A new mechanism that slows down and may even prevent the natural ageing of immune cells – one of the nine ‘hallmarks of ageing’* – has been identified by an international team led by UCL scientists.

Published in Nature Cell Biology, researchers say the discovery in-vitro (cells) and validated in mice was ‘unexpected’ and believe harnessing the mechanism could extend the life of the immune system, allowing people to live healthier and longer, and would also have clinical utility for diseases such as cancer and dementia.

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A team of scientists has found why elderly people are more susceptible to COVID-19 and are working to reverse the aging process of the body’s immune system.

Scientists from the Technion-Israel Institute of Technology say they have found a way to rejuvenate the aging process of the body’s immune system. Prof. Doron Melamed and doctoral student Reem Dowery sought to understand why the elderly population is more susceptible to severe cases of COVID-19 and why the vaccines seem to be less effective and wane faster among this population. The results of their work were published this month in the peer-reviewed, online medical journal Blood.
The secret begins with B cells, also known as B lymphocytes. These are the cells that produce antibodies against any pathogen that enters the body. They play a key role in protecting people from viruses and diseases.
B cells do not just disappear. They turn into “memory” B cells so that if the body is exposed to a previous pathogen, the individual will not get sick. That is because the immune response will be fast and robust, and it will eliminate the pathogen, often without the individual knowing he or she had been exposed to it.

“Imagine you are growing into adulthood, and you become an adult and then an older person,” Melamed said. “You accumulate in your body many memory cells. You are exposed all the time to pathogens, and hence you make more and more memory cells. Because these are so long-lived, there is no room left for new B cells.”
What happens when a new pathogen, such as the coronavirus, comes along? There are no young B cells that can recognize it. That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. As noted, this happens because of the body’s need for homeostasis, something that Melamed’s lab discovered a decade ago. But this year, they took the discovery another step and figured out a mechanism to override the system.
“We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.”

It also means that, over time, specific drugs or treatments can be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells.

Source: http://www.jpost.com/

Researchers say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers the immune system sends out to destroy infected cells. Until now, COVID vaccines have focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.

As reported in the journal Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body.

“Companies should reevaluate their vaccine designs,” says Mohsan Saeed, a virologist at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and co-corresponding author of the paper.

Saeed, an assistant professor of biochemistry at the School of Medicine, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs.

“This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”

Saeed got involved when computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay contacted him. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells.

“The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology.

“We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.

Source:  https://www.futurity.org/

Biomedical engineers at Duke University have developed a self-assembling nanomaterial that can help limit damage caused by inflammatory diseases by activating key cells in the immune system. In mouse models of psoriasis, the nanofiber-based drug has been shown to mitigate damaging inflammation as effectively as a gold-standard therapy. One of the hallmarks of inflammatory diseases, like rheumatoid arthritis, Crohn’s disease and psoriasis, is the overproduction of signaling proteins, called cytokines, that cause inflammation. One of the most significant inflammatory cytokines is a protein called TNF. Currently, the best treatment for these diseases involves the use of manufactured antibodies, called monoclonal antibodies, which are designed to target and destroy TNF and reduce inflammation.

Although monoclonal antibodies have enabled better treatment of inflammatory diseases, the therapy is not without its drawbacks, including a high cost and the need for patients to regularly inject themselves. Most significantly, the drugs also have uneven efficacy, as they may sometimes not work at all or eventually stop working as the body learns to make antibodies that can destroy the manufactured drug. To circumvent these issues, researchers have been exploring how immunotherapies can help teach the immune system how to generate its own therapeutic antibodies that can specifically limit inflammation.

The graphic shows the peptide nanofiber bearing complement protein C3dg (blue) and key components of the TNF protein, which include B-cell epitopes (green), and T-cell epitopes (purple)

“We’re essentially looking for ways to use nanomaterials to induce the body’s immune system to become an anti-inflammatory antibody factory,” said Joel Collier, a professor of biomedical engineering at Duke University. “If these therapies are successful, patients need fewer doses of the therapy, which would ideally improve patient compliance and tolerance. It would be a whole new way of treating inflammatory disease.”

In their new paper, which appeared online in the Proceedings of the National Academy of Sciences (PNAS), Collier and Kelly Hainline, a graduate student in the Collier lab, describe how novel nanomaterials could assemble into long nanofibers that include a specialized protein, called C3dg. These fibers then were able to activate immune system B-cells to generate antibodies. “C3dg is a protein that you’d normally find in your body,” said Hainline. “The protein helps the innate immune system and the adaptive immune system communicate, so it can activate specific white blood cells and antibodies to clear out damaged cells and destroy antigens.”

Due to the protein’s ability to interface between different cells in the immune system and activate the creation of antibodies without causing inflammation, researchers have been exploring how C3dg could be used as a vaccine adjuvant, which is a protein that can help boost the immune response to a desired target or pathogen.

Source: https://pratt.duke.edu/

Immunotherapies, such as checkpoint inhibitor drugs, have made worlds of difference for the treatment of cancer. Most clinicians and scientists understand these drugs to act on what’s known as the adaptive immune system, the T cells and B cells that respond to specific threats to the body.

New research from an international team co-led by George Hajishengallis of the University of Pennsylvania School of Dental Medicine suggests that the innate immune system, which responds more generally to bodily invaders, may be an important yet overlooked component of immunotherapy’s success.

Their work, published in the journal Cell, found that “training” the innate immune system with β-glucan, a compound derived from fungus, inspired the production of innate immune cells, specifically neutrophils, that were primed to prevent or attack tumors in an animal model.

“The focus in immunotherapy is placed on adaptive immunity, like checkpoint inhibitors inhibit the interaction between cancer cells and T cells,” says Hajishengallis, a co-senior author on the work. “The innate immune cells, or myeloid cells, have not been considered so important. Yet our work suggests the myeloid cells can play a critical role in regulating tumor behavior.”

The current study builds on earlier work published in Cell by Hajishengallis and a multi-institutional team of collaborators, which showed that trained immunity, elicited through exposure to exposure to the fungus-derived compound β-glucan, could improve immune recovery after chemotherapy in a mouse model.

In that previous study, the researchers also showed that the “memory” of the innate immune system was held within the bone marrow, in hematopoetic stem cells that serve as precursors of myeloid cells, such as neutrophils, monocytes, and macrophages.

Source: https://penntoday.upenn.edu/

Some viruses, no matter how hard we try, remain resistant to vaccines. Now, researchers are using a different method, gene editing, as a way to make cells immune to mankind’s most difficult viruses. Led by Dr. Justin Taylor, a team at the Fred Hutchinson Cancer Research Center has targeted four infections for which there’s no protective vaccine: HIV, influenza, the Epstein-Barr virus (EBV) and respiratory syncytial virus (RSV).

The researchers used CRISPR/Cas9 technology to modify B cells, a class of white blood cells that produce antibodies to protect us from diseases. By coding the cells with genes that create specific antibodies, the team was able to make them immune without the use of a vaccine.

The researchers tested the method in both human cells in a test tube and in living mice. On average, about 30 percent of the cells produced the desired antibody. Taylor said that the mice remained protected for 83 days following the procedure, an important benchmark given that patients who receive stem cell transplants can have weakened immune systems for three to six months. To be clear, Taylor doesn’t have anything against traditional vaccination. “Vaccines are great,” he said. “I wish we had more of them.”

Instead, Taylor thinks the gene editing method could work one day for diseases where we don’t have a vaccine. It may help patients who are immuno-compromised, meaning their bodies can no longer fight infections, as well as older patients whose bodies aren’t as receptive to vaccines. Gene-edited immunity might also be used to protect people faster than can be done with traditional vaccines, which could be useful during unexpected outbreaks.

Taylor’s team included Fred Hutch researchers and co-authors Howell Moffett, Carson Harms, Kristin Fitzpatrick, Marti Tooley and Jim Boonyaratanakornkit. The results will be published in the journal Science Immunology.

Source: https://www.fredhutch.org/
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