This will be familiar to most people and describes the rapid ('Immediate') allergic reaction. The symptoms produced by exposure of a sensitised person to antigen depend upon the site of contact. Hayfever (allergic rhinitis), eczema, asthma and urticaria all result from type I hypersensitivity. It is caused upon contact with antigen against which the host has pre-existing IgE antibody. IgE is present in very low levels in serum in most people (see on) - c.50ng (ie 5 × 108gm) per ml. Its' half life in serum is only 2-3 days but much of the IgE in the body is bound to high affinity receptors (Fc epsilonRI), in the bound state the half-life is ~3 weeks. The high affinity Fc epsilonRI receptors are found on mast cells and basophils. Each cell has a high density of these receptors (40-250,000 per cell) so that a wide spectrum of antigen specificities is represented. The cells are activated by the cross-linking of the Fc epsilonRI receptors via antigen binding to the bound IgE molecules.
Such cross-linking leads to rapid degranulation (60-300 secs) of the mast
cells and the release of primary inflammatory mediators stored in
the granules. These mediators cause all the normal consequences of an
acute inflammatory reaction - increased vascular permeability, smooth
muscle contraction, granulocyte chaemotaxis and extravasation etc. Mast
cell activation via Fc epsilonRI also leads to the production of two other
type of mediators. These secondary mediators, unlike the stored
granule contents, must be synthesised de novo and comprise
arachadonic acid metabolites (prostaglandins and leukotrienes) and
proteins (cytokines and enzymes).
| molecule | SOME SPACES | effects |
| Primary mediators | ||
| Histamine | Vascular permeability, sm contraction | |
| Serotonin | vascular permeability, sm contraction | |
| ECF-A | eosinophil chaemotaxis | |
| NCF-A | neutrophil chaemotaxis | |
| proteases | mucus secretion, connective tissue degradation | |
| Secondary mediators | ||
| Leukotrienes | vascular permeability, sm contraction | |
| Prostaglandins | vasodilation, sm contraction, platelet activation | |
| Bradykinin | vascular permeability, sm contraction | |
| Cytokines | numerous effects inc. activation of vascular endothelium, eosinophil recruitment and activation | |
The type I response has an early and a late component.
Mirroring the two types of mediators, one can see two components to the type I response.A very rapid early response occurs when you are challenged with an antigen to which you are sensitised which is apparent within a few minutes and maximal after about 20 minutes. If the challenge is cutaneous it produces the so-called 'wheal and flare' - raised patch surrounded by a pink effusion. The late response seen after some hours is characterised by cellular infiltrate which gives a hard but barely pigmented nodule in the case of skin.
That these responses are caused by distinct mediators can be shown with inhibitory drugs. Arachadonic acid metabolism inhibitors, such as indomethacin, block only the late response. Sodium cromoglycate which blocks mast cell activation and degranulation blocks both early and late responses.
Incidence and genetic susceptibility
Some 20-30% of the population exhibit type
I hypersensitivity or atopic allergy to common environmental substances.
There is a genetic component to atopic allergy such that if both your
parents exhibit this susceptibility you are more than 2 × more likely to
do so and if neither parent has manifest allergies you are less than half
as likely to when compared to the population as a whole. Some individuals
have multiple and severe allergies, typically both hayfever and eczema;
these individuals are termed atopic and frequently have raised total serum
IgE levels (10 -100 × normal). There is a correlation between total
[IgE] and atopy.
Allergens
Numerous ideas have been put forward as to what property might distinguish antigens which stimulate a sufficient IgE response to generate type I hypersensitivity (allergens) from those antigens which rarely or never do so. However no common property has yet been discerned. below is a list of common allergens.
Systemic anaphylaxis
While we are probably all familiar with the consequences of a localised type I reaction (anaphylaxis) which are unpleasant and annoying, the consequences of a generalised reaction are potentially fatal. Ingestion of nuts or seafood, insect bites (venom), and drug injection may all cause life-threatening reactions in highly sensitised individuals. Death in such cases is due to systemic release of vasoactive mediators leading to general vasodilation and smooth muscle contraction resulting in sudden loss of blood pressure, massive oedema and severe bronchiole constriction (systemic anaphylaxis).
Information provided by: http://www-immuno.path.cam.ac.uk