TMED7 acts as immune system on/off switch

waltky · Feb 28, 2012

Immune system response breakthrough...

Scientists Discover Off-Switch to Regulate Immune System
February 28, 2012 : Scientists have discovered a cellular "off-switch" that could allow doctors to control the bodys immune response in a host of diseases, and could boost the efficiency of vaccines against diseases like HIV and malaria.

The so-called "off-switch" is a protein called TMED7. Researchers at Irelands Trinity College Dublin say in normal, healthy cells, the protein calms the immune system after it is done fighting a bacterial infection. Anne McGettrick co-led the study that identified TMED7. She likens the immune system to an orchestra with many different sections, and TMED7 to one of the instruments. It is the first member of a family of proteins to be identified as an important regulator of the immune system. Why thats exciting to us is because the more we can tweak just small aspects of our immune system, and the more we understand about how each bit works, the more likely we are to understand whats going wrong in diseases - why some people get different symptoms - and that when their immune system goes wrong we can work out which pathways are going wrong, McGettrick said.

Without TMED7 acting as a brake, McGettrick says the immune system would rage out of control after neutralizing a bacterial infection. Researchers knocked out the protein and then infected the cells with a bacterium. They found the cellular immune response became over-activated. McGettrick believes developing drugs, or vaccine adjuvants, that crank up the immune system by removing TMD7 from cells could help boost the effectiveness of vaccines, against HIV and malaria. Vaccines work better when the body's immune system response is robust. Thats the next avenue that we want to go down to see if knocking out this gene is a candidate for a vaccine adjuvant, McGettrick said.

The researchers also imaged unaltered cells, and then exposed the cells to a bacterial microbe, to see TMED7 at work. It allowed the immune system to work for the length of time that it needed to work and then it moved in to do its job [of stopping the immune attack], McGettrick said. In the case of autoimmune diseases, in which the bodys immune system goes into over-drive and attacks its own tissues, tweaking TMD7 and other immune regulators, according to McGettrick, could lead to treatments to reduce the severity of the attack. An article by Anne McGettrick and colleagues describing discovery of the immune system off-switch protein, TMD7, is published in Nature Communications.

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Gator Monroe · Feb 28, 2012

A cure for Psoraisis (Great)

waltky · Mar 28, 2012

Later in life, it's good to have had childhood diseases...

Childhood Exposure to Germs Can Bolster Immune System
March 27, 2012 - A new study suggests that getting a little dirty might be good for your health.

The research found that adult mice raised in a germ-free lab environment were more likely than normal lab mice to develop allergies, asthma and other serious autoimmune disorders, in which normally defensive immune system cells turn against the body’s tissues and organs. There are more than 80 autoimmune disorders, including common allergies such as hay fever; rheumatoid arthritis, which attacks the joints; Crohn’s disease, an inflammatory bowel condition; and juvenile diabetes.

Richard Blumberg, a professor at Harvard Medical School and chief of gastroenterology at Brigham and Women’s Hospital in Massachusetts, says medical researchers in 1989 sought to explain these varied autoimmune disorders with what they called the “hygiene hypothesis." “The hypothesis has stated or suggested that early-life exposure to microbes is a very important determinant of later life sensitivity to allergic and so-called autoimmune diseases, such as hay fever, asthma, inflammatory bowel disease and others," said Blumberg.

The hygiene hypothesis proposed that all the washing and scrubbing people were doing with the increasingly popular anti-bacterial soaps and lotions could be making them sick by altering their immune systems. But this theory had not been tested, until now. Blumberg and colleagues have found the first biological evidence that childhood exposure to germs keeps the adult immune system in check, preventing the development of some autoimmune diseases. They compared a group of mice raised in a typical environment filled with bacteria, to a group of mice raised in a sterile environment.

The researchers discovered that inflammation in the lungs and colon of the adult germ-free mice was being caused by over-active killer T cells. These cells normally fight infection, but in these mice they were targeting healthy tissue - an autoimmune condition seen in asthma and ulcerative colitis. But Blumberg says the normal mice whose immune systems had been “educated” by exposure to a microbe-rich enviornment did not have the same inflammatory response. “What was really most remarkable to us was the fact that once the education event provided by the microbes occurred in early life, it was durable and lasted throughout the life of the animal," he said. "And if that educational event provided by microbes was not given, it was impossible to educate the animal later in life.”

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waltky · Dec 8, 2012

Pesticides may be causing rise in allergies...

Pesticide Suspected in Rising Food-Allergy Cases
December 07, 2012 : Food allergies are on the rise globally, and a new report says the culprit could be increasing worldwide exposure to dichlorophenols, chemicals used in agricultural pest-killers and in the chlorine used to disinfect drinking water.

According to the U.S. Centers for Disease Control and Prevention, allergies to foods such as milk, wheat, peanuts, soy and shellfish shot up 18 percent in the United States between 1997 and 2007. Other studies have shown that environmental pollution is on the rise. Researchers at the Albert Einstein College of Medicine in New York suggest there is a link between the two trends.

They analyzed health data from the 2005-2006 U.S. National Health and Nutrition Examination Survey, in which more than 10,000 Americans took part. The researchers identified more than 2,500 individuals with measurable levels of dichlorophenols chemicals found in pesticides and chlorinated water in their urine. The study team, led by allergist and immunologist Elina Jerschow, narrowed their sample down to 2,200. Out of this group, Jerschow says, 411 of the subjects had some sort of food allergy. People who had high levels of dichlorophenols were about 80 percent more likely to have allergic sensitization to foods than people who had low levels of dichlorophenols in the urine," she said.

The team found that more than a thousand of the participants had an environmental allergy that was not linked to the chemicals. Theres evidence that people with protected immune systems, which have not been challenged by foreign substances, are ultimately more likely to develop allergies. Jerschow thinks that may help explain her study's findings. If you think about people who have a lot of allergies, they may be particularly prone to keep the environment specifically clean," she said. "And so they may use more bactericidal agents and more insecticides and pesticides and thats how they can have more levels of dichlorophenols.

People are exposed to dichlorophenols not only through tap water, but handling fruits and vegetables, according to Jerschow, who says pesticide residues on farm produce may be a greater source of exposure to the chemicals than tap water. Allergic reactions from food range from a mild rash to anaphylaxis, a systemic reaction that can lead to death within a few minutes. An article by Elina Jerschow and colleagues on food allergies and dichlorophenols is published in the Annals of Allergy, Asthma and Immunology.

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Richard Powell · Jan 25, 2013

Health care issues make people affected. Therefore this post is presented in common interest of people so that they can heve closer view of it.

waltky · Aug 19, 2013

Boosting the immune system to fight cancer...

Immune system boost 'fights cancer'
18 August 2013 > A way of firing up the body's immune system in order to attack cancer has been discovered by US researchers.

The immune system is delicately balanced so it attacks invaders but not the body's own tissues. Animal studies suggested that shifting the balance could open up new treatments for cancer, the team from the Children's Hospital of Philadelphia said. The findings were published in Nature Medicine. There are many diseases caused by the immune system turning on the body's own tissues - such as type 1 diabetes or multiple sclerosis.

'New cancer immunotherapy'

One popular area of research in both cancer and autoimmune diseases has been Treg cells. They are a part of the immune system which normally calm everything down to prevent the immune system attacking the body. The researchers were trying to disrupt Treg's function - effectively taking the brakes off the immune system - so it would attack cancer. One of the researchers, Dr Wayne Hancock, said: "We needed to find a way to reduce Treg function in a way that permits antitumor activity without allowing autoimmune reactions."

Researchers carried out the tests on a type of lung cancer

The researchers bred mice which lacked a chemical needed for Tregs to work effectively. They then used a drug which produced the same effect in normal mice. In both experiments, the shift in the immune system restricted the growth of a type of lung cancer. "It really moves the field along towards a potentially major, new cancer immunotherapy," Dr Hancock said. However, this is still a long way from any treatment for patients with cancer. Further tests will be needed to see if the same processes can be manipulated in the human immune system before it could even be tested in clinical trials.

Dr Emma Smith, from Cancer Research UK, said: "Turning the power of our immune system against cancer is a promising field of research and something scientists around the world, including our own, are studying. "These findings go another step towards developing new treatments that act in this way, but the research is still at an early stage and we don't know yet whether this approach will be safe or effective in people."

http://www.bbc.co.uk/news/health-23724220
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waltky · Apr 30, 2016

Innate immunity can fight infection w/o antibiotics...

Scientists Use Natural Immunity to Fight Infection Without Antibiotics
April 28, 2016 - Antibiotic resistance has made infections hard to fight, even life-threatening in many cases. Scientists in Sweden, however, may have found an alternative to using antibiotics.

In a mouse model, the scientists trained the bodys natural immune system, called innate immunity, to disarm and destroy a bacterium that causes a kidney infection, often in children. The innate immune system is the front line of the body's defenses, and it works in two different ways to fight infections. The first is what researchers call a "good antibacterial defense" that targets and kills the invading pathogen.

A microbiologist reads a panel to check on a bacterium's resistance to an antibiotic in the Infectious Disease Laboratory at the federal Centers for Disease Control and Prevention in Atlanta.

The second causes inflammation the redness, swelling and fever that accompany an illness or injury. It's a vital part of the immune response but also can cause significant tissue damage, and in some cases it can contribute to the progress of the disease or infection. "So the question has been: Can you find a way of treating infections by stopping the bad part of the immune defense and still keep the antibacterial defense?" said Catharina Svanborg, a professor of clinical immunology at Lund University in Sweden. "This is what we have done in our model.

Flipping a switch

Svanborg and her fellow researchers found that the two parts of the process are controlled by two different molecules, so they just turned off the inflammation molecule. By blocking it, they found they could take advantage of the part of natural immune defense that promotes healing. It is a surprise because this technology has not been used in this way to treat infections," she said. "So, it was an unexpected finding ... but it was a logical step to take." Svanborg and her colleagues published their findings in the journal Science Translational Medicine.

She said investigators are planning more tests, this time to see whether the innate immune system can take on other pathogens, such as those that cause pneumonia. The picture is the same for all these different categories, and conceptually, what weve done is to say: Instead of killing the bacteria directly, we are harnessing the immune system in such a way that the tissue damage is suppressed and the symptoms are suppressed, Svanborg said. Given the growing seriousness of bacterial infections that dont respond to antibiotics, Svanborg thinks its only a matter of time before some illnesses are treated using the immune system alone.

http://www.voanews.com/content/scie...ht-infection-without-antibiotics/3307299.html
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FreshAir · Apr 30, 2016

when I went to Mexico they hung chicken out in the heat, I think what doesn't kill you can sometimes make you stronger.... the flip side is, some will die

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waltky · Nov 7, 2016

Trans-poo-sion?...

Gut bacteria 'may help drugs fight cancer'
Mon, 07 Nov 2016 - Bacteria living deep inside the digestive system seems to alter how cancer drugs work, a study suggests.

Immunotherapies - which harness the body's own defences to fight tumours - can clear even terminal cancer in a small proportion of patients. However, a small study by the University of Texas found those harbouring a more diverse community of gut bugs are more likely to benefit. Cancer Research UK said understanding gut bugs had "great potential". The human body is home to trillions of micro-organisms - estimates suggest our own tissues are so heavily outnumbered that our bodies are just 10% human. And a growing wealth of studies shows these microbes can influence our immune systems and have been implicated in auto-immune diseases and allergies.

Higher levels

Immunotherapies are one of the most exciting breakthroughs in treating cancer. They work by taking the brakes off the immune system to help it to attack tumours more easily. The research group compared the gut bacteria in 23 patients who responded to the therapy and 11 who did not. Dr Jennifer Wargo, a melanoma surgeon and scientist, told the BBC News website: "We found a night-and-day difference in the diversity of bacteria species in the faecal samples." The study, presented at the National Cancer Research Institute's Cancer Conference in Liverpool, found Ruminococcus bacteria in much higher levels in those that responded to treatment. It suggests that it may be possible to boost the effectiveness of immunotherapy by altering the balance of bacteria in the gut.

'Scratch the surface'

Procedures such as a trans-poo-sion - a transplant of faecal matter containing beneficial bacteria - are already used as a treatment for some diseases. Dr Wargo added: "It is hugely plausible I think - we still need to dig a little deeper, but I think we're on to something. "I think it really does shape our body's immune response as a whole and to cancer." It is not yet clear if the differences in bacteria are the cause of the better response. People with diets containing more fruit and vegetables tend to have a richer set of gut bugs, so it is possible that it is those with a healthier lifestyle that respond better to therapy. "It might point to a healthy diet increasing your chances, which I think would be a great message," she added.

Gut bacteria

Sir Harpal Kumar, chief executive of Cancer Research UK, said: "Our bodies are filled with trillions of bacteria, and we are just beginning to scratch the surface of understanding their great potential. "It's really interesting and exciting to see new evidence emerge on the close connection between the immune system and the bacteria living in our guts. As this, and several other studies, have shown, manipulating these bacteria could be exploited in future to help patients respond better to treatment."

http://www.bbc.co.uk/news/health-37874918
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waltky · Jun 21, 2017

New Biomarker to Guide Cancer Immunotherapy...

Scientists Find New Biomarker to Guide Cancer Immunotherapy
June 20, 2017 — Scientists said on Monday they had pinpointed a particular type of immune system cell that could predict more precisely if cancer patients are likely to respond to modern immunotherapy medicines.

The discovery, reported in the journal Nature Immunology, suggests doctors and drug developers will need to get smarter in zeroing in on those people who stand to benefit from the expensive new drugs, which are revolutionizing cancer care. Drugs such as Merck's Keytruda, Bristol-Myers Squibb's Opdivo, Roche's Tecentriq and AstraZeneca's Imfinzi can boost the immune system's ability to fight tumors, but they only work for some patients.

The current widely used benchmark when giving cancer immunotherapy is a protein called PDL-1. However, many experts view PDL-1 as a "blunt instrument", since it does not match precisely to drug response, leading to the consideration of other measures, such as the level of mutation in tumors. The latest research adds a further twist by highlighting therole of so-called tissue-resident memory T-cells.

A lymphoma patient receives cellular immunotherapy as part of a study at the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Researchers from the University of Southampton and La Jolla Institute for Allergy and Immunology found that lung cancer patients with lots of this cell type in their tumors were 34 percent less likely to die than others. "Having made the first baby steps with PDL-1 testing, we need to be smarter by using new tests," said Christian Ottensmeier, a Cancer Research UK scientist who worked on the study. "PDL-1 testing is a little bit like saying 'you've got a Ferrari because it is red.' Many Ferraris are red and many tumors that are PDL-1 positive will respond to immunotherapy, but on its own that is not sufficient."

Ottensmeier and colleagues now plan further clinical trials to see how well their biological predictor can pick out patients who will benefit from taking Opdivo. Industry analysts expect the new generation of cancer immunotherapy drugs to generate tens of billions of dollars in annual sales by early next decade, with lung cancer the biggest single market.

https://www.voanews.com/a/scientists-find-new-biomarker-to-guide-cancer-immunotherapy/3907606.html
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See also:

Living Drugs New Frontier for Cancer Patients Out of Options
June 12, 2017 — Ken Shefveland's body was swollen with cancer, treatment after treatment failing until doctors gambled on a radical approach: They removed some of his immune cells, engineered them into cancer assassins and unleashed them into his bloodstream. Immune therapy is the hottest trend in cancer care and this is its next frontier - creating “living drugs” that grow inside the body into an army that seeks and destroys tumors.

Looking in the mirror, Shefveland saw “the cancer was just melting away.” A month later doctors at the Fred Hutchinson Cancer Research Center couldn't find any signs of lymphoma in the Vancouver, Washington, man's body. “Today I find out I'm in full remission - how wonderful is that?” said Shefveland with a wide grin, giving his physician a quick embrace. This experimental therapy marks an entirely new way to treat cancer - if scientists can make it work, safely. Early-stage studies are stirring hope as one-time infusions of supercharged immune cells help a remarkable number of patients with intractable leukemia or lymphoma. “It shows the unbelievable power of your immune system,” said Dr. David Maloney, Fred Hutch's medical director for cellular immunotherapy who treated Shefveland with a type called CAR-T cells. “We're talking, really, patients who have no other options, and we're seeing tumors and leukemias disappear over weeks,” added immunotherapy scientific director Dr. Stanley Riddell. But, “there's still lots to learn.”

A photo shows the cell processing facility at the Fred Hutchinson Cancer Research Center where workers create customized cellular immunotherapies for patients, in Seattle, Washington

T cells are key immune system soldiers. But cancer can be hard for them to spot, and can put the brakes on an immune attack. Today's popular immunotherapy drugs called “checkpoint inhibitors” release one brake so nearby T cells can strike. The new cellular immunotherapy approach aims to be more potent: Give patients stronger T cells to begin with. Currently available only in studies at major cancer centers, the first CAR-T cell therapies for a few blood cancers could hit the market later this year. The Food and Drug Administration is evaluating one version developed by the University of Pennsylvania and licensed to Novartis, and another created by the National Cancer Institute and licensed to Kite Pharma. CAR-T therapy “feels very much like it's ready for prime time” for advanced blood cancers, said Dr. Nick Haining of the Dana-Farber Cancer Institute and Broad Institute of MIT and Harvard, who isn't involved in the development.

‘There's a desperate need’

Now scientists are tackling a tougher next step, what Haining calls “the acid test:” Making T cells target far more common cancers - solid tumors like lung, breast or brain cancer. Cancer kills about 600,000 Americans a year, including nearly 45,000 from leukemia and lymphoma. “There's a desperate need,” said NCI immunotherapy pioneer Dr. Steven Rosenberg, pointing to queries from hundreds of patients for studies that accept only a few. For all the excitement, there are formidable challenges. Scientists still are unraveling why these living cancer drugs work for some people and not others. Doctors must learn to manage potentially life-threatening side effects from an overstimulated immune system. Also concerning is a small number of deaths from brain swelling, an unexplained complication that forced another company, Juno Therapeutics, to halt development of one CAR-T in its pipeline; Kite recently reported a death, too. And, made from scratch for every patient using their own blood, this is one of the most customized therapies ever and could cost hundreds of thousands of dollars.

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