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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/11184

Title: IgG-mediated Immune Suppression: the Effect on the Host Immune System
Authors: Brinc, Davor
Advisor: Lazarus, Alan H.
Department: Laboratory Medicine and Pathobiology
Keywords: Hemolytic Disease of the Newborn
Antibody-mediated immune suppression
Immune regulation
Issue Date: 30-Jul-2008
Abstract: One of the most effective immunological interventions for human disease prevention is the administration of anti-red blood cell (RBC) IgG, more specifically, anti-D IgG, for prevention of hemolytic disease of the fetus and newborn (HDN), a serious and potentially fatal condition caused by the maternal immune response against the Rhesus (Rh) blood group system D antigen on fetal RBC. Despite its widespread clinical use, the mechanism of the suppressive anti-RBC IgG effect is not fully understood. In a murine model of immunity to foreign RBCs, transfusion of mice with IgG-opsonized RBCs strongly attenuated the antibody response compared to transfusion of untreated RBCs. This model was used to study the anti-RBC IgG effect on the host immune response. Contrary to the predominant theories of the anti-D effect, here it is shown that IgG-mediated RBC clearance is not sufficient for the attenuation of antibody responses. IgG-opsonized RBCs internalized by the mononuclear phagocytic cells could stimulate T and B cell responses against RBC antigens. This thesis also shows that the adaptive tolerance at the T or B cell level is not the reason for the attenuation of the antibody response. Instead, IgG selectively prevented the appearance of antigen-primed RBC-specific B cells and, surprisingly, induced the host B cell response against the IgG in complex with RBCs. These results suggest that the inability of RBC-specific B cells to recognize and present RBC-specific epitopes may explain the inhibitory IgG effect.
URI: http://hdl.handle.net/1807/11184
Appears in Collections:Doctoral
Department of Laboratory Medicine and Pathobiology - Doctoral theses

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