American journal of reproductive immunology and microbiology : AJRIM最新文献

The theoretical causes of recurrent spontaneous abortion may be several. Gill and others have suggested that the human disease may be mimicked by the rodent genetic diseases, as exemplified by the T locus in mice. He would suggest that there may be lethal recessive gene phenomena which may cause repeated abortion, or if the abortion is prevented by immunological means the birth of genetically defective individuals. The evidence presented here shows that prevention of abortion by immunological treatment, that is immunisation of the wife with paternal lymphocytes, is associated with a very high success rate, and the children born do not have more than the normal incidence of birth defects. Thus far, over the 7 years of study, the children also appear to develop normally. Probably the reason for this is that the methods of selection for treatment tend to exclude quite effectively those couples with pure genetic problems. In particular, the the exclusion of women who have had more than one live child removes a group of women who might have lethal recessive problems which would only affect 25-50% of the offspring. The interactive gene products that may produce abortion of all pregnancies, suggested as a theoretical concept by Gill, would be expected to show an incidence no more than the square root of the frequency of the recessive disease, and are probably too few to be seen even in the more than 1,500 couples we have studied.

Female mice from four congenic strains were bred to males of the same four strains to determine the effect of maternal-fetal disparity at major histocompatibility complex (MHC) and the effect of non-MHC minor histocompatibility antigens on the weight of the feto-placental unit. An increase in feto-placental weights was found in all three of the four strains that could be evaluated when mother and fetus differed at multiple minor histocompatibility loci, irrespective of whether disparity at the MHC was present. No increase in feto-placental weights was found when mother and fetus differed at the MHC alone. The fact that these results were found in all strains studied suggests that the effect of maternal-fetal disparity at multiple minor histocompatibility antigens (minor HA) on the weight of the feto-placental unit is biologically significant. We conclude that if the increase in weight of the feto-placental unit results from immunostimulation, then minor histocompatibility antigens are the primary target of the maternal immune response to the histocompatibility antigens of the fetus.

The porcine zona pellucida represents a unique immunocontraceptive target antigen. Initial active immunization studies using crude or partially purified zona components as immunogens resulted in adverse, nonreversible effects on ovarian folliculogenesis, but more recent findings in nonhuman primates indicate that such effects are not as severe and are reversible. Consequently, current efforts are directed toward identifying a zona immunogen that elicits contraceptive antibodies that produce no adverse effects on the ovary. Other studies are in progress to determine optimal injection/immunization format, proper immunogen dosage, and appropriate adjuvant for use in the zona-antizona immunocontraceptive system. Recent data have been very encouraging and emphasize the contraceptive efficacy of this approach to reproduction control.

The presence of immunosuppressive early pregnancy factor (EPF) in the maternal serum has so far been associated with gestation. Its presence in the serum of women with gestational trophoblastic tumors was investigated. The results indicate that while EPF activity was detected in the serum of women with choriocarcinoma, no such activity was detected in the serum of women with hydatidiform mole, leading to the novel use of EPF as a marker to distinguish these two clinical situations. Results of the experiments also suggest that EPF moiety present in the maternal serum during pregnancy may be of different molecular entity than that present in the serum of women with choriocarcinoma.

Human and rabbit antibodies to trophoblast-lymphocyte cross-reactive (TLX) antigens were employed in an enzyme-linked immunosorbent assay (ELISA) to identify and characterize the TLX alloantigen system on human platelets. Neither washing nor extraction in chaotrope or acid altered platelet TLX. The antigen was significantly changed by pronase and trypsin digestion, but Folch extraction yielded antigen in the hydrophilic interface, suggesting carbohydrate. Rabbit antibodies prepared to HLA-negative human syncytiotrophoblast TLX antigens were shown by platelet ELISA to have the same specificity and similar allotypy as anti-TLX antibodies from secondary (2 degrees) spontaneously aborting women. Patients with normal pregnancies before becoming 2 degrees aborters had both IgG and IgM antibodies to TLX. Anti-TLX in patients who never had a normal pregnancy were predominantly IgG. ELISA reactions performed with different concentrations of protein in the buffers detected anti-TLX activity in buffers containing high protein concentrations. This has been observed in studies of blocking antibodies in graft-versus-host disease and immune responses to tumor cells. Platelet TLX offers a new genetic and immunological approach to study similarities of the host-parasite relationships in pregnancy, transplantation, and cancer.

Two monoclonal antibodies raised against human amnion, GB3 and GB5, were used in an indirect immunoperoxidase method to investigate the expression of amnion antigens by spiral arteries in pregnant and nonpregnant uterine tissues. GB3 showed focal reactivity with occasional spiral arteries in the placental bed throughout pregnancy, but no GB3-staining was observed in nonpregnant endometrium. In contrast, GB5 showed bandlike circumferential reactivity with spiral arteries at all gestational ages examined. GB5-positivity showed no relation to the presence of endovascular or perivascular trophoblast. In nonpregnant endometrium, GB5 labeled rare spiral arteries. However, in a premenstrual specimen showing pseudodecidual change, there was circumferential reactivity with GB5 resembling that in pregnancy. The reaction patterns of GB3 or GB5 were not similar to those for two other basement-membrane components, fibronectin and type IV collagen. The results suggest that expression of the GB5 antigen may in part be regulated by hormones.

The beta-subunit of human chorionic gonadotropin (hCG) conjugated to tetanus toxoid is being investigated as a vaccine for human fertility control. Initial clinical trials indicated that the level of antibody response induced by such an immunogen was not always sufficient to prevent pregnancy. Therefore, efforts are being made to evaluate new carriers for the beta-subunit and to select adjuvants to yield a more efficient vaccine. In the present report, we demonstrate that conjugates of the beta-subunit of hCG with muramyl dipeptide (MDP), or its nonpyrogenic derivative murabutide, may have potential as an effective antipregnancy vaccine. The copolymer of beta hCG and MDP administered with Al(OH)3 to mice induced a high anti-beta hCG response, better than that induced by the conjugate of beta hCG to tetanus toxoid given with Al(OH)3. Moreover, the antibodies induced by such an immunogen were competent for neutralizing the biological activity of hCG in vivo. Even more interesting, a copolymer of beta hCG and of murabutide induced high levels of biologically active antibodies. This immunogen may represent a promising candidate for the development of an efficient vaccine for human fertility control.

Fourteen unvaccinated and seronegative ewes were experimentally infected with bovine virus diarrhoea virus around day 60 of pregnancy. Two other groups of pregnant ewes served as control animals. The animals were followed with ultrasound scanning to study the status of the fetus and with frequent blood sampling for analysis of progesterone and 15-keto-13,14-dihydro-PGF2 alpha, two hormones that could reflect the propagation of the infection. The unvaccinated ewes responded to the infection with abortion, resorption of the fetus, mummification or no changes at all. The endocrinological changes reflected in a most adequate way the pathological changes in the uterus. Detailed endocrinological studies can contribute to the understanding of the pathogenesis of some infectious diseases that affect reproduction.