Euroimmun/Lund University Meeting Heiko Herwald Lund University Sweden Lübeck July 7, 2016

Sepsis is a complex syndrome Infecting pathogen Site of infection Disease spectrum Streptococcus pyogenes Staphylococcus aureus Escherichia coli Salmonella spp. Inf path - >800 diff species? Site of infection – diiferent outcome

“The microorganisms. turn out. to be rather more like bystanders “The microorganisms ... turn out ... to be rather more like bystanders. It is our response to their presence that makes the disease. Our arsenals for fighting off bacteria are so powerful ... that we are more in danger from them than the invaders.” Lewis Thomas (1972)

Host parasite interactions Streptococcus pyogenes Staphylococcus aureus Escherichia coli Salmonella spp.

Pathogenesis of Severe Sepsis Infection Microbial Products (exotoxin/endotoxin) Cellular Responses Platelet Activation Coagulation Activation Kinins Complement Cytokines TNF-, IL-1, IL-6 Oxidases Coagulopathy/ Disseminated Intravascular Coagulation Vascular/Organ System Injury Endothelial damage Endothelial damage Multi-Organ Failure Death

cell culture in vivo patient material sample processing RT-PCR mass spectroscopy sample processing BiaCore Bio-Plex IVIS electron microscopy microscopy

QuantStudio™ 7 Flex Real-Time PCR System RT-PCR Real-Time PCR System broad range of real-time PCR-based applications through multiplexing capabilities interchangeable block formats. With a simplified exceptional reproducibility with minimal well-to-well and instrument-to-instrument variation.

SPR biosensor BiaCore T200 label-free system for detailed studies of biomolecular interactions measurements in real-time analyze interactants ranging from ions to viruses small concentrations needed

Bio-Plex 200 System Bio-Plex suspension array system automates the reading of 96-well plates reliable multiplex assay solution that permits analysis of up to 100 biomolecules in a single sample yielding up to 9,600 data points in about 35 min

In Vivo Imaging Instruments PerkinElmer IVIS non-invasive real-time measurements in living animals 2D and 3D quantitative bioluminescence and fluorescence with fast and low dose CT imaging the system is capable of both luminescence and fluorescence modes of imaging

Electron microscopy electron microscopy high resolution morphological studies structural studies

Microscopy microscopy tissue morphology histology immuno-histology co-localization

cell culture in vivo patient material sample processing RT-PCR mass spectroscopy sample processing BiaCore Bio-Plex IVIS electron microscopy microscopy