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Mechanism of type I allergic reactions

In this article Andreas J. Bircher explains the mechanism of type I allergic reactions.

The adaptive immune system is central in any immune defence, including allergic reactions. Before the body reacts to foreign intruders, it first has to encounter the antigen and identify it as potential danger. In allergies, the immune system produces an unnecessary, exaggerated defence reaction.

First allergen exposure

At the first allergen exposure, the patient may get sensitized. This step includes antigen presentation, the production of specific IgE antibodies, and their binding on mast cells or basophils. Allergic symptoms are only elicited if the sensitized patient is again exposed to the same allergen.

Illustration depicting how immunological memory is established. First, antigens are taken up by dendritic cells. The antigens presented by dendritic cells in the lymph node are then recognized by T cells, which upon their activation become so-called helper T cells. Meanwhile, B cells pick up the antigen and process it. Once processed, the antigen is presented on the surface of the B cell. The helper T cells bind to the antigen and then release cytokines that stimulate the B cells. Once stimulated, B cells undergo proliferation and differentiation in antibody-producing plasma cells and memory B cells. The memory B cells remain in the immune organs and elicit a new immune reaction at a subsequent allergen exposure.Development of immunological memory. (click to enlarge)

  1. After the invasion of an intruder, antigen-presenting cells (APCs; ie dendritic cells or Langerhans cells) take up and process the antigen.

  2. They then present it to T helper cells on special cell surface proteins. These proteins are called major histocompatibility complex (MHC) or human leukocyte antigen (HLA) molecules and represent an identification system present on all body cells (except on red blood cells and platelets) allowing to distinguish self from foreign.

  3. The T helper cells then stimulate B cells.

  4. The B cells turn into plasma cells and start to produce antibodies. Some antibodies bind to the surface of mast cells and basophils. A single plasma cell clone (family) produces large amounts of exact copies of just one specific antibody (eg IgG antibodies against a protein structure on a virus or IgE antibodies against a pollen protein). IgG antibodies are protective against microbes, IgE bound on mast cells against parasites.

  5. Memory is established through memory B cells, which can again produce exactly the same antibody upon re-exposure to a given antigen. Such memory B cells will persist throughout life. Therefore, once sensitization has taken place, it will usually persist lifelong.

Sensitization takes about five to seven days and involves a number of complex steps, which are tightly regulated. But also damping or stopping the immune response, eg by T regulatory cells, is crucial. The immune system should not start to produce antibodies against the body’s own cells or organs and it should know when to stop – otherwise severe damaging inflammation or autoimmune diseases could occur.

Further allergen exposure

If the same allergen is encountered again, a specific immune response is triggered almost immediately. This process is much faster than the initial sensitization phase.

  1. As soon as the patient is re-exposed to the particular allergen, memory B cells boost the production of specific antibodies.

  2. The allergen further activates effector cells, such as mast cells and basophils. Mast cells are aligned in the skin, lung, and gut, while basophils are in circulation. Depending on the type of allergen and the ‘port of entry’, symptoms such as nettle rash (ie urticaria), bronchospasm (ie asthmatic attack), or intestinal symptoms occur. Mast cells and basophils synthesize a large array of pro-inflammatory mediators: chemokines, cytokines, histamine, leukotrienes, prostaglandins, and others. Among these, histamine is probably the best known. It may cause skin wheals, an itchy and running nose, tightening of the bronchi, and rapid bowel movements. These are altogether symptoms, which may help to eliminate the parasites in a protective immune response.

© University of Basel
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Allergies: When the Immune System Backfires

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