Immu 5: Allergy Flashcards
Name 1 cytokine released from damaged epithelium secondary to exposure to an allergen/worm ?
TSLP
describe the Th2 mediated response
- stressed/damaged epithelium releases signalling cytokines eg TSLP
- these cytokines act on Th2 cells, Th 9 cells and ILC2 cells
- promoting the selectionof IL4, IL5, IL13
- these act on eosinophils and basophils
- TSLP and other cytokines also activate follicular Th2 cells which releases IL4
- IL4 stimulated B cells to produce IgE and IgG4
- skin dendritic cells promote the secretion of Th2 cytokines
Which T cells are involved with allergy response ?
Th2 cells
Which T helper cells recognise pathogen structures like PAMPs? (2)
Th1 and Th17
List 3 important cytokines released by Th2 cells in an allergic response ?
IL-4
IL-5
IL-13
3 lymphocyte cell types involved in initial allergen response
- Th2 cells
- Th9 cells
- ILC2 cells
Which cytokine released by Th2 cells is considered the master switch that causes Isotype switching of B cells to IgE ?
IL-4
What protein on the surface of dendritic cells signals to naïve T cells in food allergy?
OX40
How do allergens/worms cause Histamine and leukotriene release ?
What is the effect of these mediators?
They cause cross linking of IgE receptor on mast cells, which causes release of Histamine, leukotriene and prostaglandins
Oral vs skin / resp exposure to allergen
- Oral: IgG and IgA mediated sensitisation
- Skin/resp: IgE sensitisation
what happens when an allergen is ingested through the oral route
T regs derived from the GI mucose will inhibit IgE sythesis to keep the immune system in balance
Which allergies develop in infants ? (2)
Atopic dermatitis
Food allergies - milk, egg, nuts
Which allergies develop in children ?
Asthma
allergic Rhinitis
Which allergies tend to develop in adults ? (4)
Drug allergies
Oral allergy syndrome
Occupational allergies
Bee sting allergy
Name a bio marker for anaphylaxis?
What is peak concentration?
What releases this marker?
Mast cell tryptase
- is useful in anaesthetics to rule out anaphylaxis when there is acute hypotension and rash
Peak concentration = 1-2 hours after exposure
Systemic degranulation of mast cells during anaphylaxis results in increased serum tryptase
What is the gold standard test for food and drug allergy ?
Challenge tests
- can be done in clinic to see if food or drugs promotes an allergic response
Give 3 different types of anaphylaxis other than IgE ?
IgG- e.g monoclonal antibodies
Complement- dialysis membranes
Pharmacological- aspirin and NSAIDS
What is a cause of Throat swelling which mimics anaphylaxis (rare)?
C1 inhibitor deficiency
What is the most important treatment of Anaphylaxis ?
IM adrenaline (outer aspect of thigh)
how is anaphylaxis managed
- IM ADRENALINE
- 100% oxygen
- fluid replacement
- inhaled bronchodilators (salbutamol)
- hydrocortisone 100mg IV
- chlorpheniramine 10mg IV
What is a cause of delayed food induced anaphylaxis ?
Beef, pork,lamb
Tick bites
Gelatine in vaccines can do it as well
what are the clinical features of an IgE mediated response
- minutes to hours after exposure
- angioedema, urticaria, flushing, itching, cough, SOB, nasal congestion, wheeze, red watery eyes, d+v, hypotension
- usually at least 2 organ systems involved
- symptoms are reproducible
- allergic symptoms can be triggered by cofactors
how can we investigate allergic disease
- skin prick and blood test
- lab measurements of allergen-specific IgE
- component-resolved diagnosis
- basophil activation test
- challenge test
- during an acute episode - serial mast cell tryptase
- blood and/or urine antihistamine
Describe specific IgE sensitisation test
What is a +ve test?
Rule with antihistamines before doing this test?
Skin prick and blood tests
- higher concentration = more symptoms
- higher affinity to target = increased risk
- Measure the local wheal and flare response to controls and allergens
+ve test = wheal ≥ 3mm greater than the negative control
Antihistamines: stop these 48 hrs before test (do serum IgE levels if they cannot stop this for whatever reason)
Do Skin prick and blood tests determine allergy?
No - a positive IgE test only demonstrates sensitisation, NOT clinical allergy (i.e. IgE is a risk factor for allergy, it is not synonymous with allergy)
how does the skin prick test work
- positive control (histamine)
- negative control (diluent)
- inject a standardised solution of allergen
- positive test = wheal >3mm greater than negative control
- antihistamines to be discontinued for 48 hrs before the test
describe the serum specific IgE blood test
allergen bound to a sponge and the specific IgE will bing to the allergens
washed over with anti-IgE antibody tagged with fluorescent label
what is the basophil activation test
- measurement of basophil response to allergen IgE cross linking
- detect food allergy
- activated basophils increase the expression of CD63, CD203, CD300 protein on their cell surface
mechanisms of anaphylaxis
IgE - mast cells, basophils - histamine + PAF
- food, insect venom, ticks, penicillin
IgG - macrophages, neutrophils - histamine + PAF
complement - mast cells, macrophages - PAF + histamine
- biologicals, blood and IgG transfusions
pharmacological - mast cells - leukotrienes + histamine
- NSAIDs including aspirin, opiates, neuromuscular and quinolones
complement - lipid excipients, liposomes, dialysis membranes and PEG
difference between food allergy and food intlerance
allergy = adverse effects arising from specific immune response that occurs reproducibly on exposure to a given food
intolerance = non-immune reactions that include metabolic, pharmacological and unknown mechanisms
A 15-year-old boy with a history of asthma and hayfever who notices an urticarial and angioedema skin rash shortly after eating peanuts. What is the most appropriate initial diagnostic test?
Skin prick test
Test that can be done to detect IgE to single protein components, especially useful for peanuts and allergies so that you don’t have to do challenge test
Component Resolved Diagnostics (CRD)- A.k.a. Radioallergosorbent Test
A 55-year-old man who attends A&E with angioedema involving the lips and tongue which has developed over previous hours. He has a history of hypertension and is taking an ACEi and CCB. Clinical examination shows a pulse of 75bpm, BP of 150/90, RR of 18/min and O2 sats of 78% on air. What is the most likely diagnosis?
ACEi induced angioedema
What does epipen contain in children and adults?
- 300mg adrenaline- ADULT
- 150mg adrenaline- CHILDREN
- Prednisolone 20mg OD
- Antihistamine (Cetirizine 10mg OD)
What is oral allergy syndrome?
- Limited to oral cavity, swelling and itch: only 1-2% cases progresses to anaphylaxis
- Sensitisation to inhalant pollen protein lead to cross reactive IgE to food
- Onset after pollen allergy established: affect adults > young children
A 35-year-old man with tree pollen hay fever and immediate lip tingling and swelling immediately after eating apples. What is the most likely explanation for IgE hypersensitivity ?
Cross reactive IgE sensitisation between hay fever and apple allergens
