Polyacryl starch microparticles have been developed as a new mucosal vaccine adjuvant intended for use in oral vaccination. The main objectives of this thesis were to evaluate the efficacy of these polyacryl starch microparticles and to study their uptake through mucosal tissues. Secreted or surface components of Salmonella enterica serovar Enteritidis were used in free form or were conjugated to or mixed with the microparticles in vaccination studies in mice in order to find components suitable for use in a future combination vaccine against enteric bacteria such as enterotoxigenic Escherichia coli. The immune response elicited using secreted proteins from S. enterica serovar Enteritidis was shown to be mainly directed against flagella-related antigens and partly by LPS. Flagellin was purified and used in C3H/HeJ mice that do not respond to LPS. Strong immune responses were observed even when the flagellin was given orally alone. Recombinant Salmonella atypical fimbriae (SafB/D) complexes, a conserved structure within Salmonella species, were also studied and shown to be immunogenic after administration both subcutaneously and nasally, but not orally. Oral challenge using live bacteria, showed that mice orally immunised with the secreted antigens, resulted in a lower degree of infection than that seen in non-vaccinated mice. Similarly, mice that had been immunised with purified free flagellin had a lower degree of infection than untreated mice. However, with mice, immunised with SafB/D complexes plus rCTB, only the subcutaneous route resulted in a lower degree of infection than seen in untreated mice. The polyacryl starch microparticles were effective as an adjuvant with secreted proteins, but did not potentiate the immune response in the study using flagellin. Confocal laser-scanning and transmission electron microscopy demonstrated that the microparticles were taken up by pig respiratory nasal mucosa mounted in horizontal Ussing chambers. Although anticytokeratin 18 stained mucus-producing cells, M cells were not seen in the studied area. Changing the route of administration of the microparticles conjugated with serum albumin can cause differences in the IgG-subclass ratios. The mucosal immune response measured as specific s-IgA levels, was induced by oral but not parenteral immunisation.

Helicobacter pylori (H. pylori) is a human-specific gastric pathogen which is responsible for a spectrum of diseases ranging from superficial gastritis to gastric and duodenal ulceration, and which is also highly associated with gastric cancer. The pathogenesis of severe gastric disorders caused by H. pylori is multifactorial and involves complex interactions between the microbe and the gastric mucosa. H. pylori expresses several adhesion proteins. These molecules have important roles in the establishment of persistent infection and chronic inflammation, which cause tissue damage. The aim of this thesis was to study the attachment of this bacterium to human gastric epithelium, mediated by blood group antigens in both health and disease. One of the bestcharacterized H. pylori adhesins is the histo-blood group antigen binding adhesin (BabA), which binds specifically to the Lewis b antigen (Leb) in the gastric mucosa. A protective mucus layer lines the stomach. The mucosal glycosylation patterns (GPs) vary between different cell lineages, different locations along the gastrointestinal (GI) tract and different developmental stages. In addition, GPs undergo changes during malignant transformation. MUC5AC is a mucin molecule produced by the surface epithelium. Three distinctly different types of human gastrointestinal tissue were studied by bacterial adherence analysis in situ. MUC5AC is the most important carrier of Leb and the new results demonstrate that it forms major receptors for H. pylori adherence. By analysing an H. pylori babA-deletion mutant, a novel adhesin-receptor binding mode was found. Surprisingly, the mutant bound efficiently to both human gastric mucosa and to gastric mucosa of Leb transgenic mice. The sialylated and fucosylated blood group antigen, sialyl-dimeric-Lewis x (sdiLex), was structurally identified as the new receptor. A positive correlation was found between adherence of H. pylori to sialyl-Lewis x (sLex) and elevated levels of inflammation response in the human gastric mucosa. These results were supported by detailed analysis of sialylated and fucosylated blood group antigen glycosylation patterns and, in addition, in situ bacterial adherence to gastric mucosa of experimentally challenged Rhesus monkey. The cognate sialic acid-binding adhesin (SabA) was purified by the retagging technique, and the corresponding sabA-gene was identified. H. pylori lipopolysaccharide (LPS) contains various Lewis blood group antigens such as Lewis x (Lex) and Lewis y (Ley). Additional bacterial adherence modes, which are independent of the BabA and/or SabA adhesins, could possibly be mediated by Lex interactions. Adherence of a clinical isolate and its corresponding Lex mutant to human gastric mucosa with various gastric pathologies was studied in situ. The results suggest that H. pylori LPS plays a distinct but minor role in promotion of bacterial adhesion. Taken together, the results suggest mechanisms for continuous selection of H. pylori strains, involving capacity to adapt to changes in the local environment such as shifts in cell differentiation and associated glycosylation patterns. Adherence of H. pylori is dependent on both the BabA and the SabA adhesin. Multi-step dependent attachment mechanisms may direct the microbes to distinct ecological niches during persistent infections, driving the chronic inflammation processes further toward the development of peptic ulcer disease and/or malignant transformation. Key words: H. pylori, BabA, adhesin, Lewis b, MUC5AC, sialyl-dimeric-Lewis x, chronic inflammation, SabA, Lewis x, LPS.

IL-12 family cytokines IL-23 and IL-27 play an important role linking innate and adaptive immunity, and regulating T-cell responses. The production of IL-12, a structurally similar cytokine, is decreased in chronic HIV infection; therefore IL-23 and IL-27 may also be influenced by HIV infection. I hypothesized that HIV inhibits LPS-induced IL-23 and IL-27 production in human MDMs by suppressing the activation of signalling pathways regulating their expression. In vitro HIV-infection of MDMs did not have any effect on basal secretion of IL-23 or IL-27; however, HIV inhibited LPS-induced production of IL-12/23 p40 and IL-23 p19, and IL-27 EBI3 and IL-27 p28 mRNA expression, and IL-23, IL-12/23 p40 and IL-27 secretion. In order to evaluate the molecular mechanisms by which HIV inhibits IL-23 and IL-27 in LPS-stimulated MDMs, the signalling pathways regulating their expression were evaluated. The PI3K, p38 MAPK, and JNK MAPK pathways were found to positively regulate LPS-induced IL-27 secretion. Interestingly, in vitro HIV infection inhibited LPS-induced p38 and JNK MAPK activation in MDMs. In summary, I have shown that HIV inhibits IL-23 and IL-27 production in LPS-stimulated MDMs and that HIV may inhibit LPS-induced IL-27 production through the inhibition of p38 and JNK MAPK activation. It is currently unknown whether PKCs regulate LPS-induced IL-23 or IL-27 in human monocytes/macrophages. I demonstrated that classical PKCs differentially regulate LPS-induced IL-23 and IL-27 secretion within THP-1 cells, primary monocytes, and MDMs. Classical PKCs were found to positively regulate LPS-induced IL-12/23 p40 and IL-27 p28 mRNA expression and IL-12/23 p40, IL-23, and IL-27 secretion in primary human monocytes. Similarly, the classical PKCs were found to positively regulate IL-27 p28 mRNA expression and IL-27 secretion in THP-1 cells. However, classical PKCs did not regulate LPS-induced IL-27 production in MDMs, or LPS-induced IL-23 production in THP-1 cells. Overall, this demonstrates that classical PKCs differentially regulate LPS-induced IL-23 and IL-27 production in different myeloid cells.

In recent years projects have increasingly used Last Planner System (LPS) in building construction. However project managers still struggle with figuring out how the LPS could be applied on their specific projects. One main reason for this struggle is that explicit instructions for systematically applying LPS are not available. This thesis offers practitioners and researchers an account of LPS implementation challenges and an indication of how LPS can be applied. The thesis qualitatively aggregates the results of 26 test case projects of LPS applications to show researchers and practitioners reasons why LPS was applied, what benefits were realized and what challenges were found during the implementation. Senior and mid-level managers in AEC industry were surveyed to assess the implementation challenges that they encountered. The main findings of this analysis are; (1) that practitioners have used LPS for the purpose of making plans more reliable, (2) get smooth work flow (3) improve productivity. The survey findings imply that improvements in LPS implementation strategies can be made which will facilitate LPS adoption by the industry. The findings of this thesis suggest that further research on the integration of LPS into work and business processes of project teams is needed to further the widespread use of LPS throughout the building industry.

Antibiotic resistance is an ongoing global medical crisis and we are in great need of new antibacterial agents to combat rapidly emerging resistant pathogens. Tigecycline is one of few drugs that have been introduced into medicine during the last two decades. It is a broad-spectrum third generation tetracycline that is active against multidrug-resistant bacteria that cause complicated infections. In this thesis I examined the development of tigecycline resistance in Escherichia coli and associated in vitro and in vivo fitness effects. Selections of spontaneous E. coli mutants revealed relatively high accumulation rates of changes in the multidrug efflux system AcrAB-TolC regulation network and in heptose biosynthesis and transport pathways important for lipopolysaccharide (LPS) synthesis. Both groups of mutations led to reduced susceptibility to tigecycline and slower growth compared to the wild-type bacteria. Additional in vitro fitness assays and in vivo competitions showed that LPS mutants were less fit than efflux mutants, providing a possible explanation for why up-regulation of multidrug efflux pumps is the main tigecycline resistance mechanism reported in clinical isolates. Tigecycline was designed to evade the two most common tetracycline resistance mechanisms conferred by Tet proteins, efflux and ribosomal protection. However, tigecycline is a substrate for the tetracycline modifying enzyme Tet(X). Screening of Tet protein mutant libraries showed that it is possible to select Tet mutants with minimal inhibitory concentrations of tigecycline that reach clinically relevant levels. Mutations in Tet proteins that permitted a better protection from tigecycline frequently exhibited reduced activity against earlier generations of tetracyclines, except for the Tet(X) enzyme mutants, which were better at inactivating all tested tetracyclines. This is particularly worrisome because different variants of Tet(X) have recently spread to multidrug-resistant pathogens through horizontal gene transfer. Therefore, Tet(X) mutants with improved activity threaten the medical future of tetracyclines. Multidrug resistance is easily disseminated through horizontally spreading conjugative plasmids. pUUH239.2 is an example of a successful conjugative plasmid that caused the first clonal outbreak of extended spectrum β-lactamase-producing Klebsiella pneumoniae in Scandinavia. This plasmid was formed after rearrangements between two different plasmid backbones and it carries resistance genes to multiple antibiotic classes, heavy metals, and detergents.

Σα αρνητικά και θετικά κατά Gram βακτήρια E. coli και S. αureus αντίστοιχα αναγνωρίζονται και δεσμεύονται στην επιφάνεια των αιμοκυττάρων της C. capitata. Η πρόσδεση των βακτηρίων ενεργοποιεί τόσο τις β1 ιντεγκρίνες, όσο και σηματοδοτικά μονοπάτια που περιλαμβάνουν τα μόρια μεταγωγής σήματος Ras, Raf, MEK, ERK, FAK, Src, και GRB2. Οι παραπάνω ενεργοποιήσεις, σε συνδυασμό με τη συμμετοχή του κυτταροσκελετού της ακτίνης και της τουμπουλίνης, καταλήγουν στην επαγωγή της έκκρισης μορίων απαραίτητων για την κυτταροφαγία των βακτηρίων που είναι και το τελικό αποτέλεσμα των παραπάνω διαδικασιών. Σα συνθετικά πολυμερή σφαιρίδια, αλλά και πιθανόν και άλλοι αβιοτικοί παράγοντες, παρότι δεν έχουν καμία προηγούμενη εξελικτική σχέση με τα αιμοκύτταρα, ως σύγχρονο προϊόν της ανθρώπινης γνώσης, αναγνωρίζονται και δεσμεύονται στην επιφάνεια των αιμοκυττάρων από άγνωστους μέχρις στιγμής υποδοχείς. Η κυτταροφαγία τους προωθείται μέσω ενεργοποίησης σηματοδοτικών μονοπατιών που περιλαμβάνουν την ενεργοποίηση των μορίων FAK, Src και MAP κινασών καθώς και με τη συμμετοχή του κυτταροσκελετού της ακτίνης και της τουμπουλίνης. Ο LPS αναγνωρίζεται και δεσμεύεται στην επιφάνεια των αιμοκυττάρων, ενεργοποιεί άγνωστους μέχρις στιγμής υποδοχείς και διαμέσου σηματοδοτικών μονοπατιών που περιλαμβάνουν τις Ras, ενεργοποιεί τις MAP κινάσες και το σύστημα της έκκρισης. Αν και ενεργοποιεί και τις τρεις MAP κινάσες, μόνο η ERK και η p38 απαιτούνται τόσο στη διαδικασία της έκκρισης, όσο και στη διαδικασία της ενδοκυττάρωσής του. Η FAK, αν και ενεργοποιείται από τον LPS, δεν εμπλέκεται στην διαδικασία της ενδοκυττάρωσής του. Σα παραπάνω δείχνουν ότι τα αιμοκύτταρα έχουν αναπτύξει διακριτούς μηχανισμούς για την κυτταροφαγία των παθογόνων, των μικρομορίων και των αβιοτικών παραγόντων, γεγονός που δείχνει την ικανότητα εξέλιξης των εντόμων έτσι ώστε να καλύπτουν τις ανάγκες της επιβίωσή τους. / Gram negative and Gram positive bacteria, E. coli and S. αureus respectively, are recognized and they are bound on the C. capitata hemocyte surface. After binding, they activate β1 integrins and intracellular signalling pathways, involving the kinases Ras, Raf, MEK, ERK, FAK, Src, and GRB2. This signal transduction, with the participation of the cytoskeleton of actin and tuboulin filaments, leads to a regulated secretion, that is a prerequisite for phagocytosis. Latex beads and probably other abiotic factors, despite having no previous evolutionary relation to the hemocytes, being a new product of human knowledge, are recognized and they are bound on the hemocyte surface, by hitherto unknown receptors. They activate intracellular signalling pathways that involves FAK, Src and MAP kinases and they promote, with the participation of actin and tuboulin cytoskeleton, their phagocytosis. LPS is recognized and bound on the hemocyte surface and activates so far unknown receptors and through unknown intracellular signalling pathways involving Ras, activates the MAP kinases and the regulated secretion. Although it activates all three MAPKs, only the ΕRΚ and p38 are required not only for the secretion, but also for its internalization. Although FAK is activated by LPS, it does not get involved in the process of its internalization. All of the above mentioned results indicate that the hemocytes have developed distinct mechanisms for phagocytosis of pathogens, micromolecules and abiotic factors, a fact that underlines insects evolutionary adaptations, so that they can survive.

<p>Nitric oxide (NO) is an endogenous gaseous signaling molecule produced by three NO synthase isoforms (NOS1, 2, 3) and important in host defense. The induction of NOS2 during bacterial sepsis is critical for pathogen clearance but its sustained activation has long been associated with increased mortality secondary to multiple organ dysfunction syndrome (MODS). High levels of NO produced by NOS2 incite intrinsic cellular dysfunction, in part by damaging macromolecules through nitration and/or nitrosylation. These include mitochondrial DNA (mtDNA) and enzymes of key mitochondrial pathways required for maintenance of normal O2 utilization and energy homeostasis. However, animal studies and clinical trials inhibiting NOS2 have demonstrated pronounced organ dysfunction and increased mortality in response to live bacterial infections, confirming that NOS2 confers pro-survival benefits. Of particular interest here, the constitutive NOS1 and NOS3 have been linked to the up-regulation of nuclear genes involved in mitochondrial biogenesis but no comparable role has been described for NOS2. <italic> Therefore, I hypothesized that NOS2 is indispensible for host protection but must be tightly regulated to ensure NO levels are high enough to activate mitochondrial and other pro-survival genes, but below the threshold for cellular damage.</italic></p><p>This hypothesis was explored with two major Aims. The <italic>first Aim</italic> was to define the role of NOS2 in the activation of mitochondrial biogenesis in the heart of <italic>E. coli</italic>-treated mice. The <italic>second</italic> was to investigate the ability of NOS2 to be transcriptionally regulated by an enzyme previously shown to induce mitochondrial biogenesis, heme oxygenase-1 (HO-1). This hypothesis was tested using an <italic>in vivo</italic> model of sublethal heat-killed <italic>E. coli</italic> (<italic>HkEC</italic>) peritonitis in C57B/L6 (Wt), NOS2-/-, and TLR4-/- mice. Additionally, <italic>in vitro</italic> systems of mouse AML-12 or Hepa 1-6 cells pretreated with HO-1 activators or <italic>Hmox1</italic> shRNA prior to inflammatory challenge with lipopolysaccharide (LPS) +/- tumor necrosis factor-&alpha; (TNF-&alpha;). For the first Aim, Wt, NOS2-/-, and TLR4-/- mice were treated with (<italic>HkEC</italic> and cardiac tissue analyzed for mitochondrial function, expression of nuclear and mitochondrial proteins needed for mitochondrial biogenesis, and histological expression of NOS2 and TLR4 relative to changes in mitochondrial mass. For the second Aim, Wt mice were pretreated with hemin or carbon monoxide (CO) to activate HO-1 prior to <italic>HkEC</italic>-peritonitis. Liver tissue in these animals was evaluated at four hours for HO-1 induction, <italic>Nos2</italic> mRNA expression, cytokine profiles, and nuclear factor (NF)-&kappa;B activation. Liver cell lines were pretreated with hemin, CO-releasing molecule (CORM), or bilirubin one hour before LPS exposure and the <italic>Nos2</italic> transcriptional response evaluated at two and 24 hours. The MTT assay was used to confirm that <italic>in vitro</italic> treatments were not lethal. </p><p>These studies demonstrated that <italic>HkEC</italic> induced mtDNA damage in the heart that was repaired in Wt mice but not in NOS2-deficient mice. In KO mice, sustained mtDNA damage was associated with the reduced expression of nuclear (NRF-1, PGC-1&alpha;) and mitochondrial (Tfam, Pol-&gamma;) proteins needed for mitochondrial biogenesis. The findings thus supported that NOS2 is required for mitochondrial biogenesis in the heart during Gram-negative challenge. Evaluation of the relationship between HO-1 and NOS2 in murine liver was more complex; HO-1 activation in <italic>HkEC</italic>-treated Wt mice attenuated 4-hour <italic>Nos2</italic> gene transcription. In liver cell lines, hemin, CORM, and bilirubin were unable to suppress <italic>Nos2</italic> expression at the time of maximal induction (2 hours). <italic>Nos2</italic> was, however, suppressed by 24 hours, suggesting that the regulatory impact of HO-1 induction was not engaged early enough to reduce <italic>Nos2</italic> transcription at 2 hours. It is concluded that NOS2 induction in bacterial sepsis optimizes the expression of the mitochondrial biogenesis transcriptional program, which subsequently can also be regulated by HO-1/CO in murine liver. This provides a potential new mechanism by which immune suppression and mitochondrial repair can occur in tandem during the acute inflammatory response.</p> / Dissertation

Macrophage-derived inflammation contributes to chronic inflammation in adipose tissue in obesity and is also linked to the development of skeletal muscle (SM) insulin resistance. The long-chain n-3 PUFA have been shown to modulate cytokine secretion from macrophages, though subsequent effects on SM inflammation and function are unknown. A model of macrophage conditioned media (MCM) was used to examine effects of n-3 PUFA on macrophage inflammation and consequent effects on SM cells. Treatment of RAW 264.7 macrophages with long-chain n-3 PUFA decreased LPS-induced MCP-1 and IL-6 gene expression and MCP-1 secreted protein. In turn, MCM from n-3 PUFA-treated macrophages decreased TNF-α and IL-6 gene expression in LPS-stimulated L6 SM cells, but did not affect insulin-stimulated pAkt content. Long-chain n-3 PUFA did not affect gene expression of inflammatory signaling intermediates NF-κB and TLR4. Overall this thesis suggests that long-chain n-3 PUFA are important nutritional strategies for reducing macrophage-derived inflammation, with ensuing benefits in SM inflammation. / NSERC-CGS, Ontario Graduate Scholarship

Reproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early-conceptus development. The ovarian-derived sex steroids estradiol and progesterone are known to affect functionality of the oviduct. Advances in microarray and NanoString technology allow for gene expression analysis to increase understanding of processes critical for fertility. Studies were conducted to investigate mechanisms regulating oviductal function in cattle and mice by using the Bovine Gene 1.0 ST array and the Mouse Gene 430-2.0 arrays (Affymetrix Inc., CA), respectively. For the first study, oviducts were collected from heifers assigned to luteal or follicular phase groups. In the second study oviducts were collected from immature mice with a global deletion of estrogen receptor-1 (ESR1) and their wild-type littermates at 23 days of age or 48 hr after treatment with 5 IU of PMSG. Following microarray hybridization, the resulting datasets were analyzed using Partek Genomics Suite 6.6 (Partek Inc., MO). The results of the first two studies illustrated a dynamic hormonal regulation of the oviductal epithelium and revealed the identity of novel genes affecting fertility in cattle and gave us insights into the genes regulated by estrogen and ESR1 in mice. Many genes identified as differentially regulated are believed to play an integral role in the regulation of oviductal inflammation. Therefore, the objective of the third study was to test the hypothesis that intraperitoneal administration of E. Coli-derived lipopolysaccharide induces the expression of inflammatory mRNAs in the mouse oviduct. Mice were treated with 0, 2 μg or 10 μg of LPS from E. Coli. and killed 24 h later. Oviducts were collected for determination of inflammatory gene expression by a targeted NanoString approach using the nCounter GX Mouse Inflammation Kit (NanoString Technologies, Wa). Results indicate that systemic treatment with LPS induces inflammation in the oviducts of mice and provides evidence of a repeatable animal model of oviductal inflammation. Overall, data from these studies extends our knowledge of the mechanisms regulating oviductal functions and immune response, as well as identified target molecules and processes to improve production animal and human fertility.

Krav om förbättrad spillvattenrening och städer som förgrenar sig över större områden är några av anledningarna till att dagens avloppsledningsnät får allt längre ledningssträckor. Att med gravitationens hjälp föra avloppsvatten framåt kräver ett kontinuerligt fall som vid långa avstånd kan innebära mycket schaktning, den ekonomiskt mest belastande delen vid nyinstallation av avloppsledningsnät. Ett fördelaktigt alternativ kan vara trycksatt avloppssystem, som sedan 70-talet har kompletterat de traditionella självfallssystem i kuperade och bergiga områden. På senare tid har trycksatt avloppsystem fått större användningsområde utanför sina etablerade bruksområden med anledning av skärpta krav på rening och kostnadseffektivitet. Självfallssystem är dock det mest använda avloppssystemet i urbana områden. För ett bostadsområde i utkanten av centrum, utanför de båda systemens vedertagna användningsområden, vore det därför intressant att undersöka vilket av avloppssystemen som är bäst lämpat. För VA-branschen generellt vore det också intressant att utreda hur de båda systemen står sig vid en jämförelse. Med anledning av detta var syftet med examensarbetet att jämföra trycksatt avloppssystem med självfallssystem på grundval av ekonomi, miljö och kapacitet. I tillägg undersöktes om några generella slutsatser kunde fastställas utifrån fallstudien. Undersökningen baserades på ett bostadsområde i utkanten av Fredrikstad centrum, som nyligen projekterats med självfall. Ett teoretiskt trycksatt avloppssystem projekterades. Ekonomi värderades utifrån drift- och underhållskostnader samt grund- och reinvesteringskostnader. Kapaciteten jämfördes numeriskt och via dimensioneringsmodeller. Vad gäller den miljömässiga jämförelsen utvärderades systemet med hjälp av rapporter utgivna av Svenskt Vatten och Norsk Vann. Det planerades en utbyggnad för området till dubbla antalet fastigheter vilket visade sig bli avgörande för det ekonomiska resultatet. Den vitala faktorn var de höga investerings- och driftskostnaderna för pumpenheterna vilket gjorde självfallssystemet mer ekonomiskt lämpligt. Även ur ett miljömässigt perspektiv var självfallssystemet marginellt bättre, givet att riskeffekterna inte rankades inbördes. Kapacitetsmässigt dimensioneras självfallssystem för nästan det dubbla flödet jämfört med trycksatt system, vilket ger det trycksatta systemet en kapacitet mer anpassad till behovet. Generellt sett antydde resultatet att trycksatt system var mer gynnsamt vid glesare bebyggelse. / As a result of stricter treatment requirements and city expantion the length of the sewer network is steadily increasing. To drain wastewater by gravity requires a continuous slope which often results in great excavation - a very costly part in the process. An advantageous alternative could be a pressurized sewer system, which has been a useful complement to traditional gravity systems in hilly or rocky areas since the 70’s. Even though pressurized sewer systems lately have tended to be more frequently used outside their common application area due to stricter requirements on treatment and cost-efficiency, gravity systems are still the most common sewer system in urban areas. Concerning this, it would be intresting to investigate which of the two systems that suites a residental area on the outskirts of a city center best, since the area is outside the traditional usage of the two established systems. In addition it would be interesting for the wastewater industry in general to investigate how the two systems compare.  For this reason the aim of this master thesis was to compare pressure sewer systems with gravity systems on the basis of economy, environment and capacity. In addition, it was examined whether any general conclusions could be determined from the case study. The survey was based on a residental area in the outskirts of Fredrikstad city center, recently designed with a gravity system. A theoretical pressure sewer system was designed. Economy was evaluated based on the operating and maintenance costs and basic and reinvestment costs. The capacity was compared numerically and through design templates. As for the environmental comparison, an evaluation was done on the basis of reports from the Swedish Water &amp; Wastewater Association and Norwegian Water BA. An expansion to double the number of real properties was planned for the area of study, which proved to be crucial to the financial results. The gravity system was most appropriate from an economic standpoint and the vital factor was the high investment and operating costs for the pumping units. Even from an environmental point of view, the gravity system was maginally better. Given that the risk effects are not ranked relative to each other. In terms of capacity the gravity system was dimensioned for almost twice the flow compared to the pressure sewer systems, which gave the pressure sewer system a more adusted capacity. The result indicated that the pressure sewer system is favorable in densely built flexible areas.