T Cell
© Wikimedia Commons
Healthy human T cell.
Immune cells are like the Hatfields and McCoys of our bodies--once wronged, they never, ever forget. This is how we gain immunity, and it's why vaccines work: Immune cells develop a memory of an invading pathogen, and they build an alert system to find and fight it should it ever return. But a new study by Stanford researchers adds a new wrinkle to this long-held immune theory. It turns out immune cells can develop this memory-like state even for pathogens they've never met. This may come from exposure to harmless microbes -- or the memories may actually be borrowed from other, more experienced cells.

The findings could help explain why babies and small children are so susceptible to infectious diseases. They haven't been exposed to enough ever-present, mostly harmless pathogens yet, and it's the constant scuffle with these bugs that gives adult T cells a sort of cellular precognition. "It may even provide an evolutionary clue about why kids eat dirt," said the study's lead author, Stanford microbiologist and immunologist Mark Davis. Kids are drawn to dirt because they've got to expose their fledgling immune systems to something, to help build up their defenses.

Davis and his coauthors studied a group of T cells called CD4 cells, which are the same ones targeted by HIV. CD4 cells hang out in our bloodstreams and stand sentinel, sounding the cellular alarm when they spot something that doesn't belong. There are two basic classes of CD4 cells: Naive cells, which haven't been exposed to a particular bug and might take a while to mount a response, and memory-type cells, which have done battle with a pathogen and are on the lookout for it again. The memory cells can prompt action within a few hours, while naive cells might take days or even weeks--meanwhile, we're sick.

Decades ago, Davis discovered that CD4 cells reshuffle their DNA when they divide, which basically creates an army of T cells that have very specific pathogen-recognizing abilities. According to this new paper, this ability might also help them recognize pathogens they haven't even seen yet.

The researchers looked at blood samples from 26 healthy adults and figured out which T cells were responsive to which pathogens. About half of the cells looked like they were in the memory state, meaning they would have encountered a particular pathogen in the past. But then Davis and his colleagues did some tests and found out those people were never exposed to those diseases. They also tried this on newborns, using umbilical cord blood, and found the babies' cells were naive.

To test this further, the researchers took two adults who hadn't had a flu shot in five years and gave them the vaccine. After this dead-virus invasion, which is designed to give CD4 cells a new memory, the patients' CD4 memory cells proliferated. But interestingly, some of them were awakened to "remember" different bacterial and protozoan cell structures, which had nothing to do with the flu.

Playing in Mud
© Wikimedia Commons
Yum, Mud: There may be an evolutionary reason why kids are inclined to eat dirt.
How do naive cells accomplish this microbial memory generation? It's all about the environment. People are constantly exposed to countless bacteria, fungi and viruses, everywhere all of the time. T cells might act like they're reacting to something they've seen before--maybe the bacteria's proteins look similar to that of a harmless bug, and the cell is fooled. Or maybe the actual memory cells reshuffle their DNA when they replicate, which gives new cells specific properties.

"The pre-existing immune memory of dangerous pathogens our immune systems have never seen before might stem from our constant exposure to ubiquitous, mostly harmless micro-organisms, in soil and food and on our skin, our doorknobs, our telephones and our iPod earbuds," Davis explains.

So maybe drop that Purell habit and don't worry about the billions of bugs, most of which aren't harmful, that surround us all the time. They might be giving our immune systems a head start.

The research appears this week in Immunity.