29,267 research outputs found

    Why Doesn’t a Pregnant Woman Reject her Fetus

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    Overview: Recurrent Pregnancy loss (RPL) occurs when a woman has three or more consecutive miscarriages; this phenomenon happens in about 1-3% of women. Why some women reject their unborn fetus and others carry theirs to term is still unclear. There are four main theories that exist regarding why some women reject their fetus and others do not: the maternal immune system might not be capable of responding to fetal antigens due to mechanisms that induce tolerance in responding maternal cells; a “barrier” may from between mother and fetus, preventing access of maternal immune cell to fetal antigens; fetal cells may suppress the expression of their antigens; and the fetus may generate site-specific immune suppression. We will look closely at two studies that ask the questions: does the non-specific immune response increase to compensate for the decrease in specific immunity? Is there a maternal cell-mediated immune response to the fetus which needs to be blocked, and do blocking antibodies develop in all successful pregnancies? Different aspects of each theory have proven that a maternal cell-mediated response is not acquired at any stage in pregnancy to the fetus but monocyte surface expression is increased. This proves that there is an increase in the innate immune response. Future studies will look more strictly at the differences between these main theories. Background Pregnancy has become a lot safer than in the past due to technology in medicine and a higher level of education for our health care professionals. Still little is known as to why pregnancies for some women are successful and for other women they are not. 50-60% of pregnancies have a common complication called spontaneous miscarriage, defined as the spontaneous end of a pregnancy that occurs prior to 20 weeks gestation where the embryo or fetus is incapable of surviving; a less common form of miscarriage is recurrent pregnancy loss, or RPL, which occurs in 1-3% of women and is defined as three or more consecutive miscarriages prior to 20 weeks gestation (Saini V., et al. 2011). There are four different theories experts have studied to understand why this occurs. First, due to mechanisms that induce anergy, reduction or lack of an immune response to a specific antigen, the maternal immune system might not be capable of responding to fetal antigens (Koch and Platt 2007). Second, an anatomical barrier may form that prevents access of maternal immune cell to fetal antigens between mother and fetus (Koch and Platt 2007). Third, fetal cells may suppress the manifestation of alloantigens; an alloantigen is any antigen, present in only some individuals of a species, which stimulates the production of antibodies in those that lack it (Koch and Platt 2007). Finally, the fetus may create site-specific immune suppression in which maternal immune cells would then be blocked, defending the fetus while permitting the cells to produce an immune response (Koch and Platt 2007)

    Dendritic-Cell (DC)-Based Immunotherapy: Tumor Endothelial Marker 8 (TEM8) Gene Expression of DC Vaccines Correlates with Clinical Outcome

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    ABSTRACT\ud Previous studies have shown that tumor-endothelial markers (TEMs) are upregulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. \ud We reported that pro-angiogenic monocyte-derived DCs (Mo-DCs), utilized for therapeutic vaccination of cancer patients upon maturation, markedly differ in their ability to up-regulate tumor-endothelial marker 8 (TEM8) gene\ud expression. A DC vaccination trial of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma), carried out at the Cancer Institute of Romagna (I.R.S.T.) in Meldola, highlighted a significant correlation between delayed-type hypersensitivity test (DTH) and overall survival (OS). In the study, relative TEM8 mRNA and protein expression levels (mature (m) vs. immature (i) DCs), in DCs obtained for therapeutic vaccines were evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis, respectively. mDCs from six healthy donors were included for comparison purposes. Eight non-progressing patients, all DTH-positive, had a mean fold increase\ud (mfi) of 1.97 in TEM8 expression. Similarly, a TEM8 mRNA mfi = 2.7 was found in healthy donor mDCs. Conversely, mDCs from nine progressing patients, all but one with negative DTH, had a TEM8 mRNA mfi of 12.88. Thus, mDC TEM8 expression levels would seem to identify (p = 0.0018) patients who could benefit from DC therapeutic vaccination

    Immune Response Modulation by Tumor-Secreted Glycosphingolipids

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    Although originally considered merely structural components of cellular membranes, glycosphingolipids (GSL) arenow recognized as having critical effects on cellular physiology, including proliferation, differentiation, viraltransformation and ontogenesis. In addition, a vast majority of human cancers have modified GSL compositioncompared to parental normal cells. These modifications may contribute to both tumor survival and exert strikingeffects on anti-tumor immunity. In this review, we discuss mechanisms of immune modulation by tumor-secreted GSL.Fil: Lardone, Ricardo Dante. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Cely, Ingrid. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados UnidosFil: Sieling, Peter A.. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados UnidosFil: Lee, Delphine. John Wayne Cancer Institute at Providence Saint John’s Health Center. Santa Monica; Estados Unido

    Pathogen-reactive T helper cell analysis in the pig

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    There is growing interest in studying host-pathogen interactions in human-relevant large animal models such as the pig. Despite the progress in developing immunological reagents for porcine T cell research, there is an urgent need to directly assess pathogen-specific T cells-an extremely rare population of cells, but of upmost importance in orchestrating the host immune response to a given pathogen. Here, we established that the activation marker CD154 (CD40L), known from human and mouse studies, identifies also porcine antigen-reactive CD4(+) T lymphocytes. CD154 expression was upregulated early after antigen encounter and CD4(+)CD154(+) antigen-reactive T cells coexpressed cytokines. Antigen-induced expansion and autologous restimulation enabled a time-and dose-resolved analysis of CD154 regulation and a significantly increased resolution in phenotypic profiling of antigen-responsive cells. CD154 expression identified T cells responding to staphylococcal Enterotoxin B superantigen stimulation as well as T cells responding to the fungus Candida albicans and T cells specific for a highly prevalent intestinal parasite, the nematode Ascaris suum during acute and trickle infection. Antigen-reactive T cells were further detected after immunization of pigs with a single recombinant bacterial antigen of Streptococcus suis only. Thus, our study offers new ways to study antigen-specific T lymphocytes in the pig and their contribution to host-pathogen interactions

    Nutrition, diet and immunosenescence

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    Ageing is characterized by immunosenescence and the progressive decline in immunity in association with an increased frequency of infections and chronic disease. This complex process affects both the innate and adaptive immune systems with a progressive decline in most immune cell populations and defects in activation resulting in loss of function. Although host genetics and environmental factors, such as stress, exercise and diet can impact on the onset or course of immunosenescence, the mechanisms involved are largely unknown. This review focusses on identifying the most significant aspects of immunosenescence and on the evidence that nutritional intervention might delay this process, and consequently improve the quality of life of the elderly

    The bacillary and macrophage response to hypoxia in tuberculosis and the consequences for T cell antigen recognition

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    M. tuberculosis is a facultative anaerobe and its characteristic pathological hallmark, the granuloma, exhibits hypoxia in humans and in most experimental models. Thus the host and bacillary adaptation to hypoxia is of central importance in understanding pathogenesis and thereby to derive new drug treatments and vaccines

    In vivo tracking and immunological properties of pulsed porcine monocyte-derived dendritic cells

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    Cellular therapies using immune cells and in particular dendritic cells (DCs) are being increasingly applied in clinical trials and vaccines. Their success partially depends on accurate delivery of cells to target organs or migration to lymph nodes. Delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. Thus, the design of an optimal DC therapy would be improved by optimizing technologies for monitoring DC trafficking. Magnetic resonance imaging (MRI) represents a powerful tool for non-invasive imaging of DC migration in vivo. Domestic pigs share similarities with humans and represent an excellent animal model for immunological studies. The aim of this study was to investigate the possibility using pigs as models for DC tracking in vivo. Porcine monocyte derived DC (MoDC) culture with superparamagnetic iron oxide (SPIO) particles was standardized on the basis of SPIO concentration and culture viability. Phenotype, cytokine production and mixed lymphocyte reaction assay confirmed that porcine SPIO-MoDC culture were similar to mock MoDCs and fully functional in vivo. Alike, similar patterns were obtained in human MoDCs. After subcutaneous inoculation in pigs, porcine SPIO-MoDC migration to regional lymph nodes was detected by MRI and confirmed by Perls staining of draining lymph nodes. Moreover, after one dose of virus-like particles-pulsed MoDCs specific local and systemic responses were confirmed using ELISPOT IFN-γ in pigs. In summary, the results in this work showed that after one single subcutaneous dose of pulsed MoDCs, pigs were able to elicit specific local and systemic immune responses. Additionally, the dynamic imaging of MRI-based DC tracking was shown using SPIO particles. This proof-of-principle study shows the potential of using pigs as a suitable animal model to test DC trafficking with the aim of improving cellular therapies.We want to thank: Ferrán López, Rosa López, Zoraida Cervera, Pamela Martinez-Orellana, Tufaria Mussá, Massimiliano Baratelli, Diego Pérez, Sergio López from CRESA and José Luis Ruiz de la Torre and Javier Aceña (UAB) for farm and technical support; Jaume Martorell (Fundació Hospital Clínic Veterinari, UAB) for MRI support; Javier Domínguez (INIA) for the porcine antibodies; Antonio Lestuzzi, Michele Crisci and Raif Yucel for MR imaging support; Joaquim Segalés for anatomic pathology analysis; Mónica Pérez for immunohistochemical stainings; Aida Neira and Blanca Pérez for Perls staining; Eva Huerta y Marina Sibila for PCV2 PCR; David Andreu and Beatriz García de la Torre (Pompeu Fabra University, Barcelona), and Esther Blanco (CISA-INIA, Madrid), for the FMDV 3A peptide; Alicia Solórzano for critically reviewing the manuscript. This work was funded by the project AGL2010-22200-C02 of Spanish Ministry of Science and Innovation. PhD studies of Raquel Cabezón are funded by a doctoral FI fellowship from the Generalitat de Catalunya
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