Background Immune responses to infection are uniquely regulated during gestation to allow for antimicrobial defence and tissue repair, whilst preventing damage to developing fetal organs or the triggering of preterm labour.Objective A review and analysis of studies delineating gestationspecific immune modulation and intra-amniotic regulation of pro-inflammatory immunity.Search strategy Identification of the alterations between the fetus/ neonate and adult with regard to the endogenous and infectioninduced expression of molecules with immune regulatory properties, and the characterisation of intra-amniotic immune mediators that inhibit bacterial-induced pro-inflammatory cytokine production.Selection criteria English and non-English publications from 1985 to the present.Data collection and analysis An electronic literature search using MEDLINE, PubMed, articles cited in the primary sources, as well as pregnancy-related immunology research from our laboratory at Weill Medical College of Cornell University.Main results During fetal development, interleukin (IL)-23, IL-10 and IL-6, as well as T-helper-17 (Th17)-mediated immune responses, are upregulated, whereas tumour necrosis factor-a (TNF-a) and IL-1b-and Th1-mediated immune responses are downregulated in the intrauterine environment (both the fetal compartment and the amniotic compartment). Infection-related immunity during gestation is preferentially directed towards combating extracellular microbial pathogens. Amniotic fluid and the neonatal circulation contain multiple components that improve the ability of the developing neonate to tolerate microbial-induced immune activation.Conclusions The repertoire of immune mechanisms to control infection and inflammation differ between fetal and adult life. The dual mechanisms of resistance to infection and tolerance to infection-induced immune activation prevent damage to the developing fetus and the triggering of premature labour.
A DNA polymerase was isolated from human spermatozoa. In one procedure, spermatozoa were decapitated with detergent, the heads purified and then lysed with dithiothreitol, trypsin and deoxyribonuclease. DNA polymerase was isolated from the lysate by sedimentation through an 18% Metrizamide solution, solubilization with 0.8 M-KCl-0.5% Triton X-100 and sequential chromatography on DEAE cellulose, phosphocellulose and hydroxylapatite. Alternatively, the heads of intact spermatozoa, untreated with detergent, were lysed as above; the subsequent Metrizamide pellet fraction was isolated and further fractionated by gel filtration and buoyant density centrifugation. The enzyme in this fraction was solubilized with KCl-Triton X-100. Characterization by velocity centrifugation and phosphocellulose chromatography revealed that it possessed properties indistinguishable from those of the enzyme purified from isolated sperm nuclei. The DNA polymerase had an apparent molecular weight of 79,000-89,000, Mn2+ (1 mM) was the preferred divalent cation and ativity was inhibited by concentrations of potassium phosphate greater than 10 mM. The synthetic template preferences of the enzyme were dT12-18 . poly rA > poly(dA-dT) > dT12-18 . poly dA; no activity was observed with dG12-18 . poly rC or dT10.
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