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IgG-mediated Immune Suppression: the Effect on the Host Immune SystemBrinc, Davor 30 July 2008 (has links)
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.
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IgG-mediated Immune Suppression: the Effect on the Host Immune SystemBrinc, Davor 30 July 2008 (has links)
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.
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Presença de Aloanticorpos Eritrocitários em gestantes Rh negativo, atendidas na Fundação de Hematologia e Hemoterapia do Amazonas (Hemoam).Cavalcante, Francimary de Oliveira 26 October 2005 (has links)
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Previous issue date: 2005-10-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The presence of G class irregular erythrocyte alloantibodies in the blood circulation during
pregnancy may cause a series of consequences to the newborn. The alloimmunization can
occur under different situations, such as: blood incompatibility during delivery, miscarriage,
amniocentese, blood transfusion, among others, all considered being risky. This study
investigated the occurrence of regular and irregular circulating alloantibodies in women under
the care of the Program of RhD-negative Expecting Mothers (PGRhN) of the Amazonas
Hematology and Hemotherapy Foundation (HEMOAM). A retrospective study was carried
out compiling the data of all expecting mothers under care during 2003, as well as the
information regarding their newborns. A second study, prospective, was done by analyzing
the blood samples of expecting mothers under the care of the PGRhN between April and
November 2004, as well as the information on their respective babies. All tests were carried
out following the methodology presented in the American Association of Blood Bank
Technical Manual (2005). The comparison of the alloimmunization frequency between the
first (5.6%) and the second (3.5%) studies showed no significant difference. The frequency of
antibodies attached to the erythrocytes in the newborns of alloimmunized mothers were high,
67% in the retrospective study and 72.7% in the prospective study. The frequency of G class
regular alloantibodies was 87% in the prospective study and the ABO maternal-fetal
incompatibility was 17% in O type mothers with A or B type progeny. The occurrence of
irregular alloimmunization in the PGRhN is still high, comparing with the numbers of other
authors, indicating that the Program may be failing in preventing the problem to occur or
errors may have been made during the sorotherapy of patients under risk. Also, it was
observed a high frequency of G class regular alloantibodies which can cause the Hemolytic
Disease of the Newborn (HDN) due to ABO incompatibility. / A presença de aloanticorpos irregulares eritrocitários da classe G, na circulação materna, pode causar serias conseqüências ao neonato. A aloimunizacao pode ocorrer em diversas situações, consideradas de risco, como partos com incompatibilidade sanguínea, aborto, amniocentese, transfusões sanguínea, dentre outras. Neste estudo foi verificada a presença de aloanticorpos circulantes regulares e irregulares, em mulheres atendidas no Programa de Gestantes Rh Negativo (PGRhN) da Fundação de Hematologia e Hemoterapia do Amazonas (HEMOAM).
Foi realizado um estudo retrospectivo e para o qual, foram levantados os registros de gestantes atendidas durante o ano de 2003, como também, os dados de seus recém-nascidos.
Outro estudo, prospectivo, foi realizado e foram analisadas amostras de sangue de gestantes, atendidas no PGRhN entre os meses de abril a novembro de 2004, como também de seus recém-nascidos. Todos os testes utilizados foram preconizados pelo Manual Técnico da American Association of Blood Bank (2005). A freqüência de aloimunizacao no estudo Retrospectivo (5,6%) não apresentou diferença significante com a do estudo Prospectivo (3,5%). A freqüência de anticorpos fixados as hemácias, nos recém-nascidos de mães aloimunizadas, foi bastante alta, de 67% no estudo prospectivo e de 72,7% no estudo retrospectivo. A freqüência de aloanticorpos regulares da classe G foi de 87% nas gestantes do estudo prospectivo e a incompatibilidade ABO materno-fetal foi de 17% para as mães O, com filhos A ou B. O índice de aloimunização irregular no PGRhN ainda e muito alto, quando comparado aos trabalhos de outros autores, mostrando que devem estar ocorrendo falhas na prevenção e possíveis erros na administração da soroterapia, em situações de risco.
Ressalte-se ainda, a alta freqüência de aloanticorpos regulares da classe G, que podem induzir a Doença Hemolítica do recém-nascido (DHRN) por incompatibilidade ABO.
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