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 Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>