Signal transduction pathways in the immune response

The immune system is essential for defense against infections and cancer. However, an excessive immune response can lead to serious acute inflammatory disease (e.g. sepsis), autoimmunity or chronic inflammation. Measuring the functional activity of immune cells in their response to, for example, infection is difficult. Nevertheless, this is needed to determine the role of specific immune cell types in diseases and develop new therapies.
A limited number of Signal Transduction Pathways (STPs) determine the cellular function of cells, including immune cells. Simultaneous Transcriptome-based Activity Profiling of Signal Transduction Pathways (STAP-STP) technology enables measurement of activity of these STPs.
In this thesis, STAP-STP technology was applied to determine the role of abnormal STP activity in immune cells of patients with viral infections or bacterial sepsis, and to validate experimental models for sepsis. In addition, we identified the STP-based mechanism behind resistance against TNF-alpha inhibitors in patients with inflammatory bowel disease. Results can be used for diagnostic and therapy development purposes.