Immune system uses heart channel to select powerful defenders
Immune T cells take in calcium as part of a screening process in the thymus. The testing ensures that the T cells react neither too strongly nor too weakly. Each “island” in this image is an individual T cell; the height of the island indicates the amount of calcium they have taken in.
(Medical Xpress) -- When the body makes immune T cells, it relies on a molecular channel more commonly seen in nerves and heart muscles to ensure that the powerful T cells have the right mixture of aggressiveness and restraint, researchers at Washington University School of Medicine in St. Louis have discovered.
Scientists report online in Nature Immunology that fledgling T cells temporarily make a protein that creates an opening in their surfaces known as a voltage-gated sodium channel. The cells only make the protein at key points in a testing process that occurs in the thymus, an immune organ located near the heart. The channel allows the cells to hear the results of testing, which eliminates an estimated 95 percent of potential T cells.
The thymus applies a kind of Goldilocks principle, seeking the cells that are just right, rather than those that are too hot or too cold, says senior author Paul Allen, PhD, the Robert L. Kroc Professor of Pathology and Immunology. The goal is not only to screen out the T cells that wont react to invaders, but also to eliminate over-reactive T cells that could attack the body and cause autoimmune diseases. The voltage-gated sodium channel is the opening through which the T cell learns its fate.
According to Allen, the finding is an important step forward in understanding how the immune system builds a repertoire of tens of millions of T cells, each primed to fight individual bacterial and viral invaders. Understanding this process will help scientists find better ways to control and enhance the immune systems ability to fight diseases and cancer.
T cells develop in the thymus from a bone-marrow derived precursor. Each cell has a different receptor on its surface that is produced by scrambling the bodys own genetic material. The vast majority of these cells will never be activated, but some will match proteins found in infectious agents and help the body recognize and kill those agents.
After they are created, the cells are tested in the thymus. This includes tests of their ability to recognize a special molecule found on the surface of most cells. The molecule holds pieces of proteins made inside the cell in a fashion similar to a bun holding a hot dog. This display helps the T cells recognize infected cells by revealing pieces of proteins made by the infectious agent. When they encounter proteins made by bacterial or viral invaders, the T cells attack the infected cells.
During the thymus testing process, though, the hot dogs are pieces of the bodys own proteins, Allen explains. The test is repeated multiple times with samples of many different proteins. Ideally, the T cell will recognize these assemblies but will not attack them because they are proteins made by the self.
If the T cell doesnt recognize the hot dog in a bun at all, it soon dies from lack of interaction with other cells. If it attacks too strongly, the T cell needs to be killed.
What has puzzled immunologists for some time is how the results of this testing are conveyed to the T cell, Allen says. The positive selection or you passed the test signal comes from a weak interaction between the T cell and the hot dog. Weak interactions are normally associated with weak signals, and in this case the signal is a sustained flow of calcium ions into the T cell.
The voltage-gated sodium channel empowers the T cell to transform this trickle of calcium into a strong signal.
In earlier research, Allen identified a protein that helps a specific T cell pass the thymus tests. For the new study, Wan-Lin Lo, a graduate student, used a gene chip to monitor the proteins made by that cell as it passed through the thymus tests.
We learned the cells were making these voltage-gated sodium channels at exactly the right times when they needed to be more sensitive to signals from the thymus, Allen says. These channels and their ability to amplify and sustain signals are well-known from their extensive use in nerve cells and muscles including the heart.
Allen plans additional research with Washington University colleagues who work more regularly with the voltage-gated sodium channel and other similar channels to learn more about the channels functions in this unusual context.
More information: Lo W-L, Donermeyer DL, Allen PM. A voltage-gated sodium channel is essential for the positive selection of CD4+ T cells. Nature Immunology, doi:10.1038/ni.2379
Journal reference: Nature Immunology
- Research team uncovers mechanism behind drugs that cause altered immunity May 24, 2012 | not rated yet | 0
- 'Nurse cells' make life and death decisions for infection-fighting cells May 29, 2007 | not rated yet | 0
- Protein may play role in obesity, diabetes, aging Feb 15, 2012 | not rated yet | 0
- Artificial thymus tissue enables maturation of immune cells Mar 29, 2012 | not rated yet | 0
- Monitoring how T cells respond to HIV Oct 14, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Calculating on-axis elements of a solenoid
9 hours ago I wanted to mention that this solenoid has many winds over many layers. The thickness of the windings is 2.4 inches coming off of the engineering...
latitude & longitude & air pressure
10 hours ago Hi there, I have a peculiar question. Imagine that you are in a earth position, obtained by google, that gives you the latitude and longitude....
Differences of Classical Mechanics when learned with Calc vs algebra?
13 hours ago what are the differences? Every example I find usually has a derivative or integral or some kind of calculus defined concept that seems to make it...
what is the distance traveled
17 hours ago A rough sketch of experiment. Image: http://i43.tinypic.com/14t4sk5.png the red dots represent a side view of path traveled, F is downward force...
Image of a Convex Lens Cut in Half Horizontally
21 hours ago Hello everyone, A friend of mine came up with this question in class and I really do not have a good answer. Suppose you have a convex lens...
Ray tracing through optical system of thick lenses
21 hours ago Can you advise me a free software that allow to draw rays passed throught system of thick lenses (preferable in 3D)?
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology May 20, 2013 | 4.8 / 5 (24) | 8 |
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology May 20, 2013 | 5 / 5 (1) | 0 |
Melbourne researchers have identified an immune protein that has the potential to stop or reverse the development of type 1 diabetes in its early stages, before insulin-producing cells have been destroyed.
Immunology May 20, 2013 | 5 / 5 (5) | 0 |
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
US teen births have dropped to a record low, but the country still has one of the highest rates among developed nations, the US Centers for Disease Control and Prevention said Thursday.
1 minute ago | not rated yet | 0
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
17 hours ago | 4.9 / 5 (9) | 1 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
17 hours ago | 4.7 / 5 (3) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
14 hours ago | 5 / 5 (2) | 2 |
Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...
6 hours ago | not rated yet | 0
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
14 hours ago | 4 / 5 (2) | 0 |