Anti-viral rapid reaction force

December 27, 2016 by Karin Hollricher
Anti-viral rapid reaction force
The textbooks tell us that killer cells have to match their antigens exactly if they're to fulfil their task. Researchers in Bern, however, have also found that loosely attached white blood corpuscles also play a role in the immune system. Credit: Swiss National Science Foundation

After host cells have been attacked by a virus, they present parts of the pathogen on their surface. Thanks to these virus components, the killer cells patrolling in the body (CD8+ T lymphocytes) can recognise the infected cells and kill them, thereby preventing the virus from spreading further.

Until now, the orthodoxy was that were the primary component in the body's immune response. These so-called high-affinity killer cells attach themselves firmly to the antigens presented on the surface of the host cells. Then, one or two weeks after infection, we only find high-affinity killer cells in the blood. The low-affinity killer cells that carry fewer matching receptors have always been believed to be rejects from the production of these white blood corpuscles.

However, Jens Stein and his colleagues at the University of Bern have for the past four years been busy investigating the behaviour of the low-affinity killer cells, and they now doubt the current wisdom. They have found indications that these less precise cells also make a contribution to the immune response. After a brief activation phase, they launch an initial, quick attack on an intruder while high-affinity killer cells are proliferating in massive numbers in order to attack the pathogen in a mighty, second wave. "This is still just a hypothesis, but our experiments suggest that it is the case", says Stein.

The researchers injected killer cells into test mice that had been provided with a receptor against a specific antigen such as might come from a virus. In addition, the animals were given that present assorted antigens to the killer cells, activating them and thus prompting an . Using a special two-photon microscope, the researchers followed what happened in the lymph nodes of the anaesthetised mice. Stein and his colleagues developed this method specifically for this type of experiment, and it enabled them to determine precisely where and when the cells interacted with each other.

Quicker, but less thorough

"To our surprise, all the killer cells reacted with the dendritic cells – regardless of which peptide the dendritic cells presented", says Stein. "So all the T cells prepare themselves for their role as killer cells. They initiated the differentiation and began to proliferate".

However, there was a major difference among these encounters: if there was a strong link between dendritic cells and the killer cells, the molecular dialogue lasted longer. If dendritic cells had the lesser matching version of the molecule on their surface, and if the link was looser, then the T cells were activated and were prompted to begin proliferating. But these T cells abandoned their contact with the dendritic cells very quickly and then migrated to the exits of the lymph nodes in order to go virus-hunting. At the same time, these low-affinity cells acquired their killer function more quickly than the cells whose receptors were highly suited to the peptide on offer. The high-affinity T cells, meanwhile, did not remain very long in contact with the dendritic cells and proliferated; their were also activated and made to proliferate.

"We interpret this and other data as meaning that low-affinity cells are a small, rapid-response group", says Stein. "High-affinity killer cells come into play later, but are all the more numerous, presumably more accurate and quite possibly more effective". At least, this was the case in the mice. There has as yet been no verification of this in human tests.

Explore further: Researchers find how Ebola disables the immune system

More information: Aleksandra J. Ozga et al. pMHC affinity controls duration of CD8T cell–DC interactions and imprints timing of effector differentiation versus expansion, The Journal of Experimental Medicine (2016). DOI: 10.1084/jem.20160206

Related Stories

Researchers find how Ebola disables the immune system

December 6, 2016
A new study at The University of Texas Medical Branch in Galveston sheds light on how Ebola so effectively disables the human immune system.

New anti-cancer strategy mobilizes both innate and adaptive immune response

July 1, 2016
Though a variety of immunotherapy-based strategies are being used against cancer, they are often hindered by the inability of the immune response to enter the immunosuppressive tumor microenvironment and to effectively mount ...

Study may show the way to more effective vaccines

August 21, 2015
Scientists at the University of Bonn, together with colleagues from the USA and Japan, have shed light on an important immune mechanism. Their work shows how the body provides the important killer cells with a helper in the ...

Vision of immune cells rallying to destroy invaders captured for the first time (w/ Video)

August 18, 2015
This information will help researchers design better vaccines that recruit the very effective killer cells to join the fight.

Harnessing the 'Natural Killer' within us to fight cancer

May 23, 2016
Our bodies are constantly and successfully fighting off the development of cells that lead to tumours - but when there is disruption to this process cancer is free to develop.

Recommended for you

Genetic immune deficiency could hold key to severe childhood infections

July 18, 2017
A gene mutation making young children extremely vulnerable to common viruses may represent a new type of immunodeficiency, according to a University of Queensland researcher.

What are the best ways to diagnose and manage asthma?

July 18, 2017
What are the best ways to diagnose and manage asthma in adults? This can be tricky because asthma can stem from several causes and treatment often depends on what is triggering the asthma.

Large multi-ethnic study identifies many new genetic markers for lupus

July 17, 2017
Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus.

Study finds molecular explanation for struggles of obese asthmatics

July 17, 2017
A large, bouquet-shaped molecule called surfactant protein A, or SP-A, may explain why obese asthma patients have harder-to-treat symptoms than their lean and overweight counterparts, according to a new study led by scientists ...

Team identifies potential cause for lupus

July 14, 2017
Leading rheumatologist and Feinstein Institute for Medical Research Professor Betty Diamond, MD, may have identified a protein as a cause for the adverse reaction of the immune system in patients suffering from lupus. A better ...

Immunosuppression underlies resistance to anti-angiogenic therapy

July 14, 2017
A Massachusetts General Hospital (MGH) research team has identified a novel mechanism behind resistance to angiogenesis inhibitors - drugs that fight cancer by suppressing the formation of new blood vessels. In their report ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.