Even in times of renewable energy revolution fossil fuels will play a major role in energy supply, transportation, and chemical industry. Therefore, increasing demand for crude oil will still have to be met in the next decades by developing new oil re-serves. To cope with this challenge, companies and researchers are constantly seeking for new methods to increase the recovery factor of oil fields. For that reason, many enhanced oil recovery (EOR) methods have been developed and applied in the field. EOR methods alter the physico-chemical conditions inside the reservoir. One possibility to achieve this is to inject an aqueous solution containing special chemicals into the oil-bearing zone. Polymers, for example, increase the viscosity of the injected water and hence improve the displacement of the oil to the production well. The injection of surfactant solutions results in reduced capillary forces, which retain the oil in the pores of the reservoir. Some surfactants form viscoelastic solutions under certain conditions. The possibil-ity to apply those solutions for enhanced oil recovery has been investigated by some authors in the last years in low salinity brines. Reservoir brines, however, often contain high salt concentrations, which have detrimental effects on the properties of many chemical solutions applied for EOR operations. The Triphenoxymethane derivatives, which were the subject of study in this thesis, form viscoelastic solutions even in highly saline brines. The aim of this thesis was to investigate the efficiency and the mode-of-action of this new class of chemical EOR molecules with respect to oil mobilization in porous media.

Even in times of renewable energy revolution fossil fuels will play a major role in energy supply, transportation, and chemical industry. Therefore, increasing demand for crude oil will still have to be met in the next decades by developing new oil re-serves. To cope with this challenge, companies and researchers are constantly seeking for new methods to increase the recovery factor of oil fields. For that reason, many enhanced oil recovery (EOR) methods have been developed and applied in the field. EOR methods alter the physico-chemical conditions inside the reservoir. One possibility to achieve this is to inject an aqueous solution containing special chemicals into the oil-bearing zone. Polymers, for example, increase the viscosity of the injected water and hence improve the displacement of the oil to the production well. The injection of surfactant solutions results in reduced capillary forces, which retain the oil in the pores of the reservoir. Some surfactants form viscoelastic solutions under certain conditions. The possibil-ity to apply those solutions for enhanced oil recovery has been investigated by some authors in the last years in low salinity brines. Reservoir brines, however, often contain high salt concentrations, which have detrimental effects on the properties of many chemical solutions applied for EOR operations. The Triphenoxymethane derivatives, which were the subject of study in this thesis, form viscoelastic solutions even in highly saline brines. The aim of this thesis was to investigate the efficiency and the mode-of-action of this new class of chemical EOR molecules with respect to oil mobilization in porous media.

Most of the old oil fields in China have reached high water cut stage, in order to meet the booming energy demanding, oil production rate must be kept in the near future with corresponding IOR (Improving Oil Recovery) methods. Z106 oilfield lies in Shengli Oilfields Area at the Yellow River delta. It was put into development in 1988. Since the oil belongs to heavy oil, the oil-water mobility ratio is so unfavourable that water cut increases very quickly. Especially for reservoir Ng21, the sand rock is sediment from river channel, the permeability heterogeneity and heavy oil properties together lead to extremely poor water flooding efficiency. In order to improve the oil recovery, IOR methods are needed urgently. Considering all practical situations for this reservoir and present technique level, polymer flooding method has been selected as an IOR test with numerical simulation. For polymer flooding, since polymer resolution has the capability of enlarging water viscosity, it controls the mobility of water phase and at the same time improves the driving efficiency. During polymer flooding simulation, many factors must be taken into account for the construction of mathematical model, such as inaccessible pore volume, polymer shear thinning effect, polymer adsorption, relative permeability reduction factors, etc. All simulations were done with black oil model with polymer option in ECLIPSE. Simulation results for a theoretical river channel reservoir with serious permeability heterogeneity and heavy oil, and simulation results for practical reservoir Ng21, both have shown that polymer flooding is a feasible method for IOR. For reservoir Ng21, with polymer slug size of 0.235 PV, polymer concentration at 1.5 kg/m3, the final oil recovery after polymer flooding could reach 12.8%, the enhanced oil recovery is about 5%. If only the developable oil reserve being taken into account, the final oil recovery is about 34%, and enhanced oil recovery from polymer flooding is more than 12%. For such heavy oil river channel reservoir to reach such a final oil recovery, it could be concluded as a great success. Since there are still many such oil reservoirs in Shengli Oilfields Area, polymer flooding will be of great importance for improving oil recovery in this area in the near future.

In der vorliegenden Arbeit werden Synthesen von sterisch anspruchsvollen sekundären wie auch tertiären Aminen und Enaminen untersucht. Ein Großteil der Arbeit befasst sich mit der Darstellung von N-Chloraminen, die im weiteren Verlauf zu sek. und tert. Aminen und Enaminen, mit Hilfe von metallorganischen Reagenzien und N,N,N',N'-Tetramethylethylendiamin (TMEDA), umgesetzt werden. Die dabei resultierenden Amine werden, auf Grund ihrer gehinderten Rotation, NMR-spektroskopisch untersucht. Dabei werden diverse dynamische Effekte bei verschiedenen Temperaturen beobachtet und gedeutet. So lassen sich auf diese Weise Rotationsbarrieren berechnen und vergleichen. Das gibt Aufschluss über die sterische Hinderung von verschiedenen Alkylgruppen. Weiterhin wird eine Eliminierung von Olefinen bei tert. Aminen beobachtet, welche der Hofmann-Eliminierung ähnelt. Diese verläuft anders als in Lehrbüchern beschrieben. Außerdem werden die Aktivierungsenergie und Isotopeneffekte der Eliminierung untersucht. Diese Zersetzung erfolgt auch mit Alkalimetallen als Katalysatoren. Eine Herstellung von neuartigen Enaminen aus 'turbo'-Amiden und gespannten Verbindungen wie Cyclooctin wird ebenfalls beschrieben. Die Enamine werden durch NMR-Spektroskopie auf ihren Olefincharakter untersucht. Eine neue Synthese von hochsubstituierten Pyrrolidinen und entsprechenden Iminiumsalzen, aus sek. tert-Octylaminen, wird vorgestellt. Diese Darstellung ist eine Erweiterung der Hofmann-Löffler-Freytag-Reaktion, welche eine radikalische Ringschlussreaktion beinhaltet. Die Darstellung der Iminiumsalze erfolgt metallfrei, durch die Oxidation mit N-Bromsuccinimid (NBS).:Abkürzungsverzeichnis VIII Abbildungsverzeichnis XII 1 Einleitung 1.1 Bedeutung von Aminen 1.2 Alkylierung von N -Haloaminen 1.3 Sterische Hinderung und Dynamische NMR-Spektroskopie 1.4 Zielstellung 2 Ergebnisteil 2.1 Darstellung neuer, sekundärer Amine als Vorstufen weiterer Synthesen 2.2 Darstellung tertiärer Amine 2.2.1 Darstellung diverser N -Chloramine für die elektrophile Aminierung 2.2.2 Reaktionen an N,N-Dichloraminen 2.2.3 Alkylierungen am tert-Butyl-tert-octylamin 2.2.4 Elektrophile Aminierungen an weiteren N-Chloraminen 2.2.4.1 Cycloalkylierung zu tert. Aminen 2.2.4.2 Isopropylierung am Stickstoff 2.2.4.3 Einführung der Neopentylgruppe 2.2.4.4 Versuche der Einführung tertiärer Gruppen 2.2.5 Synthese von tertiären Enaminen 2.2.6 Reaktion zwischen gespannten Verbindungen und Metallamiden 2.2.7 Acylierungen von sterisch anspruchsvollen Aminen 2.2.8 Synthese von tertiären Aminen aus Amiden 2.2.9 Ringschlussreaktionen zu möglichen CAAC-Vorläufern 2.3 Untersuchungen zur Hofmann-Eliminierung bei tertiären Aminen 2.3.1 Untersuchung der Aktivierungsenergie der Eliminierung 2.3.2 Hofmann-Eliminierung katalysiert durch Alkalisalze 2.3.3 Untersuchungen zum Isotopeneffekt 2.3.4 Zersetzungen von tertiären Aminen durch Methanol 2.4 Dynamische NMR-Spektroskopie bei tertiären Aminen 2.4.1 Rotamere in der C2V -Symmetrie 2.4.2 Rotamere in der C2H-Symmetrie 2.4.3 Komplexe dynamische Rotamere 3 Zusammenfassung und Ausblick 4 Experimenteller Teil 4.1 Experimentelles Arbeiten 4.1.1 Arbeiten unter inerten Bedingungen 4.1.2 Umkondensation 4.1.3 Säulenchromatographie 4.2 Analytisches Arbeiten 4.2.1 NMR-Spektroskopie 4.2.2 GC-MS 4.2.3 Analytischer Gaschromatograph 4.2.4 HRMS 4.3 Elementaranalyse 4.4 Röntgeneinkristallstrukturanalyse 4.5 Synthesevorschriften 4.5.1 Synthese von tert-Butyl-diisopropylamin (2) 4.5.2 Synthese von tert-Butyl-diisopropylamin (2) und Di-tert-Butylamin (14) 4.5.3 Synthese von N -(1-Adamantyl)-N-tert-octylamin 23 4.5.4 Synthese von N -tert-Octyl-tritylamin 24 4.5.5 Synthese von N -(2,6-Dimethylheptan-2-yl)acetamid (26) 4.5.6 Synthese von 2-Amino-2,6-dimethylheptan (27) 4.5.7 Synthese von 2-Azido-2,6-dimethylheptan (28) 4.5.8 Synthese von N -Isopropyl-2,6-dimethylheptan-2-amin (29) 4.5.9 Synthese von N -(1-Adamantyl)-2,6-dimethylheptan-2-amin (32) 4.5.10 Synthese von 4-Chlor-3,3,5,5-tetramethylmorpholin (34a) 4.5.11 Synthese von 2,2'-(Chlorimino)bis(2-methylpropan-1-ol) (34b) 4.5.12 Synthese von N -tert-Butyl-N -chlorcyclohexylamin (34c) 4.5.13 Synthese von N -Chlor-N -isopropyl-N -tert-octylamin (34d) 4.5.14 Synthese von N -(1-Adamantyl)-N -chlor-N -tert-octylamin 34e 4.5.15 Synthese von N -(1-Adamantyl)-N -chlor-2,6-dimethylheptan-2-amin (34f) 4.5.16 Synthese von 8-Chlor-7,7,9,9-tetramethyl-1,4-dioxa-8-azaspiro- [4.5]decan (34g) 4.5.17 Synthese von 4-Chlor-3,3,5,5-tetramethylmorpholin-2-on (34h) 4.5.18 Synthese von N -Chlor-N -tert-butyl-N -tritylamin (34i) 4.5.19 Synthese von Di-tert-butyldiazen (37) 4.5.20 Synthese von N -(1-Adamantyl)-neopentylamin (38d) 4.5.21 Synthese von N -tert-Butyl-N -cyclohexyl-N -tert-octylamin (40b) 4.5.22 Synthese von N -tert-Butyl-N -cyclopentyl-N -tert-octylamin (40c) 4.5.23 Synthese von N -tert-Butyl-N -isobutyl-N -tert-octylamin (40d) 4.5.24 Synthese von N -tert-Butyl-N -sec-butyl-N -tert-octylamin (40e) 4.5.25 Synthese von N,N -Diisopropyl-tert-octylamin (40f) 4.5.26 Synthese von N 1,N 4-Di-tert-butyl-2,2,4-trimethyl-N 1-(2,4,4-trimethylpentan-2-yl)pentan-1,4-diamin (43) 4.5.27 Synthese von 8-Cyclohexyl-7,7,9,9-tetramethyl-1,4-dioxa-8-azaspiro[4.5]decan (44a) 4.5.28 Synthese von N -Cyclopentyl-2,2,6,6-tetramethylpiperidin (44b) 4.5.29 Synthese von N,N -Di-tert-butylcyclohexylamin (44c) 4.5.30 Synthese von Di-tert-butyl-cyclopentylamin (44d) 4.5.31 Synthese von N -tert-Butyl-N,N -dicyclohexylamin (44e) 4.5.32 Synthese von 8-Isopropyl-7,7,9,9-tetramethyl-1,4-dioxa-8-azaspiro[4.5]decan (46a) 4.5.33 Synthese von 4-Isopropyl-3,3,5,5-tetramethylmorpholin-2-on (46b) 4.5.34 Synthese von N -(1-Adamantyl)-N -isopropyl-N -tert-octylamin (46c) 4.5.35 Synthese von N -(1-Adamantyl)-N -isopropyl-2,6-dimethylheptan2-amin (46d) . 4.5.36 Synthese von 8-Neopentyl-7,7,9,9-tetramethyl-1,4-dioxa-8-azaspiro [4.5]decan (47a) 4.5.37 Synthese von N -Neopentyl-2,2,6,6-tetramethylpiperidin (47b) 4.5.38 Synthese von 4-Neopentyl-3,3,5,5-tetramethylmorpholin (47c) 4.5.39 Synthese von N,N -Di-tert-butyl-neopentylamin (47d) 4.5.40 Synthese von N -tert-Amyl-N -tert-butyl-neopentylamin (47e) 4.5.41 Synthese von 1,1,3-Triethyl-1H -isoindol (49) 4.5.42 Synthese von (E)-4-(Di-tert-butylamino)but-3-en-1-ol (51) 4.5.43 Synthese von N -tert-Butyl-N -tert-octyl-N -prop-1-en-2-ylamin (58a) 4.5.44 Synthese von N,N -Di-tert-butylprop-1-en-2-amin (58b) 4.5.45 Synthese von 2,2,6,6-Tetramethyl-1-(prop-1-en-2-yl)piperidin (58c) 4.5.46 Synthese von (E)-N,N -Diisopropylcyclooct-1-enamin (60a) 4.5.47 Synthese von (E)-N -(tert-Butyl)-N -isopropylcyclooct-1-enamin (60b) 4.5.48 Synthese von (E)-1-(Cyclooct-1-en-1-yl)-2,2,6,6-tetramethylpiperidin (60c) 4.5.49 Synthese von 1,2:3,4:5,6-tris(hexamethylen)benzol (61) 4.5.50 Synthese von (Z)-2-(Diisopropylammonio)-3-oxocyclooct-1-enolat (62) 4.5.51 Synthese von N -(2,4,4-trimethylpentan-2-yl)acetamid (66a) 4.5.52 Synthese von 2-Phenyl-N -(2,4,4-trimethylpentan-2-yl)acetamid (66b) 4.5.53 Synthese von Di-tert-butyl-ethenylamin (69) 4.5.54 Synthese von 1-(1-Methoxyvinyl)-2,2,6,6-tetramethylpiperidin (71) 4.5.55 Synthese von N -tert-Butyl-N -isobutyl-N -isopropylamin (75) 4.5.56 Synthese von 1-tert-Butyl-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrroliumchlorid (77a) 4.5.57 Synthese von 1-tert-Butyl-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrroliumbromid (77b) 4.5.58 Synthese von 1-(1-Adamantyl)-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrroliumbromid (77f) 4.5.59 Synthese von 1-(tert-Butyl)-5-butyl-2,2,4,4-tetramethylpyrrolidin (79c) 4.5.60 Synthese von 1-(tert-Butyl)-2,2,4,4,5-pentamethylpyrrolidin (79d) 4.5.61 Synthese von 5-(Dibrommethyl)-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrrol (80) 4.5.62 Synthese von 1-(1-Adamantyl)-2,2,4,4,5-pentamethylpyrrolidin (85) 4.5.63 NMR-Daten von 2,2'-(tert-Butylazadiyl)bis(2-methylpropanal) (101)

Despite measures on the European level to increase the compatibility between the HE sectors of the member states, the recent literature exposes variations in their efficiencies. To gain insights into these differences we split the efficiency term according to the two management levels each university is confronted with. Utilizing a recent advancement in the method to measure efficiency, we separate short-term (transient) and long-term (persistent) efficiency, while controlling for unobserved institution specific heterogeneity. While the first term reflects the efficiency of the individual universities working within the country, the second term echoes the influence of the country specific overall HE structure. The cross-country comparison displays if the overall efficiency difference between countries is related to individual performance of their universities or their HE structure. This allows more purposeful policy recommendation and expands the literature regarding the efficiency of universities in a fundamental way. Choosing Italy and Germany as two important illustrative examples we can take advantage of a novel dataset including characteristics of institutions in both countries for an exceptional long period of time from 2001 to 2011. We show that the Italian universities exhibit a higher overall efficiency value than their German counterparts. With the individual universities working at the upper bound of efficiency in both countries, the overall inefficiency as well as the gap between the countries is caused by persistent, structural inefficiency. To expedite a true European Area of Higher Education future measures should hence aim at the country specific structure, not solely at affecting the activities of single universities.

As same as other countries in the world, China is also facing the problem of a severe shortage of energy. Specifically, the demand for natural gas is rising explosively after the energy consumption structure has changed from oil to gas. Due to various reasons and motivations, shale has been considered having great reserves and believed in alleviating the energy crisis. Nevertheless, the massive investment in developing shale has a disappointing interest with low-yielding production. Scholars have done many researches and experiments for investigating the causes and increasing the productivity of shale formation, in field and in laboratory respectively. Based on the statistics, more details, and further discussion, in this dissertation a probable method for more effectively producing was demonstrated. Although the hydro-fracturing technology has been conducted in field frequently, sometimes the decrease of permeability has been observed after the treatment. To figure out this phenomenon, the investigation started from the basic characterization of matrix. Believed in the most component in shale, quartz consisted of silica which could dissolve in fluid. Been assigned as variables, temperature, pH, and salinity have been implemented for explanation of dissolution. Temperature played a great role in the process. Combined with confining pressure, the reconsolidation happened inside samples. Through more experiments the mechanism of reconsolidation has been discovered that both confining pressure and temperature are necessary for gelling in fracture. Perspective on the whole formation, well logs were a super supplement to laboratory experiments. It serviced not only a further confirmation, but also pointed out the relationship between desorption capacity and different components. Samples from upper and lower formations have been used for going further. The exchange which exists between N2 and CH4 could be a great idea to exploit gas from reservoir. Feldspar supported space for adsorbed gas, and it was also easy to release. In contrast, the organic matter in which a network of pores developed has ability to trap the gas deeply because of the specific surface area. Quartz had positive effect on production because of containing the organic matter, while the influence of clay minerals on adsorption and desorption could be neglected. Based on the analysis of reconsolidation and desorption, an idea has been conceived using foam as fracturing fluid for increasing gas production. Compared to the pure fluid, foam has less water, which could prevent the reconsolidation. Nitrogen could be the gas to foam. The exchange between N2 and CH4 will increase the production of gas. In order to serve the condition that increases the time of exchange and makes negative effect on reconsolidation simultaneously, the foaming test with ABS and K12 has been evaluated first. For better stability of foam more experiment have been done. Three formulas were recommended which could keep the balance between the increasing viscosity and decreasing volume. The work interpreted in this thesis has enhanced our understanding of microscopic properties of shale and was expected to make contribution to further research of fracturing and production design.

Most of the old oil fields in China have reached high water cut stage, in order to meet the booming energy demanding, oil production rate must be kept in the near future with corresponding IOR (Improving Oil Recovery) methods. Z106 oilfield lies in Shengli Oilfields Area at the Yellow River delta. It was put into development in 1988. Since the oil belongs to heavy oil, the oil-water mobility ratio is so unfavourable that water cut increases very quickly. Especially for reservoir Ng21, the sand rock is sediment from river channel, the permeability heterogeneity and heavy oil properties together lead to extremely poor water flooding efficiency. In order to improve the oil recovery, IOR methods are needed urgently. Considering all practical situations for this reservoir and present technique level, polymer flooding method has been selected as an IOR test with numerical simulation. For polymer flooding, since polymer resolution has the capability of enlarging water viscosity, it controls the mobility of water phase and at the same time improves the driving efficiency. During polymer flooding simulation, many factors must be taken into account for the construction of mathematical model, such as inaccessible pore volume, polymer shear thinning effect, polymer adsorption, relative permeability reduction factors, etc. All simulations were done with black oil model with polymer option in ECLIPSE. Simulation results for a theoretical river channel reservoir with serious permeability heterogeneity and heavy oil, and simulation results for practical reservoir Ng21, both have shown that polymer flooding is a feasible method for IOR. For reservoir Ng21, with polymer slug size of 0.235 PV, polymer concentration at 1.5 kg/m3, the final oil recovery after polymer flooding could reach 12.8%, the enhanced oil recovery is about 5%. If only the developable oil reserve being taken into account, the final oil recovery is about 34%, and enhanced oil recovery from polymer flooding is more than 12%. For such heavy oil river channel reservoir to reach such a final oil recovery, it could be concluded as a great success. Since there are still many such oil reservoirs in Shengli Oilfields Area, polymer flooding will be of great importance for improving oil recovery in this area in the near future.

Inhalt der Arbeit sind theoretische und experimentelle Untersuchungen zum Einfluss akustischer Wellen auf das Verhalten mehrphasiger Strömungen in porösen Medien. Die Arbeit schlug mittels Frequenzanalyse Anregungsfrequenzen mit erhöhter Wahrscheinlichkeit den Strömungsvorgang positiv für die Erdölförderung zu beeinflussen. Die vorgeschlagenen Frequenzen erzielten auf verschiedenen Parametern erfolgreich eine positive Beeinflussung des Wasserdurchbruchspunktes, des Entölungsgrades und der relativen Permeabilität. Zur Erhöhung der Aussagekraft der Daten wurden Verfahren der multivariaten Statistik erfolgreich eingesetzt. Zudem wurden positive Rückkopplungseffekte mit dem Einsatz oberflächenaktiver Substanzen nachgewiesen. In einem abschließenden Schritt konnte die Wirkung des Verfahrens zudem durch Kombination mehrere Frequenzen optimiert werden. Diese von hoher Wichtigkeit geprägten Charakteristika zeigen klar das Potential des Verfahrens zum Einsatz als Verfahren der verbesserten Erdölförderung (EOR) auf.:1. Kurzfassung 5 2. Einleitung 6 2.1. Die primäre und sekundäre Förderphase 7 2.2. Tertiäre Fördermethoden 9 2.3. Akustische Verfahren 14 2.4. Aufgabenstellung 17 3. Grundlagen 18 3.1. Projektvorstellung 19 3.1.1. Vorstellung der Sonde 20 3.1.2. Eingrenzung der Laborparameter 22 3.2. Einordnung des Verfahrens in den Stand der Technik 23 3.2.1. Impuls- und Frequenzverfahren 23 3.2.2. Frequenzbereiche 25 3.3. Auswertemethoden 27 3.3.1. Frequenzanalysen 27 3.3.2. Flutversuche und relative Permeabilität 28 3.3.3. Imbibitionsversuche 32 3.4. Grundlagen der mathematischen Methoden 33 3.4.1. Fouriertransformation 34 3.4.2. Gradientenverfahren 34 3.4.3. Regressionsanalyse 37 4. Laborarbeiten 39 4.1. Versuchsaufbau 39 4.1.1. Flutanlage 39 4.1.2. Imbibitionsgefäße 42 4.2. Versuchsdurchführung 44 4.3. Der Versuchsplan der Flutexperimente 48 4.4. Voruntersuchungen 49 4.4.1. Gesteinsproben 49 4.4.2. Fluidproben 50 5. Datenauswertung 52 5.1. Frequenzanalyse 52 5.2. Flutversuche 55 5.2.1. Ergebnis der Regressionsanalyse 59 5.3. Imbibitionsversuche 61 5.4. Phänomenologische Untersuchungen 63 5.4.1. Injektivitätsveränderung 63 5.4.2. Instabile Emulsionsbildung 65 5.5. Weitergehende Forschungsansätze 67 5.5.1. Rückkopplungseffekte mit Tensiden 67 5.5.2. Bohrlochregeneration 69 6. Diskussion 71 7. Zusammenfassung 75

Die kontinuierliche Rezirkulation von Immunzellen durch periphere und sekundäre lymphatische Organe (SLOs) ist Bestandteil der Immunüberwachung und wichtig für die Aufrechterhaltung und Funktionsbereitschaft des Immunsystems. Der homöostatische Chemokinrezeptor CCR7 vermittelt dabei nicht nur die Rezirkulation von Lymphozyten durch SLOs, sondern scheint auch an der homöostatischen Rezirkulation von Lymphozyten durch nicht-lymphoide periphere Gewebe beteiligt zu sein. Im Rahmen dieser Arbeit wurde mithilfe von CCR7-defizienten Mäusen die funktionale Bedeutung von CCR7 für die homöostatische Rezirkulation von Lymphozyten durch das Peritoneum untersucht und nachgewiesen, dass CCR7 der dominante Chemokinrezeptor ist, der unter physiologischen Bedingungen die Transitzeit von Lymphozyten durch das Peritoneum festlegt. Die gestörte Rezirkulation von Lymphozyten begünstigte außerdem die Entstehung von tertiären lymphoiden Organen (TLOs) in der Magenschleimhaut von CCR7-defizienten Mäusen. Untersuchungen zur zellulären und molekularen Grundlage dieser und weiterer pathomorphologischer Veränderungen in der Magenschleimhaut von CCR7-defizienten Mäusen verdeutlichten die Funktion von CCR7 für die Etablierung von zentraler und peripherer Toleranz gegenüber gastrischen Antigenen. Fehlt CCR7, dann entwickelten Mäuse eine spontane Autoimmungastritis, welche durch gastritogene CD4+ T-Zellen verursacht wurde, deren Aktivierung auch unabhängig von Lymphknoten und TLOs erfolgte. Die Entstehung von TLOs wird auch bei einer durch Helicobacter pylori ausgelösten chronischen Gastritis beobachtet. Die Expression des homöostatischen Chemokinrezeptors CXCR5 und seines Liganden CXCL13 ist mit der Entwicklung dieser TLOs korreliert worden. Unter Verwendung eines Mausmodells für H. pylori-induzierte chronische Gastritis konnte gezeigt werden, dass CXCR5 die Ausbildung von TLOs vermittelt und eine Rolle für die Induktion von H. pylori-spezifischen T-Zell- sowie humoralen Immunantworten spielt. / Homeostatic recirculation of immune cells through peripheral and secondary lympoid organs (SLOs) is required for immune surveillance and the maintenance and functionality of the immune system. The homeostatic chemokine receptor CCR7 controls not only lymphoid cell trafficking to and within SLOs, but also seems to be involved in the homeostatic recirculation of lymphocytes through non-lymphoid peripheral tissues. Within the scope of this work we investigated the functional relevance of CCR7 for the homeostatic recirculation of lymphocytes through the peritoneal cavity and could show, that CCR7 is the dominant chemokine receptor which defines the transit time of lymphocytes in the peritoneal cavity under physiological conditions. Impaired recirculation of lymphocytes also promoted the development of tertiary lymphoid organs (TLOs) in the gastric mucosa of CCR7-deficient mice. Analysis of the cellular and molecular mechanisms underlying these and other pathomorphological alterations in the gastric mucosa of CCR7-deficient mice provided further evidence regarding the function of CCR7 for the establishment of central and peripheral tolerance towards gastric antigens. Mice that lack CCR7 spontaneously developed autoimmune gastritis, which was caused by gastritogenic CD4+ T-cells. Such autoreactive T cell responses were also initiated in the absence of lymph nodes and TLOs in CCR7/LT-alpha double-deficient mice. Development of TLOs is also observed during chronic gastritis induced by Helicobacter pylori. The expression of the homeostatic chemokine receptor CXCR5 and its ligand CXCL13 has been correlated with the development of these TLOs. Using a mouse model for H. pylori-induced chronic gastritis, we could show that CXCR5 is responsible for the development of TLOs and also plays a role for the induction of H. pylori-specific T and B cell responses.

No description available.