Hypersensitivity/allergy L4 Flashcards
What are the 3 cayses of hypersensitivity
Allergy, reactions to infections, autoimmune diseases
What are type 1,2,3 from
Antibody mediated, sometimes via th2 response
What is thpe 4 mediated by
Delayed t cell responses , 17,1,cd8
What hppens on first exposure in type 1
Pamp from allergens like pollen in hay fever can cause actication of apc like dc and macrophages. Apc allows th2 differentiation. Th2 then via TD responses binds b cells via cd40, secretion of il4,il13 can cause class switching to ige, mast,baso and eosinophil attraction too
Ige then binds fcr e on the mast or basophils causing it to be sensitised for secondary exposure
Which cytokines from th2 ade important in th2 ewsponse and ige response in type 1 hypersensitivity
Il4,13 and 5 for eosinophil production
What are mast or basophils exposed to ige on fiest exposure
Sensitised for secondary eg pollen again
What happens on secondary exposure
Instanr degranulation of things like tnf a, histamine
Lipid production of things like pgd2
All cause inflammation eg in airway
Where are type 1 allergens usually found and give examples
Mucosal surfaces
Wg food, pollen, drugs
What types of genetic polymorphisms can affect hypersensitivity type 1
Mhc, il 4, fcr e on mast and basophils
Which ab are made against alletgens in type 2 which mediate hypersensitivity
Igg and igm
Where are allergens in type 2 found
Cell bound eg rh on rbc
How does complement have a part in type 2
Gets actucated by igg and igm via c1q, produces opsin coating the cell with allergen on it for phagocytosis.
Also mac which kills the cells too
What other yype of ab mediated killing in type 2 to innocent cells
Adcc via fcr on cells like eosinophils and nk cells which then kill the cells cia granules
What are frustrated phagocytes and how does this cause tissue damage in type 2
When they try engulf the complement or ab coated cells with allergens on them via fcr or c3b recetors. Too larhe fells cause release of lysosomal products = tissue dmaage
Explain haemolytic disease of newborn as a type 2 example
If a chuld has rh ag on their rbc and mother is nevstice. She makes anti rh in her first pregnancy. Usually igg. On second pregnancy, anti rh will cross placenta and fix complement and themselebs on rbc causing the killing of rbc = anemia
What causes brain damage in haemolytic disease
Hg breakdown into billirubin
What treatment is used for haemolytic disease
Uv to interfere with billirubin
Ab which bund rbc wne block anti rh
How can drugs inruce haemolytic diaease
Can bind rh which then attract ab for the frugs
Ehat is responsible for type III eg RA
Igg complex with soluble allergens to form immune complexes (ICs)
What happens to ICs not cleared
Deposited on tissue causig damage, inflammation and blockage wg of kidney
Which size ICs are good and why
Large ic can be removed by complement activation wnd therefore c3b qnd mac mediated removal
What do small ic bind to which causes mast cell degranulation causing problems
Fcr y on mast or basophils
What happens when small ics bind to neutrophils via fcr y
Cant be phagocytosed well. Causes rekease of lysosomal content for tissue damage
What happens if the small ic bind macrophages
Macrophage pahgocytosis releases inflammatory cytokines and other mediators of inflammation
What determines site of immunopathology eg skin, kidney, joints
Where allergen is deposited eg via iv, subcutaneous, inhalation
What happens in thpe 4 on first exposure
Allergen taken up by apc which then travel to lymph and cause differentiation eg into th1 response or cd8 if mhc1.
What happens on reexposure
Memroy t cells instantly release cytokines like ifny, il2 which acticates macrophages sexreting inflammatory like tnfa,il8,gm-csf
Dermatitis of rhe skin can be caused by metals like nickel. How
Taken in by skin barrier if disrupted. Causes peptide modification. The modified perise prwsented on cells like langerhans skin cells
Move to lymph to activate th1 differentiation
Acticate macrophages can secrete inflammatory cytokines like tnf a
What allergen example allows cd8 reapinse in type 4
Urushiol oil in poison ivy which modifies peptides
Explain the poison ivy xausing blisters
Langerhans can present on mhc II so cd8 kill the cells eg via granzymes. This causes blistering of the skin
What is the hygiene hypothesis
Causes lack or inbalance between th1 and th2 responses because lack of pathogen exposure increasint sensutivrt to allergens
How can environment impact allergy predisposition
Cigarettes, air pollution, microbiota changes, low fibre diets can all allow type 1 responses and also type 4 if epi barrier disrupted for dermatitis
How does th2 affect airway
Inflammation and collagen build up refuces lumen space eg in asthma
What is the most prevalent hypersensitivity for atopic allergy
Type 1 ige th2
How does type 1 allow early pahse of asthma
Reaction to allergens causes mast cell effects like bronchoconstriction eg via ltc4, mucus building, vasodilation etc via eg histamine
How can ige in gi tract be an issue
Causes comiting and diarrhoea by histamine h1 causing broncho and smooth muscle constriction
Does histamine increase mucus
Yes
What are allergy treatments
Antihistamine
Epinephrine if anaphylaxis to relax airways
Bronchodilators
How does desensitatuon cia immunitherapy work
Allergen ticen in small doses to reduce ige respinses and allow igg4 class switching instead which blocks binding to fcr e
Name a biological therapy for atopic allergies
Ma which block ige cross linking via binding fc on ige to stop fcr e binding on mast/baso
