Hypersensitivity I (IMMUNOLOGY) Flashcards
What is hypersensitivity?
Usually an exaggeration of normal immune mechanisms that results in bystander damage to the self
What is type I hypersensitivity?
An IgE-mediated antibody response t an external antigen (allergen)
What is the hygiene hypothesis?
Improved sanitation and decreased incidence of infectious disease has result in a world that is too clean leasing to increased predisposition to allergic conditions during childhood
How does a type I hypersensitivity reaction come about?
Stimulation of allergen-specific T-cells by allergen-derived peptides, presented by dendritic cells ( in context of MHC molecules) results in differentiation of CD4+ T-cells into effector TH2 cytokine producing cells
TH2 cells produce IL-4, IL-5, and IL-13 which coordinated the allergic response by regulating IgE synthesis by B cells, stimulating the differentiation and egress of eosinophils at site of allergen exposure
What are specific features of a Type I hypersensitivity reaction?
Asthma Urticaria Angioedema Allergic rhinitis Allergic conjunctivitis Diarrhoea and vomiting Anaphylaxis
What are common allergens?
House dust mites Pollen Animal dander Foods Drugs Latex Bee & wasp venom
What is angioedema?
Self limiting, localised swelling of subcutaneous tissues or mucous membranes
Non-pitting oedema
Often without clear demarcation
Generally not itchy unless associated with urticaria
What occurs with mast cells upon first exposure to an allergen?
Express receptors for Fc region of IgE antibody on their surface (Fc-eppsillon-R1). When they encounter with allergen, B cells produce antigen-specific IgE antibody and the allergen is cleared
What occurs with mast cells upon second exposure to an allergen?
Allergen binds to IgE-coatedmast cells and disrupts cell membrane causing degranulation and release of vasoactive mediators (histamine, tryptase) also increase cytokines and leukotrienes transcription
What is the role of mast cells in the inflammatory cascade?
Increase blood flow
Contraction of smooth muscle
Increased vascular permeability
Increased secretions mucosal surfaces
Which type of asthma is a type I hypersensitivity reaction?
Extrinsic atopic asthma
What occurs when an allergic reaction happens in the lung?
Histamine and other inflammatory mediators are released causing muscle spasms (wheeze), mucous inflammation (increased sputum production) and inflammatory cell infiltrate (sputum often yellow, associated with chronicity)
What are the clinical features of anaphylaxis?
Itch of palms, soloed feet and genitalia Wheeze Flushing, urticaria Conjuctivital infection Rhinorrhea, angioedema Feeling impending doom, loss of consciousness , death Angioedema of ups and mucous membranes laryngeal obstruction,s stridor Hypotension, cardiac arrythmias, MI Oral itching, vomiting, diarrhoea, abdominal pain
What can cause spontaneous mast cell degranulation?
Morphine + other opiates
Non-steroidal anti-inflammatories (e.g. aspirin)
Thyroid disease
Idiopathic
Physical urticaria (due to pressure or heat)
What causes Samter’s Triad (aspirin-induced asthma)?
Aspirin and other NSAIDs
Nasal polyps
Asthma
Salicylate sensitivity
What are elective investigations to discover allergies?
Skin prick test
Quantitate IgE to putative allergen
Challenge test
How can an allergy be diagnosed during an acute anaphylactic episode?
Evidence of mast cell degranulation
Serum mast cell tryptase levels
How does a skin prick test work?
Expose patient to standardised solution of allergen extract through a skin prick to the forearm
What is a positive reaction to a skin prick test?
Local wheal and flare response
What precautions must be taken before a skin prick test?
No anti-histamines for at least 48 hrs
Which common aeroallergens are tested in a skin prick test?
house dust mites Animal dander Grass pollen Birch pollen Moulds
What are the advantages of a skin prick test?
Cheap
Quick
Unrivalled sensitivity for most allergens
Patient can see result
What are the disadvantages of a skin prick test?
Requires experience for interpretation
Very rarely may induce anaphylaxis (1:3000)
What does an allergen-specific IgE test measure (RAST/ELISA)?
Amount of IgE serum that’s directed against a specific allergen
What sensitivity does an allergen-specific IgE test have?
70-75%
Why isn’t total IgE measured to investigate allergies?
There are other causes of elevated IgE and significant allergic disease can occur without IgE elevation
What is tryptase?
Product of mast cell degranulation
When does tryptase reach it’s peak after allergen exposure and when does it return to baseline?
After 1-2 hrs
Baseline after 6 hrs
What is diagnosing allergens & resultant reaction important for?
Targeted avoidance
How can mast cell activation be blocked?
Mast cell stabilisers such as sodium cromoglycate - stabilise mast cell membranes
How is sodium cromoglycate administered?
Topical spray when allergen exposure is predictable
How do anti-histamines function?
They are H1 receptor antagonists - block biological effects of histamines
How should anti-histamines be used?
Prophylactically and to control symptoms
How to leukotriene receptor antagonists work?
Block effects of leukotrienes which hare synthesised by mast cells after activation
Which anti-inflammatory can be used for allergies and how does it work?
Corticosteroids
Inhibits format not inflammatory mediators, e.g. platelet activation factors / prostaglandins / cytokines
How is anaphylaxis managed?
Self-injectable adrenaline (EpiPen) acts on beta-2-adrenergic receptors to constrict arterial smooth muscle - increases blood pressure - limit vascular leakage
Date bronchial smooth muscle - decrease airflow obstruction
What is immunotherapy?
Controlled exposure to increasing amounts of allergen via subcutaneous injections to possibly inhibit anaphylaxis
