Allergic Diseases Flashcards
What type of Hypersensitivity causes anaphylaxis?
Type 1
What type of hypersensitivity is caused by IgG antibodies?
Type 2 and Type 3
How does IgE antibody cause allergic reaction?
Mast cell activation
What is the atopic triad?
eczema, hayfever, and asthma – the atopic triad because they so often occur together.
Pathophysiology of asthma and rhinitis?
- Exposed to allergen
- Inflammation of upper and lower airways
- Nasal congestion
- Tonsillar and adenoidal enlargement
- Narrowing of nasopharyngeal area
- Oedema and mucus in lungs
- Airway constriction and hyperreactive airways
Rhinitis; what are initial symptoms?
- Blocked/runny / itchy nose
- Sneezing
- Often with eye symptoms (itching, burning, watery eyes, redness)
What are the 2 types of rhinitis?
Allergic and non-allergic
What type of hypersensitivity is allergic rhinitis?
Type 1
What is allergic rhinitis mediated by?
exaggerated IgE mediated immune responses
What do type 1 hypersensitivities include?
- Atopic diseases, which are an exaggerated IgE mediated immune responses (i.e., allergic: asthma, rhinitis, conjunctivitis, and dermatitis)
- Allergic diseases, which are immune responses to foreign allergens (i.e., anaphylaxis, urticaria, angioedema, food, and drug allergies).
Describe type 1 hypersensitivity. What is it mediated by?
Is also known as an immediate reaction and involves immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen. This results in mast cell degranulation and release of histamine and other inflammatory mediators.
What can allergic rhinitis then be classified into?
Seasonal or perennial rhinitis
Treatment for allergic rhinitis?
Antihistamines and intranasal steroids
What is asthma?
•isease of inflammation & hyper-reactivity of small airways
What is an aeroallergen?
any airborne substance, such as pollen or spores, which triggers an allergic reaction
In childhood, which aero-allergic stimuli are of key pathogenic importance in asthma?
house dust mite
What are the immediate symptoms of asthma mediated by?
IgE-mediated
Damage to airways can be caused by the late phase response of asthma. What are damaged airways then hyperreactive to?
Non-allergic stimuli e.g. fumes
Pathogenesis of asthma?
- Allergen presented to APC
- APC induces T cell proliferation and differentiation into Th2 cells
- Th2 cells secrete cytokines (IL4, IL-5, IL-13)
- IL-5 induces eosinophils, causing proliferation
- IL-4 and IL-13 stimulate B cells maturation to plasma cells which secrete IgE antibodies
- IgE antibodies activate mast cells and basophils
- Allergic reaction
What do mast cells release?
- Histamine
- proteases
- prostaglandin D2
- leukotrienes
- a variety of cytokines
Which cytokines do Th2 cells release during asthma?
IL4, IL-5, IL-13
What is effect of IL-4?
- Stimulation of activated B-cell and T-cell proliferation
- Differentiation of B cells into plasma cells
- IL-4 drives the immunoglobulin (Ig) class switch to IgG1 and IgE and up-regulates MHC class II production.
What is effect of IL-5?
- Stimulates B cell growth and increases immunoglobulin secretion - primarily IgA
- It is also a key mediator in eosinophil activation.
What is effect of IL-13?
The overexpression of IL-13 induces many features of allergic lung disease, including airway hyperresponsiveness, goblet cell metaplasia, mucus hypersecretion and airway remodelling which all contribute to airway obstruction.
What are the 3 classifications of dermatitis?
- Eczema
- Contact dermatitis
- Other types of dermatitis
Define atopic
denoting a form of allergy in which a hypersensitivity reaction such as eczema or asthma may occur in a part of the body not in contact with the allergen.
What are the 2 types of eczema?
Atopic and non-atopic
What is now thought to be a major trigger in atopic disease?
House dust mite
Clinical presentations of eczema?
Intense itching, blistering/weeping, cracking of skin
Treatment for eczema?
Topical steroids and moisturisers
What is filaggrin?
a filament-associated protein that binds to keratin fibers in epithelial cells
How can filaggrin contribute to eczema?
- Filaggrin plays a key role in epidermal barrier function
- Reduction in filaggrin (genetic) leads to disruption of barrier and initial allergen exposure can happen more easily
- This association with atopic eczema emphasises the importance of barrier dysfunction in eczema pathogenesis
What is contact dermatitis?
a type of eczema that causes inflammation of the skin when you come into contact with a particular substance
Explanation of the interplay among the barrier, allergy and pruritus as a trinity
- Environment + reduced filaggrin –> barrier disruption (and hapten exposure)
- This leads to contact dermatitis-like reaction which is mediated by inflammatory Th1 lymphocytes recognising hapten determinants
- This chronic hapten exposure leads to development of atopic dermatitis (Th2)
- This leads to high IgE –> allergic march
- Also leads to IL-31 which leads to pruritus
Summary of sensitisation and acute phase response
Summary of late phase inflammation
What is most important test in diagnosing allergies?
Specific IgE testing (>0.35 KuA/L)
- Patient’s blood added to allergen
- Confirm whether antigen secreted is IgE
- Amount of IgE?
What reading of IgE is ‘positive’ when diagnosing allergies?
>0.35 KuA/L
What is a skin prick test?
- You have a positive control (histamine) and negative control (saline)
- Place drops of control onto forearm
- Skin under drop is then gently pricked
- Prick should not penetrate and draw blood
- Observe if itchy, red bump forms
Disadvantages of skin prick test?
There are false positives and negatives, and a slight risk of anaphylaxis. The prick should not penetrate and draw blood. Antihistamines may mask the response
For a positive result, what does the size of the wheal in a skin prick test need to be?
>2mm wheal (2mm more than negative control)
What is involved in an intradermal allergy test?
- The test involves injection of a small amount of the suspected allergen under the surface of the skin
- After about 20 minutes the area is examined for a reaction at the site.
Ad/disadvantages of intradermal test?
Ad: more sensitive than the skin prick test and can usually provide more consistent results
Disad: more invasive/uncomfortable
What is the intradermal test typically used for?
Drug allergies
What is involved in a basophil activation allergy test?
Measures antibodies that are bound to basophils by flow-cytometry (measures degree of cell activation) after exposure to allergen
What is the gold standard test for allergy?
Graded challenge test
What is a graded challenge test?
allergist gives you a small amount of a drug/allergen in gradual increasing doses while observing you to watch for a reaction
What is allergen immunotherapy?
Allergen immunotherapy (sometimes called desensitisation treatment) is a treatment for allergy. It involves giving increasing doses of an allergen.
How can immmunotherapy be delivered?
- Subcutaneous
- Sublingual
When would allergen immunotherapy be given?
- Life threatening reactions to Wasp & Bee sting
- Severe Hay fever
- Animal dander allergy
What is immunotherapy not useful in?
- Multiple allergies
- Food allergy
- Eczema
- Spontaneous Urticaria
Effects of immunotherapy?
- Improves quality of life of treated individuals
- Reduces symptoms of allergy and medication use
- Improved tolerance to allergens
- Decreases immediate and late phase reactions
- Prevents the development of new allergic sensitisation
- Decreases skin-prick test reactivity
- Diverts TH2 response to TH1 or mops up allergen before IgE response
- Th1 tend to have dampening effect on immune response
What are 2 categories of adverse food reactions?
Immune-mediated reactions –> food allergy
Non-immune mediated reactions –> food intolerance
Why can food allergies and asthma occur together?
Both IgE mediated
What are the major food allergens?
Water soluble glycoproteins 10-60 kD
- Cow’s milk
- Egg
- Legumes - peanut; soybean; tree nuts
- Fish
- Crustaceans / molluscs
- Cereal grains
Clinical manifestations of adverse reactions to food?
–Gastrointestinal: vomiting, diarrhoea, oral symptoms
–Respiratory (upper & lower): rhinitis, bronchospasm
–Cutaneous: urticaria, angioedema
–Anaphylaxis
Drug allergies
History to consider in drug allergy:
–Indication for the drug
–Detailed description of the reaction
–Time between drug intake and onset of symptoms
–Number of doses taken before onset
–Aware of pharmacological effects and non-immunological ADR
Is the initial phase of sensitisation clinically silent?
Yes
How does re-exposure to allergen in hypersensitivity lead to a reaction?
- The allergen cross-links two specific IgE receptors, creating a bridge and resulting in mast cell degranulation.
- Degranulation releases preformed (histamine etc) followed by newly formed mediators (e.g. prostaglandin, leukotrienes, thromboxane A2) which results in clinical manifestations of IgE-mediated allergic reactions
Basophils have protein receptors on their cell surface that bind which antibody?
IgE –> It is the bound IgE antibody that confers a selective response of these cells (e.g. release histamine and serotonin during allergic reactions)
What do basophils contain?
Basophils do not ingest foreign cells. They contain granules filled with histamine. When basophils encounter allergens, they release histamine. Histamine increases blood flow to damaged tissues, resulting in swelling and inflammation.
