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How Allergens cause the disease
How does it happen?
The allergic reaction is a special condition of Inflammation, a process used by the body to direct elements of the immune system to sites of tissue damage or invasion of elements which are recognised by the body as "non-self" (foreign). During each and every inflammatory response three main events occur, i) increased blood flow, ii) increased capillary permeability, iii) migration of the body's defense cells into interstitial tissue from the blood stream and surrounding tissues.
Hayfever signs and symptoms are induced by a combination of two closely interrelated processes, mast cell degranulation (a rapid response to allergen invasion) and the influx of inflammatory cells (a longer-term response). An important aspect of allergic reactions is the phenomenon of hypersensitivity where smaller and smaller amounts of an allegen are needed to cause symptoms each time the individual is challenged.
Allergy is an over-reaction of the immune system
Hayfever Mechanism Stages
STAGE I - First presentation of allergen to the cells
Before seasonal allergy sufferers encounter a certain (patient dependent) concentration of allergen, they will have no symptoms. Their system has to first be "sensitised" to the allergen again. Right at the beginning of the season when the pollen is just starting to be in high concentrations in the air the process of sensitisation begins.
When allergen is inhaled it rests on the lining of the nose and is absorbed into the nasal tissues (the spaces around the cells of the nasal mucosa) by non-specific binding of allergen to mucosal receptors and subsequent absorption into tissues.
Note: allergen does not get into the actual cells of the nasal mucosa or the blood stream. The entire process of hayfever symptom production takes place in the spaces between the cells of the nasal mucosa (interstitial spaces), not inside them.
STAGE II
The Internalised allergen is then picked up by allergen presenting cells which are specialised cells which take up the allergen and use its presence to indicate to other cells of the immune system that an invasion has occurred. Allergen Presenting Cells are one of around 13 white blood cell types.
STAGE III
The Antigen Presenting Cells stimulate the production of IgE-bearing B-Lymphocytes. IgE is an immune system protein (antibody) specially designed to recognise foreign materials. It is produced by "activated" B-lymphocytes. B-lymphocytes are natural immune system cells produced in the bone marrow. They are found as white blood cells patrolling in the blood stream and as a reservoir residing in the lymphatic system. When they meet an antigen (allergen) in the presence of T-lymphocytes, they manufacture immunoglobulin molecules to recognise that particular protein/glycoprotein, which may then be picked up by Mast Cells (see STAGE IV).
STAGE IIIa
As B-lymphocytes are releasing IgE for uptake by Mast Cells, T-Lymphocytes are stimulated to help activate the migration of inflammatory cells to the site of invasion. T-lymphocytes are natural immune system cells which can detect specific abnormalities in cells. When a cell is under stress it signals this by changes in its surface composition. These changes are recognised by T-lymphocytes and they then send chemical signals (Cytokines eg. Interleukins, Colony Stimulating Factor) to stimulate a counter-attack. T-lymphocytes are made in the thymus and are found patrolling in the blood stream and are found as permanent residents in the lymph nodes, spleen, liver, gut, lung, skin, etc, searching and monitoring for invasions. Several subsets of T-lymphocytes exist which have important regulatory functions for immunologic responses (eg. T-Helper cells, T-Suppressor cells).
STAGE IV - Sensitisation of Mast Cells
The key to the rapid onset of the allergic reaction is the mast cell. This is a specialised cell found in the connective tissues. It is full of preformed mediators, chemicals which "mediate" (induce) an effect on the body.
When IgE meets a mast cell it "sticks" to special receptors on the mast cell surface forming a mast cell-IgE complex called a sensitised mast cell. Sensitised mast cells are essentially primed to release all of their mediators.
STAGE V - Degranulation of Mast Cells
Sensitised mast cells meet an allergen particle with the same surface characteristics as the one which triggered the formation of the IgE. The IgE binds the allergen and the mast cell degranulates: this releases a series of pre-formed mediators, sets in motion a process to synthesise additional mediators and aids in the stimulation of inflammatory cell migration to the site of invasion. The net result is the symptoms experienced by the patient.
The mediators released or synthesised as a result of sensitised mast cell degranulation induce the first symptoms patients experience.
- The key preformed mediator for immediate symptom production is histamine:
- The key synthesised mediators for immediate symptoms are the prostaglandis and leukotrines.
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