Intrauterine immunology in allergy and infection

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Medicine

Sammanfattning: Pregnancy is interesting from an immunological point of view. The maternal immune system has to tolerate the fetus and at the same time also protect against infection. The placenta is not a completely tight barrier: in fact, cells can pass through in both directions. Allergy often starts early in life and intrauterine factors have been proposed to play a role in development of allergy. The overall aim of this thesis was to study the innate response to infection and the presence, origin and specificity of IgE antibodies in the placenta, and furthermore the effect of maternal allergy on lymphocytes in the newborn child. Histological chorioamnionitis most often corresponds to an intrauterine bacterial infection and in this thesis, we have investigated different factors in the placenta in relation to chorioamnionitis. In the first study, we investigated TLR2 expression. We demonstrated that expression of TLR2 was lower in placentas with chorioamnionitis compared to healthy placentas. This suggests that TLR2 could be involved in the response to pathogens in the placenta. In the second study, we analyzed the presence of IgE in the placenta in relation to two different intrauterine infections; chorioamnionitis and malaria. There was no effect of either type of infection on the presence of IgE antibodies. In the third study we investigated the amount of macrophages (Hofbauer cells) in the placenta in relation to chorioamnionitis. There was a decrease of the macrophages in infected placentas compared to controls. The intriguing finding of IgE antibodies in the villous stroma of placenta made us curious about their origin and specificity. In paper IV, we established a method to elute placental IgE. By comparing the specificity profile of placental IgE with that of maternal plasma and cord blood, we could conclude that placental IgE most probably is of maternal origin. We also demonstrated that it could be allergen specific. In the last paper of this thesis, neonatal immune phenotype and response in relation to maternal allergy was investigated. We could not see an effect of maternal allergic disease on the phenotype of neonatal T- or B cells, proliferation or presence of regulatory T cells in CBMC in response to allergen stimulation. This indicates that the intrauterine environment of allergic mothers does not affect the neonatal response to allergens or the phenotype of neonatal lymphocytes. The factors studied could, however, still have a role in relation to later allergy development in the children. Taken together, the work presented here contributes to the understanding of the role of the placenta and the intrauterine environment in infection and allergy. The work herein demonstrates that chorioamnionitis affects the TLR2 expression and presence of CD68+ Hofbauer cells in the placenta. It also indicates that placental IgE originates from the mother and that it can be allergen specific. Furthermore, we could not detect any difference in phenotype of T and B cells or the immune response to allergen stimulation in neonates of allergic mothers as compared to neonates of non-allergic mothers.

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