AbstractsBiology & Animal Science

Infectious diseases constitute a major global health problem. The presenting clinical picture results from a mixture of direct toxic actions by the microbiological agent and of the immune response mounted by the host. There is often a rapid onset, which may constitute a diagnostic and therapeutic challenge, whereas in other cases an extensive investigation over a long time period can fail to identify a causal microbial agent. The aim with this thesis was to study the cellular immune response with phenotypical assays, in patients with severe infections with focus on sepsis. We assessed if our findings could serve as biomarkers and provide valuable diagnostic and possible also therapeutic information. In the first part (paper I) we examined surface markers on white blood cells from patients with severe infections. In some instances our analysis could differentiate between infections of bacterial and viral origin. In the second part (paper II-IV) we examined the incidence and nature of the immune alterations found in patients with sepsis and septic shock. We identified a protein (Wnt5a) that inhibited differentiation of monocytes to monocyte-derived myeloid dendritic cells (Mo-mDC), which may play a role in the DC depletion often seen in sepsis. Also, as indicated by cell surface phenotype, a large inter-individual variation of immune activation and immunosuppression was detected in patients with sepsis, with a dominance of immunosuppression in patients with septic shock. Finally, different types of immature myeloid immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) were found in patients with sepsis; Mo-MDSCs were preferentially expanded in patients with gram-negative sepsis, whereas granulocytic MDSCs (PMN-MDSCs) accumulated in patients with gram-positive sepsis. We conclude that the immune response during severe infections shows large inter-individual variations and biomarker guided therapy could be useful in individualised treatment. Det är en utmaning att behandla patienter med allvarliga infektioner eftersom immunförsvaret reagerar olika på olika mikroorganismer. Immunförsvarets reaktion har i sin tur en stor betydelse för symtombild, kliniska fynd och prognos. Vid blodförgiftning (sepsis) förändras dessutom sannolikt immunsvaret under det kliniska förloppet. Man tror att det inledningsvis vid sepsis sker en aktivering av det proinflammatoriska immunförsvaret. I de fall där aktiveringen blir för kraftig skapas en förödande antiinflammatorisk negativ återkoppling med risk för sekundära infektioner och död. Den här avhandlingens mål var att undersöka om en utökad analys av vita blodkroppar kan ge information av värde för diagnostik och behandling av patienter med allvarliga infektioner med fokus på sepsis. I den första studien granskade vi ytmarkörer på vita blodkroppar från patienter med antingen sepsis, borrelia, tuberkulos, körtelfeber, influensa eller bindvävssjukdom. Vi kunde där se att vissa markörer framträdde vid en halvakut bakteriell…