Max Löhning: A strong eye on the immune system memory
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- Prof. Max Löhning, Experimental Immunology at the Charité, Berlin, previously at the University Hospital of Zurich. Quelle: private
07.02.2008 -
Max Löhning pursues his goals calmly and in a well thought-out manner. Piece by piece, Löhning is bringing clarity to the bewildering world of the body's immune system. In doing so, the immunologist is delving deep into the cells on a molecular level. Only then will the 38-year-old - currently a professor at the Charité-Universitätsmedizin – be able to answer the burning questions that drive him forward. The most important of these is: How does the human immune system actually remember the pathogens that it has previously encountered? And how can this knowledge be therapeutically applied?
For decades, doctors have exploited immunological memory to prevent disease – each vaccination prepares the body for specific foreign aggressors, and in the worst cases makes sure that the body is equipped with the appropriate weapons. Sometimes, however, the memory can’t be protectively trained, for example in the case of chronic viral infections such as HIV. Or the immune system reaction is over-the-top - itself a danger to the body. For example, during rheumatic diseases, a misguided memory system can sometimes produce too many inflammation-provoking messenger substances that attack the body's own tissues.
Chronic inflammation processes still misunderstood
Immunologists such as Löhning want to better understand the mechanisms of immunologic memory, with the long-term aim of developing new therapies. “Most of all, we still don’t have a good understanding of chronic inflammation processes“, he says. Using the example of viral infections, Löhning is focusing on a number of specific cells that form after coming into contact with pathogens: the memory cells. Targeted changes in the genome of these cells provide the basis for certain immune responses to be stored for later emergency use. "Interestingly, memory cells can only learn to produce certain messenger substances and not others, depending on the environment in which they are activated," says Löhning. "This quirk means that they can be programmed to encourage or inhibit inflammatory processes."
Andreas Radbruch: The immunologist and Director of the German Arthritis Research Centre (DRFZ) in Berlin is dedicated illuminating the body's immune system. He is working on collaborative projects with Löhning. |
Over a series of experiments, the native of Koblenz has been able to identify a range of signals that guide the production of specific messenger substances in the memory cells. It is hoped that with a more precise knowledge of these tiny molecules, technically referred to as cytokines, it will eventually be possible to program the cells to order. This stage of reprogramming the misguided memory cells is proving to be a particular challenge. So far, Löhning has only succeeded in diminishing the release of certain messenger substances - the key to a complete switching on or off, or some other reswitching, is yet to be found.
Nevertheless, the ambitious researchers have recently succeeded in taking another crucial step forward. "We wanted to know whether the immune cells that have already produced immune substances (effector cytokines) can develop memory cells," explains Löhning. "To date, it has been assumed that these cells die off very quickly." However, for this reason, a therapeutic application of these cells is problematic. As Löhning and colleagues have reported in the specialised magazine Journal of Experimental Medicine (2008, 21 January), it appears that memory cells with a long lifespan can indeed be extracted from immune cells which have discharged effector cytokines. Firstly, the researchers succeeded in isolating these cells, transferring them into new organisms, and, once there, observing their behaviour over time. The surprising result: Many lived for many years after the initial infection, and had actually transformed into memory cells. These had the best response to a very specific virus. "This meant we had come a big step closer to creating customised memory T cells," says Löhning. This is important for people with protracted infectious diseases, who must depend on immune cell therapies. Immune cells will be taken from these patients, trained with an immune response, and then reinstated in the body. "We now know that these treatments can also be effective in the long run, because memory cells are able to develop," says Löhning.
Similarly, he believes that the procedure could be important in the development of alternative vaccinations in cases where straightforward immunisation with antibodies has failed. At some point, this could well include the AIDS-causing HIV. This deadly virus constantly changes its surface structure, and is therefore difficult to recognise for antibodies. "Customised memory T cells could therefore be in a position to effectively combat the virus, despite its camouflage", hopes Löhning. "But it will be some years of work before we get that far."
Experiments taking months
Löhning has become accustomed to the fact that immunological research often only proceeds in tiny steps – a single experiment can last many months. Whereas others might find this nerve-racking, Löhning sees it as a challenge. Meticulous to the end, focusing intensively on a single question – this is his world. Furthermore, the new science of molecular immunology still offers plenty of room for new discoveries. Thereby, collaboration with other disciplines is a must. Thus, Löhning is working jointly with neurologists, mathematicians and biophysicists on theoretical models of memory mechanisms in the immune and nervous systems in order to probe deeply into and shed light on their modes of functioning.
Löhning’s interest in medicine was awakened very early – both parents are practicing doctors. However, the underlying mechanisms held more appeal than the direct treatment of patients. "I would often wish to better understand the causes of the disease in order to intervene more effectively," he admits. For this reason, whilst still at school, Löhning decided to study biology, through which he could tackle medical issues with molecular-biological means.
From Zurich to Berlin
This was a good decision, which has eventually led to a number of prizes and scholarships for the researcher. In early 2006, Löhning took the chair at the Volkswagen Foundation-supported Professorship for Experimental Immunology at the Charité-Universitätsmedizin in Berlin, necessitating his move from the University Hospital of Zürich to the German capital. Of his new employers, he has only praise: "In Berlin, clinical application comes together with the most fundamental basic research - it's an excellent environment for my work."
As in Zürich, Löhning has much to gain from his new location, and not only professionally. As an aficionado of antique furniture and glass curiosities, he is a frequently delighted visitor to Berlin’s many flea markets. This world of haggling and rummaging is a soothing counterpoint to laboratory work, says the researcher. Whether for old bottles, lamps, or a silver spoon, his enthusiasm is great. "I usually end up buying nothing," he says, "it is enough to chat to the people, to get a sense of the city, and take in the atmosphere." Modern dance and spoken-word also deeply interest the scientist. Spanning Sasha Waltz and Sarah Kane, Löhning’s artistic loves paint a very different picture to that of the dedicated researcher. Here, outside the laboratory, he likes to be surprised.
