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05/03/2006
Tough Decisions for Bees and Immune Cells
There must be something about Cornell University that spurs
obsessive interest in animal behavior. I recently wrote about
Cornell’s Kevin McGowan and his studies of crows that have
continued since 1989. Now I find that Cornell biologist Thomas
Seeley and his colleagues, Kirk Visscher at University of
California-Riverside and Kevin Passano at Ohio State
University, have spent 10 years studying the swarming of
honeybees. (Visscher got his Ph.D. at Cornell.) Brian Trumbore
called my attention to an April 14 Wall Street Journal article by
Sharon Begley that discusses how animals decide on courses of
action. Begley mentioned Seeley’s studies on how bees decide
where to settle after leaving a hive.
Seeley’s group published their work in the May-June issue of
American Scientist. We’ve previously discussed the well-known
waggle dance used by bees to communicate the location of
sources of food to their hive mates. Seeley’s group has tagged
and recorded the behavior of thousands of bees and has shown
that the waggle dance is also used in the real estate game as well.
When a hive gets crowded, the queen and some thousands of
bees leave the hive and clump together on a tree or some other
temporary location. There they quietly await the decision as to
where they should establish their new home. In the wild, this
new home is likely to be in a hollow in a tree. To select the best
place for their new abode, several hundred scouts go out looking
for good spots. When they find a hollow, back they come to the
clump and start waggling. The more the scout likes a particular
hollow, the more enthusiastic the scout’s waggling. A scout’s
enthusiasm can be measured by the number of circuits it makes
around the dance floor. As the other scouts report in with their
own dances, they observe their fellow scouts’ degrees of
enthusiasm for their sites.
Seeley’s team found that, as the bees revisit their original sites,
their enthusiasm diminishes and the number of circuits on the
dance floor decreases significantly. If a scout isn’t very enthused
to start with, it quickly stops dancing and is ripe for trying a new
site recommended by other scouts. Gradually, the most
enthusiastic scouts gather support and a larger number of scouts
visit that site.
When about 15 scouts gather at one site, the scouts return to the
hive and alert the bees to prepare for takeoff to their new home.
They do this by making their ways through the cluster and
pressing their vibrating thoraxes against the other bees. This
stimulates the bees to warm up their wing muscles. In the
process, each bee warms up to about 95 degrees Fahrenheit and,
when everyone is warmed up, off they go to their new home.
The time taken to reach a decision was 16 hours in one case cited
in an article by Susan Lang on the Cornell Web site.
Do the bees make the correct decision? To check this out the
researchers offered so-so nest sites and superb ones. They found
that the scouts might make a hundred waggle circuits for a really
good site and only 12 for the mediocre site. The swarms chose
the best site almost all the time. Do the bees wait for a consensus
or is just a quorum required before they take off? Appledore
Island in Maine, location of at least some of the experiments, has
few trees, so the scientists could offer nest boxes that were of
different sizes and appeal. In one experiment they offered two
equally good sites. As soon as 15 bees converged on one of the
sites, the swarm took off for that site. This, even though some
scouts were still dancing feverishly for their site. It just takes a
quorum, not total consensus.
Bees communicate by waggle dancing. What about the cells in
our body? I’ve been mulling over an article by Daniel Davis in
the February Scientific American titled “Intrigue in the Immune
Synapse”. Davis is a professor of immunology at Imperial
College London who turned from physics to immunology,
specializing in high-resolution microscopy studies of immune
cell interactions. The immune cell is sort of like a bee scout,
except that the immune cell isn’t looking for good real estate.
The immune cell wanders about searching for evildoers that
would make us ill or even kill us if given a chance. When the
immune cell bumps into another cell, it has to make a decision as
to whether the other cell is a healthy normal cell or an abnormal
cell. If the cell is normal, the immune cell goes off to check out
other cells. If the cell is abnormal and the immune cell is a
“killer” cell it will polish off the bad cell. If the immune cell is a
“helper” cell it will alert killer cells to go after the offending cell.
If the immune cell makes a mistake and kills a normal cell, you
may have an autoimmune disease such as MS. If the immune
cell doesn’t kill an abnormal cell, you may end up with cancer.
How does a normal cell communicate to a killer immune cell that
it’s normal and should be left alone by the killer? Davis was
involved in finding the first images of this process in killer cell
interactions in 1999. In 1995, Abraham Kupfer of the National
Jewish Medical and Research Center in Denver had wowed the
assembled immunologists at a conference with 3-D images of
immune cells interacting with each other. Kupfer’s pictures
showed proteins aggregating, forming bull’s-eye structures at the
contact area between two cells. These bull’s-eye patterns were
remarkably similar to the patterns at the main connections
between neurons called synapses.
In our brain, the synapses between neurons are stable and long-
term arrangements. In the case of immune cells, the synapse
forms where the membrane of the immune cell bumps into the
membrane of another cell. The synapse is broken when the
normal cell convinces the immune cell that all is well. The
bull’s-eye pattern forms when “adhesion” molecules form a ring
that holds the membranes of the two cells together. The immune
cell’s receptors move inside the ring and proteins in the other cell
move towards the center to offer up protein fragments known as
antigens to the immune cell receptors. If the immune cell
receptors consider the antigens to be “normal”, the synapse is
broken and the cells go their separate ways.
The title pages of the Scientific American article show very large
photos of a normal B cell contacting a natural killer cell. It
shows a cluster of proteins from the B cell at the synapse. The
presence of these proteins apparently tells the killer cell that the
B cell is healthy. The picture also shows acidic clumps of
material in the killer cell that it would inject through the synapse
to kill the B cell if it found the b cell abnormal. The high-
resolution microscopy that shows these features is truly amazing.
Strangely, the article does descrbe the microscopic techniques
used to make such revealing images of cells interacting. It’s not
just plain old “looking-through-a-microscope” microscopy. For
one thing, fluorescent dyes are used to “label” different proteins.
Back in 1873, Ernst Abbe showed that an optical microscope had
fundamental limitations could not resolve features smaller than
about 200 nanometers. This so-called “diffraction limit” spurred
the development of electron microscopes and the various
scanning microscopes we’ve discussed in earlier columns.
However, in recent years, this fundamental limit has been
broken. For example, at the Max Planck Institute for
Biophysical Chemistry in Germany, workers have developed a
new optical microscope involving lasers and a technique too
complicated to discuss here. (OK, you’re right, I don’t
understand it!) Suffice to say that workers at Max Planck have
reported this year that they have resolved features in cells only
40 nanometers in size. Furthermore, these workers are optimistic
that they haven’t yet reached the limit of resolution of their
technique and that optical microscopy might be extended down
to the molecular level. We can expect many more amazing
pictures of cells in action in the future.
Allen F. Bortrum
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