BODY'S INFECTION FIGHTERS CHATTER A LOT
The best defense is a
good offense, especially when it comes to the immune system. The troops that
respond to an infection are split into two squadrons, and, until recently, it
seemed that the two were independent, without much interaction
Now, in a paper
published in Nature Immunology, a
team of scientists from the Virginia Tech Carilion Research Institute and the
University of Alabama at Birmingham say that the immunology boot camp is more
communication-intensive than initially thought -- a discovery that could help
efforts to produce more effective vaccines.
"We have two
populations of T cells," said Kenneth Oestreich, an assistant professor at
the Virginia Tech Carilion Research Institute, referring to the immune system
squadrons. "Before this study, we didn't know if the types of cells were
entirely separate, or if they could transition into one another. Now, this
study suggests that memory cells may arise directly from the effector cell
population."
In this case, memory
cells are not the ones in the brain helping people recall facts.
These cells work in
the body's immune system and retain information about threats from invaders,
allowing the body's natural defenders to mount a quick, more powerful response
if the same threat is encountered again.
The T cells -- white
blood cells -- break down into the two groups as a part of the adaptive immune
system, and they're programmed to respond when a pathogen enters the body.
One squadron,
composed of effector cells that release large volumes of antibodies, goes in
with guns blazing to destroy the enemy. In the process, they release a lot of
energy while metabolizing glucose -- referred to as glycolytic activity.
The memory cells
that make up the other group are stealthy. Sleeper cells, they gather
information to prepare the body for the next battle against this type of
pathogen. They use far less energy and, as a result, have a much smaller
glycolytic signature.
In addition to
infections, vaccines also cause the body to produce memory cells, ready to join
the war effort if a full-force infection invades.
The effector cell
and memory cell groups have always appeared as independent populations, but
scientists saw something intriguing in this most recent study.
"Our data
suggest that the memory cell is actually a transitioning effector cell that has
slowed its glycolytic programming," said Oestreich, who is also an
assistant professor of biomedical sciences and pathobiology in the
Virginia-Maryland Regional College of Veterinary Medicine.
All cells, including
effector and memory cells, are copied from DNA templates and proliferate in the
body.
In this
transcription process, two proteins -- T-bet and Bcl-6 -- play major roles.
T-bet is highly expressed in the effector cells, with a small amount of Bcl-6,
while the opposite is true in memory cells, where Bcl-6 expression exceeds that
of T-bet.
"Mechanistically,
we figured out that these two factors, T-bet and Bcl-6, functionally
interact," Oestreich said. "T-bet antagonizes Bcl-6's function."
When an infection
invades the body, the immune system increases the presence of interleukin-2, a
molecule that signals the need for white blood cells to begin fighting. With
high interleukin-2 levels, T-bet floods the system. As the infection and
interleukin-2 wane, Bcl-6 levels increase. Oestreich and his team found that
the excess Bcl-6 binds to genes involved in glycolytic programming, effectively
shutting down the effector cells' activity.
"The Bcl-6
influx is what leads the cell down the memory pathway," Oestreich said.
"The Bcl-6 factor targets and turns off the high-energy-producing signals
and induces the memory profile."
This research
started in the laboratory of Amy Weinmann, then a professor at the University
of Washington, and continued when Weinmann relocated her laboratory to the
University of Alabama at Birmingham, while Oestreich started his own laboratory
at the Virginia Tech Carilion Research Institute.
Oestreich's team
also continued this research, and they plan to determine how this information
can be used to improve vaccine efficacy.
By studying the
exact targets of Bcl-6, Oestreich says, researchers can understand how memory
cell formation occurs naturally, which will allow for more therapeutic options
to bolster the immune system.
"Your memory
cells are there to detect recurring pathogens and eliminate them before you
even suspect you're ill," Oestreich said. "If we could push the
immune system to become that much stronger, we may be able to create better
vaccines."
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