Local reaction triggers.
Ingested or inhaled allergen.
Systemic reaction triggers.
Give examples of allergens.
Seasonal exposure such as tree and grass pollens.
Perennial exposure such as house dust mite, animal dander from cats and dogs, and fungal spores.
Accidental exposure such as insect venom from wasp and bee stings, medicines, latex, foods like milk, peanuts, nuts etc...
Two mechanisms in type I HS.
Abnormal adaptive immune response against the allergens leading to Th2 response and IgE production.
Mast cell activation in sensitised individuals.
Why is the location of mast cells important?
Because different clinical allergic disorders depend on the location of the mast cells.
What is an allergy?
A reaction to the environment which should have resulted in a Th1 response, but instead resulted in a Th2 response leading to an IgE response.
What is the hygiene hypothesis?
Children exposed to animals, pets and microbes in the early postnatal period appear to be protected against certain allergic diseases.
Give examples of features of the environment that protects against allergies.
Developing countries with large family sizes in rural homes and with livestock.
This is usually accompanied by low antibiotic use, high helminth burden and poor sanitation with a high orofaecal burden.
Give examples of an environment which puts you at risk of developing allergies.
A westernised country with a small family size, affluent and urban homes.
High antibiotic use and low or absent helminth burden.
Good sanitation with low orofaecal burden.
Explain old friends hypothesis/biodiversity hypothesis.
Western lifestyle induces alteration of the symbiotic relationships with parasites and bacteria leading to dysbiosis of the microbiome at mucosal surfaces such as the gut.
What is dysbiosis?
Compositional and functional alterations of microbiome.
What is a microbiome?
The complete genetic content of all the microorgansisms that typically inhabit in the body, such as the skin or the GI tract.
Give examples of conditions that can arise from a loss of microbiota diversity.
Immune diseases such as Crohns, UC, T1DM, Celiac disease, allergy and MS.
Metabolic diseases such as obesity and T2DM.
Origin of mast cells.
In the bone marrow by haematopoeitic tissues.
Where do mast cells mature?
In mucosal and epithelial tissues such as the GI tract, skin and resp epithelium.
It also matures in connective tissue surrounding blood cells.
What causes maturation of stem cells?
Binding to Fc'epsilon'RI (a high affinity IgE receptor, (The Fc portion of IgE))
Binding to SCF (Stem cell factor)
What happens to a mast cell when it binds to Fc'epsilon'RI?
It leads to degranulation of of mast cells and release of inflammatory mediators.
Give examples of important mast cell mediators.
Leukotriens C4, D4 and E4
Explain the immune mechanism reaction of allergic exposure in 1st exposure of the allergen.
A Th2 response where there is IgE mediated triggering of the mast cells.
The antigen-specific IgE binds to a high affinity IgE receptor (the FcepsilonRI portion of the mast cell).
Explain the immune mechanism allergic reaction of the 2nd exposure of an allergen.
There is IgE cross-linking where the allergen binds to the antigen-specific IgE.
This leads to triggering of release of granule contents (mast cell degranulation) such as histamine and chemokines, as well as synthesis of new mediators such as leukotrienes and prostaglandins.
This leads to increased vascular permeability, vasodilation, bronchial constriction.
What is this?
Wheal (raised white parts)
This is called urticaria.
What is urticaria caused by?
Caused by mast cell activation within the epidermis.
By mediators such as histamine and leukotriens/cytokines.
What is atopic dermatitis?
Prolonged allergic reaction of urticaria.
What is this?
What is angioedema caused by?
Mast cell activation in the deep dermis by mediators such as histamine and bradykinin.
Where will you see angioedema?
Upper resp airways
Give an example of a systemic allergic reaction.
Clinical responses in anaphylaxis.
Increased vascular permeability leading to hypotension and cardiovascular collapse.
Vasodilation leading to generalised urticaria and angioedema.
Brochial constriction leading to breathing problems.
Treatment of anaphylactic shock.
Clinical response to IM epinephrine.
Reversal of peripheral vasodilation and reduces the oedema + alleviates hypotension.
Reverses airway obstruction and bronchospasms.
Inhibits mast cell activation.