Immunologic influences on reproductive biology: sperm gametogenesis and maturation in the male and female genital tracts.
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Biomedical subjects
Publications and source records attributed to A E Beer.
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Critical features of the trophoblast for immune protection in the mother are: 1) it is resistant to cytotoxic lymphocytes and antibodies; 2) it forms a physical barrier to immune effector cells, but not antibody, preventing them from reaching the fetus; 3) it signals the migration of suppressor and other functionally hyporesponsive lymphocytes into the uterine decidua and uterine lymphatics; 4) it promotes the production of maternal serum MLR blocking antibody with paternal antigen specificity. Some of these immunological features are lacking in women with recurrent abortions of immune etiology. Eleven women who aborted an additional time post immunization with paternal leukocytes were compared with 26 women who delivered infants at term post immunization. It was found that those who aborted: 1) shared more HLA D/DR and MT locus antigens with their spouses; 2) were more hyporesponsive in MLR to paternal antigens pre and post immunization; 3) failed to develop female serum MLR blocking factors post immunization; 4) failed to develop humoral antibodies to B cell alloantigens; and 5) had lymphocytes in the uterine decidua mantling the conceptus and in the uterine lymphatics that were reactive/cytotoxic to paternal stimulating alloantigens. These results are in sharp contrast with the immunodynamics of peripheral blood leukocytes and decidual leukocytes to paternal alloantigens in women who delivered infants at term post immunization.
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Colostral lymphocytes (CL) from mothers 2 to 4 days post-partum and autologous maternal peripheral blood lymphocytes (PBL) were investigated for (1) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (2) target binding ability, (3) interferon (IFN)- and interleukin 2 (IL2)-induced augmentation of NK activity, (4) lectin-dependent cellular cytotoxicity (LDCC), and (5) the ability of culture-derived soluble suppressor factor(s) to inhibit the NK activity of normal allogeneic lymphocytes. CL depleted of adherent cells and Percoll-separated NK-enriched subpopulations of CL demonstrated significantly lower NK and ADCC activities compared to autologous PBL. However, the target binding ability of CL was comparable to autologous PBL. Although the residual NK activity of CL was augmented by IFN and IL2, the activity was not enhanced to the same level shown by autologous PBL. CL also demonstrated a significant enhancement of LDCC activity, although the activity was not stimulated to the levels shown by PBL. Culture supernates of CL manifested greater suppression of the NK ability of allogeneic PBL than culture supernates produced by autologous PBL. These results are consistent with a model that suggests differential partitioning of lymphocyte subpopulations between colostrum and peripheral blood.
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Critical features of the trophoblast for immune protection in the mother are: (1) its resistance to cytotoxic lymphocytes and antibodies; (2) it forms a physical barrier to immune effector cells, but not antibody, from reaching the fetus; (3) it signals the migration of suppressor and other functionally hyporesponsive lymphocytes into the uterine decidua and uterine lymphatics; (4) it promotes the production of maternal serum MLR (mixed lymphocyte reaction) blocking antibody with paternal antigen specificity. Some of these immunological features are lacking in women with recurrent abortions of immune etiology. Eleven women who aborted an additional time after immunization with paternal leukocytes were compared with 14 women who delivered infants at term post-immunization. It was found that those who aborted: (1) had HLA antigen profiles that did not differ significantly from those of control fertile couples or from observed antigen frequencies in North American Caucasians; (2) shared more HLA A, B, D/DR, and MT antigens with their spouses than controls; (3) were not more hyporesponsive in MLR to paternal antigens pre- and post-immunization when compared to controls; (4) failed to develop female serum MLR blocking factors post-immunization; (5) failed to develop humoral alloantibodies to B-cell alloantigens; (5) had lymphocytes in the uterine decidua mantling the conceptus and in the uterine lymphatics that were reactive/cytotoxic to paternal stimulating alloantigens. These results are in sharp contrast to the immunodynamics of peripheral blood leukocytes and decidual leukocytes to paternal alloantigens in women who delivered infants at term post-immunization.
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Large numbers of maternal lymphocytes are present in breast milk. We asked whether exposure of an infant to maternal lymphocytes during the process of breast feeding would have an effect on the subsequent reactivity of a patient to a maternal-donor related renal transplant. We studied the posttransplant course of 55 patients who had received a primary maternal-donor transplant. Twenty-seven recipients had been breast-fed during infancy and 28 recipients had not been breast-fed. A history of breast feeding was associated with a more favorable posttransplant course as measured by the percentage of patients who had no rejection episodes during the first posttransplant year (P less than or equal to .006). The one-year graft function rate for breast-fed recipients was 82%; this was statistically significantly better than the 57% measured for non-breast-fed recipients (P less than or equal to .05). Statistical significance of differences between groups was not attained when results were evaluated over a five-year interval. A difference between breast-fed and non-breast-fed recipients was not apparent when we evaluated a somewhat smaller group of patients who had received a paternal donor transplant. From these observations we conclude that the process of breast feeding during infancy may result in a measurable immunologic benefit to the recipient of a subsequent maternal-donor related renal transplant.
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Banked human milk has been widely used, although its composition and nutritional adequacy for preterm infants are uncertain. We randomized 76 healthy infants of less than or equal to 1500 gm birth weight to ad lib feedings of frozen BHM or a protein-mineral-calorie-enriched formula (Similac Special Care) designed to sustain intrauterine accretion rates; BHM contained 2.2 gm fat/100 ml and 60 kcal/100 ml (gross energy). Infants fed BHM ingested more milk (197 vs 165 ml/kg/day) but less gross energy (118 vs 143 kcal/kg/day); grew less rapidly in weight (15 vs 30 gm/day), length (0.7 vs 1.1 cm/wk), and head circumference (0.8 vs 1.2 cm/wk); and were discharged at a lower weight (2200 vs 2348 gm) and older age (61 vs 47 day) than infants fed formula (P less than 0.02). At 37 weeks' postmenstrual age, infants fed BHM were less responsive to Brazelton inanimate stimuli (mean total score 5.0 vs 7.5; P less than 0.02). With few exceptions, blood amino acids, pH, and serum electrolyte values were similar in both groups. The different caloric intake of our feeding groups may explain only part of the large difference in growth rate. Donor milk should not be fed to preterm infants unless it has been analyzed and the feedings shown to provide a nutrient intake considered appropriate to the needs of these infants.
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In summary, the routine administration of Rh immune globulin to Rh-negative women at risk has decreased the incidence of isoimmunization from 13 per cent to less than 2 per cent. Studies have shown that with the antepartum administration of 300 micrograms of Rh immune globulin to all Rh-negative women the incidence can be decreased still further to 0.07 per cent. Careful attention must be paid to all possible antepartum sensitizing situations, such as vaginal bleeding, premature labor, amniocenteses, and extrauterine manipulations. Cost-benefit analyses do show that benefits justify the extra expense of +35 to +40 per injection. The benefits and costs of routine Du typing versus its elimination for more sensitive testing remains somewhat controversial at this point.
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Bank milk collected by manual expression was less likely to be contaminated than milk collected by other methods. Contamination with coliforms and gentamicin-resistant Gram-negative rods was related to the pumps used by donors in their homes. Stringent precautions reduced but did not eliminate contamination.
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Women with recurrent consecutive spontaneous abortions of unknown etiology compared with those with recurrent spontaneous abortions of known etiology had a significantly increased frequency of sharing HLA antigens at the A, B, and D/DR loci with their spouses. This major histocompatibility complex (MHC) homozygosity was generally associated with female (responder) and male (stimulator) hyporeactivity in mixed lymphocyte culture reactions. The results indicate that MHC homozygosity between spouses is associated with postfertilization pregnancy wastage in humans.