lecture 14- coeliac disease

Question 1

What is coeliac disease?

Answer 1

It is chronic inflammation of the small intestine, due to an unnecessary immune response to the harmless gluten protein found in wheat and grains.

Question 2

Where does coeliac disease occur, on a micro scale within the intestinal lumen?

Answer 2

It occurs at the individual villi and involves the IEL’s (Immune lymphocytes).

Question 3

What type of lymphocytes are found in the intestinal villi with regards to coeliac disease?

Answer 3

The CD3+ and CD8+ lymphocytes.

Question 4

How do Intraepithelial lymphocytes (IEL’s) act as a marker of coeliac disease?

Answer 4

Normally, there are only a small number IEL’s in the villi. They proliferate and infiltrate the villi, with heaps more found during coeliac disease.

Question 5

How are enterocytes affected during coeliac disease?

Answer 5

Enterocytes are stunted and distorted in coeliac disease patients.

Question 6

How does coeliac disease affect the crypts and villi of the small intestine brushborder?

Answer 6

The crypts are little grooves that produce new enterocytes and cover the villi. In coeliac disease, the crypts get bigger (hyperplasia) because of increased demand for new enterocytes from the villi.

Question 7

What are the clinical manifestations of coeliac disease?

Answer 7

Gastrointestinal problems; flatulence, bloating, diarrhoea, abdominal cramps.
Vitamin deficiency: Anaemia, vitamin deficiencies.

Question 8

What are the 2 genes that are present in all coeliac disease sufferers?

Answer 8

HLA-DQ2 or HLA-DQ8. Note that a small population do have this gene, but don’t have coeliac disease.

Question 9

What is the role of early infant environment in preventing coeliac disease?

Answer 9

Breastfeeding is protecting because it exposes the infant to gluten via breastmilk. Too much early exposure though can end up promoting coeliac disease.

Question 10

What are the names of the two gluten proteins that cause coeliac disease?

Answer 10

Gliadins and Glutenins

Question 11

Where does coeliac disease occur, on a micro scale within the intestinal lumen?

Answer 11

It occurs at the individual villi and involves the IEL’s (Immune lymphocytes).

Question 12

What type of lymphocytes are found in the intestinal villi with regards to coeliac disease?

Answer 12

The CD3+ and CD8+ lymphocytes.

Question 13

How do Intraepithelial lymphocytes (IEL’s) act as a marker of coeliac disease?

Answer 13

Normally, there are only a small number IEL’s in the villi. They proliferate and infiltrate the villi, with heaps more found during coeliac disease.

Question 14

How are enterocytes affected during coeliac disease?

Answer 14

Enterocytes are stunted and distorted in coeliac disease patients.

Question 15

How does coeliac disease affect the crypts and villi of the small intestine brushborder?

Answer 15

The crypts are little grooves that produce new enterocytes and cover the villi. In coeliac disease, the crypts get bigger (hyperplasia) because of increased demand for new enterocytes from the villi.

Question 16

What are the clinical manifestations of coeliac disease?

Answer 16

Gastrointestinal problems; flatulence, bloating, diarrhoea, abdominal cramps.
Vitamin deficiency: Anaemia, vitamin deficiencies.

Question 17

What are the 2 genes that are present in all coeliac disease sufferers?

Answer 17

HLA-DQ2 or HLA-DQ8. Note that a small population do have this gene, but don’t have coeliac disease.

Question 18

What is the role of early infant environment in preventing coeliac disease?

Answer 18

Breastfeeding is protecting because it exposes the infant to gluten via breastmilk. Too much early exposure though can end up promoting coeliac disease.

Question 19

What are the names of the two gluten proteins that cause coeliac disease?

Answer 19

Gliadins and Glutenins

Question 20

what is it about the Gliadin and Glutenin polypeptides as proteins that makes them uneasy to digest?

Answer 20

They have high Proline and Glutamine content. They are resistant to digestion proteases and they pass through the intestinal epithelium intact.

Question 21

What happens to the undigested gluten polypeptides when they pass through the intestinal epithelium?

Answer 21

They are deanimated by an enzyme called ‘tissue transglutaminase’ (tTG). This enzyme converts glutamine to -ve glutamate.

Question 22

What occurs during the interaction of the deamidated gluten peptides and the antigen presenting cells of the immune system?

Answer 22

The negatively charged glutamate will bind to the antigen presenting cell, which are the HLA-DQ2 or HLA-DQ8 molecules.

Question 23

How is the immune response triggered once the gluten peptides have bound to the antigen presenting cells?

Answer 23

The CD4+ cells recognise the deamidated peptides when they bind to the MHC-11 molecules as dangerous. Thus it triggers cytokine release.

Question 24

How do the enterocytes of the small intestine respond to the inflammation from the gluten peptides?

Answer 24

The cells start to synthesise stress proteins (MIC-A and MIC-B). The t-cells bind to these two molecules within the cell and this induces apoptosis of the enterocyte.

Question 25

How does the inflammation caused by the gluten peptides alter behaviour of the intraepithelial lymphocytes?

Answer 25

The IEL’s have a reduced activation threshold and they become self-reactive and proliferate uncontrollably. They also kill enterocytes via apoptosis.

Question 26

How is coeliac disease tested for?

Answer 26

HLA-DQ haplotyping, or checking for the presence of HLA-DQ2/DQ8 and searching for gluten peptide or transglutaminase antibodies.

Question 27

What is the major health risk for undiagnosed sufferers of coeliac disease?

Answer 27

small bowel lymphoma or other gastrointestinal tract cancers.