Atopy, allergy and delayed type hypersensitivity 2 Flashcards
Skin prick testing
Allergen extract applied as drops
Top layers of epidermis punctures with lancet
A wheal with flare response after 15 minutes is positive
Result needs interpretation in clinical context
Detection of allergen specific IgE in vitro
Performed by radioallergosorbant assay a very long time ago
Now usually by ELISA
- plastics coated with purified allergen of interest
- incubate with patient serum
- IgE antibodies in sera of sensitised patient bind to allergens
- immobilised IgE antibodies detected with polyclonal anti-IgE detection antibody
Nasal decongestants
e.g. omymetazoline
Act on alpha1 adrenoreceptors to cause vasoconstriction
Only for short term use
Topical and systemic
B2 agonists
e.g. salbutamol
Act on lung B2 adrenoreceptors
Cause smooth muscle relaxation
Epinephrine
Systemic adrenergic effects oppose vasodilatation and bronchoconstriction
Mast cell stabilisers
e.g. 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
H1 antihistamines
Inverse agonists at H1 histamine receptor
Best used before exposure to allergen
1st generation e.g. chlorpheniramine
- considerable sedation, drug interactions
2nd generation e.g. cerizine, loratidine, desloratidine, fexofenadine
- no/ minimal sedation, once daily
Leukotriene receptor antagonists
Only UK drug is montelukast
Effective in reducing early allergic responses, but inferior to H1 antihistamines
Unlike antihistamines, beneficial in chronic asthma, which is the main indication for their use
Treatment of allergic disease: corticosteroids
Reduce immune activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the innate immune system
Their onset of action is delayed and they must be taken regularly
Corticosteroids
Inhlaed
- e.g. beclamethasone, fluticasone
Nasal
- e.g. beclamethasone, mometasone, fluticasone
Also for skin and opthalmic drops
Topical preparations may cause local and even systemic side effects
Oral, intravenous and depot preparations available
Treatment of allergic disease: omalizumab
Monoclonal antibody directed against IgE
Used for atopic asthma
Treatment of allergic disease: allergen specific immunotherapy
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
- reduced in mast cell responsiveness
- reduce allergen- specific IgE levels
Type IV, delayed type hypersensitivity
Mediated by antigen- specific effector T cells
- antigen specific: implies that a specific antigen stimulus is required, which is then processed and presented to relevant T cells which are responsible for reaction
- effector T cell: T cells that have previously met antigen and are primed to produce a rapid, robust response
Because it takes time to process and present antigen, these reactions do not develop for at least 24 hours following exposure
Contact dermatitis: sensitisation
Sensitising agents are typically highly reactive small molecules which can penetrate skin
These react with self proteins to create protein hapten complexes that are picked up by langerhans cells, which migrate to regional lymph nodes
Langerhands cells process and present the antigen together with MHCII
In some susceptible individuals, the complexes are recognised as foreign
The activated T cells then migrate to the dermis
Hapten
Small molecule which cannot produce an immune response by itself, but can bind to a protein to alter its immunogenicity
