Countering ‘Memory Loss’ In The Immune System

On December 26, 2010, in Immunology, by Christopher Fisher, PhD

After recovering from a cold or other infection, your body’s immune system is primed to react quickly if the same agent tries to infect you. White blood cells called memory T cells specifically remember the virus or bacterium and patrol the body looking for it. Vaccines work on the same principle: Harmless fragments of a virus or bacterium provoke the immune system to generate memory T cells that can attack the real thing later on.

As time passes, however, this specific immunity can wear off. That is because not all memory T cells live long enough to foster long-term immunity.

MIT biologists have now demonstrated the conditions that favor development of long-term memory T cells over short-term memory T cells, which can respond quickly but do not stick around for very long after the initial infection. That discovery could help vaccine designers better tailor their formulas to elicit long-term memory immunity, says Jianzhu Chen, MIT professor of biology and member of the David H. Koch Institute for Integrative Cancer Research.

Chen and Herman Eisen, emeritus professor of biology, are senior authors of a paper on the work that appeared in the Proceedings of the National Academy of Sciences the week of Dec. 13.

In the PNAS study, the MIT team looked at mice infected with influenza. In mice, as in humans, influenza virus stimulates T cells, whose job is to kill infected cells. Every T cell is programmed to recognize different foreign proteins (also called antigens) located on the surfaces of infected cells. When a T cell binds to the antigen, the T cell becomes activated and starts rapidly reproducing, creating an army of cells that can identify and destroy the invader.

Once the infection is eliminated, most of the activated T cells die off, but a few of them stick around, in case the virus comes back. These are short-term memory T cells. Because they have already battled the virus and reproduced many times, they survive only weeks or months after the initial infection. (T cells can only divide a certain number of times before they die.)

A set of long-term memory T cells also develops during infection. These cells are programmed differently, so they can persist for decades. Recipients of the smallpox vaccine, for example, have been shown to still have T cells against the virus up to 70 years later, says Eisen.

Until now, it has been unclear how these different cell types develop. In their new study, Eisen and Chen investigated the role three factors: T-cell location, the amount of antigen exposure, and length of exposure.

Scientists already knew that T cell contact with a large amount of virus provokes development of short-term memory T cells, says Eisen. Chen and colleagues discovered that large amounts of antigen also suppress development of long-term memory T cells. Those cells only develop when exposed to a small amount of the antigen for a short period of time.

For example, if you have an infection in the respiratory tract, nearby T cells will be exposed to many viruses and become short-term memory cells. Those cells hang around the respiratory tract, ready to pounce quickly if the same virus re-infects you, but they eventually die off.

In more distant parts of the body, T cells are exposed to only small amounts of the virus, and some of those cells become long-term memory T cells specific to that virus. These maintain a low level of constant vigilance in case the virus ever returns.

Ulrich von Andrian, professor of immunopathology at Harvard, says the new study’s major contribution is its experimental support of existing theories. “It builds on ideas that have been around for a while, that were not rigorously tested by experiments, for the most part,” says von Andrian, who was not part of the research team.

When developing vaccines, the goal is usually to generate a stable population of long-term memory T cells. This study suggests that the best way to do that is to give a small amount of antigen, and, for vaccines that require multiple injections, not to give them too frequently.

“The general rule of thumb is that you don’t want to give a large amount of antigen on a short-term basis,” says Chen. He adds that the amount of antigen for inducing a long-term memory T cells likely varies depending on the route of immunization and the form of antigen, and so the dosage for each vaccine will have to be determined through experiments.

He says the findings will likely not impact flu-vaccine design because existing dosages have already been optimized over many decades. However, the findings should be applicable to vaccines now under development for other diseases, such as HIV, tuberculosis and dengue fever, says Chen.

Material adapted from MIT.

Four ways to avoid getting sick during the holiday season

By Madison Park, CNN

(CNN) — The Badger family holidays are filled with medical catastrophes.

One year, Melissa Badger’s niece stopped breathing at the Thanksgiving table because of a strep infection. In 2003, Badger’s son came down with a severe fever and ended up in the emergency room on Christmas. On Christmas Eve 2005, Badger tripped on ice while delivering presents to needy families and sprained her ankle.

This year, Badger’s husband complains of cold-like symptoms — fatigue, coughing and a sore throat. Badger struggled with a bug going around her office that was giving everyone stuffy noses and cold symptoms.

“Now, we get to worry about that lingering cold all of us have, since we’re hosting family this Christmas Eve,” said Badger. Hosting family means more than 30 people at their Beloit, Wisconsin, home.

Illness for many of us seems to knock at the most inopportune moments — after finishing a year-end project, before a holiday or after taking exams.

It had Shannon Duffy, who spent this Thanksgiving in bed with the flu, asking: “Is too much excitement and anticipation of the holiday season a bad thing? Or is it that my immune system just gets so overloaded with life stresses that when I step back and take a break, it is like an open invitation for the flu bug to intervene?”

With Mom sick in bed, Duffy’s sons had to microwave their TV dinners for Thanksgiving.

“I’ve been sick a lot during the holidays,” said the Palm Springs, California, resident. “If it’s not Thanksgiving, it’s Christmas.”

There are a few theories why sickness comes at the worst time.

“The holidays are a virus-distribution system,” said Dr. William Schaffner, chair of the department of preventive medicine at Vanderbilt University. “They help us distribute the viruses, influenza and other common cold virus from person-to-person because of close contact.”

1) Achoo to you, and you, and you

Flu season reaches its height in late fall and early winter. This is because viruses circulate better in the colder weather, said Dr. Philip Tierno, director of microbiology and immunology at New York University’s Langone Medical Center.

It’s not only cold and flu bugs that become active during colder seasons. CDC: Seasonal FluView

Other viruses, such as the norovirus and rotavirus, become more active during winter. Norovirus, known as the stomach flu, easily spreads through contamination in food, drink and surface contact. The virus is found in the stool and vomit of infected people. Rotavirus also causes diarrhea, vomiting, fever, and abdominal pain.

Advice: If you’re sick, cough into the crook of your arm.

If someone is coughing or wiping his or her nose, don’t hug or kiss the person. Use common sense, Tierno said.

5 Immunity boosting tips for moms

2) The sea of humanity … at the mall

Think of the holiday traditions: catching a show, shopping at a crowded mall, attending holiday parties.

All this means you’re indoors in crowds and exposed to everyone’s germs. As people cluster indoors, they use the same doorknobs, banisters and surfaces after wiping their noses or sneezing.

“During the winter season, we’re more subject to crowding, touching something that’s not hygienic and crowding,” Tierno said.

People get less fresh air, too.

“They don’t open up windows to get fresh air. They don’t go outside as much during cold weather. They decide to stay in, so any virus that may be present would be more easily spread,” he said.

Advice: Practice frequent hand-washing (at least 20 seconds wiping both the top, bottom of hands and between the fingers prior to eating and drinking) or use hand sanitizers.

Occasionally open the window to let fresh air circulate.

Must-know winter health & safety tips

3) Germs fly free

Air travel means if there’s a small flu outbreak on the West Coast, that virus could be in New York in less than five hours.

“Human travel is synonymous with virus travel,” said Shaffner, an infectious disease expert.

When family members travel across the country, they’re bringing along pathogens that have been in their communities and exposing them to new places.

It’s not only the act of being in an enclosed cabin of a car, bus, train or plane, Shaffner said.

“Remember we’re talking about being on an airplane, getting to the airplane, making your way through the crowds and other crowds in the other end,” he said. “It is just as important as the airplane.”

Advice: The Centers for Disease Control and Prevention recommends everyone older than 6 months old be vaccinated for influenza. Get your flu vaccine to reduce chances of getting sick.

Dr. Sanjay Gupta talks to Sebelius about flu shots

4) You’re super-stressed before vacation

End-of-the-year projects, reports, final exams — it could be all that work before break that spikes a stress hormone in your body.

“The increased cortisol level induces likelihood of infection during the holidays,” said Dr. Robert Hasty, assistant professor of internal medicine at Nova Southeastern University’s medical school.

Cortisol is a natural hormone that responds to stress, lowering immunity and making you more susceptible to infections.

The interval between acquiring a virus and becoming sick takes about 48 to 72 hours. You may have become infected when you were stressed and the symptoms may start to show right when you go on holiday break.

Advice: Stress might be unavoidable, but try getting enough sleep and hydrating.

Prevent the stress hormones from wreaking havoc by better planning, avoiding traffic, buying presents earlier.

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