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Biomedical subjects

A E Beer

Publications and source records attributed to A E Beer.

At least 91 records · Page 5Linked to original sources

Pathogenesis of Rh immunization in primigravidas. Fetomaternal versus maternofetal bleeding.

Rh immunization occurring during a first pregnancy with no history of preceding abortion or transfusion may result when Rh incompatible fetal to maternal bleeding ensues early enough in the gestation to initiate a maternal immune response before parturition. Alternatively, the initial antigenic stimulus could be the consequence of maternal to fetal transfer of Rh-incompatible erythrocytes while the patient herself was in utero or at the time of her own delivery. These hypotheses were tested by 1) analysis of the blood group and Rh of 22 Rh-immunized primigravidas, their infants, and their own mothers; 2) comparison of the number of fetal cells in the maternal circulation during the antepartum period in 20 women at high risk for fetal to maternal bleeding with their matched controls; and 3) Rho (D) antibody determinations in 70 Rh-negative infants born to Rh-positive mothers. The results indicate that antepartum fetal to maternal bleeding is the usual cause of Rh immunization in primigravidas, and the Rh-negative woman with blood group A, B, or AB who gestates an ABO-compatible Rh-positive male is at highest risk. The antepartum use of anti-Rho (D) immune globulin has potential prophylactic value in this situation.

ABO Blood-Group System↗

In vitro studies on the T-lymphocyte population of human milk.

Human milk lymphocytes (ML) can be partially purified and propagated in vitro as a means of assessing their immunological function. When exposed to a variety of stimuli known to activate T lymphocytes, ML respond in a unique manner that indicates a selected population of immunocompetent cells. ML are hyporesponsive to to nonspecific mitogens and respond in a reduced manner to histocompatibility antigens on allogeneic cells. In most cases, they are completely unresponsive to C. albicans although blood lymphocytes from the same patients respond to the antigen. The Kl capsular antigen of E. coli induces significant proliferation in lymphocytes obtained from milk, but fails to stimulate blood lymphocytes. This dichotomy of reactivity does not appear to result from suppressive factors or cells in milk or insufficient adherent cell function. Rather it appears to reflect the accumulation of particular lymphocyte clones in the breast and the local nature of mammary tissue immunity at the T-lymphocyte level.

Antigens, Bacterial↗

Immunogenetic factors in preeclampsia and eclampsia. Erythrocyte, histocompatibility, and Y-dependent antigens.

Determination of ABO and HL-A antigens and sex ratio of infants born to 46 women with preeclampsia or eclampsia, in comparison with normal controls, disclosed no predominant blood group, HL-A haplotype, or qualitative difference in maternal-fetal incompatibility. These results suggest that a link between immunologic mechanisms and the pathogenesis of toxemia syndromes, if present at all, must be associated with feto-placental tissue-specific antigens.

ABO Blood-Group System↗

Histoincompatibility and maternal immunological status as determinants of fetoplacental weight and litter size in rodents.

Studies conducted upon inbred strains of mice, hamsters and rats have shown that following the interstrain matings the now familiar covert reactivity of pregnant females to the alloantigens of their conceptuses may benefit the latter in two ways; firstly, it exerts a significant influence upon placental weight, and indirectly upon the birth weight of the fetus-allogeneic placentas tending to be heavier than syngeneic placentas, and mothers specifically presensitized against alien paternal tissue antigens gestate fetuses with heavier placentas than normal females. Specifically tolerant mothers, on the other hand, produce smaller, F1 hybrid, fetoplacental (fp) units. The classic notion that the disparity between the birth weights of F1 hybrid and homozygous offspring is due to hybrid vigor has been challenged by the finding that DA and (DA times F1)F1 hybrid blastocysts transferred to the uteri of genetically tolerant (DA times F1)F1 hybrid rats produce fp units of similar weight Maternal immunological reactivity against the fetus qua allograft may make a significant contribution here. Additional support for the premise that maternal reactivity against fetal alloantigens in some way promotes the growth of the fp unit was afforded by the finding that excision of the para-aortic lymph nodes (which drain the uterine horns) from females before interstrain matings resulted in smaller fp units than in females subjected to sham operations. The finding with one rat strain combination that passive immunization of females with serum against their F1 hybrid conceptuses promoted the growth of the latter suggests that a humoral rather than a cellular immunity may be involved. Secondly, in the three species studied, it was observed that genetic disparity between a conceptus and its mother significantly improved its chances of implantation and development to term.

Animals↗

Immunologic benefits and hazards of milk in maternal-perinatal relationship.

Aside from nutritional significance, milk affords infant mammals immunologic benefits. However, it is not without immunologically based hazards. These stem from its antigenicity and the fact that in certain species that receive their maternal immunologic endowment postpartum, hemolytic disease of the newborn may be mediated by colostral antibodies. Awareness that viable leukocytes are ingredients of colostrum and milk has stimulated interest in the significance of these cells. Skin grafting tests on foster-nursed rats and mice have given circumstantial evidence that, in these species, leukocytes may be transmitted naturally from the mother's blood stream to the suckling's blood stream through the milk, and that these cells may be beneficial (adoptive immunization) or, in some genetic contexts, harmful (initiating graft-versus-host disease). In man, too, studies on necrotizing enteritis and other disease provide increasing support for the thesis that leukocytes in milk fulfill a protective function, possibly as a consequence of their "natural" transplantation.

Animals↗

Maternally acquired runt disease.

Without altering the structural integrity of the placenta by irradiation or drugs, we have shown that it is possible to immunize females both adoptively and actively against the paternally inherited transplantation antigens of their fetuses. Such immunization causes a high incidence of runt disease among the litters. Although the putative chimeric status of the affected offspring has yet to be confirmed, the results of our experiments support the thesis that runt disease is caused by the activities of "unwanted" immigrant lymphocytes from the maternal circulation. Our results suggest that immunologically activated cells are more likely to cross the placenta than normal cells and that this greater mobility may not be related to the immunologic specificity of the activated cells. Two factors may have contributed to the apparent failure of numerous previous attempts to demonstrate the capacity of transplantation immunity to affect the well-being of a fetus or, more correctly, its placenta, in the way that might be expected of a homograft. (i) Investigators were preoccupied with obtaining a classic type of rejection, in utero, analogous to the rejection of an orthotopic skin homograft. The birth of consistently healthy-looking litters, interpreted as a failure of the experiment, convinced the investigators of the efficacy of nature's solution of the homograft problem and there was no reason for them to suspect its possible limitations. Observation of the litters for several weeks might have uncovered the phenomenon of maternally induced runt disease. (ii) Most investigators resorted to hyperimmunization of the mothers. This would have facilitated the synthesis of protective isoantibodies capable of interfering with the expression of the potentially harmful cellular immune response (6). Ever since the abnormalities of runt disease were first described they have repeatedly been compared to those observed in patients with certain lymphomas (17). Various theories have been propounded as to how maternally transmitted graft-versus-host reactivity might lead to the development of these tumors. In mice it has been established that graft-versus-host reactivity may result in a high incidence of lymphomas (18). Recent analysis indicates that this graft-versus-host reactivity unmasks and activates normally latent and undemonstrable oncogenic viruses (19). The work we describe in this article may have some relevance to the possible clinical significance of transplacental cellular mobility in man. We suggest that the relatively high incidence of lymphomas in children might also be, in part at least, due to unmasking of oncogenic viruses by subclinical graft-versus-host reactivity mediated by immunocompetent cells of maternal origin. The statistical evidence that male infants are at greater risk than females (20) is concordant with our observation that maternally induced runts include a significantly higher proportion of males than females (10).

Animals↗