Allergy Flashcards
1
Q
What happens in early phase allergic reaction?
A
- exposure to allergens* leads to the rapid development of symptoms
- this reaction develops within seconds or minutes of exposure
- results from the binding of allergens to pre-formed IgE antibodies on the surface of mast cells and basophils
2
Q
What happens after IgE binding?
A
- IgE binds its specific allergen
- Cross-linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
- The intracellular portion of the receptor becomes phosphorylated
- The resulting intracellular cascade leads to cellular activation
- Mast cell ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators
3
Q
Review the Leuokortiene delayed allergy reaction
A
4
Q
What are the Pharmacological effects of mast cell mediators and leukotrienes
A
- Wheal and flare on skin
- Discharge and sneezing from the nose
- Red eyes
- wheezing from the lungs
5
Q
What are the general characteristics of allergens?
(4)
A
- Proteins (there are a few minor exceptions)
- Physical properties that favour transition across mucus membranes
- Biologically active, often enzymes
- Have moderate homology with self-proteins
6
Q
What is Anaphylaxis?
- clinical features seen?
- common triggers
A
- ‘Generalised allergic’ reaction
- Systemic release of histamine causes generalised vasodilatation & fluid loss from circulation to tissues
- Cutaneous: hives, angioedema
- Gut histamine release: vomiting, diarrhoea
- Mucosal histamine release: laryngeal oedema, bronchoconstriction
- Circulation: vasodilatation, hypotension
- Food, drugs and insect venom commonest triggers in UK
- Cardinal features: typical symptoms, multi-system and dramatic, rapidly follows exposure to allergen and tends to improve fairly quickly thereafter
7
Q
What is Oral allergy syndrome?
- clinical symptoms
A
- IgE directed against pollen proteins cross-reacts with homologous proteins in plant-derived foods
- Oral itching upon exposure to raw fruit, nuts and vegetables
- In UK:
- Pollen = mainly birch
- Food = mainly Rosaceae fruits (apples)
8
Q
What is Rhinitis?
A
- Sneezing, rhinorhoea, blockage due to a type 1 allergy
- Lower airway obstruction
- Wheeze due to type 1 allergy
- Allergens/ symptoms may be:
- Seasonal: pollens, moulds
- Episodic: occupational, animal dander
- When symptoms are chronic, the inflammation becomes established and cannot be explained simply in terms of mast cell degranulation
9
Q
What happens in late phase allergic reaction?
A
- The early phase reaction to an allergen is followed some hours later by a second ‘late phase reaction’
- Biopsy of the late phase shows infiltration with inflammatory cells – particularly CD4 T cells, eosinophils and mast cells;
- largely Th2 cells produced
- IL-4,5,9,13
- largely Th2 cells produced
10
Q
Explain the relevance of T cell subsets in allergy and the
Th2 hypothesis
A
- Th2 responses to allergens have been consistently associated with allergic disease
- Biopsies of allergic inflammation are rich in T cells expressing Th2 cytokines
- T cells from allergic patients stimulated with allergen in the laboratory produce Th2 cytokines
- Plenty of reasons to believe that Th2 responses may be important in allergy:
- IL-4 is required for B cell class switching to IgE
- IL-4 and IL-13 promote mucus hypersecretion
- IL-5 is required for eosinophil survival
- IL-9 recruits mast cells
11
Q
Explain the Hygiene hypothesis in allergy aetiology?
A
- Low hygiene levels, high pathogen load, helminth infection proposed to:
- Skew immunity from Th2 to Th1
- Induce regulatory T cells
- High hygiene levels, low pathogen load, absence of helminth infection proposed to:
- Skew immunity towards Th2
- Reduce production of regulatory T cells
12
Q
How is allergy detected/ tested for?
A
- in vivo: skin testing
- in vitro: ELISA
- this tests for allergen-specific IgE antibodies
13
Q
What are treatments for allergy: Symptom relievers
A
- B2 agonist
- Eg salbutamol
- Act on lung B2 adrenoreceptors, cause smooth muscle relaxation
- Nasal decongestion
- eg oxymetazoline
- Act on α1 adrenoreceptors to cause vasoconstriction
- Only for short-term use (can cause physiological dependence)
- Topical and systemic
- Epinephrine
- Systemic adrenergic effects oppose vasodilatation and bronchoconstriction
14
Q
What are treatments for allergy: Drugs acting on early-phase mediators
A
- H1 Antihistamines
- Leukotriene receptor antagonists
- Mast cell stabilisers
15
Q
What are Mast cell stabilisers?
- how do they work
- efficacy
A
- Eg sodium cromoglycate
- Reduce mast cell degranulation by unknown mechanism
- Not orally absorbed – topical use only
- Short half-life requires frequent dosing
- Main benefit is steroid-free, but efficacy very poor
19
Q
What is Omalizumab
- how does it work
- used in?
A
Omalizumab is a monoclonal antibody directed against IgE, used for atopic asthma (amongst other things)
20
Q
Explain the use of Allergen-specific immunotherapy
- what are the 5 main immunological effects
A
- Allergen doses administered by subcutaneous injection or sublingually
- Provide long-term protection
- Mainly venom allergy and rhinitis
- Multiple immunological effects:
- Induce regulatory T cell responses to allergens
- Reduce Th2 responses
- Induce allergen-specific IgG antibodies
- Reduction in mast cell responsiveness
- Reduce allergen-specific IgE levels
21
Q
What is the difference between contact dermatitis (Type IV sensitization) and type 1 allergy?
A
22
Q
What is the difference between Skin prick testing vs patch testing?
A
