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Hygiene hypothesis



In medicine, the hygiene hypothesis states that a lack of early childhood exposure to infectious agents, and later a lack of exposure to helminths as adults, increases susceptibility to allergic diseases [1].

Contents

Overview

First proposed by David P. Strachan in an article published in the British Medical Journal (now BMJ), in 1989 [2], the hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were presumably exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. Despite this, the infectious microorganisms or infectious microorganism-components believed to be responsible for these effects have yet to be identified and incorporated into medical practice and the contribution of hygiene levels to the rise of allergic disease has yet to be established[3].

Mechanism of Action

Allergic diseases are caused by inappropriate immunological responses to innocuous antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. Observations of this down-regulation led to the development of the first proposed mechanism of action of the hygiene hypothesis, which stated that insufficient stimulation of the TH1 arm of the immune system lead to an overactive TH2 arm, which in turn led to allergic disease [4].

The original proposed mechanistic explanation for the hygiene hypothesis fell out of favor because the incidence of several TH1-mediated autoimmune diseases, including inflammatory bowel disease (IBD), multiple sclerosis (MS), and type I diabetes, is increasing in the same populations that have had an increase in allergic disease. An alternative mechanistic explanation was proposed that hypothesized that the developing immune system, if it does not receive stimuli from infectious agents, fails to properly develop T cells with a regulatory function. A person lacking these regulatory cells would then be more likely to develop autoimmune diseases because of an insufficiently repressed TH1 response and more likely to develop allergic diseases due to an insufficiently repressed TH2 response[5]. To use a rough analogy, an unbridled immune system (without T regulatory cells) has the dynamic of a rowdy, unchaperoned beer party. It is likely to overreact to slight or non-existent insults (analogous to allergic disease) and may even attack members of its own party (analogous to autoimmune disease). The role of the T regulatory cells of the immune system is similar to that of the bouncer, keeping the beer party in check.

The old friends hypothesis is a further refinement of the hygiene hypothesis, which hypothesizes that T regulatory cells can only become fully effective if they are stimulated by exposure to several particular varieties of microorganisms and parasites. These consist of organisms that present only low levels of pathogenicity, which have coexisted with human beings throughout our evolutionary history. In recent times the development of hygienic practices and effective medical care have diminished or eliminated these microorganisms and parasites so that humans are no longer exposed to them during development. Examples of organisms that may be important for proper development of T regulatory cells include lactobacilli, various mycobacteria, and certain harmless helminths. The T regulatory cells learn to respond to harmless or beneficial organisms by damping down the aggressive reaction of the TH2 cells and other immune system components to the antigens presented by these organisms. As a result, a properly developed immune system is unlikely to aggressively attack harmless allergens or self cells. Thus, as proposed by the hygiene hypothesis, both a virulent environment and a sterile environment are detrimental to optimal immune system development.

Recent research has explored the effects of parasites on development of the immune system, and demonstrated that parasites may have beneficial effects for sufferers of multiple sclerosis[6] and Crohn's Disease[7] The rationale is that our immune systems evolved under constant assault from a variety of parasites, most of which had to modulate our immune response (so that our immune system would not attack them) in order to succeed. Developing without the challenge of defending ourselves against parasites can lead our immune systems to attack our own cells or over-respond to harmless antigens, leading to asthma, hay fever, IBD, colitis, Crohn's disease, multiple sclerosis, and perhaps other autoimmune diseases. Hence the increase in allergic and autoimmune diseases in the relatively clean and sterile industrialized world may be in part due to a decrease in parasite exposure.

See also

References

  1. ^ Strachan DP. Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax 55 Suppl 1:S2-10.: S2-10, 2000.
  2. ^ Strachan DP. Hay fever, hygiene, and household size. BMJ 299: 1259-1260, 1989.
  3. ^ Schaub B, Lauener R and von ME. The many faces of the hygiene hypothesis. J Allergy Clin Immunol 117: 969-977, 2006. Article online
  4. ^ Folkerts G, Walzl G, Openshaw PJ. Do common childhood infections 'teach' the immune system not to be allergic? Immunol Today 2000; 21(3):118-120. PubMed
  5. ^ Guarner F, Bourdet-Sicard R, Brandtzaeg P, Gill HS, McGuirk P, van EW, Versalovic J, Weinstock JV and Rook GA. Mechanisms of disease: the hygiene hypothesis revisited. Nat Clin Pract Gastroenterol Hepatol 3: 275-284, 2006. PubMed
  6. ^ Annals of Neurology Association between parasite infection and immune responses in multiple sclerosis
  7. ^ British Medical Journal A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors

Additional References

1. Camateros P, Moisan J, Henault J, De SJ, Skamene E and Radzioch D. Toll-like receptors, cytokines and the immunotherapeutics of asthma. Curr Pharm Des 12: 2365-2374, 2006.

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Hygiene_hypothesis". A list of authors is available in Wikipedia.
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