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
- 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 skin barrier and allergy
Skin defects (i.e. epithelial barrier issues) are a significant risk factor for the development of IgE antibodies via Th2 responses e.g. in atopic dermatitis
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, Treg in the GI mucosa will inhibit IgE synthesis and promote tolerance
List some theories behind the increasing prevalence of allergic disorders.
- Hygiene hypothesis - reduced childhood infection increases allergy susceptability
- Lack of vitamin D and fatty acids in diet
- Loss of symbosis with gut and respiratory bacteria due to altered composition and biodiversity
- Increase in epithelium-damaging agents due to industrialisation
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
How is allergic disease diagnosed
History
Examination
Allergen specific IgE (sensitisation) tests
- Skin prick
- Serum IgE (RAST)
Functional allergen tests
- Mast cell tryptase
- Basophil activation test
- Allergen challenge
List some clinical features of IgE-mediated allergic responses.
Symptoms are repoducible:
Skin
* Angioedema
* Urticaria
* Flushing
* Itching
Respiratory
* Cough
* SoB
* Wheeze
GI
* Nausea, diarrhoea, vomiting
Vascular and brain
* Hypotension, shock
* Sense of impending doom
State some examples of co-factors that could trigger an allergic response.
- Exercise
- Alcohol
- NSAIDs - break GI tract
- Viral infection - in children
List some investigations that may be conducted during an acute allergic episode.
- Serial mast cell tryptase
- Blood/urine histamine
Does a postive skin prick/specific IgE test demonstrate allergy?
No - it demonstrates sensitisation
What features of the specific IgE test are used to predict 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