StemCell Therapy

Antibodies taken from rabbits can improve the survival rates of leukemia and myelodysplasia patients who are receiving stem cell transplant from an unrelated donor.

Researchers from Virginia Commonwealth University (VCU) have found that rabbits' antibodies trick the body immune system into accepting the stem cell from an unrelated donor. They claim that this discovery will improve the survival rates of leukemia and myelodysplasia patients.

Researchers had conducted a study on groups of patients who were going to receive stem cells.

Scientists injected rabbits' anti-thymocyte globulin (ATG) into one group of patients who were going to receive stem cells from an unrelated donor whereas the other group received the stem cells from a related donor.

After the transplantation, scientists studied the outcomes of patients who received a transplant of stem cells from an unrelated donor and compared the result with people who had received stem cells from a related donor.

Scientists were stunned to find that the outcomes after implanting the cells were very similar in terms of mortality, relapse and development of graft-versus-host disease (GVHD), a common complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body.

Like us on Facebook

"Unfortunately, we can't always find a related (genetically similar) donor for patients in need of stem cell transplantation," said Amir Toor, hematologist-oncologist at VCU School of Medicine, in a statement. "Obtaining better outcomes with unrelated donor stem cell transplants could represent a significant advancement in extending the lives of more patients with blood cancers."

Usually, when an unrelated donor stem is implanted into the body, the body immune system immediately rejects it. However, scientists found that rabbits' antibodies trick the immune system into accepting it.

Rabbit anti-thymocyte globulin ATG works by reducing T-lymphocytes, a key component of the immune system.

Read more from the original source:
Hope for Leukemia and Myelodysplasia Patients from Rabbits' Antibodies

SEATTLE, June 26, 2012 (GLOBE NEWSWIRE) -- Immune Design Corp. announced today the appointment of Roger M. Perlmutter, M.D., Ph.D., as a member of its Board of Directors. Dr. Perlmutter recently served as the Executive Vice President, Research and Development, at Amgen Inc., where he oversaw the company's worldwide research and development operations.

"On behalf of Immune Design, I want to welcome Roger as a new member of the Board of Directors. As both an internationally recognized executive leader in the Pharmaceutical and Biotechnology industry and as an accomplished academician in the field of Immunology and Biology, his appointment will further strengthen our company and our quest of shaping the immune system to develop novel immune therapies that we are developing at Immune Design," commented Dr. Carlos Paya, Immune Design's Chief Executive Officer.

"Immune Design has advanced a pioneering approach towards the development of new prophylactic and therapeutic vaccines," stated Dr. Perlmutter. "I look forward to working more closely with the board and management at Immune Design, and welcome this opportunity to help transform vaccine development in the years to come."

Dr. Perlmutter served as Executive Vice President for Research and Development at Amgen, Inc. from 2001 until 2012, where he led the registration efforts for numerous new drugs including Sensipar(TM), Prolia(TM) Nplate(TM) and Xgeva(TM). Prior to joining Amgen, Dr. Perlmutter was for many years Professor and Chairman of the Department of Immunology at the University of Washington in Seattle, and an Investigator of the Howard Hughes Medical Institute. He also served at Merck & Co. from 1997 to 2001, including as Executive Vice President for Worldwide Discovery and Preclinical Research.

Dr. Perlmutter is member of the American Academy of Arts and Sciences, an elected Fellow of the American Association for the Advancement of Science, and is a director of StemCells, Inc. (STEM) and the Institute for Systems Biology. A graduate of Reed College, Portland, OR., and current chairman of the Reed College Board of Trustees, Dr. Perlmutter received his M.D. and Ph.D. degrees from Washington University, St. Louis, Mo. in 1979.

About Immune Design Corp.

Immune Design is a privately held, clinical-stage biotechnology company based in Seattle, Washington, and formed in 2008 to bring together some of the world's leaders in the field of molecular immunology to develop vaccines for the treatment and prevention of infectious and malignant disease. The company employs advanced and leading edge methods to precisely control the activation and context of antigen presentation by dendritic cells in order to shape the desired adaptive immune response. This goal is accomplished through the application of two proprietary technology platforms that activate the immune system by distinct mechanisms.

Additional information can be found on the company's website at http://www.immunedesign.com.

The Immune Design logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=13428

Read more:
Immune Design Corp. Announces Appointment of Dr. Roger Perlmutter as a Member of Its Board of Directors

ScienceDaily (June 21, 2012) A team of researchers led by UC Davis Health System has found that human alpha-defensin 6 (HD6) -- a key component of the body's innate defense system -- binds to microbial surfaces and forms "nanonets" that surround, entangle and disable microbes, preventing bacteria from attaching to or invading intestinal cells.

The research describes an entirely new mechanism of action for defensins, an important group of molecules known to bolster the defenses of circulating white blood cells, protect cellular borders from invasive pathogens and regulate which "friendly" microbes can colonize body surfaces. The discovery provides important clues to inflammatory bowel diseases, especially Crohn's disease, which may be caused, in part, by deficiencies in HD6 levels or function.

A paper describing the work appears in the June 22 issue of the journal Science.

"During the past 25 years, researchers have learned a lot about the biological function of defensins, but the role of HD6, a particular molecule that is highly expressed in the intestines, was a mystery," said Charles L. Bevins, professor of microbiology and immunology at UC Davis. "We now know that HD6 has a very unique role in the body's innate immune system. Its ability to latch onto microbial surfaces and self-assemble to cast a fibrous net around bacteria, including pathogens like Salmonella and Yersinia, as well as fungi and protozoan parasites, gives the intestine, a critical part of the body, a powerful and broad spectrum of defense against potential threats."

Bevins is co-senior author of the paper along with his UC Davis colleague Professor Andreas Bumler, an expert in bacterial pathogenesis; UCLA Emeritus Professor Robert I. Lehrer, whose laboratory was the first to discover defensins in the early 1980s; and Professor Wuyuan Lu, a synthetic protein chemist from the University of Maryland School of Medicine whose work provided clues to HD6's subtle and unique properties. First author Hiutung Chu, a graduate student in the Bevins lab who is now a fellow at the California Institute of Technology, was a driving force on the nine-year quest to solve the HD6 puzzle.

About the protein HD6

Defensins are a family of structurally related, small peptides with antibiotic activity found throughout nature in plants and animals. Humans make six different alpha-defensins. Two of these, HD5 and HD6, are secreted by Paneth cells, specialized secretory cells located within the folds of the small intestinal lining. HD5 has well-known antibacterial properties while the function of HD6 had been unknown. The defensin-rich secretions of Paneth cells work in conjunction with nearby intestinal stem cells to maintain micro flora balance and renew intestinal cellular surfaces.

Chu's graduate work focused on characterizing the biological activity of HD6 in studies using cultured intestinal epithelial cells and transgenic mouse models. Although Chu and Bevins anticipated HD6 activity would be very similar to other alpha-defensins, which kill pathogens by poking holes in the microbial membrane, their early research studies repeatedly showed that HD6 did not kill bacteria. Puzzled, they then looked for other possible functions, collaborating with UC Davis professors Angela Gelli and Scott Dawson to see if HD6 might kill only certain bacteria, fungi or parasites. It did not.

After two years into the project and feeling frustrated about the negative results, Bevins and Chu carefully reviewed the experimental data. That's when they recognized two crucial pieces of information. The first was that whenever HD6 was added to suspensions of either bacteria or fungi, a white haze, or precipitate, formed in the solution (see image below). The second was that early studies conducted in collaboration with Bumler had shown that while HD6 did not kill the bacterial pathogen Salmonella, it protected transgenic mice from an otherwise lethal infection.

"When we put these two results together, we were able to systematically show that HD6 was inhibiting microbial invasion and uncover HD6's unique structure and function at multiple levels," said Bevins.

Excerpt from:
Immune system molecule weaves cobweb-like nanonets to snag Salmonella, other intestinal microbes

SARANAC LAKE, N.Y.--(BUSINESS WIRE)--

The Trudeau Institute today announced that faculty member Laura Haynes, Ph.D., was awarded a grant from the National Institutes of Health (NIH) to study how aging impacts the immune systems response to influenza infection and vaccination. Entitled Aging and Immunity to Infections, the award is one of the largest program grants funded this year by the NIHs National Institute on Aging, amounting to more than $9 million over a five-year period. The grant further funds Dr. Haynes breakthrough study regarding age-related decline in immune functionality that was just released online in the scientific journal Aging Cell.

Infectious diseases, such as influenza, lead to increased disease and mortality in the elderly. Annually in the United States, influenza causes 200,000 hospitalizations and 36,000 deaths, 90 percent of which occur in older adults. Additionally, the elderly are more vulnerable to infection because vaccine efficacy is significantly reduced in older populations. While it is well known that the adaptive immune response to influenza infection and immunization declines with aging, the Haynes laboratorys recent studies found that there are additional changes in the immune system that had not been previously appreciated. These newly discovered changes contribute significantly to the age-related decline in immune function.

Earlier research from Dr. Haynes lab has shown that there are age-related declines in the function of immune cells that respond to vaccination. Specifically, immune cells from aged individuals show slower and reduced overall functional responses when compared with cells from younger individuals. They also successfully demonstrated that these changes are intrinsic to the immune cells themselves. That is, even if aged cells are transferred into young hosts, they still exhibit reduced function.

Breakthrough Research in the Immune Response in the Elderly Leads to NIH Grant

Dr. Haynes recent investigation of the factors responsible for the decline in immune response to vaccination in elderly patients has led to a major breakthrough. Their study, led by postdoctoral fellow Julie Lefebvre, was published online on June 11, 2012 in the scientific journal Aging Cell. The study demonstrates that, in addition to intrinsic defects in aged immune cells, there are changes in the aged environment, including secondary lymphoid tissues such as the spleen and lymph nodes. These changes are the result of disorganized expression of molecules that direct immune cell movement. The result is that immune cells in aged individuals are not directed properly, and their response is slower as a result.

This revelation helps explain how aging impacts the immune system and the mechanisms involved. Only when the specific defects are determined can strategies be developed to overcome these defects and develop more effective vaccines for the elderly.

Importantly, this study also demonstrates that one of the main factors responsible for this delay is an age-related change in the molecules that direct the movement of immune cells. Small molecules in the immune system, known as chemokines, are responsible for the proper movement of immune cells during a response to vaccination or infection. Proper movement of the cells is essential for a robust immune response since many immune system cells function via direct cell-to-cell contact with each other. Without this contact, the immune response is much less effective. This is the first time this kind of mechanism has been appreciated in aged individuals.

Future Research Focuses on How Aging Impacts Response to Flu and Infection

With the support of the $9 million multi-year grant from the NIH, the Trudeau research will focus on how aging impacts the immune response to influenza infection and vaccination and then importantly move this research to human trials.

More here:
Trudeau Institute announces $9 Million Translational Research Award

Stop hating your belly fat! Some of it may save your life.

In a paper appearing Wednesday in the journal PLOS ONE, Loyola University Chicago researchers found that a particular kind of belly fat is involved in regulating the immune system, opening the door for new kinds of drugs for autoimmune diseases like Crohn's and lupus.

The flab in question is a sheet-like tissue called the omentum that lines the abdominal cavity. Though parts of the omentum have been used to promote healing in injured tissues for more than a century, the mechanism by which it works has not been well understood, researchers said.

But "we now have evidence that the omentum is not just fat sitting in the belly," senior author Makio Iwashima said in a statement Wednesday.

Iwashima and his team tested the effects of mouse omentum cells by growing them in the same medium with mouse T cells -- the front- line troops of the immune system -- and antibodies. Normally these T-cells would have been activated by the presence of the antibodies and proliferated, but in this case the T-cells died instead. The omentum cells did not, however, kill inactive T-cells.

Follow us

At first blush, killing immune cells doesn't sound like a good idea. But without proper controls, an overactive immune system can damage the body when it begins attacking normal tissue, as seen in autoimmune disorders like lupus.

The researchers think omentum cells emit some kind of molecular signal that tamps down the immune system. If that signal is isolated, it could form a basis for a new class of immunosuppressant drugs for autoimmune disease patients and people with organ transplants, who need to rein in their immune systems in order to prevent their bodies from rejecting donor organs.

Iwashima and his team also found that the omentum is full of mesenchymal stem cells, which can differentiate into many different cell types, suggesting that the membrane plays a key role in tissue regeneration and repair for damaged organs.

SOURCE: Shah et al. "Cellular basis of tissue regeneration by omentum." PLoS ONE 7(6): e38368.

Go here to read the rest:
Your Gut Is Good For You: Benevolent Belly Fat Modulates Immune System, Helps Repair Tissue Damage

Blocking "don't destroy me" signals that normally sit on the surface of tumor cells and render them resistant to immune-cell attack slows the growth of a broad range of human cancers when they're implanted in mice, researchers have found.

The approach, reported by immunologists at the Stanford University School of Medicine, was effective against ovarian, breast, colon, bladder, liver, prostate and brain cancer cells. If the work can be repeated in people, the approach may someday help doctors marshal defender cells in patients' own bodies to fight cancers, the researchers said.

Key to the work is a cell protein called CD47, which is already being investigated in the treatment of leukemia.

CD47 sits on cell membranes and communicates with various immune cells, including macrophages, which gobble up foreign invaders in the body. It plays an important role in the normal life cycle of healthy red blood cells, telling macrophages to leave the cells alone.

In the study, the scientists injected the animals with antibodies that bind to CD47 and block out its protective signal.

"If we can block this signal, we can get the immune system to eat [the cancer cells] up," said Stephen Willingham, a postdoctoral researcher in the laboratory of immunologist Dr. Irving Weissman at Stanford and first author of a paper about the work.

The Stanford team examined cancer cells removed from patients with a variety of types of solid tumors. They found that CD47 studded the membranes of almost all of the cancer cells in their sample, suggesting that it is a molecule common to all cancers.

Placing the cells in lab dishes, the team administered an antibody: a protein that binds to CD47 and blocks it from warding off immune system cells. Macrophages ate the cells.

The researchers then implanted human tumor cells in mice for further study. They allowed the cancers to grow, and administered the antibody against CD47.

Antibody treatment inhibited the growth of almost all of the solid tumors and was able to wipe out some smaller cancers altogether, according to the report, which was published Monday in the journal Proceedings of the National Academy of Sciences.

See the article here:
Cancer research targets a key cell protein

Washington, March 22 (ANI): Scientists have created powerful new cells from cheek lining tissue, which could offer the answer to disorders of the immune system.

While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.

A team from Cardiff's School of Dentistry led by Professor Phil Stephens, with colleagues from Stockholm's Karolinska Institute, have found a new group of cells with a powerful ability to suppress the immune system's action.

The team took oral lining cells from the insides of patients' cheeks and cloned them. Laboratory tests showed that even small doses of the cells could completely inhibit the lymphocytes.

The breakthrough suggests that the cheek cells have wide-ranging potential for future therapies for immune system-related diseases.

Existing immune system research has focussed on adult stem cells, particularly those derived from bone marrow. The cheek tissue cells are much stronger in their action.

"At this stage, these are only laboratory results. We have yet to recreate the effect outside the laboratory and any treatments will be many years away.

However, these cells are extremely powerful and offer promise for combating a number of diseases. They are also easy to collect - bone marrow stem cells require an invasive biopsy, whereas we just harvest a small biopsy from inside the mouth," said Dr Lindsay Davies, a member of the Cardiff team.

The findings have just been published online in Stem Cells and Development. (ANI)

Here is the original post:
Powerful cheek cells offer promise for combating immune system diseases

ScienceDaily (Mar. 21, 2012) Powerful new cells created by Cardiff scientists from cheek lining tissue could offer the answer to disorders of the immune system. While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.

A team from the School of Dentistry led by Professor Phil Stephens, with colleagues from Stockholm's Karolinska Institute, have found a new group of cells with a powerful ability to suppress the immune system's action.

The team took oral lining cells from the insides of patients' cheeks and cloned them. Laboratory tests showed that even small doses of the cells could completely inhibit the lymphocytes.

The breakthrough suggests that the cheek cells have wide-ranging potential for future therapies for immune system-related diseases. Existing immune system research has focused on adult stem cells, particularly those derived from bone marrow. The cheek tissue cells are much stronger in their action.

Dr Lindsay Davies, a member of the Cardiff team, said: "At this stage, these are only laboratory results. We have yet to recreate the effect outside the laboratory and any treatments will be many years away. However, these cells are extremely powerful and offer promise for combating a number of diseases. They are also easy to collect -- bone marrow stem cells require an invasive biopsy, whereas we just harvest a small biopsy from inside the mouth."

The findings have just been published online in Stem Cells and Development. The team has now been funded by the Medical Research Council to investigate the cloned cells further.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Cardiff University.

More here:
Powerful new cells cloned: Key to immune system disease could lie inside the cheek

Public release date: 21-Mar-2012 [ | E-mail | Share ]

Contact: Stephen Rouse RouseS@cardiff.ac.uk 44-292-087-5596 Cardiff University

Powerful new cells created by Cardiff University scientists from cheek lining tissue could offer the answer to disorders of the immune system.

While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.

A team from Cardiff's School of Dentistry led by Professor Phil Stephens, with colleagues from Stockholm's Karolinska Institute, have found a new group of cells with a powerful ability to suppress the immune system's action.

The team took oral lining cells from the insides of patients' cheeks and cloned them. Laboratory tests showed that even small doses of the cells could completely inhibit the lymphocytes.

The breakthrough suggests that the cheek cells have wide-ranging potential for future therapies for immune system-related diseases. Existing immune system research has focussed on adult stem cells, particularly those derived from bone marrow. The cheek tissue cells are much stronger in their action.

Dr Lindsay Davies, a member of the Cardiff team, said: "At this stage, these are only laboratory results. We have yet to recreate the effect outside the laboratory and any treatments will be many years away. However, these cells are extremely powerful and offer promise for combating a number of diseases. They are also easy to collect bone marrow stem cells require an invasive biopsy, whereas we just harvest a small biopsy from inside the mouth."

The findings have just been published online in Stem Cells and Development. The team has now been funded by the Medical Research Council to investigate the cloned cells further.

###

Continued here:
Key to immune system disease could lie inside the cheek

Mixing the stem cells of an organ recipient with those of the donor could help to keep the body's picky immune system from rejecting transplants.

kalewa/Shutterstock

One of the greatest challenges in medicine is the need for replacement organs. Every 10 minutes another person's name is added to the national organ transplantation waiting list, the length of which now exceeds 100,000. Eighteen of these people die each day. Those who are fortunate enough to receive an organ often have to take immunosuppressive drugs for the rest of their lives, thus making them more vulnerable to other infections, and even then their new organs may gradually be rejected by their immune system.

One potential way to overcome this problem is through the creation of a chimeric immune system by mixing the immune (hematopoetic) stem cells of the recipient with that of the donor. As explained in last week's issue of Science Translational Medicine:

According to Greek mythology, the Chimera was a fire-breathing creature made of parts from different animals: the body of a lioness, a snake's head at the end of the tail, and the head of the goat. Sightings of this fearsome beast portended any of a number of terrible disasters. In the context of organ transplantation, a "chimera" can indicate both desirable and disastrous outcomes. For example, hematopoietic chimerism, in which the immune cells in the graft recipient come from both the host and the donor, may promote graft tolerance, but may also cause graft-versus-host disease (GVHD), in which the donor immune cells attack the healthy tissue of the host.

The underlying problem behind rejection and GVHD -- both of which shrink the potential donor pool -- is matching. Now, a novel procedure has come one step closer to overcoming the matching problem and achieving transplantation tolerance. In an exciting, albeit small, study the University of Louisville team transplanted mismatched, unrelated donor kidneys into eight patients along with a mix of donor hematopoetic stem cells and a special population of tolerance-inducing facilitator cells (FCs). These FCs have been shown in animal models to improve engraftment (acceptance of the graft) and avoid GVHD. The results and potential meaning are well-summarized by Science Translational Medicine:

Five of eight kidney transplant recipients exhibited durable chimerism and were weaned off immunosuppressive therapies by one year after transplantation, with no signs of GVHD or engraftment syndrome. If confirmed in larger patient cohorts, this approach to transplantation could free some patients from the difficulties associated with lifelong immunosuppression and add transplantation as a viable option for patients for whom no matched donors exist.

An editorial written in STM about the study says that this procedure "may potentially have an enormous, paradigm-shifting impact on solid-organ transplantation" and that "few transplant developments in the past half-century have been more enticing than these that put transplantation tolerance within our grasp." This editor followed up with the primary investigator of the study, Dr. Suzanne Ildstad from the Institute for Cellular Therapeutics at the University of Louisville, to ask about the future of the procedure as well as other applications that are being explored:

Your paper refers to applications "not only in sold organ and cell transplant recipients but also for ... hemoglobinopathies, inherited metabolic disorders, and autoimmune diseases." What other applications are currently being explored using this novel chimeric approach?

We are currently working on applying this procedure to sickle cell disease, thalassemia, metachromatic leukodystrophy, and in the near future, type 1 diabetes.

Link:
A Chimeric Immune System: Fixing the Problem With Organ Transplant

This photo taken Thursday, March 8, 2012, Lindsay Porter is seen in her home in Chicago. Lindsay Porter's kidneys were failing rapidly when a friend offered to donate one of his. Then she made an unusual request: Would he donate part of his immune system, too? (AP Photo/M. Spencer Green)

WASHINGTON Lindsay Porter's kidneys were failing rapidly when a friend offered to donate one of his. Then she made an unusual request: Would he donate part of his immune system, too?

Every day for the rest of their lives, transplant recipients must swallow handfuls of pills to keep their bodies from rejecting a donated organ. The Chicago woman hoped to avoid those problematic drugs, enrolling in a study to try to trick her own immune system into accepting a foreign kidney.

It's one of a series of small, high-stakes experiments around the country that has researchers hopeful that they're finally closing in on how to help at least some transplant patients go drug-free. The key: Create a sort of twin immunity, by transplanting some of the kidney donor's immune-producing cells along with the new organ.

"I'm so lucky," says the 47-year-old Porter, who stumbled across the research at Chicago's Northwestern University. Porter was able to quit her pills last summer, a year after her transplant, and says, "I feel amazing."

These experiments are a big gamble. If the technique fails, patients could lose their new kidney, possibly their lives. Doctors stress that no one should try quitting anti-rejection drugs on their own.

Why risk it even in a careful scientific study? Anti-rejection medications can cause debilitating, even deadly, side effects, from fatigue and infections to an increased risk of cancer and kidney damage.

Without the drugs, "the hope for me is I'm able to keep this kidney for the rest of my life," Porter says.

Across the country, Stanford University is testing a slightly different transplant method and hosted a reunion earlier this month for about a dozen kidney recipients who've been drug-free for up to three years.

"These people who are off their drugs, they're cured," says Dr. Samuel Strober, who leads the study of Stanford's approach. "If they have to be on drugs the rest of their life, it doesn't have the same meaning of `cure.'"

Read the original here:
Kidney Transplant Patients Seek Life Without Immune-Suppressing Drugs

Replacing immune cells in a mouse model of Rett syndrome, a developmental brain disorder, improved symptoms, suggesting a new target for treatment.

Rett syndrome is a devastating genetic disease in which brain developmentalong with communication and motor skillsregresses after about 18 months of normal development. While previous work on this disease has focused on its neurological basis, new research published online yesterday (March 18) in Nature suggests that the immune system may be a target worth investigating: in a mouse model of the disease, bone marrow transplants significantly improved symptoms, extending lifespan far and beyond what was expected, increasing size and reducing tremors.

Its a very interesting, very provocative paper that could potentially be very important both for the basic biology of the disease as well as translational aspects of it, said Qiang Chang, who studies the molecular mechanisms of Rett syndrome at the University of Wisconsin and was not involved in the new study. But I think this is the type of work that probably raises more questions than it answers.

Rett syndrome is caused by many different mutations in the Mecp2 gene, which lies on the X-chromosome and regulates thousands of other genes by binding to and altering methylation marks attached to DNA. Posing a further challenge to understanding the diseases mechanism, Mecp2 is expressed in many tissues in the body. Every cell type has methylation, but the methylation patterns may be different cell to cell, said Zhaolan Zhou, who studies epigenetics and Rett syndrome at the University of Pennsylvania and did not participate in the research. If thats the case, Mecp2 may regulate and participate in different pathways in different cells.

However, because Rett syndrome is a brain disorder, most of the research has focused on Mecp2s activity in neuronsand not without good reason. Its extremely highly expressed in neurons, and its thought that the protein plays an important role in the maturation of neurons and brain circuit, said Chang. Children with Rett syndrome are born essentially normal with symptoms showing up some 18 months later, and thats the window when Mecp2 is dramatically upregulated in the brain, he added.

But the new research suggests that brain cells may not present the full picture. After reading a paper published a decade ago about how Mecp2 mutations slow T-cell growth, neuroimmunologists Nol Derecki and Jonathan Kipnis from the University of Virginia School of Medicine decided to further investigate immune system interactions with Rett syndrome.

They focused on microglia, which are classic immune cells that happen to live in the brain, said Derecki. Microglia taken from the brains of mice lacking Mecp2 were less able to respond to invaders and were very much impaired in a number of their functions, he said. If the immune system, including the microglia, was functioning in an impaired way, replacing the impaired immune system with a normal immune system might improve the disease somewhat.

The researchers irradiated 4-week old male mice that lacked Mecp2 to kill off their immune cellsincluding microgliaand then injected their bones with marrow from normal mice. The idea was that the non-mutated stem cells in bone marrow would generate normal immune cells that then could migrate into and repopulate the brain.

Because male mice only have one X-chromosome, if their single copy of Mecp2 is missing, they are incredibly sick: they live just 8 weeks on average, are small, and have tremors and breathing irregularities. But the mice that received bone marrow transplants survived much longerthe oldest mouse at this point is just under a year, said Dereckiand they looked and acted much more like normal mice.

The mice werent cured, however; while some of their symptoms were reduced, the brain cells still carried the mutant copy of Mecp2. It certainly is a disease of neurons, and the neurons still have their own problemsbut its also likely a disease of many other cell types, said Derecki. We dont think microglia cause the disease, but we think that when they malfunction, they make the disease much worse.

Read this article:
Immune Role in Brain Disorder?

Because everyones immune system is different, its impossible to predict with absolute certainty how any given person will react to a specific medication. In the not-too-distant future, however, at-risk patients may get their own custom-altered mouse, with an immune system thats a copy of their own. Medications could be tried out on the mouse first, and if it showed no adverse reactions, then the person could receive them. If the person had an autoimmune disease, the mouse could also provide valuable insight into its treatment. A team led by Columbia University Medical Centers Dr. Megan Sykes has recently developed a method of creating just such a personalized immune mouse.

The process begins by transplanting bone marrow stem cells from the human subject, along with a one-cubic-millimeter chunk of their thymus tissue, into a mouse with a disabled immune system. The thymus is an organ in the immune system, and the sample of it is implanted in the mouses kidney capsule, which is a thin membrane surrounding the kidney.

It incubates there for six to eight weeks, within which time it becomes seeded with the stem cells, which have been circulating in the mouses bloodstream. This in turn causes it to create a number of types of human immune cells, resulting in a robust and diverse human immune system matching that of the donor. Previous efforts have reportedly not been successful in creating a complete system, or have been hampered by the mice rejecting the human material.

Besides being used to test responses to medications, the personalized immune mice might also play a key role in developing individualized immunotherapies. These would allow patients to more successfully fight infections or cancer, or to accept transplanted tissue.

Additionally, Dr. Sykes plans on using the mice for research into type 1 diabetes, to determine how diabetic patients immune systems are different from those of non-diabetics, before the disease develops.

A paper on the research was recently published in the journal Science Translational Medicine.

Source: Columbia University Medical Center

See the original post here:
Peoples' immune systems can now be duplicated in mice

Newswise New York, NY (March 14, 2012) Columbia University Medical Center (CUMC) scientists have developed a way to recreate an individuals immune system in a mouse. The personalized immune mouse offers researchers an unprecedented tool for individualized analysis of abnormalities that contribute to type 1 diabetes and other autoimmune diseases, starting at the onset of disease. The findings were published today in the online edition of Science Translational Medicine.

The mouse model could also have clinical applications, such as predicting how a particular patient might respond to existing drugs or immunotherapies, reports senior author Megan Sykes, Michael J. Friedlander Professor of Medicine and Professor of Microbiology & Immunology and Surgical Sciences (in Surgery) at CUMC. Dr. Sykes is also Director for the Columbia Center for Translational Immunology. In addition, the model might prove useful for developing individualized immunotherapies for fighting infection or cancer or for lessening a patients rejection of transplanted tissue.

Researchers have been searching for new ways to tease apart the various factors that contribute to autoimmune disease. While large-scale studies of human populations have provided important clues to the genetic basis of immune diseases, they have offered little information about the specific role the genes play, says Dr. Sykes. Its difficult to isolate these mechanisms when looking at groups of patients who have had disease for different lengths of time or have been receiving different treatments. And the fact that they already have the disease makes it difficult to distinguish what underlies and propagates the autoimmune process.

Several research groups have attempted to create a personalized immune mouse. However, each model has had significant limitations, such as an inability to generate the full complement of immune cells and incompatibilities between tissues used to recreate the human immune system, leading to graft-versus-host disease.

Dr. Sykes model, in contrast, is able to recreate a robust and diverse human immune system, including T cells, B cells, and myeloid cells (which generate a variety of immune cells), free of immune incompatibilities.

The model is made by transplanting human bone marrow stem cells (also known as CD34+ cells), along with a small amount (approximately 1 cubic mm) of HLA-matched immature thymus tissue, into an immunodeficient mouse. (The HLA, or human leukocyte antigen, system mediates interactions among various immune cells.) The thymus tissue is implanted into the mouses kidney capsule, a thin membrane that envelops the kidney and serves as an incubator. Within six to eight weeks, the transplanted thymus tissue is seeded by circulating human CD34+ cells (which are infused into the mouses bloodstream), and begins generating human immune cells from the CD34+ cells.

A key to the models success was the teams discovery that freezing and thawing the transplanted thymus tissue, as well as administering antibodies against CD2 (a glycoprotein that mediates T cell development and activation), depletes mature T cells from the tissue graft. This prevents rejection of the human CD34+ cells and graft-versus-host disease, while preserving function of the thymus tissue.

Dr. Sykes intends to use the personalized immune mouse to study type 1 diabetes. We hope to find out what is fundamentally different about patients immune systems, compared with those of healthy individuals, before any disease develops, she says.

The studies should also reveal more about the genetics of type 1 diabetes. A number of HLA-associated genes have been linked to type 1 diabetes, she explains. About a third of the population has one of more of these genes. But a much smaller percentage of the population actually develops the disease. What this means is, the HLA genes are necessary, but not sufficient, to cause type 1 diabetes. Using the personalized immune mouse, we expect to learn more about the role that non-HLA genes play in the disease.

Dr. Sykes paper is entitled, A model for personalized in vivo analysis of human immune responsiveness. Her coauthors are Hannes Kalscheuer (Harvard Medical School, Boston, MA, and CUMC), Nichole Danzl (CUMC), Takashi Onoe (Harvard and CUMC), Ted Faust (Harvard and CUMC), Robert Winchester (CUMC), Robin Goland (CUMC), Ellen Greenberg (CUMC), Thomas R Spitzer (Harvard), David G. Savage (CUMC), Hiroyuki Tahara (CUMC), Goda Choi (CUMC), and Yong-Guang Yang (Harvard and CUMC).

Read the original here:
"Personalized Immune" Mouse Offers New Tool for Studying Autoimmune Diseases Model May Allow Development of ...

Public release date: 14-Mar-2012 [ | E-mail | Share ]

Contact: Karin Eskenazi ket2116@columbia.edu 212-342-0508 Columbia University Medical Center

New York, NY (March 14, 2012) Columbia University Medical Center (CUMC) scientists have developed a way to recreate an individual's immune system in a mouse. The "personalized immune mouse" offers researchers an unprecedented tool for individualized analysis of abnormalities that contribute to type 1 diabetes and other autoimmune diseases, starting at the onset of disease. The findings were published today in the online edition of Science Translational Medicine.

The mouse model could also have clinical applications, such as predicting how a particular patient might respond to existing drugs or immunotherapies, reports senior author Megan Sykes, Michael J. Friedlander Professor of Medicine and Professor of Microbiology & Immunology and Surgical Sciences (in Surgery) at CUMC. Dr. Sykes is also Director for the Columbia Center for Translational Immunology. In addition, the model might prove useful for developing individualized immunotherapies for fighting infection or cancer or for lessening a patient's rejection of transplanted tissue.

Researchers have been searching for new ways to tease apart the various factors that contribute to autoimmune disease. "While large-scale studies of human populations have provided important clues to the genetic basis of immune diseases, they have offered little information about the specific role the genes play," says Dr. Sykes. "It's difficult to isolate these mechanisms when looking at groups of patients who have had disease for different lengths of time or have been receiving different treatments. And the fact that they already have the disease makes it difficult to distinguish what underlies and propagates the autoimmune process."

Several research groups have attempted to create a personalized immune mouse. However, each model has had significant limitations, such as an inability to generate the full complement of immune cells and incompatibilities between tissues used to recreate the human immune system, leading to graft-versus-host disease.

Dr. Sykes' model, in contrast, is able to recreate a robust and diverse human immune system, including T cells, B cells, and myeloid cells (which generate a variety of immune cells), free of immune incompatibilities.

The model is made by transplanting human bone marrow stem cells (also known as CD34+ cells), along with a small amount (approximately 1 cubic mm) of HLA-matched immature thymus tissue, into an immunodeficient mouse. (The HLA, or human leukocyte antigen, system mediates interactions among various immune cells.) The thymus tissue is implanted into the mouse's kidney capsule, a thin membrane that envelops the kidney and serves as an incubator. Within six to eight weeks, the transplanted thymus tissue is seeded by circulating human CD34+ cells (which are infused into the mouse's bloodstream), and begins generating human immune cells from the CD34+ cells.

A key to the model's success was the team's discovery that freezing and thawing the transplanted thymus tissue, as well as administering antibodies against CD2 (a glycoprotein that mediates T cell development and activation), depletes mature T cells from the tissue graft. This prevents rejection of the human CD34+ cells and graft-versus-host disease, while preserving function of the thymus tissue.

Dr. Sykes intends to use the personalized immune mouse to study type 1 diabetes. "We hope to find out what is fundamentally different about patients' immune systems, compared with those of healthy individuals, before any disease develops," she says.

Here is the original post:
'Personalized immune' mouse offers new tool for studying autoimmune diseases

Public release date: 13-Mar-2012 [ | E-mail | Share ]

Contact: Zaal Kokaia zaal.kokaia@med.lu.se 46-705-365-917 Lund University

Stroke and other diseases and injuries to the brain are often followed by inflammation, caused by a reaction of the body's immune system. This reaction has been seen as something that must be combated, but perhaps the immune system could in fact help with recovery following a stroke. A major new EU project, led by Lund University in Sweden and the Weizmann Institute in Israel, is going to study this question.

Stroke is a major public health problem, with 700 000 new cases in the EU and 30 000 new cases in Sweden each year. The EU is now investing EUR 12 million in the project TargetBraIn. The goal of the project is to gain a better understanding of the role of the immune system in stroke.

The immune system protects the body when its tissues are damaged for whatever reason. The cells of the immune system often produce inflammation, which has some negative effects, but which in time helps the original damage to heal.

Stroke is most commonly caused by a cerebral infarction (a blood clot in the brain), which starves the brain of oxygen. It is the damage caused by the lack of oxygen which activates the immune system and leads to inflammation. Until now, this has been seen as a wholly undesirable reaction. To emphasise the positive aspects of the immune system's reaction is therefore something of a paradigm shift in the field. Professor Michal Schwartz and her research group in Israel have pioneered the study of the positive role of the immune system in repairing damaged nerve cells.

Professor Zaal Kokaia, head of the Stem Cell Centre at Lund University, has long worked with stem cell therapy for brain injuries. He led StemStroke, an EU project which researched the possibility of creating new nerve cells after a stroke through transplants or by encouraging the brain to form new cells. Zaal Kokaia and Michal Schwartz are now coordinator and deputy coordinator respectively of TargetBraIn (an acronym which stands for "Targeting Brain Inflammation for Improved Functional Recovery in Acute Neurodegenerative Disorders").

"Within TargetBraIn we want to reinforce the positive effects of inflammation and reduce its negative effects. This could be achieved either by trying to change the immune system's reactions or through stem cell therapy, or both! A combination of the two methods may produce the best results", says Zaal Kokaia.

The research is still at the experimental stage, and the road to general application on patients will be long. However, as the population of Europe ages, stroke is becoming an increasingly costly disease, hence the EU investment in the field.

###

More here:
Could the immune system help recovery from stroke?

(Reuters) - Scientists, stymied for decades by the complexity of the human immunodeficiency virus, are making progress on several fronts in the search for a cure for HIV infections, a leading medical research conference was told this week in Seattle.

Promising tactics range from flushing hidden HIV from cells to changing out a person's own immune system cells, making them resistant to HIV and then putting them back into the patient's body.

A major stumbling block is the fact that HIV lies low in pools or reservoirs of latent infection that even powerful drugs cannot reach, scientists told the Conference on Retroviruses and Opportunistic Infections, one of the world's largest scientific meetings on HIV/AIDS.

"We need to get the virus to come out of the latent state, then rely on the immune system or some other treatment to kill the virus," said Dr. Kevin De Cock, director of the Center for Global Health at the U.S. Centers for Disease Control and Prevention.

HIV, which surfaced more than 30 years ago, infects more than 33 million people worldwide. Thanks to prevention measures, tests that detect HIV early and new antiretroviral drugs that can control the virus for decades, infection with the virus that causes AIDS is no longer a death sentence.

Still, questions of cost, side effects, drug resistance and ultimate lifespan, make lifelong use of antiviral drugs a less-than-ideal solution.

The International AIDS Society last year formally added the aim of finding a cure to its HIV strategy of prevention, treatment and care.

Early human trials of vaccines designed to prevent or treat infection with the difficult to target virus have proved disappointing. HIV is a "provirus" that is integrated into the DNA of a host cell, where it can remain latent or eventually reactivate.

"It has proven to be an incredibly formidable challenge to develop a vaccine," said John Coffin, professor of molecular biology at Tufts University in Boston. "In recent years the pendulum is swinging back."

Scientific advances in molecular engineering are allowing researchers to delve more deeply into the mechanism of HIV.

Read more:
Progress, no big breakthrough, in hunt for HIV cure

03-08-2011 18:15 Lecture by Kevin Ahern of Oregon State University discussing Biochemistry Basics in BB 451. See the full course at oregonstate.edu This course can be taken for credit (wherever you live) via OSU's ecampus. For details, see ecampus.oregonstate.edu Download Metabolic Melodies at http://www.davincipress.com Related courses include BB 350 - oregonstate.edu BB 450 - oregonstate.edu BB 100 - oregonstate.edu Immune System This information is provided for all of you who love learning. 1. The immune system contains the innate immunity system and the adaptive immunity system. 2. The innate system uses a Toll-like receptor that binds to the PAMP lipopolysaccharide structure on the surface of Gram negative bacteria. 3. The adaptive immune system system contains two major groups of lymphocytes (immune system cells), B cells and T cells. B cells are involved in the production of antibodies and T cells are involved in both cellular killing, as well as stimulation of the B cells. 4. Immunoglobulin G (IgG) is one of five major antibody classes made by the B lymphocytes of the humoral immune system (cellular immune system described below). IgG is the most abundant antibody in the blood serum. Others include IgA (in mucus), IgM (early responder), IgD (function uncertain), and IgE (parasite protection). 5. The structure of antibodies has several common features. First, they are composed of two sets of Heavy (H) and light (L) chains arranged in a Y shape. Both the H and L chains have constant and ...

See original here:
Bite-Sized Biochemistry #53 - Immune System

By Julie Steenhuysen

CHICAGO Scientists have found a way to trick the immune system into accepting organs from a mismatched, unrelated organ donor, a finding that could help patients avoid a lifetime of drugs to prevent rejection of the donated organ.

Of eight kidney transplant patients who have been treated with this new approach, five have managed to avoid taking anti-rejection drugs a year after their surgery, according to the study published on Wednesday in Science Translational Medicine.

And one patient, 47-year-old Lindsay Porter of Chicago, is completely free of anti-rejection drugs nearly two years after her kidney transplant.

This new approach would potentially offer a better quality of life and fewer health risks for transplant recipients

I hear about the challenges recipients have to face with their medications and it is significant. Its almost surreal when I think about it because I feel so healthy and normal, she said in a statement.

With conventional organ transplants, recipients need to take pills to suppress their immune systems for the rest of their lives. These drugs can cause serious side effects, including high blood pressure, diabetes, infection, heart disease and cancer.

This new approach would potentially offer a better quality of life and fewer health risks for transplant recipients, Dr. Suzanne Ildstad, director of the Institute of Cellular Therapeutics at the University of Louisville in Kentucky, who developed the new approach, said in a statement.

But some experts say the procedure, in which patients undergo a bone marrow transplant from an unmatched organ donor, is too risky, especially given the relative safety of kidney transplants.

We have to think about the risks and benefits. Since the current treatment is so stable, it really has to be safe, said Dr. Tatsuo Kawai, a transplant surgeon at Harvard Medical School, who wrote a commentary on the new approach in the journal.

Read the original here:
Stem cell treatment tricks immune system into accepting donor organs, study shows

Public release date: 8-Mar-2012 [ | E-mail | Share ]

Contact: David March dmarch1@jhmi.edu 410-955-1534 Johns Hopkins Medical Institutions

Using human immune system cells in the lab, AIDS experts at Johns Hopkins have figured out a way to kill off latent forms of HIV that hide in infected T cells long after antiretroviral therapy has successfully stalled viral replication to undetectable levels in blood tests.

In a report to be published in the journal Immunity online March 8, the Johns Hopkins team describes a vaccination strategy that boosts other immune system T cells and prepares them to attack HIV, before readying the virus for eradication by reactivating it.

HIV has long been known to persist in a dormant, inactive state inside immune system T cells even long after potent drugs have stopped the virus from making copies of itself to infect other cells. But once treatment is stopped or interrupted, the latent virus quickly reactivates, HIV disease progresses, and researchers say it has proven all but impossible to wipe out these pockets of infection.

Johns Hopkins senior study investigator and infectious disease specialist Robert Siliciano, M.D., Ph.D., who in 1995 first showed that reservoirs of dormant virus survived, says the resulting need for lifelong drug treatment has raised concerns about the adverse effects of decades of therapy, the growing risk of drug resistance, and the rising cost of care.

Siliciano and other AIDS scientists say the best hope for ultimately curing the disease is to force latent viruses to "turn back on," making them "visible" to the immune system's so-called cytolytic "killer" T cells and then, with the likely aid of drugs, eliminate the infected cells from the body.

In his new study, Siliciano showed that infected T cells survived after latent virus was reactivated, and were only killed off when other immune system T cells were primed before reactivation.

"Our study results strongly suggest that a vaccination to boost the immune response immediately prior to reactivating latent virus may be essential for totally eradicating HIV infection," says Siliciano, a professor at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator.

In their journal report, Siliciano and his colleagues describe their vaccination strategy and how short pieces of HIV proteins were introduced to stimulate the anti-HIV T-cell response just before reactivation of the latent virus. The incomplete viral proteins and subsequent immune system vaccination led to production of enough cytolytic T cells to attack and kill the latently infected cells.

Read more from the original source:
Vaccination strategy may hold key to ridding HIV infection from immune system