Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dendritic cells ensure immune tolerance

18.03.2009
One of the most important tasks of the immune system is to identify what is foreign and what is self. If this distinction fails, then the body's own structures will be attacked, the result of which could be an autoimmune disease such as diabetes mellitus type 1 or multiple sclerosis.

The only way to protect against these afflictions is to destroy all immune factors that turn against the body’s own tissue – in other words: immune tolerance.

A team working with LMU researcher Dr. David Vöhringer has now investigated exactly what role dendritic cells play in this process. There has long been suspicion that these cells, which are important for the body’s defenses, are also essential for the establishment and maintenance of immune tolerance.

“We investigated mice that lacked this cell type from birth,” reports Vöhringer. “It turned out that immune cells that attack the body’s own tissue survive in these animals, and thereby trigger an autoimmune response. It follows that dendritic cells play a major part in protecting against autoimmune disease.”

T cells are a type of white blood cell that are key actors in the body's immune defenses. Each T cell has a receptor on its surface for recognizing just one single antigen. Antigens are molecular structures, mostly fragments of proteins. T cells do not dock onto free antigens, however: they rely on other cells which can present antigens to them. It is the dendritic cells that are primarily responsible for this job. They present the T cells with various antigens, and if an antigen matches a receptor, then that T cell will trigger an immune response from the body.

This is how the body defends itself against pathogens and other intruders. But behind this tactic lies an element of danger to the organism: what happens if the antigen is not foreign, but originates from the body’s own tissue instead? A wrongly induced immune response can lead to a severe autoimmune disease that, if left untreated, could lead to destruction of organs or even death. So-called autoreactive T cells, which recognize the body’s own structures, must be eradicated or pacified to avoid that they can cause harm. A T cell screening process therefore takes place in the thymus, the bilobular organ in the upper thorax, to distinguish the good from the bad of these dangerous lone mavericks. Each individual T cell is tested, and the autoreactive ones destroyed.

The remaining T cells are checked a second time in the peripheral lymphatic organs of the body. This constant quality control goes on mostly in the lymph nodes and the spleen. As has been known for a while now, dendritic cells can induce peripheral tolerance although it remained unclear whether they are essential for this process. Dendritic cells migrate continuously out of tissues and organs into the lymph nodes, bringing tissue material with them and present it to T cells. Any T cell that reacts to the body’s own proteins is then deactivated or killed off.

Most recent findings have shown that dendritic cells are essential to generate and maintain immunological tolerance. “Our work on mice has proven that without dendritic cells, even the first, central screening of autoreactive T cells in the thymus runs only at reduced efficiency,” reports Vöhringer. “In these animals, the thymus releases T cells that react to the body’s own material. These are then activated in the peripheral organs – and trigger autoimmunity.”

In light of the crucial role these cells play, it is a logical question as to how autoimmunity can be triggered at all without dendritic cells. After all, it is the dendritic cells that undertake certain critical tasks during an immune response. “Among other things, they are specialized in presenting antigens to T cells, which is what makes an immune response at all possible in the first place,” says Vöhringer. “So we are left with the question as to what type of cell activates the autoreactive T cells if the supposedly most important antigen-presenting cells – the dendritic cells – are missing. We already have a few candidates for this, and are studying their function more closely now.” (suwe)

Publication:
“Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity”,
Caspar Ohnmacht, Andrea Pullner, Susan B.S. King, Ingo Drexler, Stefanie Meier, Thomas Brocker, and David Voehringer,
Journal of Experimental Medicine, 16 March 2009
DOI: 10.1084/jem.20082394
Contact:
Dr. David Vöhringer
Institute for Immunology of LMU Munich
Tel.: ++49 (0) 89 / 2180 – 75646
Fax: ++49 (0) 89 / 2180 - 9975646
E-mail: david.voehringer@med.uni-muenchen.de

Luise Dirscherl | EurekAlert!
Further information:
http://immuno.web.med.uni-muenchen.de
http://www.lmu.de

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>