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Immunogenetics and transplantation immunology

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Title Immunogenetics and transplantation immunology
Period 05 / 2002 - unknown
Status Completed
URL http://www.amc.nl/index.cfm?sid=760
Research number OND1284707
Data Supplier Website Van Loghem Instituut

Abstract

[1] Immunity against blood cells. Blood cells carry various polymorphic antigens on their cell membrane. Contact with the immune system of another individual may therefore give rise to alloimmunization. In our department, research on alloimmunization is focused on neonatal alloimmune cytopenias. We are studying both the antigens involved in the immune response, the transport of antibodies across the placenta and the effector mechanism. In previous years most of the platelet and neutrophilic polymorphic antigens have been characterized, both at the biochemical and at the molecular level. The Rhesus (Rh)-system is the red cell blood group that is most frequently involved in neonatal alloimmunization. The molecular basis of the Rh antigens is extensively studied. [2] Stem cell transplantation. Stem cell transplantation is accomplished by intravenous infusion of the graft containing the CD34 antigen expressing hematopoietic progenitor cells (HPC). After (re)infusion, the HPC migrate to the bone marrow. The cells interact with sinusoid endothelium in the bone marrow, transmigrate across the endothelial layer and anchor in specific niches in the bone marrow microenvironment, a process called homing. The first step of this process, the rolling and adhesion to bone marrow endothelium, might be partly mediated by specific adhesion molecules. To identify these so-called "adressins" a panel of immortalized bone marrow endothelium cell lines (BMEC) has been constructed. So far, our results do not indicate the presence of bone marrow-specific endothelial cells. Some preliminary data suggest involvement of the CD34-antigen itself in this process. In the coming years we will focus our research on stem cell homing more on the role of chemokines in this process. [3] Immunophenotypic and genotypic analysis of leukemias and lymphomas. The sublaboratory Immunocytology of the Department of Experimental Immunohematology carries out diagnostic services in the field of hemato-oncology for hospitals in the Netherlands. To perform this task at a high level, new technologies are being developed. The research is mainly directed at the detection of minimal residual disease (MRD) by means of PCR. [4] Transendothelial migration and signal transduction. In response to inflammatory stimuli and/or chemokines, leukocytes migrate out of the blood stream towards the source of the inflammatory agent(s). This extravasation requires adhesion to and migration across the endothelial monolayer that lines the blood vessels. This transendothelial migration is a well-orchestrated process, which involves various types of adhesion molecules on the leukocyte, i.e. selectins, integrins and molecules such as CD31 and CD47. The relevant counterstructures on the endothelial cells include E-selectin, ICAM and VCAM. In addition to the heterotypic cell-cell adhesion, there is increasing evidence that adherent leukocytes trigger signaling pathways in endothelial cells that reduce endothelial homotypic cell-cell adhesion and thereby facilitate the subsequent transendothelial migration. Within the Department of Experimental Immunohematology, two research lines are directed at elucidating the molecular basis of leukocyte transmigration. The relevant issues are addressed by using a multidisciplinary approach that includes cell biology, immunology, biochemistry and molecular biology.

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Classification

A70000 Public health and health care
D21300 Biochemistry
D21400 Genetics
D21500 Histology, cell biology
D21800 Immunology, serology
D23120 Oncology
D23220 Internal medicine

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