Tag Archives: immune cells

Blocking Protein Curbs Memory Loss

Impeding VCAM1, a protein that tethers circulating immune cells to blood vessel walls, enabled old mice to perform as well on memory and learning tests as young mice, a Stanford study found. Mice aren’t people, but like us they become forgetful in old age. In a study  published online May 13 in Nature Medicine, old mice suffered far fewer senior moments during a battery of memory tests when Stanford University School of Medicine investigators disabled a single molecule dotting the mice’s cerebral blood vessels. For example, they breezed through a maze with an ease characteristic of young adult mice.

The molecule appears on the surfaces of a small percentage of endothelial cells, the main building blocks of blood vessels throughout the body. Blocking this molecule’s capacity to do its main job — it selectively latches onto immune cells circulating in the bloodstream — not only improved old mice’s cognitive performance but countered two physiological hallmarks of the aging brain: It restored to a more youthful level the ability of the old mice’s brains to create new nerve cells, and it subdued the inflammatory mood of the brain’s resident immune cells, called microglia.

Scientists have shown that old mice’s blood is bad for young mice’s brains. There’s a strong suspicion in the scientific community that something in older people’s blood similarly induces declines in brain physiology and cognitive skills. Just what that something is remains to be revealed. But, the new study suggests, there might be a practical way to block its path where the rubber meets the road: at the blood-brain barrier, which tightly regulates the passage of most cells and substances through the walls of blood vessels that pervade the human brain.

 

We may have found an important mechanism through which the blood communicates deleterious signals to the brain,” said the study’s senior author, Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, co-director of the Stanford Alzheimer’s Disease Research Center and a senior research career scientist at the Veterans Affairs Palo Alto Health Care System. The lead author of the study is Hanadie Yousef, PhD, a former postdoctoral scholar in the Wyss-Coray lab. The intervention’s success points to possible treatments that could someday slow, stop or perhaps even reverse that decline. Targeting a protein on blood-vessel walls may be easier than trying to get into the brain itself. “We can now try to treat brain degeneration using drugs that typically aren’t very good at getting through the blood-brain barrier — but, in this case, would no longer need to,” Yousef said.

Source: http://med.stanford.edu/

Micromotors Deliver Oral Vaccines

Researchers are working on new generations of oral vaccines for infectious diseases. But to be effective, oral vaccines must survive digestion and reach immune cells within the intestinal wall. As a step in this direction, UC San Diego nanoengineering researchers have developed oral vaccines powered by micromotors that target the mucus layer of the intestine.

The work appears in the ACS journal Nano Letters. It’s a collaboration between the labs of nanoengineering professors Joseph Wang and Liangfang Zhang at the UC San Diego Jacobs School of Engineering.

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The lack of needles is one reason oral vaccines are attractive. Another reason: oral vaccines can generate a broad immune response by stimulating immune cells within the mucus layer of the intestine to produce a special class of antibody called immunoglobulin A (IgA). The NanoLetters paper documents the team’s efforts to use magnesium particles as tiny motors to deliver an oral vaccine against the bacterial pathogen Staphylococcus aureus. When coated over most of their surfaces with titanium dioxide, magnesium microparticles use water as fuel to generate hydrogen bubbles that power their propulsion.

To develop the oral vaccine, the researchers coated magnesium micromotors with red blood cell membranes that displayed the Staphylococcal α-toxin, along with a layer of chitosan to help them stick to the intestinal mucus. Then, they added an enteric coating that protects drugs from the acidic conditions of the stomach.

The micromotors safely passed through the stomach to the intestine, at which point the enteric coating dissolved, activating the motors. Imaging of mice that had been given the vaccine showed that the micromotors accumulated in the intestinal wall much better than non-motorized particles. The micromotors also stimulated the production of about ten times more IgA antibodies against the Staphylococcal α-toxin than the static particles.

Source: http://jacobsschool.ucsd.edu/

How To Turn On Cancer-Killing Immune Cells

A remote command could one day send immune cells on a rampage against a malignant tumor. The ability to mobilize, from outside the body, targeted cancer immunotherapy inside the body has taken a step closer to becoming reality. Bioengineers at the Georgia Institute of Technology have installed a heat-sensitive switch into T-cells that can activate the T-cells when heat turns the switch on. The method, tested in mice and published in a new study, is locally targeted and could someday help turn immunotherapy into a precision instrument in the fight against cancer.

Immunotherapy has made headlines with startling high-profile successes like saving former U.S. President Jimmy Carter from brain cancer. But the treatment, which activates the body’s own immune system against cancer and other diseases, has also, unfortunately, proved to be hit-or-miss.

In patients where radiation and traditional chemotherapies have failed, this is where T-cell therapies have shined, but the therapy is still new,” said principal investigator Gabe Kwong. “This study is a step toward making it even more effective.”

Cancer is notoriously wily, and when T-cells crawl into a tumor, the tumor tends to switch off the T-cellscancer-killing abilities. Researchers have been working to switch them back on.

Kwong’s remote control has done this in the lab, while also boosting T-cell activity. In the study, Kwong’s team successfully put their remote-control method through initial tests in mice with implanted tumors (so-called tumor phantoms, specially designed for certain experiments).

Source: http://www.rh.gatech.edu/