Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U-M scientists use 21st-century technology to probe secrets of M. tuberculosis

27.05.2004


Computer model shows why some get sick after TB infection, while others don’t



University of Michigan microbiologists have created a virtual model of the human immune system that runs "in silico" to study what happens inside the lungs after people inhale Mycobacterium tuberculosis, the bacterium that causes TB.

The computer model is helping scientists learn more about this ancient pathogen, and why some people are able to fight off the infection, while others get sick. U-M scientists believe the answer could be hidden inside structures called granulomas, which immune cells build to surround and contain invading M. tuberculosis bacteria.


"Granulomas are the hallmark of tuberculosis," says Denise Kirschner Ph.D., an associate professor of microbiology and immunology in the U-M Medical School. "It’s the immune system’s fail-safe response to infection. If the immune system can’t clear the pathogen, it gets out the masonry and walls it off."

Kirschner presented research results and an analysis of time-lapse computer animations showing granuloma formation at a May 26 seminar during the American Society for Microbiology’s annual meeting held here this week.

"M. tuberculosis has been living with people for at least 4,000 years," says Kirschner. "Because the bug has had all those years to get to know us so well, it has evolved several effective ways to circumvent the immune system’s ability to detect and kill invading pathogens. Scientific knowledge of how the immune system interacts with M. tuberculosis is slowly improving, but we are far from prevention or an effective vaccine. It’s important to understand TB, because the disease is a serious and growing public health problem."

According to Kirschner, approximately 2 billion people worldwide are infected with M. tuberculosis, and the disease kills about 3 million people every year. In the early stages of infection, tuberculosis can be treated with powerful antibiotics, but there is no cure. And multi-drug-resistant strains, which are essentially untreatable, are becoming more common.

The immune system’s immediate response to the presence of M. tuberculosis in the lungs is to surround the bacteria with immune cells called macrophages, which signal other immune cells to join them for a group assault on the invading bacteria, Kirschner says. About 90 percent of the time, these multi-cellular structures called granulomas are enough to stop the bacteria from spreading. Although the individual will always be infected with TB bacteria, the disease will remain in a latent phase and produce no symptoms, unless it flares up again later in life.

Between 5 percent to 10 percent of the time, however, granulomas fail to contain the bacteria. Unless the disease is diagnosed and treated, TB bacteria will continue to spread through the lungs, eventually producing severe respiratory symptoms and death.

Since granulomas are the key counter-offensive in the war between the human host and M. tuberculosis, Kirschner and U-M post-doctoral fellows Jose Segovia-Juarez, Ph.D., and Suman Ganguli, Ph.D., programmed their computer model with experimental data from studies - directed by University of Pittsburgh collaborator Joanne Flynn, Ph.D. - of research animals infected with TB. They then created time-lapse animations demonstrating what happens as a granuloma forms after initial infection with the bacteria.

When they analyzed the results of the computer simulation, Kirschner and her research team found new clues to the immune system’s containment process:

- Granulomas that were unable to contain TB bacteria were packed with inactive macrophages, making it impossible for T cells to get inside the granuloma and properly signal the macrophages to attack and kill M. tuberculosis bacteria. - The arrival time, number and location of "educated" T cells, which had been primed by the immune system to signal macrophages to attack M. tuberculosis, were crucial to the success of the immune response.

- The slow reproduction rate of M. tuberculosis bacteria, which doubles about every two days, helps the bacteria survive undetected inside macrophages for long periods of time.

Mathematical models are a valuable addition to experimental research, because they make it possible to study complex biological systems with many variables in ways that would be impossible in humans or research animals.

"Here we used a new approach called agent-based modeling, which allowed us to track the individual behavior of specific cells in the system and how they contributed to the collective outcome," Kirschner says. "This is one of first applications of this method in studies of infectious diseases within the host."



Kirschner’s research is funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

Note: Animations of granuloma formation described in this story can be viewed in AVI format on the Web at http://malthus.micro.med.umich.edu/lab/abm/movies/. The first version (clearance.avi) shows what happens to the granuloma when the immune system is able to destroy the bacteria. The second version (containment.avi) shows granuloma formation when infection is contained. The third version (dissemination.avi) shows what happens to the granuloma when the infection is not contained.

Cells are color coded as follows: Inactive macrophages (green), activated macrophages (blue), infected macrophages (orange), chronically infected macrophages (red), T cells (pink), necrotic tissue (brown) and extracellular bacteria (yellow).

Additional Contact:
Kara Gavin, kegavin@umich.edu, 734-764-2220

Sally Pobojewski | EurekAlert!
Further information:
http://malthus.micro.med.umich.edu/lab/abm/movies/

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

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

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>