions of pro-peptides? (2)
Direct collagen formation and prevent formation of fibrils (insoluble proteins) in cells - a build up of fibrils can lead to cell death.
What pattern of inheritance does OI follow?
Autosomal dominant.
Is “dominant negative” so even if heterozygous for mutant gene, patient will still be affected.
What is bone normally consisted of?
Hydroxyapatite (form of calcium phosphate) and collagen. It is then mineralised.
How does OI affects bone structure?
Abnormal collagen causes abnormal mineralisation, leading to skeletal abnormalities and bone weakness.
Symptoms of OI? (6)
- Weakened bones
- Shortened height
- Blue sclera (white of the eye)
- Loss of hearing
- Hyper-mobility
- Poor teeth development
Most common form of OI?
Type 1
How many forms of OI are there?
4
Most severe form of OI?
2
What is anaphylaxis?
An acute type 1 hypersensitivity reaction as a result of a IgE mediated immune response to an antigen.
What is the normal process of antigen detection and response?
- Lymphocyte activation occurs after antigen binding to IgM antibody, stimulating proliferation and secretion of antibodies.
- As response continues it will switch to IgG.
How does this normal response change in allergic reactions?
Instead of switching to IgG it switches to IgE.
IgE antibody binds to IgE receptors (FCeRI) on the surface of mast cells and causes them to degranulate, releasing several inflammatory mediators.
What are mast cells?
Contain granules of inflammatory mediators such as histamines and leukotrienes.
Where are mast cells found?
Throughout body in connective tissue and epithelial mucosae (intestinal and respiratory).
Effects of mast cells? (6)
1) Vasodilation
2) Increased fluid movement out of blood leading to oedema
3) Bronchoconstriction
4) Hypotension
5) Heart contraction decreases so HR increases slightly
6) Contraction of smooth muscle of intestinal walls
What is urticaria?
Raised and red rash caused by stimulation of epithelial connective tissue, causing vasodilation and oedema.
What is allergic rhinitis?
a.k.a hay fever
Irritation of nasal mucosa due to inhalation of allergens, sometimes causing nasal secretions.
How is anaphylaxis treated?
1) Increasing blood pressure by laying down with feet in the air
2) IV
3) Antihistamines and anti-inflammatory glucocorticoids
4) Bronchodilators and oxygen
5) Adrenaline (vasoconstrictor)
