Flashcards in Allergy Deck (34):
What is hypersensitivity?
Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host.
What is the immunopathogenesis of type II (cytotoxic) hypersensitivity?
IgG/IgM Ab response against combined self/foreign antigen at the cell surface- complement activation/phagocytosis/ADCC.
What are the clinical features of type II hypersensitivity?
- Onset minutes to hours
- Cell lysis and necrosis
What is a common antigen that stimulates type II reactions?
What diseases are associated with type II hypersensitivity?
- Erythroblastosis fetalis,
- Goodpasture's nephritis
What is the immunopathogenesis of type III (immune complex) hypersensitivity?
IgG/IgM Ab against soluble antigen- immune complex deposition.
What are the clinical features of type III hypersensitivity?
- Onset 3-8h
What is type III hypersensitivity traditionally associated with?
What is the immunopathology of type IV (delayed) hypersensitivity?
Antigen specific T-cell mediated cytotoxicity
What are the clinical features of type IV hypersensitivity?
- Delayed onset 48-72h
- Erythema induration
Which antigens are commonly associated with type IV hypersensitivity?
- Metals-e.g nickel
- (tuberculin reaction)
- Poison ivy
What disease is commonly associated with type IV hypersensitivity?
What is the hygiene hypothesis?
- Stimulation by microbes is protective
- Epidemiological data – Increase in Allergy
- Animal Models – T1DM, EAE, Asthma
- Increased atopy (Asthma) after anti-parasitic Rx
- Prevention of autoimmunity (Crohn’s) by infections
- Pro-biotics in pregnant women
- Mechanism – Th1 Th2 deviation
What are the genetic influences on the immune response?
- Polygenic diseases
- Cytokine gene cluster IL3,5,9,13
- IL12R; IL4R
- IFNg; TNF
- NOT sufficient for disease
- ONLY susceptibility
What are allergens?
- Antigens that initiate an IgE-mediated response
- First encounter results in innate & IgM response
What happens to the allergen during a conventional immune response?
- Allergen requires processing
- Presentation to T cells & cytokine release
- Results in delineation of T-helper subsets into different types
What is the immunopathology of type I hypersensitivity (allergic)?
IgE Ab mediated mast cell and basophil degranulation- release of preformed and de novo synthesized inflammatory mediators
What are the clinical features of type I hypersensitivity?
- Fast onset (15-30 min)
- Wheal and flare
What cells are involved in the late phase response?
- Central role for Th2 T cell
What is the role of the Th2 cell?
- Multiple cytokine release.
- epithelial cell damage
- airway remodelling
- survival and activation of eosinophils
- bronchial hyperreactivity
What is the atopic triad?
What are the features of rhinitis?
- ALLERGIC - PERENNIAL or SEASONAL
- Blocked nose, runny nose - often with eye symptoms
- House dust mite, animal danders, pollens
- Treatment – Antihistamines & Nasal steroids
What are the features of asthma?
- Disease of INFLAMMATION and HYPER-REACTIVITY of small airways
- In childhood - AERO-ALLERGIC stimuli - HOUSE DUST MITE key pathogenic importance
- IMMEDIATE symptoms are IgE-mediated
- DAMAGE TO AIRWAYS due to LATE PHASE RESPONSE
- DAMAGED AIRWAYS ARE HYPER-REACTIVE to non-allergic stimuli e.g. fumes
What are the features of atopic dermatitis?
- DERMATITIS – MANY DIFFERENT TYPES
- ATOPIC CONTACT - ALLERGIC/NON-ALLERGIC
- CLINICALLY - Intense itching, blistering/weeping, cracking of skin
- HOUSE DUST MITE now thought to be MAJOR TRIGGER in atopic disease
- Topical Steroids and moisturisers
What is anaphylaxis?
An acute, potentially life-threatening, IgE mediated systemic hypersensitivity reaction.
What are the diagnostic tests used in the diagnosis of allergy?
- Specific IgE (>0.35 KuA/L)
- Skin prick test (>3mm wheal) SPT Video
- Intra-dermal test
- Oral challenge test – Gold standard
- Basophil activation test
- Component resolved diagnostics
What are the advantages and disadvantages of using specific IgE?
Safe but false positives and negatives.
What are the advantages and disadvantages of using the skin prick test?
- Patient satisfaction
- False negatives
- False positives
- Slight risk
What symptomatic treatment can be given for allergies?
Antihistamines, Steroids, Adrenaline
What kind of allergies is immunotherapy good for?
- Life threatening reactions to Wasp & Bee sting
- Severe Hay fever
- Animal dander allergy
What kind of allergies is immunotherapy not good for?
- Multiple allergies
- Food allergy
- Allergic rashes – Eczema, Urticaria
What are the various mechnisms behind immunotherapy?
- Ratio of Th1 cytokines to Th2 cytokines is increased following specific immunotherapy (SIT)
- Functional regulatory T cells are induced.
- Production of IL-10 by monocytes, macrophages, B cells and T cells is increased.
- Expression of TGF is increased and, together with IL-10, TGF might contribute to regulatory T-cell function and immunoglobulin class switching to IgA, IgG1 and IgG4. These immunoglobulins compete with IgE for allergen binding, decreasing the allergen capture and presentation that is facilitated by IgE in complex with the high-affinity receptor for IgE (FcRI) or the low-affinity receptor for IgE (FcRII).
- SIT reduces number of mast cells and ability of mast cells to release mediators.
- Recruitment of eosinophils and neutrophils to sites of allergen exposure is also reduced.
What are the major food allergens?
- Water soluble glycoproteins 10 - 60 kd
- COW’S MILK
- LEGUMES - PEANUT; SOYBEAN; TREE NUTS
- CRUSTACEANS / MOLLUSCS
- CEREAL GRAINS