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Hygiene Hypothesis: Illness As a Painful but Valuable Lesson for a High-Strung Immune System

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Hygiene Hypothesis: Illness As a Painful but Valuable Lesson for a High-Strung Immune System 10 Issue 13 Hygiene Hypothesis: Illness as a Painful but Valuable Lesson for a High-Strung Immune System MODERNITY HAS PROTECTED HU M ANITY FRO M M ANY DISEASES . YET IN DOING SO , IT HAS ALSO SPURRED THE PROGRESSION OF ALLERGIC DISEASES . THEIR PREVALENCE RISES AT ALAR M ING PACES , ESPECIALLY IN M ODERN NATIONS . THE HYGIENE HYPOTHESIS IS A POPULAR THEORY THAT EXPLAINS THIS PARADOXICAL RELATIONSHIP AS A CONSEQUENCE OF DECREASED MICROBIAL EXPOSURE . JUST AS THE I mm UNE SYSTE M IS NECESSARY TO Ran Ran & Tiffany Chan QUELL PATHOGEN -INDUCED ILLNESSES , IT SEE M S THAT PATHOGENS ARE ALSO NECESSARY TO SUBDUE DISEASES CAUSED BY THE I mm UNE SYSTE M . MUCH EVIDENCE SUPPORTS AND REFUTES THIS IDEA . THIS ARTICLE PROVIDES A CRITICAL PERSPECTIVE ON BOTH SIDES OF THIS ENIG M A AND ALSO ATTE M PTS TO CONSTRUE A CONSOLIDATED PERSPECTIVE . ver the last two decades, a single agreed starting point. Yet from article provides a broad overview of plethora of epidemiological this sea of ideologies, the hygiene the literature concerning the hygiene Odata has emerged suggesting hypothesis has attracted attention, hypothesis: its evidence, mechanisms, that the prevalence of allergic diseases is generating both support and contention and shortcomings. increasing at a dramatic rate, especially (Vercelli, 2006). While it has evolved in developed countries. An intense greatly since conceptualization, the LESSONS FROM EpiDEMIOLOGY debate followed over the possible central tenet of this hypothesis remains causative factors and mechanisms. unchanged: microbial exposures early The prevalence of allergies, asthma, In this heavily deliberated field, it in life can reduce the likelihood of atopic eczema, and other diseases seems that the idea that multifactorial developing allergic diseases and other associated with immune dysregulation determinants are responsible is the immune hypersensitivity diseases. This has increased dramatically. Figure 1 Th1 and Th2 are mutually inhibitory immune responses IL-4 Allergies IL-4 Th2 IL-5 Asthma IL-9 Atopic eczema IL-13 Naive APC Helper T cell IFNy Insulin TNFa dependent Th1 IL1B diabetes IL-12 mellitus Normal immune effects can be subcategorized into several streams. The effects mediated by T-helper cell 1 (Th1) and T-helper cell 2 (Th2) are two well characterized streams that are mutually inhibitory – mediators in the Th1 stream actively suppress the Th2 stream and vice versa (Figure 1). Mounting the appropriate immune response is pivotal in preventing and clearing disease as well as minimizing immune-mediated pathologies. Inappropriate Th1 and Th2 responses can often have detrimental and even fatal effects. An overly strong Th2 response is often observed in atopy, allergies, and asthma. November 2008 11 exposure to pollen and other pathogens (Mutius, 2007). Limited Th1 activity This strengthened the idea that exposure to microbes was Th2 activity inversely correlated to the risk of developing allergies. remains high Recent studies also show that children in families of low Adult is socioeconomic status have reduced risk of developing atopy predisposed to Seldom Exposure to Microbes allergic diseases (Garn & Renz, 2007). Presumably, these children do not have ready access to antibiotics and are also exposed to more microbes in their diet. However in the United States, African- Baby - Constitutive Th2 Activity American and Hispanic-American children, who belong to the two main lowest socioeconomic groups, demonstrate high prevalence of asthma and allergies (Webber et al., 2002). Microbes spurr Th1 activity The hygiene hypothesis suggests that children coming from Th1 suppresses large families who live in poorer conditions are protected Th2 activity against allergic diseases. This does not appear to be the Adult is resistant to developing case, which has ultimately led scientists to believe that other allergic diseases factors are at work. Developed versus Developing Countries Figure 2 Missing Immune Deviation in Development of Allergic The aforementioned observation can be expanded to a Diseases global level; individuals in developing countries display a significantly lower risk for allergic diseases (Figure 1) (The International Study of Asthma and Allergies in Childhood Interestingly, this trend is far from uniform pertaining to (ISAAC) Steering Committee, 1998). However, these certain demographics but not others. The recent rise in geographical trends are not coincidental. Less developed epidemiological studies has identified many social factors countries that adopt a Western lifestyle also demonstrate that predispose individuals to or protect individuals from increased risk of allergic diseases (Nowak et al., 1996). Before such diseases. Some of these factors include family size, the 1990s, the relatively poor and underdeveloped East socioeconomic status, and consideration for whether Germany saw a lower prevalence of asthma and other allergic individuals grew up in an urban or rural environment in a diseases as compared to West Germany, which had relatively developed or less developed country (Stratchan, 1989; Garn higher standards of living (Bach, 2002). Interestingly, & Renz, 2007; Nowak et al., 1996; Mutius, 2007). The hygiene when Germany was reunified in 1990, scientists found hypothesis tries to explain the relationship between allergic that prevalence of atopic eczema and allergic sensitization diseases and the many aforementioned social factors with increased in the children born in former East Germany one unifying concept: frequency of microbial exposures. (Heinrich et al., 2002). These observations led scientists to believe that factors associated with higher living standards Family Size in West Germany, which spread to East Germany after Dr. David Stratchan first proposed the hygiene hypothesis reunification, predisposed children to allergic disease. The in 1989 when he observed that cases of hay fever were resulting decrease in microbial exposure in East Germany is a inversely related to the number of siblings in a family. He likely explanation for the increase in allergic disease. hypothesized that younger siblings were exposed to more microbes through contact with their older siblings, ultimately Farm Environments and Pets preventing them from developing allergies. Several studies, such as the Swiss SCARPOL study, have shown that children raised in rural areas, particularly farms, Socioeconomic Status are protected from hay fever, asthma, and other allergies More than two hundred years before Dr. Stratchan’s (Garn & Renz, 2007). On the other hand, children living in conjecture, scientists in the 1800s noted that hay fever the same village, but not on a farm, have a much higher seemed to only affect individuals of middle or upper classes. prevalence of hay fever and atopic sensitization (Mutius, Incidences of this disease were rarely found in less affluent 2007). Arguably, children living on farms are also exposed groups such as farmers, despite their drastically increased to a wide variety of microbes in this environment. This www.meducator.org 12 Issue 13 Th2 Response Antigen presenting cells (APCs), crucial cells of the innate immune system, play an integral role Elicits production of in determining later T helper cell IgE and Th2 cytokines responses. These cells are typically Results in Allergic Diseases Helminths Combats first to recognize pathogens through Pattern Recognition Receptors (PRR), augment allay which are families of receptors that perclude are capable of binding to a vast array of pathogen associated molecular Spurrs TGF-B and patterns (PAMPs). The series of PRRs IL10 production as well as T-reg cell activity that become stimulated and their T-reg Response degree of activation influence the Figure 3 Pathogen Mediated Immune-Regulation in the Development of Allergic Diseases. maturity of APCs. Hence, exposure to pathogens programs cells of the innate association provides further support epidemiological evidence in support system to behave in ways that will later for the hygiene hypothesis. of the hygiene hypothesis, it provides impact the behaviour of cells in the Exposure to animals seems to important clues in deciphering the adaptive immune system. The details be another pivotal factor. Children who immunological mechanism behind this of this molecular pathway are relatively had a cat within the first few years of life “lesser of two evils” ideology. unclear, but the role of APCs and PRRs not only had a reduced sensitization to on T cell development has been firmly cat allergens, but also a lowered risk of LESSONS F ROM IMMUNOLO G Y established (Duez, Gosset, & Tonnel, asthma later in life (Garn & Renz, 2007). 2006). Contact with animals is thought to Missing Pathogen-Mediated Immune Toll-like receptors (TLRs), a increase exposure to microbes. Though Deviation well-studied family of PRRs, has been some exposures provide a protective While strong epidemiological and shown to play a role in T helper cell effect, some bacterial products are risk immunological evidence exist in differentiation. Thus far, ten TLRs (TLR1- factors for diseases like asthma (Mutius, support of the hygiene hypothesis, the 10) have been identified. Together 2007). mechanism is unclear. Some research they are capable of recognizing and postulates that microbial exposure distinguishing the swath of existing Timing as a Mediator for Microbial “educates” the immune system, shifting pathogens, as well as eliciting more Exposure it from a T helper cell 2 phenotype (Th2), specific adaptive immune responses.
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