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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>