Atopy, allergy and delayed type hypersensitivity 2 Flashcards
Skin prick testing
- Purpose
- Method
- Realiability
Method of detecting sensitivity to allergens in vivo
- Uses Type 1 hypersensitivity reaction
Method
- Allergen is applied as drops to skin
- Control is there: histamine, no histamine
- Epidermis is punctured with lancet
- Wait for 15 mins to observe a wheel and flare reaction
Test is not diagnostic as there can be many false positives and false negatives
Detection of allergen specific IgE in vitro
More reliable that skin prick test.
ELISA
- The well is coated with specific allergen
- Patient serum is added, if it contains IgE ab sensitised to allergen, it will bind.
- Polyclonal anti-IgR detection Ab is added to detect immobilised IgE bound to allergen
Nasal decongestant
- Mechanism
- Example
- Use
Treats symptom of allergy
- Stimulates a1 adrenoreceptors= vasoconstriction
Example
- Oxymetazoline
Use
- short term topical and systemic use
B2 agonist
- Mechanism
- Example
- Use
Acts of B2 adrenoreceptors
= smooth muscle relaxation in airway
Example
- Salbutamol
Use
- Inhaler
Epinephrine
- Mechanism
- Example
- Use
Stimulates adrenergic receptors in the sympathetic system, inhibits=
- Vasoconstriction
- Bronchodilation
Use
- 0.5mg injected intramuscularly.
Drugs that act on early phase mediators
Inhibits the effects action of histamine and leukotrienes or prevents mast cell degranulation
Examples
- H1 anti-histamines
- Leukotriene receptor antagonists
- Mast cell stabilisers
Mast cell stabilisers
- Mechanism
- Example
- Use
Reduces mast cell degranulation
- Unknown mechanism
Example
- Sodium cromoglycate
Use
- Topical use [i.e eye drops]
- Frequent dosing due to short half-life= poor efficacy
H1 antihistamines
- Mechanism
- Example
- Use
Inverse agonist of H1 receptors
- Prevents the inflammatory effects of histamines, by inhibiting its actions on cells
Example
1st generation
- Chlorpheniramine
2nd generation
- Cerizine
- Lortidine
- Desloratidine
- Fexofenadine
1st generation H1 antihistamines
Chlorpheniramine
- Causes sedation
- Drug interactions
- Adverse psychological effects [tardive dyskinesia]
2nd generation drugs better, no/minimal sedation
Leukotriene receptor antagonists
- Mechanism
- Example
- Use
Inhibits the effects of leukotriene, so inhibits
- Bronchoconstriction
Example
- Montelukast
Inferior to H1 antihistamines
- Usually used for those with chronic asthma
Mechanism of corticosteroids
Alters gene expression in leucocytes
- lymphocytes
- Innate immune cells
Steroid receptors are usually bound to Hsp90 but corticosteroids displaces it and binds instead
- Steroid-receptor complex crosses nuclear membrane than binds to regulatory gene sequences to initiate transcription
Corticosteroids examples
- Inhaled
- Nasal
- Topical
Inhaled
- Beclamathosome
- Fluticasone
Nasal
- Beclamathosome
- Mometasone
- Fluticasone
Topical
- Hydrocortisone
Omalizumab
Monoclonal antibody against IgE
- Indicated for atopic asthma
Binds to IgE, occupying their antigen binding site, preventing them from binding to allergens
- Decreases the expression of high affinity IgE receptors on mast cells= less mediator release
Type 4 delayed type hypersensitivity
Reaction mediated by antigen specific effector T cels
- Reaction does not develop until at least 24 hours as it takes time to process and present antigens, and for T cells to recognise them
Contact dermatitis
- Mechanism
Type 4 hypersensitivity reaction.
Mechanism:
- Reactive small molecules
(hapten) [sensitising agent] penetrates the skin - Small molecules for protein-hapten complex
- Protein-hapten are taken up by langerhan cells, processed via MHC 2—> migrate to lymph nodes
- Recognised by T cell cells as foreign= activation of T cells
- T cells migrate to dermis and stimulate inflammatory reaction
- Chemokines stimulate migration of macrophage= Th1 releases IFN-g to activate macrophage and increase vascular adhesion molecules
TNF-a/b= local inflammation
Poison ivy
Causes contact dermatitis
- Due to release of pentadecacathechol lipid that crosses into skin= modifies intracellular proteins
- Not everyone is susceptible
Proteins are processed and presented via MHC1 to CD8 T cells
Patch testing
Uses Type 4 hypersensitivity
Patch with specific antigen is placed on the back
- e.g nickels, chrome, cobalt, epoxy resin etc
Wait 2 days to look for inflammation
Compare contact dermatitis to type 1 allergy
- Clinical features
- Temporal
- Causative agents
- Effector mechanism
- Assessment
- Management
Clinical features
- Type 1= features of mast cell degranulation
- Type 4= eczematous skin reaction
Temporal
- Type 1= rapid, within minutes, after exposure
- Type 4= delay between exposure and symptoms
Causative agents
- Type 1= naturally occurring protein/ closet related one
- Type 2= Many causes, usually synthetic
Effector mechanism
- Type 1= Allegern-specific IgE, mast cell degranulation
- Type 2= Antigen-specific effector Th1 cells
Assessment
- Type 1= allergy clinic, skin prick, serology for allergen specific IgE
- Type 2= dermatology, skin patch testing
Management
- Type 1= avoid allergen, pharmacotherapy, immunotherapy
- Type 2= avoidance
Skin prick vs skin patch testing
- Indication
- Test format
- Positive result
- Immunology
Indication
- Skin prick= history of IgE allergy
- Patch= history of contact dermatitis
Test format
- Prick= allergen drops, puncture, read after 15 mins
- Patch= Allergen under occlusive dressing, read after 48 hours
Positive result
- Prick= wheal and flare
- Patch= Eczematous reaction
Immunology
- Prick= type 1 hypersensitivity, IgE, mast cell degranulation
- Patch- Type 4, T cell mediated
Tuberculin skin test
Type 4 reaction
- Tests previous exposure to TB (later TB)
- Allows chemoprophylaxis to reduce chance of reactivation
Method
- Tuberculin [complex of antigens from MTB] injected intradermally
- Wait for 24-72 hours to observe local inflammation
Mechanism
- Injected antigen is processed by APCs in skin
- Th1 (previously exposed to TB antigen) recognises the antigen and stimulates cytokines release
- Phagocytes and plasma into site of injection= lesion
Reliability
- Poor for active TB (esp if lungs)
Allergen-specific immunotherapy
Method of providing long-term protection for resistance allergies.
- Especially venom and rhinitis
Method:
- Small does of allergen is injected subcutaneous or sublingually.
Effects:
- T cell responses to allergens
- Reduces Th2 responses
- Allergen-specific IgG an
- Decreases mast cell responseiveness
- Decreases allergen-specific IgE levels
