Immune system B cells play a crucial role in the defence of pathogens; when they detect such an intruder, they produce antibodies that help to combat the enemy. They concurrently and continuously improve these molecules to more precisely recognize the pathogens.
Theory of colours for immunologists – sophisticatedly-designed microscopy technologies offer scientists insights into the evolution of antibody producers in the lymph node. Antibodies and immune cells are marked with different colours.
University of Birmingham/Toellner
A team of scientists with participation of the Helmholtz Centre for Infection Research (HZI) has discovered that during this process the cells are able to advance their own evolution themselves by increasing the selection pressure through previously-produced antibodies. The results are also significant for the development of new vaccination strategies.
The principle of evolution signifies the competition for limited resources and a reaction to changeable environmental conditions. This selection pressure is virtually produced by the B cells on their own; they subject themselves to an optimization cycle in the lymph node, a process which only a few of them survive, i.e. particular cells that are able to produce “better” antibody molecules as compared to those that already exist within the body. The quality of these antibodies is tested in the lymph nodes, and only those cells that are able to prove themselves here receive signals from other immune cells that assure their survival.
Every B cell carries a specific defence molecule on its surface. It recognizes certain structures of pathogens – so-called antigens – similar to the way a key fits into one specific lock. This molecule is furthermore produced in a certain form that does not remain on the cell surface; rather, it travels with blood and lymph throughout the body. If the antibody encounters an antigen, it either binds it to neutralise it, or it sends out an alarm to other players within the immune system.
At the beginning of an infection there are, figuratively speaking, several keys that do not yet fit properly. This changes in the course of a process that immunologists refer to as “somatic hypermutation”: B cells mutate those gene segments that determine the design of both the surface molecule and the soluble variation – thus influencing how strongly the antibodies attach themselves to the pathogens. Those cells, in which the optimal fit of the key increases, survive and multiply. They then produce the desired molecule in large quantities and thus help us to get healthy again.
But how do the immune cells know that they are on the right way with this arbitrary mutation process, i.e. that the key will fit better later on? Scientists from England, Germany and Switzerland have now been able to answer this question jointly in a collaborative project between Dr. Kai-Michael Toellner, University of Birmingham, and Prof. Michael Meyer-Hermann, Head of the Department Systems Immunology. They published their findings in the renowned Journal of Experimental Medicine. Meyer-Hermann makes use of mathematical models to understand diseases more thoroughly and quicker. “Systems immunology enables us to simulate, in a short amount of time, numerous experimental conditions,” he describes his area of expertise. With the aid of such mathematical simulations followed by experimental examinations, the researchers discovered that the antibody producers advance their own evolution, which represents without a doubt an alignment with the enormous selection pressure that we are subject to due to a constant threat from pathogens.
The stage for this process is the so-called germinal centres within the lymph nodes. Here, the maturing B cells encounter the antigens. The researchers’ results suggest that completed antibodies from all germinal centres re-appear at the sites of antibody production and bind there to pathogen fragments as well. They represent competition thereby for those cells that are still in the process of refining the optimal fit of their surface molecules. Once the immune cells with their “surface-key” are able to bind to the “antigen locks” more readily than the finished antibodies, they receive survival signals and their key-form asserts itself.
“This is the ‘survival of the fittest’ as previously described by Charles Darwin on a molecular level,” compares Meyer-Hermann. Studies with mice were able to be confirmed in computer simulations only under the assumption that the B cells compete with their own products – namely the antibodies – for the right to bind to antigens.
This astounding mechanism could, in the future, improve conventional vaccination methods. “It is plausible that patients could be administered, in addition to a vaccine, sufficiently-strong-binding antibodies,” explains Meyer-Hermann. “Our models constructed in the computer suggest that this method accelerates the process of identifying optimal antibodies.” The scientists suspect that the addition of antibodies manipulates the reaction to vaccination, since the newly-generated antibodies are now in competition with the externally-introduced molecules. The conditions for selection are thus intensified and the B cells react by producing optimal antibodies earlier on. The result is that vaccinations could take effect quicker.Original publication:
Dr. Birgit Manno | Helmholtz-Zentrum
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction