What happens when the immune system engages in battles with bacteria, fungi, viruses, or foreign substances? Which signalling pathways and signalling components are switched on and how do signal molecules “speak” with one another to guide the immune response? The biochemical reactions that are initiated when an organism detects “danger signals” or “foreign entities” are very complex. In this situation, cells of the immune system become activated, they start to migrate, reorganize their cytoskeleton, and produce various substances with the overall goal of protecting the organism from illness and injury. With combined efforts, scientists of the Institute for Molecular and Clinical Immunology at the Medical Faculty of the Otto-von-Guericke University, Magdeburg and the Department of Immune Control at the Helmholtz Centre for Infectious Disease (HZI) are examining which cells of the immune system interact and, importantly, how they interact with one another.
When cells of the immune system discover aggressors – bacteria, fungi or viruses – they become activated and initiate a plethora of signal cascades with the goal of neutralizing and, of possible, eliminating the invadors. The molecular events that are initiated after encounter of “foreign and/or danger” lead to dramatic functional and structural alterations within the cells. For example, cells begin to change their metabolism; they start to synthesise new proteins, growth factors, and chemical messengers, through which they communicate with one another, as well as with other cellular systems within the organism. In addition, they re-organize their skeleton, express new molecules on the cell surface, and begin to migrate to the sites from where the danger signals originated.
Understanding of the immune response
For a comprehensive understanding of the immune response, it is mandatory that the individual signal pathways, which are initiated by receptors on the surface of the immune cells after encounter of dangerous particles, are understood: How are the signal pathways within the cells interconnected and how do they guide the immune responses? For example: How do signal pathways, which are generated during viral infections by receptors for Interferons, influence other signal transduction pathways, in particular those that are regulated by the T-cell receptor? What consequences result from the crosstalk in terms of the anti-viral defence or global immunity?
Variety of tools
To answer these questions, the scientists of the HZI and the OVGU apply a variety of different tools. In addition to classical biochemical, molecular-biological, and cell-biological approaches, methods from systems biology and mathematical modeling play a central part in the research. Mathematical models are created in collaboration with physicists, engineers, and mathematicians and allow qualitative and quantitative descriptions of the complex molecular events that occur during the initial phase of immune cell activation, including the feedback mechanisms. Furthermore they provide information as to how the programmed cell death (apoptosis) that normally occurs at the end of the immune response, in order to eliminate altered, infected, or aged cells, is regulated on the molecular level.
The immunological research of the HZI and OVGU scientists at the interphase of medicine, basic biomedical research, and mathematics aims at providing novel medical applications. For example, one goal of the ongoing research is to predict potential side-effects of novel immuno-therapeutic drugs even before they are tested in clinical trials.