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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