108 - Immunopathology Flashcards
IL-1 effects 1 2 3 4 5 6 7 8
1) Fever from hypothalamus
2) Bone marrow release of neutrophils
3) Neutrophil activation
4) Fibroblast proliferation, collagen production
5) Muscle amino acid release
6) Liver acute phase protein release
7) T cell activation, production of IL-2
8) B cell activation and Ig production
Mechanism of IL-1b regulation
Synthesised in an inactive form.
Rare disease where patient develops local and systemic signs of acute inflammation in response to cold
Familial cold urticaria
How does familial cold urticaria come about?
Single nucleotide mutations of cryopyrin gene (NOD like receptor family), which is associated with IL-1-converting enzyme.
Mutation increases activity of ICE
Enzyme that activates IL-1 precursor
IL-1-converting enzyme, aka caspase 1
Broad function of NOD-like receptor family
Activates inactive IL-1
How is caspase 1 activated?
Inflammasome complex (NOD-like receptor acts as receptor) autocatalytically induces caspase 1
How does gout come about?
Consumption of purine-rich foods.
Monosodium-urate formation exceeds renal clearance capacity, precipitates into crystals (often in joints, particularly base joint of big toe)
How do uric acid crystals induce inflammation?
1
2
3
1) Crystals are recognised by cells, phagocytosed
2) NLRP3 recognises crystal.
3) Inflammasome induces caspase 1, which activates IL-1
Drug that is an IL-1 receptor antagonist
Anakinra
What is anakinra absolutely contraindicated in?
Neutropaenia
What can be used to treat gout?
Anakinra
Mechanism of inflammasome regulation
1
2
3
1) Needs two convergent signals to activate
2) Signal one is priming of cells with PAMP binding to receptor (often TLR)
3) Signal two is activation, where NOD or NLRP detect ligand.
Difference between Salmonella gastroenteritis and typhoid fever
Gastro is limited to GIT mucosa.
Typhoid fever is a systemic infection.
What can limit Salmonella to GIT?
Flagellin is detected by TLR5, inflammasome is induced, kills all Salmonella within infected cell.
Also induces IL-18 release, which promotes T-cell release of IFNg
