Immuno: Allergy Flashcards
Define allergic disorder.
Immunological process that results in immediate and reproducible symptoms after exposure to an allergen. Usually involves IgE-mediated type 1 hypersensitivity reaction.
Define sensitisation.
Detection of specific IgE either by skin prick testing or in vivo blood test
NOTE: this does NOT define allergic disease
Describe the difference between immune responses mediated by Th1 and Th2 cells.
- Pathogens that have conserved structures (PAMPs) such as bacteria are recognised by Th1 and Th17 cells
- Multicellular organisms (e.g. helminths) and allergens don’t have conserved structures but they release mediators that damage epithelial cells
- Disturbance of epithelial cells is recognised by the Th2 cells
Outline the Th2-mediated immune response.
- Damaged epithelium releases signalling molecules (e.g. TSLP)
- These cytokines will act on Th2, Th9 and ILC2 cells, which then produce IL4, IL5 and IL13
- These cytokines act on basophils and eosinophils which play a major role in the expulsion of allergens and parasites
- TSLP and other cytokines can also activate follicular Th2 cells which release IL4
- IL4 stimulates B cells to produce IgE and IgG4
What other allergic response can be initiated by parasites and allergens which is not mediated by Th2 cells?
- Allergens can cross-link IgE leading to mast cell degranulation and the release of histamines, prostaglandins and leukotrienes
- These mediators act on the epithelium causing increasing permeability, smooth muscle contraction and neuronal irritability (itching)
- This response aims to expel the parasite/allergen and is implicated in asthma, eczema and hay fever
Describe the relationship between Langerhans cells and Th2 cells.
Langerhans cells promote the secretion of Th2 cytokines
NOTE: skin defects (i.e. epithelial barrier issues) are a significant risk factor for the development of IgE antibodies via Th2 responses
What induces the production of IL4?
Peptide presentation via MHC to TCR or Th2 cells
How is oral allergen exposure different from respiratory or skin exposure with regards to developing an allergic response?
- Oral exposure promotes immune tolerance whereas skin and respiratory exposure promotes IgE sensitisation
- When an allergen is ingested orally, Tregs in the GI mucosa will inhibit IgE synthesis to keep the immune system in balance
List the allergic diseases that present in the following age groups:
- Infants
- Children
- Adults
-
Infants
- Atopic dermatitis
- Food allergy (milk, eggs, nuts)
-
Children:
- Asthma
- Allergic rhinitis
-
Adults:
- Allergic rhinitis (MOST COMMON)
- Drug allergy
- Bee allergy
- Occupational allergy
List some theories behind the increasing prevalence of allergic disorders.
- Hygiene hypothesis
- Lack of vitamin D in infancy (leads to food allergy)
- Dietary factors (reduced omega and linleic fatty acids)
- High concentration of dietary advanced glycation end-products and pro-glycating sugars which the immune system mistakenly recognises as causing tissue damage (e.g. soda)
List some clinical features of IgE-mediated allergic responses.
- Angioedema
- Urticaria
- Flushing
- Itching
- Cough
- SOB
- Wheeze
State some examples of co-factors that could trigger an allergic response.
- Exercise
- Alcohol
List some elective investigations for allergic disease.
- Skin prick and intradermal tests
- Specific IgE measurement
- Component resolved diagnostics
- Basophil activation test
- Challenge test
List some investigations that may be conducted during an acute allergic episode.
- Serial mast cell tryptase
- Blood/urine histamine
Does a postive specific IgE test demonstrate allergy?
No - it demonstrates sensitisation
What features of the specific IgE test are used to predic risk and likelihood of symptoms?
- Concentration - higher levels means more symptoms
- Affinity to the target - higher affinity means increased risk
- Capacity of IgE antibody to induce mast cell degranulation
Describe how skin prick tests are conducted.
- Expose a patient to a standardised solution of allergen extract through a skin prick on the forearm
- Use standard skin test solutions with a positive control (histamine) and negative control (dilutent)
- Measure the local wheal and flare response
- Positive result: wheal >3mm greater than the negative control
- Antihistamines should be discontinued for at least 48 hours before the test
What are the advantages and disadvantages of skin prick testing?
Advantages:
- Rapid (15-20 mins)
- Cheap
- High negative predictive value
- Increasing size of wheals correlates with higher probability of allergy
Disadvantages:
- Operator-dependent
- Risk of anaphylaxis
- Poor positive predictive value
- Limited value in patients with dermatographism or extensive eczema
Describe how specific IgE tests work.
- Allergen is bound to a sponge and mixed with the patient’s serum
- Specific IgE will bind to the allergens on the sponge (if present)
- This is washed with anti-IgE antibody which is fluorescently labelled
- Higher values are associated with allergic disorders
NOTE: good negative predictive value
List some indications for specific IgE tests.
- Patients who cannot stop antihistamines
- Patients with dermatographism
- Patients with extensive eczema
- History of anaphylaxis
- Borderline skin prick results
What is component resolved diagnostics?
- A blood test to detect IgE to single protein components (useful for peanut and hazelnut allergy)
- IgE sensitisaton to heat and proteolytic labile proteins = minor symptoms
- IgE sensitisation to heat and protolytic stable protein = major symptoms
List some indications for allergy component testing.
- Detect primary sensitisation
- Confirm cross-reactivity
- Define risk of serious reaction for stable allergens
What is mast cell tryptase used for?
- Tryptase is pre-formed protein found in mast cell granules
- Systemic degranulation during anaphylaxis results in increased serum tryptase
- Therefore, it is a biomarker for anaphylaxis
When does mast cell tryptase reach peak levels and return to baseline levels?
- Peak = 1-2 hours
- Baseline = 6-12 hours
NOTE: if it fails to return to baseline, it may suggest systemic mastocytosis
When might mast cell trypase be measured?
If the diagnosis of anaphylaxis is unclear (e.g. hypotension and rash during anaesthesia)
NOTE: it has lower sensitivity for food-induced anaphylaxis
What is the gold standard test for diagnosing food and drug allergy?
Challenge test
Describe how challenge tests are carried out.
- Increasing volumes of the offending food/drug are ingested
- Observe a reaction
- Done under close medical supervision
- Risk of severe reaction
What is a basophil activation test?
- Measurement of basophil response to allergen IgE cross-linking
- Activated basophils show increased expression of CD63, CD203 and CD300
- This is increasingly used in food and drug allergy
Define anaphylaxis.
A severe, potentially life-threatening systemic hypersensitivity reaction characterised by rapid-onset airway, breathing and circulatory problems which are often associated with skin and mucosal changes.
NOTE: skin is the most frequent organ involved
List some mechanisms of anaphylaxis.
- IgE - mast cells and basophils - histamine and PAF (triggered by food, venom, ticks, penicillin)
- IgG - macrophages and neutrophils - histamine and PAG (triggered by blood product transfusions)
- Complement - mast cells and macrophages - histamine and PAF (triggered by lipid excipients, liposomes, dialysis membranes)
- Pharmacological - mast cells - histamine and luekotrienes (triggered by NSAIDs)
List some reactions that can mimic anaphylaxis.
- Skin - chronic urticaria and angioedmea (ACE inhibitors)
- Throat swelling - C1 inhibitor deficiency
- CVS - MI and PE
- Resp - severe asthma, inhaled foreign body
- Neuropsych - anxiety/panic disorder
- Endocrine - carcinoid, phaeochromocytoma
- Toxic - scromboid toxicity (histamine poisoning)
- Immune - systemic mastocytosis
Describe the mechanism of action of adrenaline in treating anaphylaxis.
- Alpha 1 - peripheral vasoconstriction, reverses low BP and mucosal oedema
- Beta 1 - increases HR, contractility and BP
- Beta 2 - relaxes bronchial smooth muscle, reduces release of inflammatory mediators
Which supportive treatments are given alongside adrenaline in the management of anaphylaxis?
- Adult body position
- 100% O2
- Fluid replacement
- Inhaled bronchodilators
- Hydrocortisone 100 mg IV
- Chlorpheniramine 10 mg IV
List some measures that may be taken in the ongoing management of a patient who has experienced an episode of anaphylaxis.
- Referral to allergy clinic
- Investigate cause
- Written information on recognition of symptoms, trigger avoidance and indications for self-treatment with EpiPen
- Prescription of emergency kit to manage anaphylaxis
- Copy of management plan for patients, parents and school staff and GP
- Immunotherapy (if indicated)
- Refer to dietician (if food-induced)
- Advise getting MedicAlert bracelet
- Utilise patient support groups (Anaphylaxis Campaign)
Which commonly used drug can cause angioedema?
ACE inhibitors
NOTE: this can happen at any point when taking ACE inhibitors (i.e. even several years after being on ACE inhibitors)
What is the key difference between food allergy and food intolerance?
The mechanism behind food intolerance is NOT immunological
List some types of food intolerance.
- Food poisoning
- Enzyme deficiency (e.g. lactose intolerance)
List some types of food allergy.
- IgE mediated - anaphylaxis
- Mixed IgE and cell-mediated - atopic dermatitis
- Non-IgE mediated - coeliac disease
- Cell-mediated - contact dermatitis
Which investigations are usually used to confirm the diagnosis in patients with a clinical history suggestive of food allergy?
Skin prick test or specific IgE blood test
List some IgE-mediated food allergy syndromes.
- Anaphylaxis (e.g. peanut)
- Food-associated exercise-induced anaphylaxis (ingestion of food leads to anaphylaxis if the individual exercises within 4-6 hours of ingestion (e.g. wheat, shellfish))
- Delayed food-induced anaphylaxis to beef/pork/lamb (symptoms occur 3-6 hours after ingestion, induced by tick bites)
- Oral allergy syndrome (limited to oral cavity with swelling and itching, occurs after pollen allergy is established, caused by cross-reaction of IgE antibody to pollen with stone fruits (e.g. apples), vegetables and nuts)
