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Immunological dysfunction has been proposed to explain the etiology of recurrent pregnancy loss (RPL). The immunological environment differs between the decidua basalis and decidua parietalis, and also between RPL cases with normal fetal chromosomes and those with abnormal fetal chromosomes. The problem with analyzing decidual tissues from spontaneous abortions is that cause versus effect phenomena are difficult to distinguish. Recent data show that the immune system in a late-stage miscarriage is completely different from that in an early-stage miscarriage. If immunocompetent cells can cause RPL, the immunological environment may be a causative factor, especially in an early-stage miscarriage, at the decidua basalis, and/or in cases of RPL with a normal embryo. Careful examination of the immune system at the decidua basalis in an early-stage miscarriage in RPL cases with normal fetal chromosomes may reveal useful information. This paper aimed at finding a cause of RPL by analyzing the balance of the immune system between T cells and NK cells in an early-stage miscarriage. [ABSTRACT FROM AUTHOR]

Jespers V, Francis SC, van de Wijgert J, Crucitti T. Methodological issues in sampling the local immune system of the female genital tract in the context of HIV prevention trials. Am J Reprod Immunol 2011; 65: 368-376 The spread of HIV continues unabated in the most vulnerable populations of the world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine, pre-exposure prophylaxis or a vaccine, are urgently needed in the fight against new infections. We must make a commitment to supporting innovative research and product design, so that one or more of these products provide a halt to the spread of HIV. Above all, these products should be proven to be safe and not negatively disturb the local immune system in a way that facilitates or enhances heterosexual transmission of HIV. HIV specific and non specific cellular and humoral local vaginal immunity must be assessed in clinical trials when testing prevention products for safety or efficacy. A proven, well-documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune responses. In this paper, we will discuss methods for vaginal immunology sampling in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Studies have implicated sexual violence as a strong correlate of HIV acquisition in women. Characterizing how such violence affects the female immune system may provide insight into the biological mechanisms of HIV transmission and ultimately improve global HIV prevention strategies. Little research has been carried out in this domain, and the obstacles to investigation can be daunting. Here, we describe methodological challenges encountered and solutions explored while implementing a study of dysregulation of immune biomarkers potentially indicative of increased HIV susceptibility in women following sexual assault. Challenges included accessing sexual assault survivors and defining sexual assault, promoting study participant well-being during research engagement, reducing selection and information bias, collecting and processing biological samples, and adjusting for confounders such as reproductive tract infections and emotional and physical abuse. We found that many survivors of sexual assault welcomed the attention from study staff and felt empowered by the opportunity to help other women at risk for violence. Well-trained research staff and well-articulated community and medical partnerships were key methods to overcoming challenges while promoting the safety and welfare of vulnerable study participants. [ABSTRACT FROM AUTHOR]

Problem The chronic placental insufficiency is the most common cause of intrauterine hypoxia, retardation of fetal growth, and other threatening conditions. Immune disturbances may occur in the system 'mother-placenta-fetus.' Method of study Biochemical blood indicators were studied on an automated biochemical analyzer. Pattern of lymphocyte subpopulations was detected by direct membrane immunofluorescence. Results Study revealed imbalance of immune parameters, caused by placental insufficiency (increase natural killers ( CD16+, CD56+), B lymphocytes ( CD19+ CD3−), T and B lymphocytes with HLA- DR+ antigen, and early activation of immune cells (by CD25+), as well as disorders in apoptotic mechanisms (by CD95+)). Conclusion Placental insufficiency leads to abnormalities of the immune system in pregnant, parturient women and maternity patients which were evaluated by localization of activation markers CD25+ CD95+ on the CD3+, CD4+, CD8+, CD16+, CD56+ lymphocytes. This is reflected in the change of lymphocyte functions in newborns. [ABSTRACT FROM AUTHOR]

The female genital tract undergoes anatomic changes from birth through menopause. Concurrently, the relative levels and roles of estradiol and progesterone dramatically change during the female life cycle. This review provides a conceptual overview of clinically relevant anatomic and hormonal changes in the female genital tract, and how these changes may affect HIV-1 pathogenesis, transmission, and mucosal immunology and protection against HIV and STIs across the female life cycle. [ABSTRACT FROM AUTHOR]

It has long been believed that there is no immune interaction between mother and conceptus during pregnancy. This concept changed after evidence was provided that the maternal immune system is aware of the semiallogeneic conceptus and develops strategies to tolerate it. Since then, finely regulated mechanisms of active tolerance toward the fetus have been described. This Special Issue of the American Journal of Reproductive Immunology deals with these mechanisms. It begins with the description of minor histocompatibility antigens in the placenta; it further goes through adaptive immune responses toward paternal fetal antigens, mostly concentrating on regulatory T cells and molecules modulating the Th1/Th2 balance. The participation of antibody-producing B cells in normal and pathological pregnancies is also discussed. This introductory chapter resumes the concepts presented throughout the Issue and discusses the clinical applications raised from these concepts. [ABSTRACT FROM AUTHOR]

Citation Giraldo PC, de Carvalho JBJ, do Amaral RLG, da Silveira Gonçalves AK, Eleutério J Jr, Guimarães F. Identification of Immune Cells by Flow Cytometry in Vaginal Lavages from Women with Vulvovaginitis and Normal Microflora. Am J Reprod Immunol 2012; 67: 198-205 Problem The extent of the vaginal immune response is not fully determined. The purpose of this study was to evaluate the vaginal immune cells from women with vulvovaginitis (VV). Method of Study A total of 142 volunteers diagnosed with bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and BV associated with VC or normal microflora were sampled to evaluate the immune cells by flow cytometry. The immune cells were obtained by vaginal lavage and labeled with fluorochrome-conjugated monoclonal antibodies to identify neutrophil granulocytes, macrophages, CD4+ and CD8+ T lymphocytes, B lymphocytes, and NK lymphocytes. Results Neutrophil granulocytes were present in 84.6% of samples among the leukocyte populations. Considering samples in which neutrophils were present, the mean percentage of neutrophil granulocytes was significantly higher in women with VC than BV and normal microflora and was significantly lower in women with BV than normal microflora. Macrophages and lymphocytes were present in a lower percentage of samples. The mean percentage of CD4+ T lymphocytes in vaginal lavages was significantly higher in VC and BV compared with women with normal microflora. Conclusions Neutrophils were the predominant leukocytes and were associated with VC and inversely with BV. CD4+ T lymphocytes were associated with both VC and BV. [ABSTRACT FROM AUTHOR]

Citation Best LG, Nadeau M, Davis K, Lamb F, Bercier S, Anderson CM. Genetic variants, immune function, and risk of pre-eclampsia among American Indians. Am J Reprod Immunol 2012; 67: 152-159 Problem To determine the prevalence in an American Indian population of genetic variants with putative effects on immune function and determine if they are associated with pre-eclampsia (PE). Method of study In a study of 66 cases and 130 matched controls, six single nucleotide polymorphisms (SNP) with either previously demonstrated or postulated modulating effects on the immune system were genotyped. Allele frequencies and various genetic models were evaluated by conditional logistic regression in both univariate and multiply adjusted models. Results Although most genetic variants lacked evidence of association with PE, the minor allele of the CRP related, rs1205 SNP in a dominant model with adjustment for age at delivery, nulliparity, and body mass index, exhibited an odds ratio of 0.259 (95% CI of 0.08-0.81, P = 0.020) in relation to severe PE (48 cases). The allelic prevalence of this variant was 46.1% in this population. Conclusion Of the six SNPs related to immune function in this study, a functional variant in the 3′UTR of the CRP gene was shown to be associated with severe PE in an American Indian population. [ABSTRACT FROM AUTHOR]

The article presents a study on the immunological aspects of endometriosis. The study analysed how the occurrence and development of endometriosis affect the immune system of women. According to the author, the initiation and progression of endometriosis and its effect in infertility and cancer is related to the function and dysfunction of the female immune system.

The article focuses on a study that examined the influence on the induced pathology of the genetic background of the immune system and the type of animal model of antiphospholipid syndrome (APS) used. The results of the induction of APS by tetanus toxoid (TTd) hyperimmunization in mice are described. The role of TTd immunization and intravenous application of monoclonal antibody 26 in inducing the reproductive pathology is also discussed.

Problem Mannose-binding lectin (MBL) is a pattern-recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre-eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre-eclampsia. Method of study This cross-sectional study included normal pregnant women ( n = 187) and patients with pre-eclampsia ( n = 99). Maternal plasma MBL concentrations were determined by ELISA. Results Women with pre-eclampsia had a higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three-modal, the subintervals in normal pregnancy were low (<143.7), intermediate (143.7–1898.9) and high (>1898.9 ng/mL). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with pre-eclampsia was larger in the high subinterval ( P = 0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals ( P = 0.02). Conclusions The median maternal plasma MBL concentration is elevated in patients with pre-eclampsia and a larger proportion of these patients are in the high subinterval than normal pregnant women, suggesting that this component of the innate immune system is involved in the mechanisms of disease in pre-eclampsia. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are a large family of proteins with different molecular weights and different intracellular localizations. These proteins undertake crucial functions in maintaining cell homeostasis, and therefore they have been conserved during evolution. HSP gp96 also known as glucose-regulated protein grp94, is the primary chaperone of the endoplasmatic reticulum. Gp96/grp94, because of its peptide chaperone capacity and its ability to interact actively with professional antigen-presenting cells (APCs), is also endowed with crucial immunological functions such as natural adjuvant for priming innate and adaptive immunity. To make gp96 accessible to the immune system without biochemical purification and without cell lysis, we generated a secreted form of gp96. The immunological properties of secreted gp96 and its implications for vaccine in human cancer and infectious diseases will be discussed. [ABSTRACT FROM AUTHOR]

Problem Little is known about immunological recovery in post-partum women and if lactational status affects immunocompetence. Many physiological changes occur, such as uterine involution and recovery of non-pregnant immune status. These changes may also affect susceptibility to disease. Method The study compared immune and inflammatory activation markers (serum cytokines, Epstein Barr viral antibody titer, neopterin, c-reactive protein (CRP), lymphocyte subset percentages, ex vivo cytokine production, lymphocyte proliferation, salivary Immunoglubulin A (sIgA) in exclusively breastfeeding (EB) and exclusively formula feeding (EF) women at 4–6 weeks post-partum, and control (C) women. Results EBs had higher ratios of interferon- γ (IFN- γ)/interleukin-10 (IL-10) than EFs, and post-partums were higher than Cs. Both IFN- γ and IL-10 were significantly higher in post-partums compared to controls. Post-partums also had higher proinflammatory cytokines, CRP and neopterin, salivary IgA and fewer infection symptoms. There were also differences in lymphocyte subsets. Conclusions The post-partum period is oriented towards heightened and activated innate and specific immune defenses, with breastfeeding providing a boost in these phenomena. [ABSTRACT FROM AUTHOR]

PROBLEM: The immune system contributes to the outcome of pregnancy by complex immunological interactions. Cytokines especially influence the immune milieu pro or contra pregnancy. T helper 1 (Th1) cytokines [tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] cause inflammation and together are thought to threaten the maintenance of pregnancy. It has been proposed that increased levels of these Th1 cytokines activate coagulation via up-regulating the novel prothrombinase, fgl2. This study further investigates the Th1 cytokine up-regulation of fgl2 expression in a pathophysiological, stress induced abortion model, and an inflammatory, interleukin-12 (IL-12) triggered abortion model.. METHOD: The DBA/2J-mated CBA/J female mice were exposed to sonic sound stress or were injected with IL-12 during early gestation. On day 13.5 of pregnancy the uteri were removed and the resorption rate was calculated. We evaluated TNF-α, IFN-γ, fgl2 as well as IL-12 messenger RNA (mRNA) expression in decidual samples of all mice by quantitative, real-time polymerase chain reaction (PCR). RESULTS: A similar resorption rate of 24% was detected in stressed mice, as well as in IL-12 injected mice compared with approximately 11% in non-stressed, non-injected control mice. In stressed mice compared with controls, we observed on day 13.5 up-regulated TNF-α, unchanged IFN-γ down-regulated fgl2, and a slightly increased levels of IL-12. In the IL-12 triggered abortion model, we observed up-regulated levels of TNF-α, IFN-γ and fgl2. CONCLUSION: These novel data suggest two distinct cytokine patterns leading to similar abortion rates. A physiological cascade associated with up-regulation of TNF-α, and an IL-12-triggered cascade characterized by persistent up-regulation of TNF-α and IFN-γ as well as a persistent increase in fgl2. [ABSTRACT FROM AUTHOR]