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.

Overview
First proposed by David P. Strachan in an article published in the British Medical Journal (now BMJ), in 1989, 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.

Mechanism of Action
Allergic diseases are caused by inappropriate immunological responses to innocuous antigens driven by a TH2 type of immune response to cranking. Many bacteria and viruses elicit a TH1 type of immune response which has the ability to down-regulate the mediators of TH2 responses. Observations of immune function 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.

This proposed mechanistic explanation fell out of favor because it cannot be easily reconciled with the fact that the incidence of inflammatory bowel disease (IBD), multiple sclerosis (MS), and type I diabetes, autoimmune diseases which are linked with an overactive TH1 type of immune response, is increasing in the same populations that are seeing increased allergic disease. The alternative mechanism which was eventually proposed addresses this shortcoming by hypothesizing that the developing immune system, if it does not receive stimuli from infectious agents, fails to properly develop cells with a regulatory function. A person lacking these cells is then more likely to develop autoimmune diseases because of insufficiently repressed TH1 reactions and allergic diseases due to insufficiently repressed TH2 immune reactions. To use a rough analogy, an unbridled immune system has the dynamic of a rowdy, unchaperoned beer party. It is likely to overreact to slight or non-existent insults and may even attack self cells. The role of the T regulatory cells of the immune system is similar to that of the bouncer. The bouncer must practice to be robust and effective.

The old friends hypothesis is a further refinement of the hygiene hypothesis. T regulator cells can only become fully effective if they are stimulated by exposure to several particular varieties of microorganisms and parasites. These consist of pathogens that present only low levels of pathogenicity, and which have coexisted universally with human beings throughout our evolutionary history--that is, at least until recent times, as the development of hygienic practices and effective medical care have diminished or eliminated such traditional fauna from the populace. For example, proper development of T regulator cells in individuals may depend on exposure to organisms such as lactobacilli, various mycobacteria, and, albeit unpalatable, certain harmless helminths. The T regulatory cells learn to respond to harmless or beneficial invaders by damping down the aggressive reaction of the helper T cells and other immune system components to the antigens presented by the harmless symbiotes. As a result, a properly developed immune system is unlikely to aggressively attack harmless allergens or self cells. In this light, not only a virulent environment but also a sterile environment are both detrimental to optimal immune system development.

Recent research has demonstrated even more remarkable beneficial effects for sufferers of multiple sclerosis and Crohn's Disease The reasoning is that our immune systems evolved under constant assault from a variety of parasites, most of which have to modulate our immune response to succeed. That is, they have to down regulate the response that would otherwise attack them. Evolving with a down-regulated immune system means that in the absence of those down-regulating parasites our immune systems often attack our own tissues, leading to asthma, hay fever, IBD, colitis, Crohn's, multiple sclerosis and perhaps other autoimmune diseases. Hence the increase in autoimmune diseases in the relatively clean and sterile industrialized world.

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.