Correlation of Group C Meningococcal Conjugate Vaccine Response with B- and T-Lymphocyte Activity

Despite the success of conjugate vaccination against meningococcal group C (MenC) disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration

Einfluss von anthropogenen Schadstoffen (PAK und PCB) auf terrestrische Invertebraten urbaner Oekosysteme Abschlussbericht

Das Projekt wurde von August 1993 bis Mai 1997 durchgefuehrt. Ziele waren die Erarbeitung (a) von Wirkschwellen fuer organische Schadstoffgruppen (PAK, PCB) und Schwermetalle im Boden fuer Destruenten urbaner Oekosysteme, (b) von Biotestsystemen zur Bewertung der Lebensraumfunktion belasteter Boeden und (c) von Hinweisen zur kontrollierten Nutzung belasteter Flaechen. Diese Fragestellungen wurden bearbeitet durch Freilanduntersuchungen auf stillgelegten Rieselfeldern der Stadt Berlin zur Abundanz, Artendiversitaet und Dominanzstruktur terrestrischer Anneliden (Lumbriciden, Enchytraeiden), durch Biotests unter Verwendung kontaminierter Rieselfeldboeden und aufdotierter Boeden (BaP, Fla, PCB 52, Cd, Cu) und durch Untersuchung zur Akkumulation, Elimination und Biotransformation bei Anneliden. Auf 12 der 17 untersuchten Rieselfeldstandorten wurden keine Regenwuermer gefunden, auf zwei keine Enchytraeiden. Die Enchytraeidenabundanz lag zwischen 500 und 12.500/m"2 und damit weit unter der von Kontrollflaechen (25.000 bis 280.000/m"2). Die Annelidenfeindlichkeit der Rieselfeldboeden wurde durch den Koederstreifen-Test und durch Biotests mit Enchytraeus crypticus, E. albidus, E. buchholzi und Eisenia f. fetida bestaetigt. Die Oekotoxizitaet der rieselfeldtypischen Schadstoffkombinationen wurde durch den sauren Boden-pH und Bodenumlagerungen verstaerkt. Die Toxizitaet der organischen und anorganischen Schadstoffe fuer Anneliden wurde durch Kurz- und Langzeituntersuchungen im Agar-Testsystem bestaetigt. Die Untersuchungsmethoden koennen zur Bewertung komtaminierter Boeden herangezogen werden. (orig.)The project was conducted from August 1993 until May 1997. The objectives were (a) an elaboration of effect concentrations and index values for organic contaminants (PAH, PCB) and heavy metals in soil of conurbations for the community of decomposers, (b) the improvement of a biotest system for the evaluation of the habitat function of contaminated soils and (c) to obtain informations concerning a controlled utilization of contaminated areas. For that purpose field investigations in former sewage water irrigation areas of Berlin, Germany, concerning the abundance, species composition and dominance structure of terrestrial annelids (Enchytraeids, Lumbricids) were performed, as well as bioassays using contaminated soils of these sites and soils spiked with bezo(a)pyrene, fluoranthene, PCB 52, Cd and Cu and experiments on accumulation, elimination and biotransformation in annelids. 12 of the 17 sites investigated lacked earthworms, while only 2 sites lacked enchytraeids. The abundance of enchytraeids was in the range of 500 to 12.500/m"2, compared to 25.000 to 280.000/m"2 on reference sites. The hostility of the soils of former irrigation fields to annelids was confirmed by lamina bait tests and by bioassays with Enchytraeus crypticus, E. albidus, E. buchholzi and Eisenia f. fetida. The ecotoxicity of the combined contaminants was enforced by the acidity and the degradation of the soils. The toxicity of organic and inorganic contaminants to terrestrial annelids was definitely proved by reproduction tests in the agar test system. The applied methods of investigation can be used for evaluation of contaminated soils. (orig.)Available from TIB Hannover: F98B1125+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman