Lecture 9- Chronic inflammation

Question 1

What causes chronic inflammation?

Answer 1

Acute inflammation which fails to resolve

Question 2

What are the origins of chronic inflammation?

Answer 2

Monocytes are recruited by chemotatic stimuli, these then differentiate macrophages these then activate the adaptive immune system which may sustain the chronic inflammation

Question 3

What are the mechanisms through which macrophages regulate inflammation, angiogensis and repair?

Answer 3

Relase of reactive oxygen species, cytokines, chemokines and proteases fro remodelling of the extracellular matrix

Question 4

What is the role of tH1Cells?

Answer 4

Secretion of interferon-gamma which stimulates tH1 development and activates macrophage responses to intracellular pathogens

Question 5

What is the role of tH2 cells?

Answer 5

Secretion of IL-4 which stimultes TH2 development and activates eosinophil responses to worms

Question 6

What is the role of tH17 cells?

Answer 6

Secretion of IL-17 and IL-21 which stimulates tH17 development and activates epithelial responses to microbes (secretion of antimicrobial substances such as defensins and GM-CSF)

Question 7

What is the role of tReg cells?

Answer 7

Secretion of cytokines such as TGFBeta which stimulates Treg development and suppression of inflammation

Question 8

Which T cell types can cause autoimmunity?

Answer 8

TH1, TH17

Question 9

Which T cell types can cause allergies?

Answer 9

TH2

Question 10

Which T cell type would a deficiency result in damage?

Answer 10

Treg as a deficency will result in excessive inflammation

Question 11

What are the symptoms of Gastroesophageal reflux disease?

Answer 11

Heartburn, regurgitation of stomach contents, upper abdominal pain

Question 12

What causes Gastroesophageal reflux disease?

Answer 12

Regurgitation of stomach acid, which contains acid, proteases such as pepsin and trypsin, bile acids

Question 13

What is the complication that can arise from Gastroesophageal reflux disease?

Answer 13

Barrett’s oesophagus where the epithelium of the oesphagus begins to take on the lining of the intestine rather than its typical squamous appearance

Question 14

What condition appears to be linked to barret’s oesophagus?

Answer 14

Oesophageal cancer

Question 15

What occured in the mouse model with the IL-1Beta oesophagus specific promotor

Answer 15

Inflammation with redness and oedema, leading to recruitment of myeloid cells secreting IL-6 followed by neutrophils, TH1 and macrophages,
Eventually stem cells were recruited from the stomach leading to the changes in the epithelial layers seen in barretts oesophagus

Question 16

What are the pathologies that may contribute to Chronic gastritis?

Answer 16

Chronic superficial gastritis, peptic ulcers, atrophic gastritis, intestinal metaplasia, dysplasia

Question 17

What is chronic superficial gastritis?

Answer 17

Presence of inflammatory cells in the gut

Question 18

What are peptic ulcers?

Answer 18

Destruction of epithelium and underlying stroma

Question 19

What is atrophic gastritis?

Answer 19

Loss of gastric glandular eptihelium resulting in a loss of acid producing cells

Question 20

What is intestinal meta plasia?

Answer 20

Replacement of intestinal epithelium with goblet cells

Question 21

What is dysplasia?

Answer 21

Loss of normal tissue differentiation, this may then proceed to cancer

Question 22

What is the cause of chronic gastritis?

Answer 22

The bacterium H.Pylori

Question 23

What are the virulence factors of H.Pylori?

Answer 23

CagA, Peptidoglycan and H.Pylori neutrophil activating protein

Question 24

What does CagA do?

Answer 24

Disassemble tight junction allowing the dangerous stomach substances to attack the unprotected functional layers
When working with peptidoglycan it can cause secretion of IL-8 through Pattern recognition receptors leading to neutrophil recruitment

Question 25

What does H.Pylori neutrophil activating protein do?

Answer 25

Causes neutrophils to release damaging reactive oxygen species, and myeloperoxidase
Macrophages are recruited
Parietal cells continue to secrete acid causing a build up of Ca2+ and the morphogenic protein sonic hedgehog, IL-1Beta acts to reduce this damage causing atrophy of parietal cells

Question 26

What are the symptoms of inflammatory bowel disease?

Answer 26

Affected areas will have redness, swelling, pain and leukocyte infiltration
Ulcers form on the epithelial lining
Wall of the bowel undergoes extensive damage and fibrotic thickening
lumen narrows due to obstruction caused by the fibrosis
Fissures in the bowel wall are created
Immune system activated with lymphocytes and granulomas present

Question 27

What are the risk factors for developing Chron’s Disease?

Answer 27

Family history (mutation in CAD15 gene which is a protein which helps the innate immune system eliminate bacteria)
Enviromental changes such as diet could be changing the commensal bacteria of the gut
Microbial factors, uncontrolled immune responses

Question 28

What is the pathogenesis of chron’s disease?

Answer 28

Enviromental trigger damages the mucosa invoking an inflammatory response, this may not be able to repair the damage in individuals with a genetic defect resulting in an uncontrolled inflammation response