Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune alarm system can both amplify and silence alerts, scientists find

26.09.2003


Chance encounter between two labs resurrects dying immune system theory



A lucky encounter between laboratories at Washington University School of Medicine in St. Louis and the University of California-Berkeley has resurrected a moribund theory about how the immune system mobilizes one of the body’s most important defensive systems: the immune system cells known as T lymphocytes.

The new findings, published online by the journal Science this week, are a key step toward understanding the intricate molecular processes that allow the body to recognize a cell infected by an invader and destroy it.


Ironically, the theory confirmed by the new results involves two cells bumping together -- the same thing that happened when Arup Chakraborty, Ph.D., professor of chemical engineering at Berkeley, called Andrey Shaw, M.D., professor of pathology and immunology at Washington University, and asked him to look over a new paper.

Chakraborty’s original paper, later merged with Shaw’s results to form the Science paper, featured a computational model of the immune synapse theory, a hypothesis formulated eight years earlier by Shaw and two coauthors in Washington University’s Department of Pathology and Immunology, Michael Dustin, Ph.D., and Paul Allen, Ph.D.

The three had speculated that when T cells bump against another type of immune system cell, the antigen-presenting cell, proteins on the surface of both cells reorganize and interact at the point of contact, potentially enhancing the transmission of a key message to the T cell: "Invaders are here, start the attack!" Because nerve cells also have specialized structures at areas known as synapses where they pass messages to each other, the authors referred to the contact between the immune cells as an immune synapse.

Shaw and colleagues had shown through years of research that specialized synapse structures formed when antigen-presenting cells and T cells bumped into each other, and that those structures were stable for an unusually long period of time. But when contacted by Chakraborty, Shaw had been in the process of writing a paper acknowledging that the latest experimental results, like several other recent experiments, seemed to suggest that the immune synapse wasn’t behaving like they expected.

"The kind of nail in the coffin came when we tested cells that were deficient in CD2AP, one of the proteins that we work with that helps form the synapse," Shaw recalls. "When we looked at those cells’ ability to form synapses, we found that in fact the cells did not form what we would call any recognizable synapse."

Despite the lack of synapses, T cells came away from the collisions activated -- as though they’d received the "attack!" message. This led Shaw to speculate that the synapse might form to deactivate the T cell.

"That was kind of disappointing to us, because this idea that the synapse would be uniquely involved in whether a cell would be turned on was this beautiful idea that we really, really liked," Shaw says.

Chakraborty’s computational model revealed a new perspective on the complex mix of factors interacting in the two types of cells, rescuing the "beautiful idea" by suggesting that the immune synapse was linked both to turning T cells on and to shutting them down. According to Chakraborty’s results, the greater the synapse’s ability to amplify the "attack!" message upon initial contact, the harder the synapse could work to shut that same message down in later stages of contact.

In collaboration with Michael Dustin, Ph.D., now at New York University Medical School, Shaw’s group was quickly able to devise an experimental test that proved Chakraborty’s interpretation correct. CD2AP, the protein whose levels had been lowered in Shaw’s most recent experiments, turned out to be involved in the synapse’s ability to dampen signaling by pushing activated receptors on the surface of the T cells toward the lysosome, a kind of cellular garbage can.

"We used the term adaptive controller, an engineering term, to describe the synapse," Shaw explains. "It helps to amplify weak signals by concentrating ligands and receptors in the same area of the cells. But at the same time, it prevents strong signals from overpowering the cells -- which in most cases would lead to cell death -- by rapidly turning off the very strongest signals.

"We only realized this with the use of a computational analysis that allowed us to see how all these different variables were playing out," he says. "There’s a lot of talk that goes around about this need for a union between computational biology and what I would call wet biology, and I think it’s hard for most of us to imagine how that would work … But this was a case where I really thought it was beautiful, it worked together so perfectly."

Shaw notes that while the new results confirm several key concepts in the immune synapse theory, there are still some aspects that need to be directly tested, including the synapse’s ability to amplify a very weak "invaders are here" signal.



Lee K-H, Dinner AR, Tu C, Campi G, Subhadip R, Varma R, Sims TN, Burack WR, Wu H, Wang J, Kanagawa O, Markiewicz M, Allen P, Dustin ML, Chakraborty AK, Shaw AS. The Immunological Synapse Balances T Cell Receptor Signaling and Degradation. Science Express, September 25, 2003.

Funding from the National Institutes of Health, the Psoriasis Foundation, the Irene Diamond Foundation, the Burroughs-Wellcome Fund, and the National Science Foundation supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://medinfo.wustl.edu/

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>