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Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn Brinc D; Lazarus AHHematology Am Soc Hematol Educ Program 2009[]; ä (ä): 185-91Anti-D is routinely and effectively used to prevent hemolytic disease of the fetus and newborn (HDFN) caused by the antibody response to the D antigen on fetal RBCs. Anti-D is a polyclonal IgG product purified from the plasma of D-alloimmunized individuals. The mechanism of anti-D has not been fully elucidated. Antigenic epitopes are not fully masked by anti-D and are available for immune system recognition. However, a correlation has frequently been observed between anti-D-mediated RBC clearance and prevention of the antibody response, suggesting that anti-D may be able to destroy RBCs without triggering the adaptive immune response. Anti-D-opsonized RBCs may also elicit inhibitory FcgammaRIIB signaling in B cells and prevent B cell activation. The ability of antigen-specific IgG to inhibit antibody responses has also been observed in a variety of animal models immunized with a vast array of different antigens, such as sheep RBCs (SRBC). This effect has been referred to as antibody-mediated immune suppression (AMIS). In animal models, IgG inhibits the antibody response, but the T-cell response and memory may still be intact. IgG does not mask all epitopes, and IgG-mediated RBC clearance or FcgammaRIIB-mediated B-cell inhibition do not appear to mediate the AMIS effect. Instead, IgG appears to selectively disrupt B cell priming, although the exact mechanism remains obscure. While the applicability of animal models of AMIS to understanding the true mechanism of anti-D remains uncertain, the models have nevertheless provided us with insights into the possible IgG effects on the immune response.|*Models, Immunological[MESH]|Adult[MESH]|Animals[MESH]|Cattle[MESH]|Disease Models, Animal[MESH]|Erythroblastosis, Fetal/etiology/immunology/*prevention & control[MESH]|Erythrocyte Membrane/immunology[MESH]|Female[MESH]|Fetal Blood/immunology[MESH]|Humans[MESH]|Immunoglobulin G/immunology/therapeutic use[MESH]|Infant, Newborn[MESH]|Isoantibodies/biosynthesis/immunology/*therapeutic use[MESH]|Lymphocyte Activation[MESH]|Lymphocyte Subsets/immunology[MESH]|Mice[MESH]|Mice, SCID[MESH]|Mice, Transgenic[MESH]|Opsonin Proteins/immunology[MESH]|Phagocytosis[MESH]|Pregnancy[MESH]|Rabbits[MESH]|Rats[MESH]|Receptors, IgG/antagonists & inhibitors/immunology[MESH]|Rh Isoimmunization/*therapy[MESH]|Rh-Hr Blood-Group System/*immunology[MESH]|Rho(D) Immune Globulin[MESH] |
