This concept of exposing people to germs at an early age (i.e., childhood) to build immunity is known as the hygiene hypothesis.
Medical professionals have suggested that the hygiene hypothesis explains the global increase of allergic and autoimmune diseases in urban settings. It has also been suggested that the hypothesis explains the changes that have occurred in society and environmental exposures, such as giving antibiotics early in life.

However, neither biologic support nor a mechanistic basis for the hypothesis has been directly demonstrated. Until now.
Researchers at Brigham and Women’s Hospital (BWH) have conducted a study that provides evidence supporting the hygiene hypothesis, as well as a potential mechanism by which it might occur.

The study was published online in the journal Science on the Science Express Web site on March 22, 2012.
The researchers studied the immune system of mice lacking bacteria or any other microbes (“germ-free mice”) and compared them to mice living in a normal environment with microbes.

They found that germ-free mice had exaggerated inflammation of the lungs and colon resembling asthma and colitis, respectively. This was caused by the hyperactivity of a unique class of T cells (immune cells) that had been previously linked to these disorders in both mice and humans.

Most importantly, the researchers discovered that exposing the germ-free mice to microbes during their first weeks of life, but not when exposed later in adult life, led to a normalized immune system and prevention of diseases.

Moreover, the protection provided by early-life exposure to microbes was long-lasting, as predicted by the hygiene hypothesis.
“These studies show the critical importance of proper immune conditioning by microbes during the earliest periods of life,” said Richard Blumberg, MD, chief for the BWH Division of Gastroenterology, Hepatology and Endoscopy, and co-senior study author, in collaboration with Dennis Kasper, MD, director of BWH’s Channing Laboratory and co-senior study author. “Also now knowing a potential mechanism will allow scientists to potentially identify the microbial factors important in determining protection from allergic and autoimmune diseases later in life.”

In light of the findings, the researchers caution that further research is still needed in humans.

http://www.sciencedaily.com/releases/2012/03/120322142157.htm

http://www.news-medical.net/health/What-is-Immunology.aspx

The “hygiene hypothesis” proposes that a lack of early childhood exposure to microbes increases susceptibility to certain diseases by suppressing development of the immune system. The new study not only supports this idea, but may also explain the whys and hows.

However, the researchers caution that they investigated mice, and this does not necessarily mean the same results would occur in humans.

The study was led by two senior authors, both from Brigham and Women’s Hospital (BWH). Dr Richard Blumberg is chief for the BWH Division of Gastroenterology, Hepatology and Endoscopy, and Dr Dennis Kasper is director of BWH’s Channing Laboratory.

Blumberg, Kasper and colleagues studied “germ-free” (GF) mice, that are bred in a sterile environment, without exposure to microbes, and specific-pathogen-free (SPF) mice raised in a normal laboratory environment.

They bred both mice to develop forms of asthma and inflammatory bowel disease (IBD) and compared their immune systems.

They found that the GF mice had more invariant natural killer T (iNKT) cells in their lungs and bowel, and developed more severe disease symptoms:

” … we show that, in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma compared to specific pathogen-free (SPF) mice,” they write.

iNKT cells help fight infection, but they can also fight the body’s own tissue, making it more susceptible to inflammatory diseases.

The researchers also found, when they exposed GF mice to germs in their first few weeks of life, they did not develop high levels of iNKT cells, and they did not develop the more severe symptoms seen in those kept germ-free.

However, if they left this until the GF mice were adults, it had no effect. So they concluded, for benefits to occur, the exposure to germs had to happen before the mice reached adulthood.

They also found the disease-protection the GF mice with early-life exposure to microbes received proved to be long-lasting.

Blumberg told the press:

“These studies show the critical importance of proper immune conditioning by microbes during the earliest periods of life.”

“Also now knowing a potential mechanism will allow scientists to potentially identify the microbial factors important in determining protection from allergic and autoimmune diseases later in life,” he added.

The researchers said their findings are a first step to understanding the global increase in allergic and autoimmunie diseases in urban settings.

However, only by doing studies on humans will we know if the same or similar mechanism is at work, with the same effect.

And, should that be the case, then we may see germ exposure in a new way: and find, perhaps, that contact with germs at the right time may actually be good for us.

http://www.medicalnewstoday.com/articles/243384.php

http://www.sciencedaily.com/releases/2012/02/120208132549.htm

http://www.sciencedaily.com/releases/2012/02/120208132549.htm

The research, led by the University of Bristol’s School of Veterinary Sciences, found that spending early life in a complex farm environment increased the number of regulatory T-lymphocytes, the cells that damp down the immune system and limit immune responses.

Dr Marie Lewis, Research Associate in Infection and Immunity at the School of Veterinary Sciences, who led the research, said: “Many large-scale epidemiological studies have suggested that growing up on a farm is linked to a reduced likelihood of developing allergic disease. However, until now, it has not been possible to demonstrate direct cause and effect: does the farm environment actively protect against allergies, or are allergy-prone families unlikely to live on farms?”

In the study, piglets were nursed by their mothers on a farm while their siblings spent their early life (from one day onwards) in an isolator unit under very hygienic conditions and were fed formula milk, therefore, reflecting the extremes of environment human babies are raised in.

The work was carried out in piglets as they are valuable translational models for humans since they share many aspects of physiology, metabolism, genetics and immunity.

The researchers demonstrated that compared to their brothers and sisters in the isolator, the farm-reared piglets had reduced overall numbers of T-lymphocytes, the immune cells which drive immune responses, in their intestinal tissues. Importantly, these dirty piglets also had significantly increased numbers of a subset of these cells, the regulatory T-lymphocytes, which pacify immune responses and limit inflammation.

This shift in the ratio of stimulatory and regulatory cells appeared to have functional effects since the farm-reared piglets also exhibited decreased antibody responses to novel food proteins when they were weaned.

Regulatory T-cells have been identified in many mammalian species, including humans, and appear to be universal regulators of immune systems and a reduction in their numbers is often associated with the development of allergies, autoimmune and inflammatory diseases.

Dr Marie Lewis explained: “At this point it is not clear exactly what caused the increased capacity for immune regulation in our farm-reared piglets. Our previous work suggests that intestinal bacteria play a pivotal role in the development of a competent immune system and these bacteria are obtained from the environment during early life.”

The researchers suggest additional work is required to determine the extent to which other farm-associated factors, such as social and maternal interactions, aerial contaminants, antigens from bedding and early nutrition, contributed to the impact of the environment on increased local and systemic immune regulation.

Further clarification of the mechanisms underlying these interactions could lead to methods of intervention during infancy to prevent the development of immune diseases in later life.

http://www.medicalnewstoday.com/releases/241396.php

Be cautious of products marketed to “clean” the air, like sprays and plug-in fresheners that release particles.

While room-sized air cleaners can reduce airborne allergens, they can generate ozone – a gas regulated by the EPA as a lung irritant in outdoor air, says Dr. Julie McNairn, an allergist and immunologist with Premier Allergy and Asthma Associates in Middletown. Look for models with the Asthma and Allergy Foundation of America’s “asthma & allergy friendly” certification (www.asthmaandallergyfriendly.com), which indicates they can reduce allergen levels by more than 75 percent and do not contribute to ozone levels in the home that exceed federal regulations.

Use bathroom and kitchen exhaust fans that vent outdoors.

Use natural ingredients for cleaning, like baking soda and vinegar, McNairn recommends, or buy products with the cleaning solution already infused into a cloth.

Use a dehumidifier to reduce the potential of mold growth in a damp basement.

If cleaning up mold – areas less than about 10 square feet can be handled without professional help, according to EPA recommendations – use bleach, not soap. Some types can serve as a food source for mold, McNairn says.

Run the fan in a central air system even when the heat and air conditioning are not on.

http://news.cincinnati.com/apps/pbcs.dll/article?AID=201010210326

Glad you asked. September is National Mold Awareness Month, and the non-profit Allergy & Asthma Network Mothers of Asthmatics recommends consumers be vigilant about preventing mold, dealing with it immediately after it occurs and to choose cleaning products wisely.

“Mold represents a health risk, especially for the approximately 50 million people in the U.S. affected by allergies,” said Nancy Sander, president of AANMA, in a press release. “Bleach and other toxic cleaners commonly advertised to kill mold spores are airway irritants known to trigger asthma and upper respiratory symptoms. We always encourage families to choose non-toxic options because they work.”

“Mold is a serious issue … Mold thrives in moisture, and in addition to the excess water from storms, … high humidity helps promote mold growth,” said Eric Green, president of Planet People, the manufacturer of Concrobium Mold Control, an EPA-registered, 2-in-1 solution that eliminates mold and prevents it from returning, with zero bleach, ammonia or harmful chemicals.

Experts recommend the following:

Detect it: To prevent mold you must stop water from getting inside your home. Keep an eye out for leaking roofs, cracked foundations, clogged drains and faulty plumbing. Regularly check around kitchen and bathroom sinks, refrigerators and attics.

Dry it: Invest in a shop vacuum or water pump, which also can be rented from a local home improvement store, that you can use to remove water in the event of sudden flooding. Once water is removed, use fans to dry out areas; open doors and windows if possible, as well as closet and cabinet doors to help allow air to circulate.

Ditch it: Don’t be reluctant to throw out water and mold-damaged items that are replaceable. If in doubt, throw it out, including carpeting, padding and ceiling tiles. If drywall has absorbed water, cut out 12 inches above the water level and replace once the room is dried out.

http://www.kansascity.com/2011/09/19/3151983/three-ways-to-fight-mold-at-home.html#ixzz1YVvBuYUX

Named Mina, the gene is part of a signaling pathway that may provide novel targets for new treatments and provide further insights into the disease-fighting immune system, explained Mark Bix, Ph.D., Immunology. Bix is senior author of the paper published in Nature Immunology.

A healthy immune system requires balance. Bix is focused on the balance of two specialized cells in one branch of the immune system. The cells are called T-helper type 1 (Th1) and T-helper type 2 (Th2). They arise from a pool of immune cells known as naïve T-helper cells that are arrested at a preliminary stage of differentiation where they are poised for a final differentiation step. During that step they are supposed to acquire specialized immune functions optimized for the control of eliciting pathogens. Chemical messengers known as cytokines control the development of naïve T-helper cells into a variety of more specialized cells, including the Th1 or Th2 cells.

That’s where Mina comes in. Researchers reported this gene works indirectly by regulating production of interleukin 4 (IL-4), a cytokine that plays a central role in balancing Th1 and Th2 cells. Using classical genetics and molecular techniques, investigators showed that Mina dampened IL-4 production by binding to a region of DNA known as the IL-4 promoter. The promoter is where IL-4 production begins. Mice that made large amounts of the Mina protein had low IL-4 levels. When Mina was eliminated, production of the cytokine jumped.

Researchers used a variety of tests involving mouse strains that made different levels of IL-4 to show the rise and fall of IL-4 indirectly controlled Th2 production. High levels of IL-4 favor production of Th2 rather than Th1.

The findings come more than a decade after Bix, then a postdoctoral fellow, started looking for why certain mouse strains mounted an immune response that favored production of either Th1 or Th2 cells. Certain diseases are characterized by an imbalance between those cells.

An imbalance favoring Th2 cells, known as Th2 bias, is linked to an increased risk of problems like allergies and asthma. Th2 cells cause the inflammation that is a hallmark of asthma. Th2 bias is also associated with increased susceptibility to the parasitic infection leishmaniasis, which remains a threat in regions around the equator.

Earlier research from Bix’s laboratory tracked Th2 bias to a region of DNA on chromosome 16 known as Dice1.2. In this study, investigators used a variety of tests to sort through 92 known or predicted genes within Dice1.2 and pinpoint Mina as a key regulator of IL-4.

IL-4 relies on a positive feedback mechanism to influence Th2 production. Newly activated T-helper cells make a small amount of IL-4. The IL-4 then returns through a pathway that includes the IL-4 receptor and transcription factors STAT6 and GATA-3 to entice more T-helper cells to become Th2 rather than Th1 cells. The new Th2 cells respond by secreting even more IL-4.

Bix described Mina as a molecular handle scientists can use to grasp the rest of the new pathway, whose other elements Bix described as links in a chain. “Each one of those links, including the gene we discovered, constitutes a novel target for therapeutic interventions that could help either promote or diminish development toward the Th2 fate,” he explained.

In this study, Bix and his colleagues also proposed a reason for the wide variation in Th2 bias between different mouse strains. The researchers pointed to a region of DNA that included the Mina promoter. They decoded the same region in five different mouse strains. Two favored Th2 production and three did not. The scientists eventually linked the differences to 21 single nucleotide polymorphisms (SNPs). SNPs are relatively common variations in the makeup of particular genes. Those SNPs distinguished mice with high numbers of Th2 cells from those with less Th2 bias. The researchers noted the same DNA region might contain other genomic variations that explain differences in Mina activity.

Mina belongs to a particular family of genes known as transcription factors. Cells use transcription factors to help carry out the instructions genes carry. Mina first surfaced in 2002 in connection with human cancer. Those earlier studies suggested Mina was a target of the Myc oncogene, or cancer gene. However, in T helper cells, Bix’s group found no evidence linking Mina expression with Myc activity.

Other questions remain. Mina lacks an obvious location for binding to the IL-4 promoter. Researchers believe another transcription factor, named NFAT, plays a role in the hookup. They noted the Dice1.2 region of chromosome 16 where Mina was found might contain other genes that contribute to Th2 balance. Mina’s role in response to a Leishmania major infection also remains unclear. Earlier research linked response to the infection to the same DNA region where Mina was found. Researchers speculated Mina might also be the foundation of that response. Other St. Jude authors of the paper are Melanie Van Stry, PhD, and Linda Chung, both of Immunology; and Madoka Koyanagi, PhD, formerly of St. Jude. The research was supported in part by the Cancer Research Institute, the Burroughs Wellcome Fund, the National Institutes of Health and ALSAC.

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer and other catastrophic diseases. Ranked the No. 1 pediatric cancer hospital by Parents magazine, St. Jude is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children, and has treated children from all 50 states and from around the world. St. Jude has developed research protocols that helped push overall survival rates for childhood cancer from less than 20 percent when the hospital opened to almost 80 percent today. St. Jude is the national coordinating center for the Pediatric Brain Tumor Consortium and the Childhood Cancer Survivor Study. In addition to pediatric cancer research, St. Jude is also a leader in sickle cell disease research and is a globally prominent research center for influenza.

Founded in 1962 by the late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world, publishing more research articles than any other pediatric cancer research center in the United States. St. Jude treats more than 5,400 patients each year and is the only pediatric cancer research center where families never pay for treatment not covered by insurance. St. Jude is financially supported by thousands of individual donors, organizations and corporations without which the hospital’s work would not be possible. In 2010, St. Jude was ranked the most trusted charity in the nation in a public survey conducted by Harris Interactive, a highly respected international polling and research firm.

http://www.medicalnewstoday.com/articles/185028.php

Studies have shown that growing up on a farm is associated with reduced risk for asthma, possibly through stimulation of the innate immune system in early life. These data are supportive of the so-called hygiene hypothesis.

Recently, researchers in Germany analyzed data from two large cross-sectional studies comparing microbial exposures of farm-dwelling and non–farm-dwelling children in central Europe.

In the PARSIFAL study (6843 participants), researchers analyzed mattress dust samples for environmental bacteria via DNA signatures, which detect bacteria that cannot be measured by culture. In the GABRIELA study (9668 participants), researchers used culture techniques to evaluate bacterial and fungal taxa in dust from children’s rooms. Both studies showed that farm-dwelling children had a lower incidence of asthma and atopy and were exposed to a larger variety of environmental microorganisms than non–farm-dwellers. Microbial diversity was inversely related to asthma risk. An inverse relationship was seen between asthma incidence rates and exposure to certain fungal and bacterial species.

Atopy, also significantly less prevalent among farm-dwelling children, was only weakly affected by microbial diversity.

http://dermatology.jwatch.org/cgi/content/full/2011/401/1