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Evolution in action: Our antibodies take 'evolutionary leaps' to fight microbes
January 06, 2009New article in the FASEB Journal explains how 'cluster mutations' help us adapt to infection
With cold and flu season in full swing, the fact that viruses and bacteria rapidly evolve is apparent with every sneeze, sniffle, and cough. A new report in the January 2009 issue of The FASEB Journal (http://www.fasebj.org), explains for the first time how humans keep up with microbes by rearranging the genes that make antibodies to foreign invaders. This research fills a significant gap in our understanding of how the immune system helps us survive.
"We've known for a long time that our antibody-forming system adapts itself to every microbe we encounter," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but what we didn't understand fully is exactly how this happens. Now that we know, we can begin to find ways to manipulate this process so illnesses can be prevented or made significantly less dangerous."
When the body encounters a foreign invader, like a virus or bacterium, it immediately begins to find a way to neutralize it by means of cellular or antibody-mediated defenses. Part of the process involves tailoring the genes that code for antibodies to specific viruses or bacteria. Researchers have known that this involves two types of genetic manipulation. One type changes a single gene at a time, and the other type changes multiple genes at the same time. In the report, scientists from Wayne State University in Detroit describe how multiple genes can be modified simultaneously to make the "evolutionary leap" necessary to stave off infection. The basic setup of the experiment treated DNA responsible for making antibody molecules with an enzyme, called activation-induced deaminase, while the DNA was being copied by RNA polymerase. Like a scanner, RNA polymerase moves across the DNA to copy it. When this scanning process moved smoothly, there were either single mutations or no mutations. When the researchers made the RNA polymerase stall along the DNA (under certain conditions), it caused several mutations at once (cluster mutations) in the DNA, adapting our antibodies for a rapid and effective response to a new microbial invader.
"As the planet warms, infectious diseases may be one the biggest threats to human survival," Weissmann added. "Nowadays, mosquitoes, parasites and viruses cause diseases in the United States that were once isolated to warmer parts of the world. They evolve, and - a la Darwin - so does our immune system each time we meet a new microbial invader."
Federation of American Societies for Experimental Biology
When the body encounters a foreign invader, like a virus or bacterium, it immediately begins to find a way to neutralize it by means of cellular or antibody-mediated defenses. Part of the process involves tailoring the genes that code for antibodies to specific viruses or bacteria. Researchers have known that this involves two types of genetic manipulation. One type changes a single gene at a time, and the other type changes multiple genes at the same time. In the report, scientists from Wayne State University in Detroit describe how multiple genes can be modified simultaneously to make the "evolutionary leap" necessary to stave off infection. The basic setup of the experiment treated DNA responsible for making antibody molecules with an enzyme, called activation-induced deaminase, while the DNA was being copied by RNA polymerase. Like a scanner, RNA polymerase moves across the DNA to copy it. When this scanning process moved smoothly, there were either single mutations or no mutations. When the researchers made the RNA polymerase stall along the DNA (under certain conditions), it caused several mutations at once (cluster mutations) in the DNA, adapting our antibodies for a rapid and effective response to a new microbial invader.
"As the planet warms, infectious diseases may be one the biggest threats to human survival," Weissmann added. "Nowadays, mosquitoes, parasites and viruses cause diseases in the United States that were once isolated to warmer parts of the world. They evolve, and - a la Darwin - so does our immune system each time we meet a new microbial invader."
Federation of American Societies for Experimental Biology
Antibodies Current Events and Antibodies News RSSGene mismatch influences success of bone marrow transplants
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New cancer target for non-Hodgkin's lymphoma
Physician-scientists from Weill Cornell Medical College have discovered a molecular mechanism that may prove to be a powerful target for the treatment of non-Hodgkin's lymphoma, a type of cancer that affects lymphocytes, or white blood cells.
On the Trail of a Vaccine for Lyme Disease: Yale Researchers Target Tick Saliva
A protein found in the saliva of ticks helps protect mice from developing Lyme disease, Yale researchers have discovered. The findings, published in the November 19 issue of Cell Host & Microbe, may spur development of a new vaccine against infection from Lyme disease, which is spread through tick bites.
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New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Sweet -- sugared polymer a new weapon against allergies and asthma
Scientists at Johns Hopkins and their colleagues have developed sugar-coated polymer strands that selectively kill off cells involved in triggering aggressive allergy and asthma attacks.
Largest gene study of childhood IBD identifies 5 new genes
In the largest, most comprehensive genetic analysis of childhood-onset inflammatory bowel disease (IBD), an international research team has identified five new gene regions, including one involved in a biological pathway that helps drive the painful inflammation of the digestive tract that characterizes the disease.
People with less education could be more susceptible to the flu
People who did not earn a high school diploma could be more likely to get H1N1 and the vaccine might be less effective in them compared to those who earned a diploma, new research shows.
Exposure to several common infections over time may be associated with risk of stroke
Cumulative exposure to five common infection-causing pathogens may be associated with an increased risk of stroke, according to a report posted online today that will appear in the January 2010 print issue of Archives of Neurology, one of the JAMA/Archives journals.
Scientists explain binding action of 2 key HIV antibodies; could lead to new vaccine design
A very close and detailed study of how the most robust antibodies work to block the HIV virus as it seeks entry into healthy cells has revealed a new direction for researchers hoping to design an effective vaccine.
New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer
Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.
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