Immune System Response in Allergy and the Allergic Cascade:

Allergy | May 7, 2014 | Author: The Super Pharmacist

Rhinitis, Antihistamine, Immune, allergy, Asthma

Immune System Response in Allergy and the Allergic Cascade:

Hypersensitivity is an Error of the Immune Response:

Everybody knows that we have a defense system against invading microorganisms such as bacteria and viruses. It is our immune system. The immune system is an amazing and complicated array of cells and chemical messenger molecules. It is interesting how the immune system can identify cells and molecules as one’s own or foreign. It is also astonishing how the immune system can decide when to mount a defense response and when not to. It can also figure out what intensity of reaction is appropriate. It knows when a threat has been taken care of and it can then bring down its level of activity to a normal baseline. Given the intricacies of the mechanisms involved and the myriads of molecules participating, it should not be a total surprise if occasionally the immune system commits errors in threat detection and response. Errors in threat detection can make the immune system attack one’s own cells and tissues, mistaking them for foreign pathogens. This can lead to autoimmune diseases. Errors in threat response can result in an excessive immune reaction to an otherwise harmless substance. Such an abnormal response is appropriately termed hypersensitivity. These errors can do more harm to the body than the foreign substance itself.

Man with CatAllergy is a type of Hypersensitivity:

Substances foreign to the body are called antigens. These could be living such as bacteria and viruses or inanimate such as dander, latex1, eggs or cooked fish. Specifically antigens are molecules that make the immune system respond. The immune system responds by activating various cells and releasing various chemical messengers. Molecules produced by the immune system specifically targeting different antigens are called antibodies. The antibodies have unique structures that enable them to identify and bind to the so many types of antigens. Antibodies are proteins (immunoglobulins ‘Ig’) and there are five well-known classes, IgA, IgD, IgE, IgG and IgM. Understanding the nature of hypersensitivity and its diverse underlying mechanisms, it is revealed that it is not a single entity and at least four specific types of hypersensitivity exist. The first type which is the fastest to occur and presents with its unmistakably detectable classic signs and symptoms is called allergy or allergic reaction. For an allergic reaction (type I hypersensitivity), the antigen is referred to as an allergen and the specific antibody is IgE.

Cells of the Immune System:

The immune system depends upon different types of white blood cells for its activities. The red blood cells are predominantly associated with transportation of oxygen around the body and do not have a direct contribution to immunity. White blood cells are specialized for distinct roles. Among them lymphocytes are especially important in the immune response. Lymphocytes are of two types, T cells and B cells; their names referring to their origins. The B cells are the ones responsible for the production of antibodies. They will do so more efficiently once they are activated to form plasma cells2. The T cells include cells which directly attack pathogens (cytotoxic ‘killer’ cells), help the immune system (helper cells) or suppress and regulate immune response (suppressor cells). The T helper cells may direct the immune response against microorganisms like bacteria (TH1 cells) or may stimulate allergic reactions (TH2 cells). White blood cells that store chemical mediators for allergic responses in granules inside them are basophils in blood and their derivative mast cells in the tissues. Other white blood cells include eosinophils, neutrophils and macrophages which contribute to the inflammation and long term effects of immune allergic responses. Of these eosinophils are noteworthy, which protect us against parasitic infections but are abundant in allergic conditions as well. Some cells are specialised to pick up the antigen and process it so that it is better identified when presented to other cells of the immune system. Such cells are rightly named as antigen presenting cells (APCs).

Chemical Mediators of the Immune System:

Chemical messengers released by cells of the immune system that activate, stimulate or regulate other cells are called cytokines. A special subgroup is the interleukins (IL) which comprise many molecules with particular roles. Of these two deserve mention. IL-43 helps produce more TH2 cells. It also stimulates conversion of B cells to plasma cells leading to increased IgE synthesis. Both these effects greatly enhance the allergic response. IL-5 stimulates B cells but also recruits eosinophils to the site of action which in turn are responsible for the long term effects of the allergic reaction. Chemical mediators released by basophils and mast cells include histamine, serotonin, bradykinin, cytokines, interleukins, leukotrienes etc. Of these, histamine4 has well-known effects contributing to allergic signs and symptoms. Many local features of allergy like swelling, flare, redness, warmth and hives can be attributed to histamine. These mediators are also responsible for the generalised effects of allergy like wheezing, respiratory distress, hypotension and shock.

First Exposure leads to Sensitization:

sneezing in flowersNow that we are familiar with the various components of the immune system, especially those related to allergic reactions, we can now describe what happens when the body is exposed to an allergen. The allergen is picked up and presented by the APCs to the TH2 cells that release IL-4 which converts B cells to plasma cells that produce large amounts of IgE antibodies specifically targeted against the allergen. The IgE is distributed throughout the body and gets attached to specific receptors on mast cells and basophils waiting for more allergen. As you can see, since the mast cells and basophils are not ‘degranulated’ yet nothing happens to the person on first exposure to the allergen. However there has been production of significant amounts of IgE antibodies and these can react with the allergen upon subsequent exposure. Therefore even though nothing will happen on the first exposure to the allergen, the person has become ‘sensitized’ to the allergen. This process of sensitization can complete within days to weeks of first exposure.

The Allergic Cascade:

If there is subsequent exposure, a series of events will occur which can culminate in a full blown allergic reaction. This series of events is called the allergic cascade. The allergen will attach to the IgE antibodies already present in the sensitized person. Since the IgE molecules are attached to mast cells and basophils and since each allergen can bind multiple antibodies, the antibodies will ‘tug’ at the membranes of these cells and cause them to release the contents of their granules. These contents especially histamine will bring about the manifestations of allergy. All this will happen within minutes to hours and is called the early phase reaction. It will subsequently subside. The released IL-5 will recruit eosinophils5 and other cells which will prolong the inflammatory reaction. This second response is called the late phase reaction. It occurs within hours of the initial reaction and may persist for a day or more. Understanding the allergic cascade is important as it provides us with knowledge of opportunities along the cascade where interventions (in the form of drugs) can block, prevent or at least reduce the signs and symptoms of allergy.

References:

1. Amr S, Suk WA. Latex allergy and occupational asthma in health care workers: adverse outcomes.Environ Health Perspect. 2004;112(3):378–81.
2. van Laar JM, Melchers M, Teng YK, van der Zouwen B, Mohammadi R, Fischer R, Margolis L, Fitzgerald W, Grivel JC, Breedveld FC, Lipsky PE, Grammer AC. Sustained secretion of immunoglobulin by long-lived human tonsil plasma cells. Am J Pathol. 2007;171:917–927. doi: 10.2353/ajpath.2007.070005.
3. Steinke JW, Borish L. Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respiratory Research. 2001;2(2):66–70.
4. Zampeli E, Tiligada E. The role of histamine H4 receptor in immune and inflammatory disorders.Br. J. Pharmacol. 2009;157:24–33.
5. Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nature Reviews Drug Discovery. 2013;12(2):117–129.

backBack to Blog Home