Respiratory Immunology 3: Allergic Disease Flashcards
(38 cards)
Hypersensitivity reactions definition?
Immune response that results in bystander damage to self (exaggeration of normal immune mechanisms), inc. allergic disease and autoimmunity
Classifications of hypersensitivity reactions?
Type 1: Immediate sensitivity (allergic diseases)
Type II: Direct cell killing
Type III: Immune complex mediated
Type IV: Delayed type hypersensitivity
Allergy definition?
IgE-mediated antibody response to an external antigen (although, not all allergic-type diseases are mediated by IgE reactions)
NOT ALL ADVERSE REACTIONS ARE ALLERGIC REACTIONS
Allergic conditions?
Asthma
Allergic rhinitis (hayfever)
Allergic conjunctivitis
Urticaria - raised itchy rash on skin, i.e: hives, welts, nettle rash
Angioedema - self-limited; localised, rapid swelling of subcutaneous tissues/mucous membranes (non-pitting oedema, often with clear demarcation and is usually not itchy, unless associated with urticaria)
Atopic eczema
Food allergy - many believe they have this and do not
Drug allergy
Diarrhoea and vomiting
Anaphylaxis
Risk factors for allergic disease?
Genetic susceptibility to allergic disease - unlikely to be cause of increasing prevalence
ENVIRONMENTAL FACTORS:
“Westernised”/industrialised countries
Small family size - later child less likely to have allergy than earlier
Factors causing immune system maturation?
Infections (bacterial/viral) contracted from siblings/peers enhance maturation and so protect against allergy and asthma
Clinical features of Type I allergic disease?
Generic feature:
Occurs QUICKLY AFTER EXPOSURE (exception - food allergies) and can be associated with > 1 organ system
Presentation is influenced by SITE OF CONTACT
THRESHOLD for reactions may be influences by co-factors, e.g: EXERCISE, ALCOHOL, INFECTION
Allergen examples?
House dust mite Pollen and animal dander Foods Drugs Latex Bee and wasp venom
Many are soluble proteins that function as enzymes
Cells involved with allergic disease and their role?
B lymphocytes - recognise antigen and produce antigen-specific IgE antibody
T lymphocytes - provide B lymphocytes with help to make IgE antibody
Mast cells - inflammatory cells releasing VASOACTIVE SUBSTANCES
Where do mast cells reside?
In tissues, esp. at interface with external environment; do not circulate in large numbers
What do mast cells do in allergic disease?
Produce vasoactive substances:
Preformed- HISTAMINE, TRYPTASE (can be measured), HEPARIN
Synthesised on demand - LEUKOTRIENES, PROSTAGLANDINS, CYTOKINES, like IL4 and TNF
Orchestrate INFLAMMATORY CASCADE - increase blood flow, contraction of smooth muscle, increase vascular permability and secretions at mucosal surfaces
Mast cell receptors?
Express Fc receptors on their surface, for Fc region of IgE antibody
How do allergies arise, specifically due to mediation by mast cells?
On encounter with allergen, B cells produce antigen-specific IgE antibody; allergen is cleared on first encounter
Residual IgE antibodies bind to circulating mast cells via Fc receptors and there is no significant consequence
After RE-ENCOUNTER with antigen:
Allergen binds to IgE-coated mast cells and disrupts cell membrane
Degranulation of mast cell releases vasoactive substances
Cytokine & LT transcription is increased
3 types of asthma classifications?
Early onset/late onset
Atopic/non-atopic
Extrinsic/intrinsic
What is extrinsic asthma?
AKA allergic asthma that is in response to external allergen and is IgE mediated
Associated with other allergic diseases
Release of histamine and other inflammatory mediator consequences?
Muscle spasm - causes bronchoconstriction (producing wheeze)
Mucosal inflammation - causes mucosal oedema and increases secretions (producing sputum)
Inflammatory cell infiltrate - infiltration of lymphocytes and eosinophils into bronchiole (produces yellow sputum); associated with chronicity
Clinical features of anaphylaxis?
Feeling of impending doom and loss of consciousness Angioedema of lips and mucous membrances Laryngeal obstruction and stridor Conjunctival injection Flushing/sweating Wheeze, bronchoconstriction HYPOTENSION Cardiac arrhythmias Urticaria Diarrhoea, abdominal pain Itching of palms, soles of feet and genitalia
Non-allergic causes of mast cell degaranulation?
AKA SPONTANEOUS MAST CELL DEGRANULATION - mast cells are hypersensitive and “twitchy”
Drugs - morphine and other opiates, aspirin and NSAIDs
Thyroid disease
Idiopathic
Physical urticaria - in response to heat or pressure
Describe aspirin induced asthma and causes?
Characterised by WHEEZE o.5-3 hrs after ingestion
Triggered by aspirin, NSAIDs (like ibuprofen)
Paracetamol and COX-2 generally alright
Samter’s triad meaning and treatment?
Asthma, nasal polyps and salicylate sensitivity (severe end of the aspirin sensitivity spectrum)
Dietary modification can reduce high prevalence of salicylates in some foods
4 steps in diagnosing allergic disease?
Confirm diagnosis
Identify causative agent - pinpoint specific allergen and target measure to reduce exposure and encourage lifestyle modification
Determine risk of future severe reaction
Determine therapy appropriateness
Specific investigations for allergic disease?
Elective investigations:
Skin prick tests (“gold standard” to support an allergy diagnosis)
Quantitative specific IgE to putative allergen
Challenge test - supervised exposure to putative antigen
During acute anaphylactic episode, look for mast cell degranulation evidence (serum mast cell TRYPTASE levels)
Skin prick test procedure and reaction?
Expose patient to standardised allergen solution and extract through a skin prick to the forearm
Positive reaction = local wheal and flare response
Skin prick test cautions?
Drugs can influence response:
Anti-histamines should be discontinued for at least 48 hrs before testing
Corticosteroids have no influence
Very rarely, may induce anaphylaxis
