CD40 Ligand and Autoantigen Are Involved in the Pathogenesis of Low-Grade B-Cell Lymphomas of Mucosa-Associated Lymphoid Tissue

Low-grade MALT-type lymphomas are malignancies of mucosal marginal-zone B cells and preceded by reactive inflammatory lymphoid tissue. Experimental observations suggest that antigen and CD40 Ligand act during cognate T/B cell interaction and are crucial for germinal center B-cell maturation generating marginal-zone B cells. To investigate the mechanisms underlying the development of extranodal MALT-type lymphomas, the immunoglobulin receptor was sequenced and analyzed for antigen specificity using heterohybridoma technology. Furthermore, CD40 ligand expression was evaluated by immunohistochemistry and by semiquantitative RT-PCR, and ligand binding to the CD40 of tumor B cells was studied using the CD40 system. Hypermutations were found in low-grade lymphomas throughout CDR1- CDR3 suggestive of positive selection through their antigen receptor. Different VH families were used and more than 69% of tumor immunoglobulins bound different mucosal antigens. CD40L expression was found in the tumor marginal zone in substantial amounts. The in vitro proliferation response of all low-grade MALT-type lymphomas was dependent on anti-CD40- mediated signals and cytokines. Our data provide evidence that autoantigen as well as the CD40L expressed by activated nonneoplastic T cells may drive the evolution of low-grade MALT-type lymphomas either directly or by paracrine mechanisms and that antigen may contribute to lymphoma pathogenesis

Genetic defects in common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent clinically manifested primary immunodeficiency. According to clinical and laboratory findings, CVID is a heterogeneous group of diseases. Recently, the defects of molecules regulating activation and terminal differentiation of B lymphocytes have been described in some patients with CVID. In this study, we show the overview of deficiencies of inducible costimulator, transmembrane activator and calcium-modulator and cytophilin ligand interactor, CD19 molecules, their genetic basis, pathogenesis and clinical manifestations

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells

Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells

Cross-presentation of cellular antigens is crucial for priming CD8<sup>+</sup> T cells, and generating immunity to intracellular pathogens—particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103<sup>+</sup> CD11b<sup>−</sup> CD8α<sup>+</sup> DCs cross-present IEC-derived ovalbumin to CD8<sup>+</sup> OT-I T cells. Similarly, in the mesenteric lymph nodes (MLNs), cross-presentation of IEC–ovalbumin was limited to the CD11c<sup>+</sup> MHCII<sup>hi</sup> CD8α<sup>+</sup> migratory DCs, but absent from all other subsets, including the resident CD8α<sup>hi</sup> DCs. Crucially, delivery of purified CD8α<sup>+</sup> LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8<sup>+</sup> T cells <i>in vivo</i>. Finally, in 232-4 mice treated with R848, CD8α<sup>+</sup> LDCs were uniquely able to cross-prime interferon γ-producing CD8<sup>+</sup>T cells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8α<sup>+</sup> intestinal DCs are indispensable for cross-presentation of cellular antigens and, in conditions of inflammation, for the initial differentiation of effector CD8<sup>+</sup> T cells. They may therefore represent an important target for the development of antiviral vaccinations

Project of an Pneumatic Drive Unit as Initial Decelerator of Hybrid Electromagnetic Launcher

The paper presents the methodology of designing a pneumatic drive unit as initial decelerator of hybrid electromagnetic launcher. The paper presents a mathematical model of binding basic design variables and its use in the design of the drive unit of the given parameters. It also presents the results of measuring the pneumatic module and a verification of the mathematical model.W artykule przedstawiono metodykę projektowania pneumatycznego modułu napędowego jako zadajnika prędkości hybrydowej wyrzutni elektromagnetycznej. Zaprezentowano matematyczny model wiążący podstawowe zmienne konstrukcyjne oraz jego wykorzystanie w procesie projektowania modułu napędowego o zadanych parametrach końcowych. Przedstawiono również wyniki badań pomiarowych modułu pneumatycznego oraz dokonano weryfikacji modelu matematycznego

Starting current limiter for electromagnetic launcher with rails

The electromagnetic launcher is a specific type of electromechanical converter. Electrical Energy from the power supply, discharging in the pulse way, is used for acceleration a moveable element (bullet). Pulse discharged of a capacitor batteries is related with a high maximum value of the starting current. The paper presents way of reducing maximum value of the starting current for the railgun module of the hybrid electromagnetic launcher.Wyrzutnia elektromagnetyczna to specyficzny rodzaj przetwornika elektromechanicznego. Energia elektryczna źródła zasilania (bateria kondensatorów) rozładowana w sposób impulsowy jest wykorzystywana do rozpędzania elementu ruchomego (pocisku). Impulsowe rozładowanie baterii kondensatorów w czasie kilku milisekund związane jest z bardzo dużymi maksymalnymi wartościami prądu rozruchowego o wartościach kilkuset kA. W artykule przedstawiono sposób ograniczenia maksymalnej wartości prądu rozruchowego dla elektromagnetycznego modułu napędowego z szynami dla hybrydowej wyrzutni pneumatyczno-elektromagnetycznej

Determination of optimal coil drive geometric dimensions of electromagnetic launcher

The paper presents the methodology enabling us to determine optimal geometric dimensions of the coil in an electromagnetic coil launcher. The paper presents a mathematical field model of the electromagnetic coil launcher and its use in the designing the drive unit of with given final velocities.W artykule przedstawiono metodykę wyznaczania optymalnych wymiarów geometrycznych cewki napędowej elektromagnetycznej wyrzutni cewkowej. Zaprezentowano matematyczny model polowy wyrzutni cewkowej oraz jego wykorzystanie w procesie projektowania modułu napędowego o zadanych prędkościach końcowych

Regelung des Blutspendewesens

Dieser Beitrag beschreibt die verschiedenen nationalen und europäischen Institutionen, Kommittees, Zulassungsbehörden und Richtlinien, die das deutsche Transfusionssystem regulieren und die für dessen Qualitäts- und Sicherheitsstandards zuständig sind. An erster Stelle steht das „Gesetz zur Regelung des Transfusionswesens (Transfusionsgesetz)” vom 1. Juli 1998. Ein weiteres Regelungselement stellen die „Richtlinien zur Blutgruppenbestimmung und Bluttransfusion (Hämotherapie)” dar, welche vom Wissenschaftlichen Beirat der Bundesärztekammer und dem Paul-Ehrlich-Institut gemeinsam herausgegeben werden. Als ein weiteres Gremium beschäftigt sich der „Arbeitskreis (AK) Blut” mit dem Stand der Technik und Wissenschaft in der Transfusionsmedizin und Hämotherapie. Kompetenzen und Zuständigkeiten der unterschiedlichen Bundes- und Landesbehörden und deren Interaktionsebenen mit den medizinischen Fachgesellschaften werden dargelegt. Schließlich werden die europäischen Organisationen und Kommittees sowohl des Europarates wie auch der Europäischen Union vorgestellt, die an der Erarbeitung europaweiter Standards und Richtlinien für die Transfusionsmedizin beteiligt sind.This article describes the various national and European institutions, committees, guidelines and regulatory bodies shaping and safeguarding the standards of the German transfusion medicine system. It refers to the content of the Transfusion Medicine Act issued in 1998 by the German parliament, the national guidelines of the German Medical Association, and the work of the „Arbeitskreis Blut”, a working party on acute issues arising in the transfusion medicine area. It covers the way the various German federal (Ministry of Health, Paul-Ehrlich-Institut, Robert Koch-Institut) and land regulatory bodies interact with experts of the various German Medical Societies to ensure a high medical standard within the transfusion medicine system. Finally, it describes the European organizations and committees, both within the Council of Europe and the European Union, which are involved in shaping European standards and guidelines in transfusion medicine