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 Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>