Type 1 hypersensitivity
Type 1 hypersensitivity describes what is also commonly referred to as an allergic reaction. An allergic reaction occurs as an altered secondary response to an antigen. Allergic reactions may vary widely, from mild forms such as hayfever, to severe anaphylaxis. The triggers of allergic reactions may also vary widely, common allergens include:
- Insect stings
- Nuts and seeds
Sensitisation is a key process in the development of an allergic response. Sensitisation is caused by a subset of T-helper cells invoking B cells to release IgE antibody molecules. These IgE (Immunoglobulin E) antibodies then bind to receptors on mast cells and basophils, which are both involved in inflammatory response, these cells now have IgE bound and are sensitized to the allergen which first triggered this cascade.
On secondary exposure the allergen can bind to the allergen specific IgE molecules presented on cell surfaces, when two of these IgE receptor-molecule complexes are activated simultaneously by an antigen molecule the cell becomes activated. Basophils and mast cells which have been activated then release of several mediators including cytokines, leukotrienes, interleukins, prostaglandins and histamine. These inflammatory mediators then trigger effects such as smooth muscle contraction, vasodilation and mucous secretion leading to the symptoms of an allergic reaction.
Histamine has a major role in allergic response, this can be seen by the marked relief of symptoms given by anti-histamines. Histamine acts by attaching to four different histamine receptors H1- H4, all of which are G-Protein coupled receptors. H1, H2 and H4 all play a role in immune response
H1 receptors are found on smooth muscle and in the endothelium when bound by histamine they trigger bronchial smooth muscle constriction and the separation of endothelial cells. These are the receptors whose pathway is blocked by anti-histamine drugs.
H2 receptors are found on vascular smooth muscle cells, when activated they cause vasodilation
H4 receptors are found on basophils and when bound aid in chemotaxis.
H1 and H2 receptors help to mediate the immune response, and so play a key role in allergic responses to allergens.
The acions of histamine via the Histamine receptors are responsible for many of the symptoms detailed below.
Allergic reactions are commonly categorised into mild, moderate and severe classes.
- Mild reactions are localised and involve only the specific area of the body that was exposed to the allergen.
Symptoms may include a rash, congestion and itchy or watery eyes.
- Moderate reactions spread to other parts or systems within the body.
Symptoms include difficulty breathing and itchiness
- Severe reactions can be life threatening as they affect the whole body and are much more intense reactions to allergens than the moderate and mild classes.
Symptoms of a severe reaction include swelling, mental confusion or dizziness, vomiting, abdominal pain and cramps.
The long term effects of allergies are mediated not just by histamine, several mechanisms contribute:
Basophils and mast cells are recruited locally and contribute to increased severity of symptoms.
Leukokines, chemokines and cytokines are released from the mast cells and basophils. These can mediate responses in blood vessels, smooth muscle and can recruit immune cells to the site.
These mechanisms all contribute to chronic symptoms, the prolonged reaction to an allergen. Although the symptoms are the same as in an actue response the prolonging of them can cause further complications, for example in patients with atopic dermatitis itching of the skin can cause lesions or can lead to repeated infections if the skin is broken.
A diagnosis is usually made by one of two methods:
- Serum assays of IgE antibodies
- Skin Test
First picture courtesy of Wikimedia Commons
Second picture courtesy of Wikimedia Commons
Immunology: an illustrated outline, David K. Male, Elsevier Health Sciences, 2004
Immunology, David K. Male, Jonathan Brostoff, Ivan Maurice Roitt, David B. Roth, Elsevier Health Sciences, 2006