III - Allergic Disease Flashcards
Define hypersensitivity reaction
Exaggerated, inappropriate immune responses to potentially harmful stimuli.
Quickly summarise the four types of hypersensitivity reaction.
I - immediate hypersensitivity - ALLERGIC disease. The binding of an antigen to specific IgE bound to its high affinity receptor on a mast cell surface results in massive and rapid cell degranulation and massive inflammatory response.
II - Direct killing
III - Immune complex mediated
IV - Delayed type hypersensitivity.
Define allergy.
What conditions does it include?
What are the two types?
IgE mediated antibody response to external antigen.
It includes asthma, hay fever, urticarial, angioedema, eczema, food allergy ,drug allergy, anaphylaxis.
1. Immune mediated - can be IgE mediated (classical allergy) or non-IgE mediated (e.g. Coeliac disease, eosinophilic gastroenteritis).
2. Non-immune mediated e.g. metabolic (lactose intolerance); pharmacologic (caffeine); IBS etc.
What is Coeliac disease?
Immune mediated (non IgE) type I hypersensitivity reaction. It is autoimmune (not an allergy or intolerance to gluten), where the immune system mistakes substances found inside gluten as a threat to the body and attacks them, damaging the surface of the small bowel.
What are the risk factors for allergic disease?
"Westernized countries" Small family size Affluent, urban homes High antibiotic use Good sanitation
Name some common allergens.
House dust mite Pollen and animal dander Foods Drugs Latex Bee & wasp venom
Generic features of Type I allergic disease
Occurs quickly after response to antigen (minutes - 2 hours)
Responses are stereotyped
May be associated with >1 organ system
Presentation is influenced by site of contact
Cofactors can affect it e.g. alcohol
Specific features of Type I allergic disease
Asthma Urticaria (hives) Angioedema Allergic rhinitis (hay fever) Allergic conjunctivitis Diarrhoea and vomiting Anaphylaxis
Pathophysiology of allergic disease:
Cells involved?
Brief description of these cells?
Cells involved:
- B lymphocytes - recognise antigen and produce specific IgE antibody.
- T lymphocytes - provide help for B cells to make IgE antibody
Mast cells - inflammatory cells that release vasoactive substances
Describe the roll of mast cells in the body in general.
Where are they found?
Functions?
What is the major reason we have them?
Resident in connective tissues, especially at the interface with the external environment (e.g. skin, lining of stomach & intestine).
Produce vasoactive substances - histamine, tryptase, heparin, leukotrienes, IL4, TNF.
They orchestrate the inflammatory cascade - increase blood flow, contraction of SM, increase vascular permeability.
They are important in the defence against parasites, and wound healing.
Describe how Antihistamines, Leukotriene receptor antagonists, sodium cromoglicate, and anti-inflammatory agents work (pharmacological ways to manage allergic disorder).
Antihistamine drugs act by blocking the action of histamine on nerve endings –> BLOCKS THE AFFECTS OF MAST CELL DGRANULATION.
Leukotriene receptor antagonists prevent the synthesis of mast cell mediators, so are often USEFUL IN ASPIRIN SENSITIVE INDIVIDUALS.
Sodium cromoglicate based drugs (incl nedocromil) block a calcium channel essential for mast cell degranulation, stabilising of the cell and preventing the release of histamine and related mediators –> STABILISES THE MAST CELLS.
Anti-inflammatory agents e.g. inhaled corticosteroids inhibit the formations of many inflammatory mediators.
Describe the roll of mast cells in allergic reaction.
They express receptors for the Fc region of IgE antibody on their surface.
On encounter with allergen, B cells produce antigen-specific IgE antibody. IgE antibody binds to the allergen, and to the mast cell, triggering mast cell degranulation.
This causes the release of histamine into the blood stream, causing increased permeability of the capillaries.
What is the difference between extrinsic and intrinsic asthma?
Extrinsic = response to external antigen (IgE mediated). Intrinsic = non-allergic (non-IgE mediated).
What does histamine (and other inflammatory mediators) do to the body?
Muscles?
Mucosa?
Muscle spasm - causes bronchoconstriction –> WHEEZE.
Mucosal inflammation - causes mucosal oedema and increases secretions –> SPUTUM PRODUCTION.
Inflammatory cell infiltrate - infiltration of lymphocytes and eosinophils into bronchioles –> SPUTUM OFTEN YELLOW.
Aspirin Induced Asthma
Who does it affect?
Clinical manifestation?
Triggered by?
Affects 20% asthmatics.
Aspirin and other NSAIDs cause mast cell degranulation.
What is Sameter’s triad?
- Asthma
- Nasal polyps
- Salicylate sensitivity
It is at the severe end of the aspirin sensitive spectrum and may require dietary modification.
Name three tests you can do for allergy.
- Skin prick tests - gold standard.
- During acute anaphylactic episode - evidence of mast cell degranulation; serum mast cell tryptase levels. Peak level is at 1-2 hous after exposure, and returns to baseline by 6 hours.
- Specific IgE test (RAST test) - measure serum amount of IgE directed against a specific allergen.
Management of anaphylaxis?
Self injectable adrenaline - acts on B2 ADR to constrict arterial SM, increasing BP; and dilate BSM to decrease airflow obstruction.
Describe immunotherapy.
New treatment:
controlled exposure to increasing amounts of allergen.
Risks anaphylaxis.
