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Review Article (review + article)
Selected AbstractsREVIEW ARTICLE: Cortical control of eye and head movements: integration of movements and perceptsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007L. Longtang Chen Abstract The cortical control of eye movements is well known. It remains unclear, however, as to how the eye fields of the frontal lobes generate and coordinate eye and head movements. Here, we review the recent advances in electrical stimulation studies and evaluate relevant models. As electrical stimulation is conducted in head-unrestrained, behaving subjects with the evoked eye and head movements sometimes being indistinguishable from natural gaze shifts, a pertinent question becomes whether these movements are evoked by motor programs or sensory percepts. Recent stimulation studies in the visual cortex and the eye fields of the frontal lobes have begun to bring both possibilities to light. In addition, cognitive variables often interact with behavioral states that can affect movements evoked by stimulation. Identifying and controlling these variables are critical to our understanding of experimental results based on electrically evoked movements. This understanding is needed before one can draw inferences from such results to elucidate the neural mechanisms underlying natural and complex movements. [source] REVIEW ARTICLE: An improved manufacturing process for Xyntha/ReFacto AFHAEMOPHILIA, Issue 5 2010B. KELLEY Summary., ReFacto® Antihemophilic Factor is a second-generation antihaemophilia A product manufactured using a process that includes therapeutic grade human serum albumin (HSA) in the cell culture medium, but is formulated without HSA as a stabilizer. Even though this second-generation antihaemophilia product has a good safety profile, a programme was implemented to eliminate all animal- and human-derived raw materials from the production process, thus producing a third-generation product. To that end, HSA has been removed from the master and working cell banks and from the culture medium. The hybridoma-derived monoclonal antibody formerly used in the purification process has been replaced by a chemically synthesized affinity peptide, and a virus-retaining filtration step has been added to enhance the clearance of large viruses, such as retroviruses. The purification process has been validated for the removal of a panel of model viruses and provides significant clearance of all viruses tested. Host cell- and process-derived impurity removal validations also were conducted, including host cell DNA and protein, in addition to the affinity peptide. Compared with the product manufactured according to the original process, these changes had no detectable effect on the structural integrity, stability or clinical efficacy of this antihaemophilia A product. The product produced by the improved manufacturing process is named XynthaÔ/ReFacto AF. [source] REVIEW ARTICLE: Hyperglycemia: a prothrombotic factor?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2010B. A. LEMKES Summary., Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaired fibrinolysis. Hyperglycemia plays an important role in the development of these hemostatic abnormalities, as is illustrated by the association with glycemic control and the improvement upon treatment of hyperglycemia. Interestingly, stress induced hyperglycemia, which is often transient, has also been associated with poor outcome in thrombotic disease. Similar laboratory findings suggest a common effect of acute vs. chronic hyperglycemia on the coagulation system. Many mechanisms have been proposed to explain this prothrombotic shift in hyperglycemia, such as a direct effect on gene transcription of coagulation factors caused by hyperglycemia-induced oxidative stress, loss of the endothelial glycocalyx layer, which harbours coagulation factors, and direct glycation of coagulation factors, altering their activity. In addition, both chronic and acute hyperglycemia are often accompanied by hyperinsulinemia, which has been shown to have prothrombotic effects as well. In conclusion, the laboratory evidence of the effects of both chronic and acute hyperglycemia suggests a prothrombotic shift. Additionally, hyperglycemia is associated with poor clinical outcome of thrombotic events. Whether intensive treatment of hyperglycemia can prevent hypercoagulability and improve clinical outcome remains to be investigated. [source] REVIEW ARTICLE: How to make a melanoma: what do we know of the primary clonal events?PIGMENT CELL & MELANOMA RESEARCH, Issue 1 2008Dorothy C. Bennett Summary Rapid advances have been made in our knowledge of the commonest genetic and epigenetic alterations found in human sporadic melanomas. Valuable recent contributions came from analyses of gene copy number by comparative genome hybridization, and from large-scale gene expression profiling. All of the commonest affected genes encode regulatory components. Loci with established importance in melanoma, like CDKN2A, BRAF and PTEN, have been joined by some less familiar genes including transcription factor sequences TBX2 and STK11 (LKB). This knowledge is reviewed in relation to the cellular signaling pathways affected by these molecules, their biological outcomes, and the implications as to what changes are required overall to generate a melanoma. The data support a model in which genesis of melanoma requires changes that (1) initiate clonal expansion, (2) overcome cell senescence, and (3) reduce apoptosis. [source] REVIEW ARTICLE: Cancer stem cells and human malignant melanomaPIGMENT CELL & MELANOMA RESEARCH, Issue 1 2008Tobias Schatton Summary Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma. [source] REVIEW ARTICLE: Medawar Redux , An Overview on the Use of Farm Animal Models to Elucidate Principles of Reproductive ImmunologyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Peter J. Hansen Citation Hansen PJ. Medawar redux , an overview on the use of farm animal models to elucidate principles of reproductive immunology. Am J Reprod Immunol 2010 Farm animals have been important models for the development of reproductive immunology. Two of the major concepts underpinning reproductive immunology, the idea of the fetal allograft and progesterone's role in regulation of uterine immunity, were developed using the bovine as a model. This volume of the American Journal of Reproductive Immunology is composed of review articles that highlight the continued relevance of farm animals as models for research in mammalian biology. It is important that a diverse array of genotypes are used to elucidate biological principles relevant to mammalian biology and human health because the nature of mammalian evolution has resulted in a situation where the genome of the most commonly used animal model, the laboratory mouse, is less similar to the human than other species like the cow. Moreover, the evolution of placental function has been accompanied by formation of new genes during recent evolution so that orthologs do not exist in any but closely related species. Given the infrastructure needs to study farm animal species, optimal utilization of these animals as models for biomedical research will require significant increases in funding to reverse a historical erosion of resources devoted to animal agricultural research. [source] REVIEW ARTICLE: Maternal Immune Responses to Trophoblast: The Contribution of the Horse to Pregnancy ImmunologyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Leela E. Noronha Citation Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. Am J Reprod Immunol 2010 The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigenicity of these invasive trophoblasts and how they affect the maternal immune system. Third, there is abundant evidence for local maternal cellular immune responses to the invading trophoblasts in the pregnant mare. The survival of the equine fetus in the face of strong maternal immune responses highlights the complex immunoregulatory mechanisms that result in materno,fetal tolerance. Finally, the parallels between human and horse trophoblast cell types, their gene expression, and function make the study of equine pregnancy highly relevant to human health. Here, we review the most pertinent aspects of equine reproductive immunology and how studies of the pregnant mare have contributed to our understanding of maternal acceptance of the allogeneic fetus. [source] REVIEW ARTICLE: Effects of Early Conceptus Signals on Circulating Immune Cells: Lessons from Domestic RuminantsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Troy L. Ott Citation Ott TL, Gifford CA. Effects of early conceptus signals on circulating immune cells: lessons from domestic ruminants. Am J Reprod Immunol 2010 While there are few similarities between mechanisms for extending corpus luteum (CL) function during early pregnancy in ruminants and primates, there is increasing evidence that conceptus-immune crosstalk in ruminants and primates affects the function of circulating immune cells at the very earliest stages of pregnancy. Most notable are changes in immune cell phenotypes with increased numbers of cells exhibiting the T regulatory phenotype and suppression of Th1 cytokines that promote tolerance to paternal alloantigens. Until recently, interferon , produced by the ruminant trophectoderm was thought to act exclusively on the uterine endometrium; however, it is now clear that this unique embryonic interferon escapes the uterus and alters gene expression in the CL and in peripheral blood leukocytes (PBL). In fact, a large number of interferon-stimulated genes are now known to be increased during early pregnancy in PBL. What is not known is how this conceptus-immune system cross-talk affects maternal immune status outside the reproductive tract. It is attractive to hypothesize that some of these effects are designed to counter-balance progesterone-induced immunosuppression so as not to place the dam at a greater risk of infection on top of the tremendous stresses already induced by pregnancy. Furthermore, recent evidence suggests that pregnancy induced changes in peripheral immune cells may aid in orchestrating establishment of pregnancy. Existing evidence points toward a greater convergence of systemic immune responses to early pregnancy signaling between ruminants and primates. [source] REVIEW ARTICLE: Endogenous Retroviruses in Trophoblast Differentiation and Placental DevelopmentAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Sarah G. Black Citation Black SG, Arnaud F, Palmarini M, Spencer TE. Endogenous retroviruses in trophoblast differentiation and placental development. Am J Reprod Immunol 2010 Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and originated from infections of the germline of the host by exogenous retroviruses. ERVs have coevolved with their hosts for millions of years and are recognized to contribute to genome plasticity, protect the host against infection of related pathogenic and exogenous retroviruses, and play a vital role in development of the placenta. Consequently, some ERVs have been positively selected and maintained in the host genome throughout evolution. This review will focus on the critical role of ERVs in development of the mammalian placenta and specifically highlight the biological role of sheep JSRV-related endogenous betaretroviruses in conceptus (embryo and associated extraembryonic membranes) development. [source] REVIEW ARTICLE: Evolution and Function of the Uterine Serpins (SERPINA14)AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Maria B. Padua Citation Padua MB, Hansen PJ. Evolution and function of the uterine serpins (SERPINA14). Am J Reprod Immunol 2010 Uterine serpins (recently designated as SERPINA14) are hormonally induced proteins secreted in large quantities by the endometrial epithelium during pregnancy. The SERPINA14 proteins belong to the serine proteinase inhibitor (serpin) superfamily, but their apparent lack of inhibitory activity toward serine proteinases suggests that these proteins evolved a different function from the anti-proteinase activity typically found in most members of the serpin superfamily. The gene is present in a limited group of mammals in the Laurasiatheria superorder (ruminants, horses, pigs, dolphins and some carnivores) while being absent in primates, rodents, lagomorphs and marsupials. Thus, the gene is likely to have evolved by gene duplication after divergence of Laurasiatheria and to play an important role in pregnancy. That role may vary between species. In sheep, SERPINA14 probably serves an immunoregulatory role to prevent rejection of the fetal allograft. It is inhibitory to lymphocyte proliferation and natural killer cell function. In the pig, SERPINA14 is involved in iron transport to the fetus by binding to and stabilizing the iron-binding protein uteroferrin. It is possible that SERPINA14 has undergone divergence in function since the original emergence of the gene in a common ancestor of species possessing SERPINA14. [source] REVIEW ARTICLE: The Interface of the Immune and Reproductive Systems in the Ovary: Lessons Learned from the Corpus Luteum of Domestic Animal ModelsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Joy L. Pate Citation Pate JL, Toyokawa K, Walusimbi S, Brzezicka E. The interface of the immune and reproductive systems in the ovary: lessons learned from the corpus luteum of domestic animal models. Am J Reprod Immunol 2010 The dynamic changes that characterize the female reproductive system are regulated by hormones. However, local cell-to-cell interactions may mediate responsiveness of tissues to hormonal signals. The corpus luteum (CL) is an excellent model for understanding how immune cells are recruited into tissues and the role played by those cells in regulating tissue homeostasis or demise. Leukocytes are recruited into the CL throughout its lifespan, and leukocyte-derived cytokines have been found in corpora lutea of all species examined. The proinflammatory cytokines inhibit gonadotropin-stimulated steroidogenesis, profoundly stimulate prostaglandin synthesis by luteal cells, and promote apoptosis. However, there is mounting evidence that leukocytes and luteal cells communicate in different ways to maintain homeostasis within the functional CL. Domestic animals have provided important information regarding the presence and role of immune cells in the CL. [source] REVIEW ARTICLE: Immunological Paradigms and the Pathogenesis of Ovine Chlamydial AbortionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Gary Entrican Citation Entrican G, Wattegedera S, Wheelhouse N, Allan A, Rocchi M. Immunological paradigms and the pathogenesis of ovine chlamydial abortion. Am J Reprod Immunol 2010 Successful mammalian pregnancy involves complex immunological interactions between the mother and foetus that are not yet fully understood. A number of immunological paradigms have been established to explain the failure of the maternal immune system to reject the semi-allogeneic foetus, mainly based on studies in mice and humans. However, as placental structure, gestation periods and number of concepti per pregnancy can vary greatly between mammals, it is not always clear how applicable these immunological paradigms are to reproduction in other species. Here, we discuss the predictions of three important immunological paradigms in relation to the pathogenesis of ovine enzootic abortion (OEA), a common cause of infectious abortion in sheep and other ruminants. OEA is caused by the intracellular Gram-negative bacterium Chlamydophila abortus that exhibits a tropism for placental trophoblast. The paradigms of particular relevance to the pathogenesis of OEA are as follows: (i) intracellular bacterial infections are controlled by TH1-type CD4+ve T cells; (ii) indoleamine 2,3-dioxygenase is expressed in the placenta to prevent immunological rejection of the semi-allogeneic foetus; and (iii) pregnancy is a maternal TH2-type phenomenon. We discuss the relevance and validity of these paradigms for chlamydial abortion and reproductive immunology in sheep. [source] REVIEW ARTICLE: Maternal and Fetal Response to Fetal Persistent Infection with Bovine Viral Diarrhea Virus,AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Thomas R. Hansen Citation Hansen TR, Smirnova NP, Van Campen H, Shoemaker ML, Ptitsyn AA, Bielefeldt-Ohmann H. Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus. Am J Reprod Immunol 2010 Problem, Infection of naïve pregnant cows with non-cytopathic (ncp) bovine viral diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection of the pregnant cow with ncp BVDV late in gestation (after day 150) results in transient infection (TI), as both the dam and fetus can mount an immune response to the virus. In contrast, if the fetus is infected with ncp BVDV early in gestation (before day 150), the fetal immune system is undeveloped and unable to recognize the virus as foreign. This results in induction of immune tolerance to the infecting BVDV strain and persistent infection (PI). Methods, Infection of naïve pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce differential gene expression in white blood cells of the dams and their fetuses, adversely affecting development and antiviral immune responses in PI fetuses. Results, Gene expression differed in maternal blood cells in the presence of PI versus uninfected fetuses. PI adversely affected fetal development and antiviral responses, despite protective immune responses in the dam. Conclusion, Fetal PI with BVDV alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses. [source] REVIEW ARTICLE: Placental Apoptosis in Health and DiseaseAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Andrew N. Sharp Citation Sharp AN, Heazell AEP, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol 2010; 64: 159,169 Apoptosis, programmed cell death, is an essential feature of normal placental development but is exaggerated in association with placental disease. Placental development relies upon effective implantation and invasion of the maternal decidua by the placental trophoblast. In normal pregnancy, trophoblast apoptosis increases with placental growth and advancing gestation. However, apoptosis is notably exaggerated in the pregnancy complications, hydatidiform mole, pre-eclampsia, and intrauterine growth restriction (IUGR). Placental apoptosis may be initiated by a variety of stimuli, including hypoxia and oxidative stress. In common with other cell-types, trophoblast apoptosis follows the extrinsic or intrinsic pathways culminating in the activation of caspases. In contrast, the formation of apoptotic bodies is less clearly identified, but postulated by some to involve the clustering of apoptotic nuclei and liberation of this material into the maternal circulation. In addition to promoting a favorable maternal immune response, the release of this placental-derived material is thought to provoke the endothelial dysfunction of pre-eclampsia. Widespread apoptosis of the syncytiotrophoblast may also impair trophoblast function leading to the reduction in nutrient transport seen in IUGR. A clearer understanding of placental apoptosis and its regulation may provide new insights into placental pathologies, potentially suggesting therapeutic targets. [source] REVIEW ARTICLE: Research on Blastocyst Implantation Essential Factors (BIEFs)AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Koji Yoshinaga Citation Yoshinaga K. Research on Blastocyst Implantation Essential Factors (BIEFs). Am J Reprod Immunol 2010 Blastocyst implantation is a process of interaction between embryo and the uterus. To understand this process, this review tries to summarize what blastocyst implantation essential factors (BIEFs) play what roles, as well as where in the uterus and at what stage of implantation process. Addition of more new data to this kind of compilation of information will help the development of diagnosis and treatment of infertility caused by implantation failure. The major, important cells of the endometrial cells that interact with invading blastocyst (trophoblast) are luminal epithelial cells, stromal cells (decidual cells) and resident immune cells. BIEFs regulate these cells to successfully maintain pregnancy. [source] REVIEW ARTICLE: The Immune System in Pregnancy: A Unique ComplexityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Gil Mor Citation Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol 2010 Abstract Placental immune response and its tropism for specific viruses and pathogens affect the outcome of the pregnant woman's susceptibility to and severity of certain infectious diseases. The generalization of pregnancy as a condition of immune suppression or increased risk is misleading and prevents the determination of adequate guidelines for treating pregnant women during pandemics. There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its responses to design the adequate prophylaxis or therapy. The complexity of the immunology of pregnancy and the focus, for many years, on the concept of immunology of pregnancy as an organ transplantation have complicated the field and delayed the development of new guidelines with clinical implications that could help to answer these and other relevant questions. Our challenge as scientists and clinicians interested in the field of reproductive immunology is to evaluate many of the ,classical concepts' to define new approaches for a better understanding of the immunology of pregnancy that will benefit mothers and fetuses in different clinical scenarios. [source] REVIEW ARTICLE: The Unique Properties of Uterine NK CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Irit Manaster Citation Manaster I, Mandelboim O. The unique properties of uterine NK cells. Am J Reprod Immunol 2009 Abstract Natural killer (NK) cells are lymphocytes of the innate immunity system that are able to kill various hazardous pathogens and tumors. However, it is now widely accepted that NK cells also possess non-destructive functions, as has been demonstrated for uterine NK cells. Here, we review the unique properties of the NK cells in the uterine mucosa, prior to and during pregnancy. We discuss the phenotype and function of mouse and human endometrial and decidual NK cells and suggest that the major function of decidual NK cells is to assist in fetal development. We further discuss the origin of decidual NK cells and suggest several possibilities that might explain their accumulation in the decidua during pregnancy. [source] REVIEW ARTICLE: Regulatory T Cells and Their Role in PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Anne Leber Citation Leber A, Teles A, Zenclussen AC. Regulatory T cells and their role in pregnancy. Am J Reprod Immunol 2010 Regulatory T cells emerge in the last years as key players in allowing fetal survival within the maternal uterus. They were shown to be a unique subpopulation of T cells expanding during human and murine pregnancy. The importance of Treg for a normal pregnancy situation was proven by studies showing that their absence impairs murine pregnancy while the adoptive transfer of Treg prevents fetal rejection. In humans, pregnancy pathologies are associated with lower Treg frequencies while therapies that improve pregnancy outcome are able to boost their number. Functional studies have shown that Treg can regulate immune cell responses directly at the fetal,maternal interface either by interacting with other cells or by inducing the expression of immune regulatory molecules. This article revises relevant literature on regulatory T cells in human and murine pregnancy. [source] REVIEW ARTICLE: The Contribution of Macrophages to Normal and Pathological PregnanciesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Takeshi Nagamatsu Citation Nagamatsu T, Schust DJ. The contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol 2010 Macrophages represent one of the major leukocyte subsets in the uterine decidua. Owing to their remarkable phenotypic plasticity, decidual macrophages can participate in diverse activities during pregnancy. At baseline, decidual macrophages are characterized by an immunosuppressive phenotype and M2 polarization, supporting feto-maternal immune tolerance. In early pregnancy, macrophage-derived pro-angiogenic factors prompt vascular remodeling within the uterine wall to ensure appropriate utero-placental circulation. Upon invasion by pathogens, pattern recognition receptors on decidual macrophages help to alter the characteristics of these malleable cells toward an M1, inflammatory phenotype. Similar inflammatory characteristics are seen in those macrophages that accumulate in the lower segment of the uterus to drive cervical ripening. Disturbances in the tight control that balances macrophage function during pregnancy can trigger the development of pregnancy complications. Here, we discuss the physiologic role of uterine macrophages at different stages of pregnancy and describe their relevance in selected pregnancy disorders. [source] REVIEW ARTICLE: Uterine NK Cells, Spiral Artery Modification and the Regulation of Blood Pressure During Mouse PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Suzanne D. Burke Citation Burke SD, Barrette VF, Gravel J, Carter ALI, Hatta K, Zhang J, Chen Z, Leno-Durán E, Bianco J, Leonard S, Murrant C, Adams MA, Anne Croy B. Uterine NK cells, spiral artery modification and the regulation of blood pressure during mouse pregnancy. Am J Reprod Immunol 2010 Reproductive success in mammals involves coordinated changes in the immune and cardiovascular as well as in the neuroendocrine and reproductive systems. This review addresses studies that identify potential links for NK cells and T cells with the local and systemic cardiovascular adaptations of pregnancy. The studies reviewed have utilized immunohistochemisty and in vivo analyses of vascular parameters by ultrasound, chronic monitoring of hemodynamics via radiotelemetric recording and intravital microscopy. At the uterine level, functional subsets of uterine natural killer cells were identified. These included subsets expressing molecules important for vasoregulation, in addition to those previously identified for angiogenesis. Spiral arteries showed conducted responses that could account for conceptus control of vasoactivity and mouse gestational blood pressure 5-phase pattern. Vascular immunology is an emerging transdisciplinary field, critical for both reproductive immunology and cardiovascular disease. [source] REVIEW ARTICLE: Interleukin-10: A Multi-Faceted Agent of PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Jessica E. Thaxton Citation Thaxton JE, Sharma S. Interleukin-10: a multi-faceted agent of pregnancy. Am J Reprod Immunol 2010 It is widely accepted that pregnancy constitutes a unique developmental event. Unprecedented intrauterine actions of angiogenesis, immunity, and neuroendocrine regulation are juxtaposed to mechanisms of senescence that enable fetal growth and protection. The suppressive and regulatory factors that facilitate healthy pregnancy are under investigation. In non-pregnant systems of infection and inflammation, the cytokine interleukin-10 (IL-10) has been widely investigated because of its potential as a key immunosuppressant in response to a multitude of inflammatory events. In the context of pregnancy, IL-10 levels increase markedly in women during early pregnancy and remain elevated well into the third trimester immediately prior to onset of labor. The role of IL-10 during pregnancy as a suppressor of active maternal immunity to allow acceptance of the fetal allograft has been a point of study. Moreover, secretion of IL-10 by a diverse set of maternal and fetal cells has proven to aid in the orchestration of normal processes of pregnancy. Interestingly, some of the more profound findings regarding the actions of IL-10 during pregnancy have manifested from research that focuses on aberrant pregnancy outcomes as a result of inflammation, hormonal imbalances, or gene,environment interactions. This review focuses on the role of IL-10 as a facilitator of successful pregnancy both as an immune suppressive agent and a mediator of cross talk between the placenta and the decidua. Importantly, we discuss investigations on adverse pregnancy conditions to further elucidate the multifarious role of IL-10 at the maternal,fetal interface. [source] REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra- and Extracellular RegulationAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Justine S. Fitzgerald Citation Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. Governing the invasive trophoblast: current aspects on intra- and extracellular regulation. Am J Reprod Immunol 2010 This review summarizes several aspects especially of regulating factors governing trophoblast invasion. Those include the composition of the extracellular matrix containing a variety of matrix metalloproeinases and their inhibitors, but also intracellular signals. Furthermore, a newly described trophoblast subtype, the endoglandular trophoblast, is presented. Its presence may provide a possible mechanism for opening and connecting uterine glands into the intervillous space. Amongst others, two intracellular signalling pathways are crucial for regulation of trophoblast functions and development: Wnt- and signal transducer and activator of transcription (STAT)3 signalling. Wnt signalling promotes implantation, placentation and trophoblast differentiation. Several Wnt-dependent cascades and regulatory mechanisms display different functions in trophoblast cells. The STAT3 signalling system is fundamental for induction and regulation of invasiveness in physiological trophoblastic cells, but also in tumours. The role of galectins (Gal) in trophoblast regulation and placenta development comes increasingly into focus. The Gal- 1,4, 7,10 and 12,14 have been detected in humans. Detailed information is only available for Gal-1, -2, -3, -4, -9 and -12 in endometrium and decidua. Gal-1, -3 and -13 (-14) have been detected and studied in trophoblast cells. [source] REVIEW ARTICLE: B7 Family Molecules as Regulators of the Maternal Immune System in PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Margaret G. Petroff Citation Petroff MG, Perchellet A. B7 family molecules as regulators of the maternal immune system in pregnancy. Am J Reprod Immunol 2010 Placental and fetal growth and development are associated with chronic exposure of the maternal immune system to fetally derived, paternally inherited antigens. Because maternal lymphocytes are aware of fetal antigens, active tolerance mechanisms are required to ensure unperturbed progression of pregnancy and delivery of a healthy newborn. These mechanisms of tolerance may include deletion, receptor downregulation, and anergy of fetal antigen-specific cells in lymphoid tissues, as well as regulation at the maternal,fetal interface by a variety of locally expressed immunoregulatory molecules. The B7 family of costimulatory molecules comprises one group of immunoregulatory molecules present in the decidua and placenta. B7 family members mediate both inhibitory and stimulatory effects on T-cell activation and effector functions and may play a critical role in maintaining tolerance to the fetus. Here, we review the known functions of the B7 family proteins in pregnancy. [source] REVIEW ARTICLE: The Role of Placental Exosomes in ReproductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Lucia Mincheva-Nilsson Citation Mincheva-Nilsson L, Baranov V. The Role of Placental Exosomes in Reproduction. Am J Reprod Immunol 2010 Cell communication comprises cell,cell contact, soluble mediators and intercellular nanotubes. There is, however, another cell,cell communication by released membrane-bound microvesicles that convey cell,cell contact ,by proxy' transporting signals/packages of information from donor to recipient cells locally and/or at a distance. The nanosized exosomes comprise a specialized type of microvesicles generated within multivesicular bodies (MVB) and released upon MVB fusion with the plasma membrane. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells. Recently, it was discovered that the syncytiotrophoblast constitutively and throughout the pregnancy secretes exosomes. The placenta-derived exosomes are immunosuppressive and carry proteins and RNA molecules that in a redundant way influence a number of mechanisms and promote the fetal allograft survival. In this review, we summarize the current knowledge on the nature of placenta-derived exosomes and discuss their role in pregnancy. [source] REVIEW ARTICLE: Immunology of Pre-EclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Christopher W. G. Redman Citation Redman CWG, Sargent IL. Immunology of Pre-eclampsia. Am J Reprod Immunol 2010 Pre-eclampsia develops in stages, only the last being the clinical illness. This is generated by a non-specific, systemic (vascular), inflammatory response, secondary to placental oxidative stress and not by reactivity to fetal alloantigens. However, maternal adaptation to fetal (paternal alloantigens) is crucial in the earlier stages. A pre-conceptual phase involves maternal tolerization to paternal antigens by seminal plasma. After conception, regulatory T cells, interacting with indoleamine 2,3-dioxygenase, together with decidual NK cell recognition of fetal HLA-C on extravillous trophoblast may facilitate placental growth by immunoregulation. Complete failure of this mechanism would cause miscarriage, while partial failure would cause poor placentation and dysfunctional uteroplacental perfusion. The first pregnancy preponderance and partner specificity of pre-eclampsia can be explained by this model. For the first time, the pathogenesis of pre-eclampsia can be related to defined immune mechanisms that are appropriate to the fetomaternal frontier. Now, the challenge is to prove the detail. [source] REVIEW ARTICLE: Sex Hormone Regulation of Innate Immunity in the Female Reproductive Tract: The Role of Epithelial Cells in Balancing Reproductive Potential with Protection against Sexually Transmitted PathogensAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Charles R. Wira Citation Wira CR, Fahey JV, Ghosh M, Patel MV, Hickey DK, Ochiel DO. Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol 2010 The immune system in the female reproductive tract (FRT) does not mount an attack against HIV or other sexually transmitted infections (STI) with a single endogenously produced microbicide or with a single arm of the immune system. Instead, the body deploys dozens of innate antimicrobials to the secretions of the female reproductive tract. Working together, these antimicrobials along with mucosal antibodies attack many different viral, bacterial and fungal targets. Within the FRT, the unique challenges of protection against sexually transmitted pathogens coupled with the need to sustain the development of an allogeneic fetus have evolved in such a way that sex hormones precisely regulate immune function to accomplish both tasks. The studies presented in this review demonstrate that estradiol and progesterone secreted during the menstrual cycle act both directly and indirectly on epithelial cells and other immune cells in the reproductive tract to modify immune function in a way that is unique to specific sites throughout the FRT. As presented in this review, studies from our laboratory and others demonstrate that the innate immune response is under hormonal control, varies with the stage of the menstrual cycle, and as such is suppressed at mid-cycle to optimize conditions for successful fertilization and pregnancy. In doing so, a window of STI vulnerability is created during which potential pathogens including HIV enter the reproductive tract to infect host targets. [source] REVIEW ARTICLE: HIV Infection in the Female Genital Tract: Discrete Influence of the Local Mucosal MicroenvironmentAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Charu Kaushic Citation Kaushic C, Ferreira VH, Kafka JK, Nazli A. HIV infection in the female genital tract: discrete influence of the local mucosal microenvironment. Am J Reprod Immunol 2010 Women acquire HIV infections predominantly at the genital mucosa through heterosexual transmission. Therefore, the immune milieu at female genital surfaces is a critical determinant of HIV susceptibility. In this review, we recapitulate the evidence suggesting that several distinctive innate immune mechanisms in the female genital tract (FGT) serve to significantly deter or facilitate HIV-1 infection. Epithelial cells lining the FGT play a key role in forming a primary barrier to HIV entry. These cells express Toll-like receptors and other receptors that recognize and respond directly to pathogens, including HIV-1. In addition, innate biological factors produced by epithelial and other cells in the FGT have anti-HIV activity. Female sex hormones, co-infection with other pathogens and components in semen may also exacerbate or down-modulate HIV transmission. A combination of innate and adaptive immune factors and their interactions with the local microenvironment determine the outcome of HIV transmission. Improving our understanding of the female genital microenvironment will be useful in developing treatments that augment and sustain protective immune responses in the genital mucosa, such as microbicides and vaccines, and will provide greater insight into viral pathogenesis in the FGT. [source] REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for TreatmentAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Alison J. Carey Citation Carey AJ, Beagley KW. Chlamydia trachomatis, a hidden epidemic: effects on the female reproduction and options for treatment. Am J Reprod Immunol 2010 The number of genital tract Chlamydia trachomatis infections is steadily increasing worldwide, with approximately 50,70% of infections asymptomatic. There is currently no uniform screening practice, current antibiotic treatment has failed to prevent the increased incidence, and there is no vaccine available. We examined studies on the epidemiology of C. trachomatis infections, the effects infections have on the female reproductive tract and subsequent reproductive health and what measures are being taken to reduce these problems. Undetected or multiple infections in women can lead to the development of severe reproductive sequelae, including pelvic inflammatory disease and tubal infertility. There are two possible paradigms of chlamydial pathogenesis, the cellular and immunological paradigms. While many vaccine candidates are being extensively tested in animal models, they are still years from clinical trials. With no vaccine available and antibiotic treatment unable to halt the increased incidence, infection rates will continue to increase and cause a significant burden on health care systems. [source] REVIEW ARTICLE: Toll-Like Receptors at the Maternal,Fetal Interface in Normal Pregnancy and Pregnancy DisordersAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Kaori Koga Citation Koga K, Mor G. Toll-like receptors at the maternal,fetal interface in normal pregnancy and pregnancy disorders. Am J Reprod Immunol 2010 Toll-like receptors (TLR) form the major family of pattern recognition receptors (PRR) that are involved in innate immunity. Innate immune responses against microorganisms at the maternal,fetal interface may have a significant impact on the success of pregnancy, as intrauterine infections have been shown to be strongly associated with certain disorders of pregnancy. At the maternal,fetal interface, TLRs are expressed not only in the immune cells but also in non-immune cells such as trophoblasts and decidual cells; moreover, their expression patterns vary according to the stage of pregnancy. Here, we will describe potential functions of TLRs in these cells, their recognition and response to microorganisms, and their involvement in the innate immunity. The impact of TLR-mediated innate immune response will be discussed via animal model studies, as well as clinical observations. [source] REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T-Cell Paradigm in PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Shigeru Saito Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010 T-helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)-, and interleukin (IL)-10 or by cell-to-cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms. [source] | |||||||||||||||||||||||||||||||||||||||||||