Immunology 6 - Allergy Flashcards
(22 cards)
What is the difference in CD4 T cell response between microbial recognition and allergen recognition?
Microbe: PAMP is recognised –> Th1 and Th17 response –> neutrophils and monocytes
Allergen: functional change recognised (eg tissue damage) –> Th2 response –> eosinophils
How does Th2 activation cause mast cell degranulation?
Th2 secretes IL4
IL4 activates B cells to produce IgE
IgE crosslink -> mast cells degranulation and secrete:
- prostaglandins
- leukotrienes
- histamines
What are innate lymphoid cells
found at mucosal barriers (skin, resp and GIT)
lack specific Ag receptors
similar to CD4 helper cells - based on cytokine profile
What does ILC2 secrete and what is its role
IL4, IL5, IL9, IL13 and amphiregulin (AREG) - epithelial barrier repair in skin and resp tract
allergic asthma, rhinitis, food allergy and eosinophilic oesophagitis
ILC > steady state inhibition for Treg cells
Which interleukins are important in Th2 cell responses?
IL4 - helps B cells to produce IgE
IL5 - expands and activates eosinophils
IL13 - mucus
What receptors does IgE bind?
FcεR1 - mast cells, basophils, eosinophils, DC
FcεR2 = above + B cells, resp/GI epithelial cells
Recall the two subtypes of mast cells and where they are found
MC (tryptase T) skin
MC (chymotryptase CT) airways
what receptors trigger mast cell degranulation?
IgE/IgG (Ab-Ag crosslinking)
- FcεR1 (IgE)
- FcγR1 and FcγR1IA (IgG)
GPCR
- MRGPRX2 - soluble mediators
Why does atopic dermatitis predispose to allergic sensitisation?
oral - promotes immune tolerance
- T-regs (from GI mucosa) inhibit IgE synthesis
- T-regs inhibit multiple pro-allergic functions such as inhibiting DC APC function, secretion of IL-10, etc.
skin and resp promotes IgE sensitisation
Why do filagrin mutations increase risk of allergic disease?
Increase risk of atopic dermatitis which increases allergen exposure
do Allergen specific IgE (Sensitisation) Tests prove diagnosis for allergic disease?
no
IgE necessary but not suffiecient for diagnosis
a positive IgE test only demonstrates sensitisation, NOT clinical allergy
only to exclude allergy
skin prick/intradermal/IgE blood test/molecular
What represents a positive result in a skin-prick allergy test?
Positive outcome = wheal ≥3mm than negative control
Antihistamines and antidepressants discontinued for 48 hours beforehand (checked with positive control)
indications for blood sensitisation IgE tests
no access to SPT/IDT
pt cannot stop antihistamines
hx of dermatographism, extensive eczema
hx anaphylaxis
decision on who needs food challenge
prediction for resolution of egg, milk, wheat allergy
monitor response to anti-IgE therapy
What can component/ molecular allergy testing be useful for?
For nuts, detection of storage protein is indicative of a stronger reaction
For wheat, detection of omega-5-gliadin is indicative of a stronger reaction
How is basophil activation used in allergy diagnostics
measures basophils response to allergen IgE cross linking
↑ expression CD63, CD203 and CD300 protein
What is a measurement of mast cell tryptase used for?
Tryptase is found in mast cell granules
Biomarker for anaphylaxis that peaks 1-2 hours following a reaction (baseline 6-12h)
Useful if diagnosis of anaphylaxis is not clear
What is the gold standard method of allergy testing?
open or blinded allergen challenge
Increasing volumes of the offending food/drug are ingested
Describe the symptoms of the oral allergy syndrome
Symptoms of allergy limited to mouth
Common allergens = birch pollen + rosacea fruit + ragweed + melons + mugwort + celery (due to cross reactivity)
What is delayed food induced anaphylaxis
to beef, pork, lamb
3-6 hours after eating red meat and gelatin
IgE antibody to oligosaccharide alpha-gal (α1, 3-galactose) found in gut bacteria
Induced by tick bites which should be avoided
What are the positive and negative controls used in skin prick testing?
Positive: histamine
Negative: diluent
Recall the management of anaphylaxis in adults
Elevate legs
100% oxygen
IM adrenaline 500 mcg
Inhaled bronchodilators
Hydrocortisone 200mg IV
Chlorphenamine 20mg IV
IV fluids
Seek help
Prevention of food allergy
breast feeding - strong FH
LEAP study - early introductio to peanuts in high risk cildren reduces development of peanut IgE sensitisation and allergy
