Immunology 2: Hypersensitivity Flashcards
Define Atopy
Atopy is a term used to describe a genetic predisposition to having hypersensitivity reactions to allergens (produce IgE antibodies).
- It refers to the tendency to develop conditions such as eczema, asthma, hayfever, allergic rhinitis and food allergies. These conditions are referred to as atopic conditions
Describe Type 1 Hypersensitivity reactions
Type 1: IgE antibodies to a specific allergen trigger mast cells and basophils to release histamines and other cytokines. This causes an immediate reaction. Typical food allergy reactions, where exposure to the allergen leads to an acute reaction, range from itching, facial swelling and urticaria to anaphylaxis.
Describe Type 2 Hypersensitivity reactions
Type 2: IgG and IgM antibodies react to an allergen and activate the complement system. This results in leading to direct damage to the local cells by cell lysis and opsonisation. The antibodies can also cause opsonisation causing antibody-mediated phagocytosis. Examples are haemolytic disease of the newborn and transfusion reactions.
Describe Type 3 Hypersensitivity reactions
Type 3: Immune complexes (antigen-antibody) accumulate and cause damage to local tissues by complement activation and infiltration of macrophages. Examples are autoimmune conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Henoch-Schönlein purpura (HSP). Localised e.g. Pigeon fancier’s lung.
Describe Type 4 Hypersensitivity reactions
Type 4: Cell mediated hypersensitivity reactions caused by T lymphocytes (mainly CD4 helper). T-cells are sensitised to antigen. Subsequent exposure > the T-cells are inappropriately activated, causing inflammation and damage to local tissues (recruitment of macrophages, other lymphocytes and neutrophils, release of proteolytic enzymes).
- Examples are organ transplant rejection and contact dermatitis (posion ivy, nickel etc.).
- slowest form, can take 2-3 days to develop.
Explain the pathophysiology of early phase allergic reactions.
Early phase:
- mast-cell degranulation occurs on subsequent exposure to the allergen due to a specific IgE antibody-allergen interaction,
- this results in a cascade of biochemical events defined as the early allergic reaction, which peaks at about 20-30 minutes post-exposure.
Explain the pathophysiology of late phase allergic reactions.
A late-phase allergic reaction (LPR) is a second wave of inflammation that occurs after the initial signs of an allergic reaction. It usually begins 2–6 hours after exposure to an allergen and peaks 6–9 hours later.
- Cytokines that are released by the mast cells and basophils act as tiny messengers to call cells such as eosinophils, neutrophils and lymphocytes to the area of inflammation. Additional cytokines are released by the TH2 lymphocytes and they attract even more of these cells of inflammation.
- These cells release chemicals which cause further damage to tissues and continue to promote inflammation.
Which investigations are performed for allergic disease?
- skin prick tests > wheal and flare reaction
- allergen specific IgE tests
- component resolved diagnostics: A number of proteins have been identified as allergens within the peanut. Identification of the specific component responsible for allergic sensitization can help to guide clinicians in stratifying patients as high- or low-risk for systemic reaction
- challenge tests
- mast cell tryptase
- non-specific markers for atopic state: total IgE and eosinophil count
Management of Allergic Disease: symptomatic and prevention
ALLERGEN AVOIDANCE
symptom management:
- antihistamine
- disease specific examples: SABA/SAMA/LAMA inhalers in asthma, decongestants in allergic rhinitis
- allergen immunotherapy
prevention (of degranulation) therapy:
- leukotriene receptor antagonist
- corticosteroids
- mast cell stabilisers
- biologics
- allergen immunotherapy
what is cromoglycate?
A mast cell stabiliser, inhibits the release of vasoactive mediators.
- effective as a prophylactic agent in asthma and allergic rhinitis, but has no role in acute attacks.
- ineffective for food allergies.
Describe allergen immunotherapy (AIT).
Involves the sequential administration of escalating amounts of dilute allergen over a prolonged period of time.
- efficacy depends on a combination of the AIT dose and overall treatment duration (total cumulative dose), meaning that lower potency AIT and/or poor adherence (each contributing to a lower cumulative dose) can limit AIT effectiveness.
Anaphylaxis management
what is the difference between anaphylaxis and an anaphylactoid reaction?
- anaphylaxis requires prior sensitisation or cross-reactivity, whereas an anaphylactoid does not require any prior sensitisation.
- anaphylactoid not mediated by IgE > substances directly activate mast cells.
- emergency treatment the same.
- distinguishing between the two is important for long-term management.
list some examples of type 2 hypersensitivity reactions
- autoimmune haemolytic anaemia
- transfusion reactions: ABO, Rhesus
- myasthenia gravis
- idiopathic thrombocytic purpura
- Good pastures syndrome
- Graves’ disease (sometimes considered type V)
Clinical symptoms of ABO transfusion reaction
- fever and rigors
- increased heart rate and breathing rate
- fall in blood pressure, dizziness
- headaches, chest or back pain
- may be fatal
Type 2 Hypersensitivity reaction management
Plasmapheresis:
- patients blood is removed via a cell separator
- cellular constituents are replaced
- plasma is replaced by plasma from someone else (fresh frozen plasma) or by pooled immunoglobulin
- approx 50% is removed each time
Immunosuppression:
- rebound antibody production limits the efficacy of plasmapheresis
- usually give a potent immunosuppressive agent to switch off B cell production of the antibody
how are type 3 hypersensitivity reactions diagnosed?
- detection of relevant antibodies in the blood e.g. in SLE you can detect antibodies against DNA
- detection of immune complexes in affected tissues
- surrogate marker: consumption of complement factors: may decrease because they are being consumed during systemic type III hypersensitivity reactions.
what is a hapten?
Small molecules that elicit an immune response only when attached to a large carrier such as protein; the carrier may be one that also does not elicit an immune response by itself.
E.g. penicillin.
how are type IV hypersenitivity reactions investigated?
- exposure to antigen: patch testing for contact dermatitis, Mantoux test for TB
- biopsy: infiltrating T lymphocytes, granuloma, activated macrophages.
