Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new understanding of how immune system targets disease

27.07.2005


Study sets foundation for new generation of vaccines for HIV, influenza

Scientists have taken a major step toward the goal of altering viruses, bacteria and tumor cells so that they demand attention from immune cells designed to destroy them. According to research published today in the journal Immunity, researchers at the University of Rochester Medical Center have determined for the first time a single biochemical feature of disease-causing molecules (pathogens) that, if changed, would force them to provoke an attack by the human immune system.

Recognizing molecules as "self," versus foreign invaders to be destroyed, is a central responsibility of the immune system. Tumors closely resemble self or "host" tissues and can confuse the system. Viruses and bacteria are immediately recognizable as foreign, but have learned to change shape so often that the system loses track of them. Pathogens use the same tricks to escape the immunity provided by vaccines.



In an effort to deny diseases the ability to hide, researchers have for years been asking a key question: Why do our bodies select certain, small pieces (epitopes) of each disease-causing molecule to trigger an immune response, while ignoring the rest? Those few, triggering protein fragments are termed "immunodominant." Unfortunately, the immune system sometimes makes poor choices about which epitopes to pay attention to, and which to ignore. Understanding of how immunodominance is conferred would enable vaccine designers to shift the immune system spotlight to parts of pathogens that they cannot change in efforts to escape detection. For example, a vaccine could be designed to target a protein fragment central to a virus’s ability to reproduce, or to invade its prey.

"Our study identified for the first time the chemical mechanism that determines immunodominance, and proved that it can be fine-tuned," said Andrea Sant, Ph.D., a professor within the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, and the study’s lead author. "If confirmed, the findings could launch a new wing of research seeking to re-engineer viruses, bacteria and tumor cells to make them hundreds of times more likely to be noticed and destroyed by our immune system."

Study Details

As part of the immune response, T cells, one type of white blood cell, partner with dendritic cells to make careful decisions about which pieces of pathogens will trigger a full-scale immune attack. Dendritic cells roam the body, checking each particle they come across for a self or invader "label." Upon encountering an invader, a dendritic cell will "swallow it," cut it up, and carry the pieces to the nearest lymph node.

Once in the lymph node, major histocompatibility complex (Mhc) proteins inside the dendritic cell present immunodominant epitopes on the cell’s surface for consideration by T cells gathered there. Once activated by high enough levels of target epitope for long enough periods of time, T cells become armed and capable of destroying the pathogen in question.

Sant’s study provides the first proof that it is something about the invader epitope itself that drives and focuses T cell response, and not some action of enzymes inside the dendritic cell as once thought. The quality determining immunodominance is the strength and lifespan (kinetic stability) of the bond between the Mhc protein and a given epitope. Kinetic stability determines whether, in the face of competing reactions within the immune system, an epitope:Mhc complex can remain intact on the dendritic cell surface long enough to demand T cell attention. Sant’s team found that immunodominant peptides were likely to stay bound to Mhc molecules for an average of 150 hours, where nondominant epitopes held on for less than 10 hours.

"What’s exciting is that kinetic stability is determined by how tightly an epitope fits into the Mhc protein, and we can control that fit with standard techniques," Sant said. "By switching out single amino acid building blocks, we were able to drastically increase the potency of the T cell response to target epitopes. If confirmed, this discovery will bring immundominance and a major portion of the immune system under our control for the first time."

Greg Williams | EurekAlert!
Further information:
http://www.urmc.rochester.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>