Friendly fire

The immune system usually shields you from disease. But sometimes, you can have too much of a good thing.

http://www.boston.com/news/globe/health_science/articles/2005/11/28/friendly_fire/?page=2
By Stephen Smith, Globe Staff | November 28, 2005

There's no escaping our past.

That's true in love. And it's true in war. It's even true on the battlefields of the human immune system.

There, the wars of old can cast a long shadow over the skirmishes of the future. Researchers at the University of Massachusetts Medical School have found that our exposure to viruses early in life can dramatically influence how we respond to disease later on -- sometimes that's a good thing, sometimes it's not.

Scientists long believed that the microscopic soldiers conscripted into the immune system's army were outfitted to attack a specific viral enemy, with a different army unleashed against each new disease.

Now, the UMass researchers have discovered that some of those soldiers can fight more than one disease.

The finding could provide indispensable clues to a couple of the enduring mysteries of the disease world: Just why is it that certain diseases -- measles, mumps, chickenpox, for example -- are so much more destructive in adults than in young children? And why do some people get so much sicker than others when infected with the same virus?

''When we encounter viral infections, it's not in a vacuum," said Dr. Katherine Luzuriaga, a UMass infectious-disease researcher involved in the work. ''It's in the context of all the other infections we've encountered."

The discovery, more than a decade in the making, was at one point considered heresy in the world of disease specialists. Not anymore. Last week, a Worcester researcher was invited to present her work at a scientific meeting in Chicago. And next month, the prestigious Journal of Clinical Investigation is scheduled to publish an 11-page treatise on the subject.

''It's a very interesting observation they have made that there are situations where the disease may be exacerbated or ameliorated depending on previous infections," said Rafi Ahmed, director of Emory University's Vaccine Center in Atlanta.

''It definitely happens, but I'm not sure how often," he said. ''It's going to be a rare occurrence is my feeling. But it's also possible that a lot of it is happening. We just don't know yet."

The hunt for answers is underway in laboratories -- and in habitats populated by those perpetually nocturnal, enduringly harried creatures known as college students.

Physicians recognize that a virus called Epstein-Barr ignites different symptoms in different patients, depending on their ages. In the very young -- toddlers, for example -- the germ lands only a glancing blow, spawning mild symptoms that vanish swiftly. Once exposed, those young children are spared future illness from the virus.

In college-aged victims, the virus sparks mononucleosis, the ''kissing disease." Just ask Rosemary Ciccarelli, a nurse-practitioner at the UMass campus infirmary in Amherst.

In her job, she helps UMass medical researchers collect blood samples from students with mono, part of a project underwritten with more than $700,000 a year in grants from the National Institutes of Health.

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As a parent, she saw what Epstein-Barr virus can do when it invades an exhausted college student's body. Ciccarelli's daughter, a student at Quinnipiac University in Connecticut, came home last December for the holidays feeling lousy.

Sure enough, she had mono, with such severe swelling in her throat that she had to endure three days in the hospital before recovering.

But why, exactly, did the daughter fall so ill from a virus that in youngsters is so benign?

''There's something more going on here than, 'Oh, you got infected by the virus,' " said Dr. Alan Rothman, a UMass infectious disease specialist also involved in the research. ''And that's what makes it interesting."

Here's what the UMass scientists suspect is happening:

When young children are exposed to Epstein-Barr, they don't have much of a history, immunologically speaking. So when disease warriors known as T cells are summoned against Epstein-Barr, only those specifically targeting the virus show up for duty.

''In the child, you have soldiers, but those soldiers will have experienced fewer wars," Luzuriaga said.

And that means the Epstein-Barr soldiers hurl smart bombs to efficiently and painlessly keep the virus in check.

But with age comes experience -- and memory. By the time someone is cresting adulthood, the immune system has been exposed to waves of viruses.

''Every time you have an infection, you activate a bunch of T cells that are effective against that virus," said Liisa Selin, a UMass pathologist regarded as a pioneer in recognizing the flexibility of disease fighters.

''Once the infection is over, those T cells go into a phase we call 'memory T cells.' They're everywhere -- they're in your organs, they're in tissue, they're in your skin, they're in your gut."

And they're waiting for the next invasion.

Disease specialists had believed that those T cells were on guard for just one disease -- the one they'd fought previously.

The UMass researchers, after analyzing the blood of students suffering from mono, have shown that T cells once summoned to attack the flu also can assault Epstein-Barr.

So when a college student is exposed to Epstein-Barr for the first time, the UMass researchers theorize, the immune system generates squadron after squadron of fighters that remember doing battle with other diseases. It's a multipronged attack that can rev up the network to a dangerously frenetic pace.

''One of the things you have to remember especially with viral infections is the symptoms people have during infection are really not caused by the virus," Selin said. ''It's your immune response that makes you ill and fatigued and gives you fever and puts you to bed."

Dr. Barbara Rehermann of the National Institute of Diabetes and Digestive and Kidney Diseases is independently pursuing related research: the role that T cells originally activated against the flu might play in hepatitis C.

Maybe, the researchers theorize, the ability of flu fighters to target hepatitis C could work to a patient's advantage, helping thwart the virus. But there's also evidence that harm could be done.

Italian researchers earlier this year reported that two patients newly infected with hepatitis C had become suddenly and severely ill. That was surprising, because hepatitis usually hangs around for decades before doing damage. It turned out that the Italian patients' flu warriors got involved in their battle against hepatitis C, inciting, perhaps, an overzealous response.

This deeper understanding of the immune system now being developed could one day yield better vaccines and smarter drugs.

''What we're trying to do is thread the needle of getting the maximum benefit from the response of your immune system," Rothman said, ''and minimizing the harm."

Stephen Smith can be reached at stsmith@globe.com.

© Copyright 2005 Globe Newspaper Company.