How Influenza Evolves – And How To Stop It From Doing So

How Influenza Evolves – And How To Stop It From Doing So.

If you become infected with the flu after getting vaccinated, your body activates an immune response that stops you from becoming ill. Although, this can trigger the virus to change into a slightly different form – one that may be more infectious.

A novel investigation from MIT reveals the mechanism responsible for this phenomenon, known as antigenic drift. The study was funded by the National Institutes of Health and the Singapore-MIT Alliance for Research and Technology and appears in the December 19 online edition of Scientific Reports, an open-access journal published by Nature.

Related articles

• How Influenza Evolves – And How To Stop It From Doing So (medicalnewstoday.com)
• Lab-Made Bird Flu Details Kept Secret (myfoxny.com)
• Influenza A (H1N1) [swine flu] (codesandstuff.wordpress.com)
• Georgetown researchers lead discovery expected to significantly change biomedical research (eurekalert.org)
• The Flu – How To Stop It! (jflahiff.wordpress.com)

Learning to tolerate our microbial self: Bacteria co-opt human immune cells for mutual benefit

The image depicts symbiotic microbes in the process of colonizing the mucosal surface of the mouse colon. Yellow cells are Escherichia coli; red cells are Bacteroides fragilis. Intestinal tissues are labeled in green with blue nuclei.

(Credit: S. Melanie Lee/Caltech)

From the 21 April 2011 Science Daily article

ScienceDaily (Apr. 22, 2011) — The human gut is filled with 100 trillion symbiotic bacteria — ten times more microbial cells than our own cells — representing close to one thousand different species. “And yet, if you were to eat a piece of chicken with just a few Salmonella, your immune system would mount a potent inflammatory response,” says Sarkis K. Mazmanian, assistant professor of biology at the California Institute of Technology (Caltech).

Salmonella and its pathogenic bacterial kin don’t look that much different from the legion of bacteria in our gut that we blissfully ignore, which raises the question: What decides whether we react or don’t? Researchers have pondered this paradox for decades.

In the case of a common “friendly” gut bacterium, Bacteroides fragilis, Mazmanian and his colleagues have figured out the surprising answer: “The decision is not made by us,” he says. “It’s made by the bacteria. Since we are their home, they hold the key to our immune system.”

What’s more, the bacteria enforce their “decision” by hijacking cells of the immune system, say Mazmanian and his colleagues, who have figured out the mechanism by which the bacteria accomplish this feat — and revealed an explanation for how the immune system distinguishes between beneficial and pathogenic organisms….

…bacteria actually live in a unique ecological niche, deep within the crypts of the colon, “and thus in intimate contact with the gut mucosal immune system,” he says.

“The closeness of this association highlights that an active communication is occurring between the bacteria and their host,” says Caltech postdoctoral scholar June L. Round.

From that vantage point, the bacteria are able to orchestrate control over the immune system — and, specifically, over the behavior of immune cells known as regulatory T cells, or Treg cells. …

…”Our immune system arose in the face of commensal colonization and thus likely evolved specialized molecules to recognize good bacteria,” says Round. Mazmanian suspects that genetic mutations in these pathways could be responsible for certain types of immune disorders, including inflammatory bowel disease: “The question is, do patients get sick because they are rejecting bacteria they shouldn’t reject?”

On a more philosophical level, Mazmanian says, the findings suggest that our concept of “self” should be broadened to include our many trillions of microbial residents. “These bacteria live inside us for our entire lives, and they’ve evolved to look and act like us, as part of us,” he says. “As far as our immune system is concerned, the molecules made by gut bacteria should be tolerated similarly to our own molecules. Except in this case, the bacteria ‘teaches’ us to tolerate them, for both our benefit and theirs.”…

Journal Reference:

1. June L. Round, S. Melanie Lee, Jennifer Li, Gloria Tran, Bana Jabri, Talal A. Chatila, and Sarkis K. Mazmanian.The Toll-Like Receptor 2 Pathway Establishes Colonization by a Commensal of the Human Microbiota. Science, 21 April 2011 DOI:10.1126/science.1206095

[Abstract only, for suggestions on how to get this article for free or at low cost, click here]

Related Articles

• Do bacteria control your brain? (boingboing.net)
• Gut Bacteria Mapping Finds Three Global Varieties (wired.com)
• Friendly Bacteria Fight the Flu (scientificamerican.com)
• What’s your gut type? (eurekalert.org)
• People Fall Into Three Categories Of Gut Microbiota : Implications for Nutrient and Medicine Uptake (jflahiff.wordpress.com)
• Humans Shown To Have Intestinal Bacteria Groups As Well As Blood Groups

  “The three enterotypes show various categories of bacteria with a different impact of the gut. Enterotype 1 is dominated by the Bacteroides intestinal bacteria, which together with a few other species of bacteria, forms a distinctive cluster of gut flora. The dominant bacteria in enterotype 2 is Prevotella. And in enterotype 3, Ruminococcus is the main bacteria, along with other species such as Staphylococcus, Gordonibacter and a species discovered in Wageningen previously, Akkermansia. Enterotype 3 is the most common.

  Furthermore, every cluster of bacteria has its own way of supplying energy. Enterotype 3, for example, specialises in breaking down mucin, a carbohydrate that enters the gut via our food. This allows the gut to absorb these fragments asnutrition for the body. All three enterotypes also produce vitamins, albeit in varying amounts. Enterotype 1 produces the most vitamin B7 (biotin), B2 (riboflavin) and C (ascorbic acid), and enterotype 2 produces mainly vitamin B1 (thiamin) and folic acid. Every enterotype, with its distinctive clusters of bacteria and functional differences, reflects a distinctive way of generating energy that is closely compatible with its host. It is also possible that the enterotypes may interact with their host on various levels, having an impact on the individual’s health.

  In March of last year, the MetaHIT consortium published the first catalogue of genes of human intestinal bacteria (also known as the second genome). These bacteria populations encode 150 times more genes than our own genome. It was shown that from a range of more than a thousand species of bacteria that live in the human gut, every individual is host to several hundred types of bacteria.

  The discovery of the enterotypes will influence the fields of biology, medicine and nutrition, making it much easier to analyse an individual’s needs. The research team sees future opportunities for personal and preventive dietary and medicinal advice.”

• Learning to tolerate our microbial self: Bacteria co-opt human immune cells for mutual benefit (jflahiff.wordpress.com)
• Deepak Chopra: Weekly Health Tip: You Are Home to Millions of Microbes! (huffingtonpost.com)
• Friendly bacteria fight the flu (nature.com)

New Findings Challenge View of Key Part of Immune Defense

Image via Wikipedia

New Findings Challenge View of Key Part of Immune Defense

From a March 3 2011 Science Daily news item

 

ScienceDaily (Mar. 3, 2011) — The natural killer cells of our immune defense are activated for an extended period after the acute infection, which challenges the prevailing view that the elevation and activation of cells quickly pass. This is shown in a study regarding vole fever that was recently published by researchers at Umeå University, Sweden in Journal of Experimental Medicine.**

***For suggestions on how to get this article for free or at low cost, click here

 

Defense mechanism against bacteria and fungi deciphered

Defense mechanism against bacteria and fungi deciphered
Mystery of ‘inactive’ defensin solved

 

Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.

From the January 21, 2011 Eureka news alert

Under standard laboratory conditions, the human beta-defensin 1 (hBD-1), a human antibiotic naturally produced in the body, had always shown only little activity against microbes. Nevertheless the human body produces it in remarkable quantities. The solution to the puzzle was the investigation process itself, as the research group led by Dr. Jan Wehkamp at the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology of the Stuttgart-based Robert Bosch Hospital found out.

Before the research group took a new approach to this research, defensins were usually tested in the presence of oxygen, although little oxygen is present, for example, in the human intestine. Starting out from the discovery that a special antibiotic-activating protein of the human body is diminished in patients with inflammatory bowel diseases, Crohn’s Disease and Ulcerative Colitis, the working group investigated how defensins act under low-oxygen conditions. During their investigations the scientists found out that under these conditions hBD-1 unfolds a strong antibiotic activity against lactic acid bacteria and yeast.

Furthermore the researchers discovered that another human protein, thioredoxin, is able to activate beta-defensin 1 even in the presence of oxygen. Moritz Marcinowski and Professor Johannes Buchner from the Department of Chemistry at the Technical University of Munich, used circular dichroism spectroscopy to elucidate the differences between the folded inactive and the unfolded active form of the protein.

Surprisingly, while almost all proteins are active only in their folded form, in the case of the small defensin the opposite is true. To activate the beta-defensin 1 the thioredoxin opens the three disulphide bridges that hold the molecule together. The molecule then opens up into the active state. Using this mechanism the body has the opportunity to selectively activate the defensin.

So far the cause of inflammatory bowel disease is unclear. Genetic as well as environmental factors seem to play a role, finally leading to a weakening of the antimicrobial barrier, which is mainly mediated by defensins. Accordingly the identified mechanism might contribute to the development of new therapies to treat affected patients.

 

Texas A&M research shows bacteria provide example of one of nature’s first immune systems

From the December 23, 2010 Eureka news release

COLLEGE STATION, Texas, Dec. 23, 2010—Studying how bacteria incorporate foreign DNA from invading viruses into their own regulatory processes, Thomas Wood, professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, is uncovering the secrets of one of nature’s most primitive immune systems.

His findings, which appear in “Nature Communications,” a multidisciplinary publication dedicated to research in all areas of the biological, physical and chemical sciences, shed light on how bacteria have throughout the course of millions of years developed resistance to antibiotics by co-opting the DNA of their natural enemies—viruses.

The battle between bacteria and bacteria-eating viruses, Wood explains, has been going on for millions of years, with viruses attempting to replicate themselves by – in one approach – invading bacteria cells and integrating themselves into the chromosomes of the bacteria. When this happens a bacterium makes a copy of its chromosome, which includes the virus particle. The virus then can choose at a later time to replicate itself, killing the bacterium—similar to a ticking time bomb, Wood says.

However, things can go radically wrong for the virus because of random but abundant mutations that occur within the chromosome of the bacterium. Having already integrated itself into the bacterium’s chromosome, the virus is subject to mutation as well, and some of these mutations, Wood explains, render the virus unable to replicate and kill the bacterium.

With this new diverse blend of genetic material, Wood says, a bacterium not only overcomes the virus’ lethal intentions but also flourishes at a greater rate than similar bacteria that have not incorporated viral DNA.

“Over millions of years, this virus becomes a normal part of the bacterium,” Wood says. “It brings in new tricks, new genes, new proteins, new enzymes, new things that it can do. The bacterium learns how to do things from this.

“What we have found is that with this new viral DNA that has been trapped over millions of years in the chromosome, the cell has created a new immune system,” Wood notes. “It has developed new proteins that have enabled it to resists antibiotics and other harmful things that attempt to oxidize cells, such as hydrogen peroxide. These cells that have the new viral set of tricks don’t die or don’t die as rapidly.”

Understanding the significance of viral DNA to bacteria required Wood’s research team to delete all of the viral DNA on the chromosome of a bacterium, in this case bacteria from a strain of E. coli. Wood’s team, led by postdoctoral researcher Xiaoxue Wang, used what in a sense could be described as “enzymatic scissors” to “cut out” the nine viral patches, which amounted to precisely removing 166,000 nucleotides. Once the viral patches were successfully removed, the team examined how the bacterium cell changed. What they found was a dramatically increased sensitivity to antibiotics by the bacterium.

While Wood studied this effect in E. coli bacteria, he says similar processes have taken place on a massive, widespread scale, noting that viral DNA can be found in nearly all bacteria, with some strains possessing as much as 20 percent viral DNA within their chromosome.

“To put this into perspective, for some bacteria, one-fifth of their chromosome came from their enemy, and until our study, people had largely neglected to study that 20 percent of the chromosome,” Wood says. “This viral DNA had been believed to be silent and unimportant, not having much impact on the cell.

“Our study is the first to show that we need to look at all bacteria and look at their old viral particles to see how they are affecting the bacteria’s current ability to withstand things like antibiotics. If we can figure out how the cells are more resistant to antibiotics because of this additional DNA, we can perhaps make new, effective antibiotics.”

 

Immune System Quiz and other KidsHealth Information Just for Kids

The Immune System Quiz uses upbeat music and wild cheering to motivate kids to progress through 10 questions.

The quiz is provided by KidsHealth, part of The Nemours Foundation‘s Center for Children’s Health Media.
See the About page for more information about this site whose content is reviewed by doctors before publication.

The Movies and Games section includes links to not only games and movies but also experiments, quizzes, and experiments.
These links are also found within Kids Health Web pages addressing specific  topics.

Here is a sampling on the sections for kids ( there are also sections for teens and for parents)

• Dealing with Feelings as bullying, cheating, getting along with siblings, fear, and money troubles
• Staying Healthy has numerous pages on how to eat right, exercise,and take preventative health measures
• Staying Safe has links about first aid, emergencies, gun safety, poisonous plants, and much more
• Health Problems discusses allergies, blood diseases, cancer, infections, and more

Structure of key molecule in immune system provides clues for designing drugs

Structure of key molecule in immune system provides clues for designing drugs

From the December 27, 2010 Eureka news alert

PHILADELPHIA – A team from the University of Pennsylvania School of Medicine and Utrecht University has deciphered a key step in an evolutionarily old branch of the immune response. This system, called complement, comprises a network of proteins that “complement” the work of antibodies in destroying foreign invaders. It serves as a rapid defense mechanism in most species from primitive sponges to humans.

In a study published in the December 24 issue of Science, the groups of John Lambris, PhD, the Dr. Ralph and Sally Weaver Professor of Research Medicine at Penn, and Piet Gros at Utrecht, detail the atomic structure of two key transient enzyme complexes in the human complement system.

Complement proteins mark both bacterial and dying host cells for elimination by the body’s cellular cleanup services and have been implicated in at least 30 diseases, including stroke, myocardial infarction, and age-related macular degeneration. The findings, Lambris says, provide a molecular scaffold for designing novel drug therapeutics….

…”Besides shedding light on a highly elegant mechanism of concerted activation and intrinsic regulation, this work also offers a detailed insight into one of the most important therapeutic targets within the complement network, which may facilitate rational drug development and could lead to novel drugs for treating complement-related diseases,” Lambris says….

Background material on complement proteins

• The complement system and innate immunity (via NCBI Bookshelf)
• The complement system (via NCBI Bookshelf in Immunology Review)
• The complement system (college lecture with flash animations)

 

UCSF team finds new source of immune cells during pregnancy

Joseph M. McCune, MD, Ph.D. is a researcher at University of California – San Francisco.

From a December 16, 2010 Eureka news alert

UCSF researchers have shown for the first time that the human fetal immune system arises from an entirely different source than the adult immune system, and is more likely to tolerate than fight foreign substances in its environment.

The finding could lead to a better understanding of how newborns respond to both infections and vaccines, and may explain such conundrums as why many infants of HIV-positive mothers are not infected with the disease before birth, the researchers said.

It also could help scientists better understand how childhood allergies develop, as well as how to manage adult organ transplants, the researchers said. The findings are described in the Dec. 17 issue of Science and at www.sciencemag.org/content/330/6011/1695.full.html.

(Accompanying scientific commentary: http://www.sciencemag.org/content/330/6011/1635.full.html)

Until now, the fetal and infant immune system had been thought to be simply an immature form of the adult system, one that responds differently because of a lack of exposure to immune threats from the environment. The new research has unveiled an entirely different immune system in the fetus at mid-term that is derived from a completely different set of stem cells than the adult system.

“In the fetus, we found that there is an immune system whose job it is to teach the fetus to be tolerant of everything it sees, including its mother and its own organs,” said Joseph M. McCune, MD, PhD, a professor in the UCSF Division of Experimental Medicine who is a co-senior author on the paper. “After birth, a new immune system arises from a different stem cell that instead has the job of fighting everything foreign.”

The team previously had discovered that fetal immune systems are highly tolerant of cells foreign to their own bodies and hypothesized that this prevented fetuses from rejecting their mothers’ cells during pregnancy and from rejecting their own organs as they develop….

Over-reactive immune system kills young adults during pandemic flu

Another reason to get a flu shot (especially young adults)…….

From the December 5, 2010 Eureka news alert

On November 19, Jason Martin returned to the Medical Intensive Care Unit (MICU) at Vanderbilt University Medical Center for the first time since he nearly died there during last year’s H1N1 flu pandemic. The tall and burly Warren County, TN, ambulance worker – a 30-year-old, father of three young children – broke down and hugged some of the nurses he recognized.

“I got sick on September 12 and didn’t come out of it for the next 20 days. I am just so grateful I came through,” Martin said, wiping his eyes.

Martin was among the first wave of critically ill middle Tennesseans, hit hard by the H1N1 flu pandemic in late 2009. A hallmark of pandemic flu throughout history, including the H1N1 pandemic, has been its ability to make healthy young and middle-aged adults seriously ill and even kill this population in disproportionate numbers.

In a paper published Dec. 5 in Nature Medicine, Fernando Polack, M.D., the Cesar Milstein Associate Professor of Pediatrics at Vanderbilt, and colleagues in Argentina and Nashville provide a possible explanation for this alarming phenomenon of pandemic flu. The study’s findings suggest people are made critically ill, or even killed, by their own immune response…

…

“We have seen this before. Where non-protective antibody responses are associated with an immune-based disease in the lung,” Polack said.

Polack has previously published evidence that a first-line immune response, primed by an imperfect antibody, can overreact in a violent and uncontrolled fashion. Patients die from lung damage inflicted by their own immune system. A molecule called C4d, a product of this biochemical cascade (the complement system), is a marker for the strength of the response.

In adults who died during the 2009 H1N1 pandemic, high levels of C4d in lung tissues suggest a massive, potentially fatal activation of the complement system.

Pulmonary and critical care physician, Todd Rice, M.D., assistant professor of Medicine at VUMC, has seen people killed by the “exuberant” and uncontrolled response of the immune system in other diseases – like sepsis….

…

While many questions remain, one thing is clear: the H1N1 vaccine offers protection. Patients who died were overwhelmingly unvaccinated. Many fell ill before a vaccine was even available. [Editor Flahiff’s empahsis]

Too Much Hygiene May Affect Immune System, Study Suggest

 

Antimicrobial used in many products such as soaps, toothpaste tied to raised allergy risks in kids

Excerpts from a November 29, 2010 Health Day news item by Robert Priedt

MONDAY, Nov. 29 (HealthDay News) — Children and teens who are overexposed to antibacterial soaps that contain the chemical triclosan may be at increased risk for hay fever and other allergies, a finding that suggests that being too clean can actually make people sick, researchers say.

The study also found that exposure to higher levels of the chemical bisphenol A (BPA) may weaken an adult’s immune system.

Triclosan is an antimicrobial agent widely used in products such as antibacterial soaps, toothpaste, medical devices and diaper bags. BPA, which is used to make many types of plastics and other consumer products, is believed to affect human hormones….

…The study findings are published in the Nov. 30 online edition of the journal Environmental Health Perspectives.