Lecture 9- Chronic inflammation Flashcards
What causes chronic inflammation?
Acute inflammation which fails to resolve
What are the origins of chronic inflammation?
Monocytes are recruited by chemotatic stimuli, these then differentiate macrophages these then activate the adaptive immune system which may sustain the chronic inflammation
What are the mechanisms through which macrophages regulate inflammation, angiogensis and repair?
Relase of reactive oxygen species, cytokines, chemokines and proteases fro remodelling of the extracellular matrix
What is the role of tH1Cells?
Secretion of interferon-gamma which stimulates tH1 development and activates macrophage responses to intracellular pathogens
What is the role of tH2 cells?
Secretion of IL-4 which stimultes TH2 development and activates eosinophil responses to worms
What is the role of tH17 cells?
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)
What is the role of tReg cells?
Secretion of cytokines such as TGFBeta which stimulates Treg development and suppression of inflammation
Which T cell types can cause autoimmunity?
TH1, TH17
Which T cell types can cause allergies?
TH2
Which T cell type would a deficiency result in damage?
Treg as a deficency will result in excessive inflammation
What are the symptoms of Gastroesophageal reflux disease?
Heartburn, regurgitation of stomach contents, upper abdominal pain
What causes Gastroesophageal reflux disease?
Regurgitation of stomach acid, which contains acid, proteases such as pepsin and trypsin, bile acids
What is the complication that can arise from Gastroesophageal reflux disease?
Barrett’s oesophagus where the epithelium of the oesphagus begins to take on the lining of the intestine rather than its typical squamous appearance
What condition appears to be linked to barret’s oesophagus?
Oesophageal cancer
What occured in the mouse model with the IL-1Beta oesophagus specific promotor
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
What are the pathologies that may contribute to Chronic gastritis?
Chronic superficial gastritis, peptic ulcers, atrophic gastritis, intestinal metaplasia, dysplasia
What is chronic superficial gastritis?
Presence of inflammatory cells in the gut
What are peptic ulcers?
Destruction of epithelium and underlying stroma
What is atrophic gastritis?
Loss of gastric glandular eptihelium resulting in a loss of acid producing cells
What is intestinal meta plasia?
Replacement of intestinal epithelium with goblet cells
What is dysplasia?
Loss of normal tissue differentiation, this may then proceed to cancer
What is the cause of chronic gastritis?
The bacterium H.Pylori
What are the virulence factors of H.Pylori?
CagA, Peptidoglycan and H.Pylori neutrophil activating protein
What does CagA do?
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
What does H.Pylori neutrophil activating protein do?
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
What are the symptoms of inflammatory bowel disease?
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
What are the risk factors for developing Chron’s Disease?
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
What is the pathogenesis of chron’s disease?
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
