Immunopathology 2 - Problems mediated by innate immunity Flashcards
What are the cardinal features of inflammation?
swelling, redness, heat, pain, loss of function
What are the actions of IL-1?
Fever, neutrophilia, neutrophil activation, collagen proliferation, amino acid release in muscle, release of acute phase proteins from the liver, T cell activation, B cell activation - plus many more
How is IL-1 synthesised?
First produced as an inactive precursor (Pro IL-1) and then cleaved at the N terminus to make mature IL-1
What is familial cold urticaria?
A mutation in cryopyrin (a NOD like receptor) which causes an inflammatory response to cold
What cleaves Pro IL-1 to activate mature IL-1?
caspase-1
What is the inflammasome?
A protein complex which activates caspase-1 to get IL-1
Which other cytokines are cleaved by the inflammasome?
IL-18 and IL-33
What does inflammasome activation require?
TLR signalling and NLR signalling
What is gout?
A disease where monosodium urate formation exceeds renal clearance capacity and precipitates into crystals - the crystals then activate the inflammasome and this leads to acute inflammation
What is anakinra?
An IL-1 receptor antagonist used for symptomatic treatment of gout
What is the contraindication for anakinra?
Neutropenia
How do macrophages detect salmonella that is replicating within them?
Via inflammasome activation
What is pyroptosis?
Cell death after inflammasome activation
How does this help the body deal with the infection?
The pathogen has to go into the extracellular space where it can be mopped up by neutrophils
What cytokine is produced because of inflammasome activation?
IL-18
What is the action of IL-18?
Induces production of IFN-gamma by T cells - to target the pathogen
What infections are patients with a mutation in IFN gamma susceptible to?
salmonella
What is metabolic syndrome?
A combination of heart disease, lipid problems, hypertension, type 2 diabetes, dementia, cancer, polycystic ovarian syndrome and non-alcoholic fatty liver disease
How does metabolic syndrome lead to the activation of inflammasomes?
The high levels of circulating fat can precipitate and form crystals which will activate inflammasomes
What cytokines are released due to the inflammasome activation?
IL-1 and TNF alpha
What is the result of IL-1?
Insulin resistance
What is the response of the pancreas to insulin resistance?
Makes more insulin - becomes overworked and can rupture
What is the response of the liver to inflammasome activation?
Inflammation which leads to hepatitis which can lead to cancer
What is the result of the inflammasome activation in blood vessels?
atherosclerosis
