IMMUNITY UNDER PRESSURE: determining immune and inflammatory responses to the environments in diving

Environmental factors shape the function of our immune system. But while flexible immunity may benefit adaptation and protect tissue and organ homeostasis, variations caused by this flexibility is also likely to affect disease risks. Consequently, there may be essential biological trade-offs in the function of the immune system, where flexibility to promote specific environmental protection comes at the prize of enhanced vulnerability to unrelated factors. Most of our understanding of how the immune system works comes from studies of defense against pathogens, but immune system development and function is also affected by common non-pathological factors. The blood gases are interesting in this regard. Oxygen in particular is a potent driver of immunity: both low (hypoxia) and high (hyperoxia) oxygen levels trigger inflammatory reactions via excess formation of reactive oxygen species. Conversely, high carbon dioxide (hypercapnia) and has been used therapeutically to inhibit inflammation during lung operations. Nitrogen is biologically inert, but ambient pressure reduction (decompression) causes it to form intravascular gas bubbles that are believed to promote inflammation. All of these factors can be conveniently studied in divers. Divers experience environmental changes ranging from brief moderate hypoxia and hypercapnia to weeks spent doing demanding work under extreme pressures and with elevated partial pressures of oxygen. This presentation covers a series of genomic studies of immune and inflammatory responses in blood from healthy divers under very different diving conditions. As blood is a highly heterogeneous tissue, we use a signal deconvolution approach to predict cellular composition in a sample on basis of established cell type-specific gene expression. Bioinformatic tools are used to interpret the biological pathways involved. Understanding how immune changes develop in response to common environmental factors may aid our understanding of the aetiology and progression of immune-related diseases. It may also point to strategies for strengthening the immune system. Results from studies of free-diving in particular may be relevant for diseases in which fluctuating oxygen levels cause intermittent hypoxia, such as obstructive lung disease and sleep apnea.