WorldWideScience

Sample records for immunologically competent cells

  1. Effects of A-bomb radiation on immunological competence

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi; Kusunoki, Yoichiro

    1992-01-01

    The purpose of this paper is to discuss the effects of A-bomb radiation on human immunological competence from the current immunological viewpoint. Early disturbance of immunological competence after A-bombing was characterized by (1) rapid decrease of lymphocytes (within one day), (2) decrease in humoral factors such as antibodies and complements (immediately), (3) decrease in neutrophils and monocytes (3-50 days later), and (4) delayed recovery of lymphocytes (more than 4 weeks). Long term effects of A-bombing on immunological competence are discussed in terms of immunocompetent cells. The peripheral lymphocyte response to PHA tended to be noticeable with aging among A-bomb survivors exposed to 2 Gy or more than the control persons. The peripheral lymphocyte response to MLC was decreased in a dose-dependent manner in A-bomb survivors aged 15 years or older at the time of A-bombing. The count of mature T lymphocytes was decreased in elderly A-bomb survivors, although neither functional nor numerical decrease in T lymphocytes was observed in younger A-bomb survivors. This could be explained by the hypothesis that the recovery of T lymphocytes is incomplete in elderly people due to thymus involution. An increased HPRT mutant cells in T lymphocytes correlated with A-bomb radiation doses. The count of B lymphocytes tended to be decreased in elderly A-bomb survivors. A functional and numerical increase in NK cells was associated with advancing age; however, this was not found to be correlated with A-bomb radiation. There was no evidence of correlation between A-bomb radiation and any of bone marrow cells, virus infection, autoimmunity, and tumor-specific immunity. (N.K.) 61 refs

  2. Effect of endosulfan on immunological competence of layer birds.

    Science.gov (United States)

    Singh, P P; Kumar, Ashok; Chauhan, R S; Pankaj, P K

    2016-07-01

    The present study was aimed to investigate the immunological competence of endosulfan insecticide after limited oral administration in White Leghorn layer chickens. A total of 20 White Leghorn birds were given endosulfan in drinking water at 30 ppm/bird/day (no observable effect level dose) for a period of 3-months. Immune competence status of layer birds and chicks hatched from endosulfan offered birds were estimated at 15-day interval in layer birds and at monthly interval in chicks using immunological, biochemical parameters, and teratological estimates. There was a significant decrease in levels of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds fed with endosulfan as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with endosulfan as compared to control. Subsequently, chicks produced from endosulfan-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to endosulfan in limited oral dosage was able to exhibit hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting cautious usage of endosulfan insecticide in poultry sheds.

  3. Host Competence: An Organismal Trait to Integrate Immunology and Epidemiology.

    Science.gov (United States)

    Martin, Lynn B; Burgan, S C; Adelman, James S; Gervasi, Stephanie S

    2016-12-01

    The new fields of ecological immunology and disease ecology have begun to merge, and the classic fields of immunology and epidemiology are beginning to blend with them. This merger is occurring because the integrative study of host-parasite interactions is providing insights into disease in ways that traditional methods have not. With the advent of new tools, mathematical and technological, we could be on the verge of developing a unified theory of infectious disease, one that supersedes the barriers of jargon and tradition. Here we argue that a cornerstone of any such synthesis will be host competence, the propensity of an individual host to generate new infections in other susceptible hosts. In the last few years, the emergence of systems immunology has led to novel insight into how hosts control or eliminate pathogens. Most such efforts have stopped short of considering transmission and the requisite behaviors of infected individuals that mediate it, and few have explicitly incorporated ecological and evolutionary principles. Ultimately though, we expect that the use of a systems immunology perspective will help link suborganismal processes (i.e., health of hosts and selection on genes) to superorganismal outcomes (i.e., community-level disease dynamics and host-parasite coevolution). Recently, physiological regulatory networks (PRNs) were cast as whole-organism regulatory systems that mediate homeostasis and hence link suborganismal processes with the fitness of individuals. Here, we use the PRN construct to develop a roadmap for studying host competence, taking guidance from systems immunology and evolutionary ecology research. We argue that PRN variation underlies heterogeneity in individual host competence and hence host-parasite dynamics. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  4. Pregnancy immunology: decidual immune cells.

    Science.gov (United States)

    Sanguansermsri, Donruedee; Pongcharoen, Sutatip

    2008-01-01

    Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.

  5. Immunologic competence in adults following thymic irradiation in infancy

    International Nuclear Information System (INIS)

    Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

    1977-01-01

    Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis

  6. Immunologic competence in adults following thymic irradiation in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

    1977-07-01

    Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis.

  7. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  8. Initiation-promotion skin carcinogenesis and immunological competence.

    Science.gov (United States)

    Curtis, G L; Stenbäck, F; Ryan, W L

    1975-10-01

    The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

  9. Single Cell Genomics: Approaches and Utility in Immunology

    Science.gov (United States)

    Neu, Karlynn E; Tang, Qingming; Wilson, Patrick C; Khan, Aly A

    2017-01-01

    Single cell genomics offers powerful tools for studying lymphocytes, which make it possible to observe rare and intermediate cell states that cannot be resolved at the population-level. Advances in computer science and single cell sequencing technology have created a data-driven revolution in immunology. The challenge for immunologists is to harness computing and turn an avalanche of quantitative data into meaningful discovery of immunological principles, predictive models, and strategies for therapeutics. Here, we review the current literature on computational analysis of single cell RNA-seq data and discuss underlying assumptions, methods, and applications in immunology, and highlight important directions for future research. PMID:28094102

  10. Single-Cell Genomics: Approaches and Utility in Immunology.

    Science.gov (United States)

    Neu, Karlynn E; Tang, Qingming; Wilson, Patrick C; Khan, Aly A

    2017-02-01

    Single-cell genomics offers powerful tools for studying immune cells, which make it possible to observe rare and intermediate cell states that cannot be resolved at the population level. Advances in computer science and single-cell sequencing technology have created a data-driven revolution in immunology. The challenge for immunologists is to harness computing and turn an avalanche of quantitative data into meaningful discovery of immunological principles, predictive models, and strategies for therapeutics. Here, we review the current literature on computational analysis of single-cell RNA-sequencing data and discuss underlying assumptions, methods, and applications in immunology, and highlight important directions for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Isotope-based immunological techniques. Their use in assessment of immune competence and the study of immune responses to pathogens

    International Nuclear Information System (INIS)

    Duffus, W.P.H.

    1984-01-01

    The influence of isotope-based techniques on both assessment of immune competence and immune response to pathogens is discussed. Immunodeficiencies acquired as a result of factors like malnutrition and concomitant disease can severely affect not only attempts to intensify and improve production but also successful immune response against important vaccines such as rinderpest and foot-and-mouth disease. Isotope-based techniques, with their accuracy, speed and small sample volume, are ideally suited for assessing immunocompetence. One of the main drawbacks remains antigen purity, an area where research should now be concentrated. Lymphocyte transformation is widely used to assess cell-mediated immuno-competence but techniques to assess biological functions such as phagocytosis and cell-mediated cytotoxicity could more usefully reflect immune status. These latter techniques utilize isotopes such as 3 H, 14 C, 32 P and 125 I. Investigation of specific cell-mediated immune response often requires a labelled target. Suitable isotopes such as 51 Cr, 99 Tcsup(m), 75 Se and 3 H are compared for their capacity to label both mammalian and parasite targets. Suggestions are made on a number of areas of research that might usefully be encouraged and supported in order to improve applied veterinary immunology in tropical countries. (author)

  12. Immunology: Exhausted T cells perk up

    Science.gov (United States)

    Williams, Matthew A.; Bevan, Michael J.

    2006-02-01

    During persistent infections, the immune cells responsible for killing infected cells and maintaining inflammation gradually stop functioning, allowing the pathogen to thrive. But can this process be reversed?

  13. Peptide modification in T cell immunology - from molecule to animal

    NARCIS (Netherlands)

    Haan, Ellen Christine de

    2003-01-01

    Chemical knowledge can be applied in the field of immunology. It provides a better understanding of how a peptide interacts with proteins and cells of the immune system. However, it is not possible to predict the outcome of peptide administration in an animal. Peptides are used in experimental

  14. Widespread immunological functions of mast cells: fact or fiction?

    Science.gov (United States)

    Rodewald, Hans-Reimer; Feyerabend, Thorsten B

    2012-07-27

    Immunological functions of mast cells are currently considered to be much broader than the original role of mast cells in IgE-driven allergic disease. The spectrum of proposed mast cell functions includes areas as diverse as the regulation of innate and adaptive immune responses, protective immunity against viral, microbial, and parasitic pathogens, autoimmunity, tolerance to graft rejection, promotion of or protection from cancer, wound healing, angiogenesis, cardiovascular diseases, diabetes, obesity, and others. The vast majority of in vivo mast cell data have been based on mast cell-deficient Kit mutant mice. However, work in new mouse mutants with unperturbed Kit function, which have a surprisingly normal immune system, has failed to corroborate some key immunological aspects, formerly attributed to mast cells. Here, we consider the implications of these recent developments for the state of the field as well as for future work, aiming at deciphering the physiological functions of mast cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Normal function of immunologic stem cells from aged mice

    International Nuclear Information System (INIS)

    Harrison, D.E.; Doubleday, J.W.

    1975-01-01

    Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

  16. The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    International Nuclear Information System (INIS)

    Borowski, J.; Jokoniuk, P.

    1977-01-01

    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

  17. Regulatory immune cells and functions in autoimmunity and transplantation immunology.

    Science.gov (United States)

    Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

    2017-05-01

    In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Cell source determines the immunological impact of biomimetic nanoparticles.

    Science.gov (United States)

    Evangelopoulos, Michael; Parodi, Alessandro; Martinez, Jonathan O; Yazdi, Iman K; Cevenini, Armando; van de Ven, Anne L; Quattrocchi, Nicoletta; Boada, Christian; Taghipour, Nima; Corbo, Claudia; Brown, Brandon S; Scaria, Shilpa; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

    2016-03-01

    Recently, engineering the surface of nanotherapeutics with biologics to provide them with superior biocompatibility and targeting towards pathological tissues has gained significant popularity. Although the functionalization of drug delivery vectors with cellular materials has been shown to provide synthetic particles with unique biological properties, these approaches may have undesirable immunological repercussions upon systemic administration. Herein, we comparatively analyzed unmodified multistage nanovectors and particles functionalized with murine and human leukocyte cellular membrane, dubbed Leukolike Vectors (LLV), and the immunological effects that may arise in vitro and in vivo. Previously, LLV demonstrated an avoidance of opsonization and phagocytosis, in addition to superior targeting of inflammation and prolonged circulation. In this work, we performed a comprehensive evaluation of the importance of the source of cellular membrane in increasing their systemic tolerance and minimizing an inflammatory response. Time-lapse microscopy revealed LLV developed using a cellular coating derived from a murine (i.e., syngeneic) source resulted in an active avoidance of uptake by macrophage cells. Additionally, LLV composed of a murine membrane were found to have decreased uptake in the liver with no significant effect on hepatic function. As biomimicry continues to develop, this work demonstrates the necessity to consider the source of biological material in the development of future drug delivery carriers. Copyright © 2015. Published by Elsevier Ltd.

  19. Ligand mobility modulates immunological synapse formation and T cell activation.

    Directory of Open Access Journals (Sweden)

    Chih-Jung Hsu

    Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

  20. Immunologic effects of hydroxyurea in sickle cell anemia.

    Science.gov (United States)

    Lederman, Howard M; Connolly, Margaret A; Kalpatthi, Ram; Ware, Russell E; Wang, Winfred C; Luchtman-Jones, Lori; Waclawiw, Myron; Goldsmith, Jonathan C; Swift, Andrea; Casella, James F

    2014-10-01

    Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses. T-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG). Compared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use. Hydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced. Copyright © 2014 by the American Academy of Pediatrics.

  1. Regulatory T Cells in HIV-Infected Immunological Nonresponders Are Increased in Blood but Depleted in Lymphoid Tissue and Predict Immunological Reconstitution

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Hartling, Hans J; Ronit, Andreas

    2014-01-01

    BACKGROUND: HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3 cells in lymphoid tissue......, and the impact of Tregs on immunological reconstitution was determined. METHODS: HIV-infected individuals on combination antiretroviral therapy for a minimum of 2 years were included. The study population included 14 immunological nonresponders (INR; CD4 T-cell count .... In contrast, responders resembled healthy controls. Finally, in INR, high level of Tregs in blood and Foxp3 cells in lymphoid tissue were associated with higher level of immunological reconstitution after 1 year of follow-up. CONCLUSIONS: In conclusion, altered distribution of Tregs was found in INR...

  2. Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis

    Directory of Open Access Journals (Sweden)

    Frank Cloutier

    2013-01-01

    Full Text Available The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP. Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.

  3. Quantitative evaluation of the hazards involved in transferring foreign cells and tissues to immunologically suppressed or deficient subjects

    Energy Technology Data Exchange (ETDEWEB)

    Bekkum, D.W. van

    1971-04-01

    It has already been pointed out in a preceding chapter that a successful take of allogenic bone marrow in primates inevitably entails a most severe early or acute form of secondary disease caused by a violent immunological reaction of the immune competent cells of the graft directed against the host. In mice and rats such an acute graft versus host disease is not seen following grafting of allogenic bone marrow, but only if substantial numbers of spleen or lymph node cells are transferred. Apparently, primate bone marrow is exceptionally aggressive compared to rodent bone marrow and it is not possible to prevent this reaction by decreasing the number of infused bone marrow cells without simultaneously eliminating the restorative effect of the graft. There are many reasons for assuming that the property to elicit a graft versus host reaction resides exclusively in the lymphoid cell series. These cells are normally to be found not only in the bone marrow and the lymphatic organs but also in the peripheral blood and in other tissues. Since surprisingly small numbers of lymphoid cells have been shown to cause graft versus host disease in completely non-reactive recipients, a calculation of the risks involved in transfusing sizable amounts of fresh blood or leukocyte concentrates to human recipients appears to be opportune. Moreover, the current attempts to restore immunological function in agammaglobulinaemic patients by implantations of allogenic foetal thymus tissue and by infusion of foetal liver and bone marrow cell suspensions (Dooren et al., 1968; Hong et al., 1968) require a critical analysis of the risks involved. Finally, the rapidly advancing clinical transplantation of organs - all of which contain scattered lymphoid cells - seems to necessitate a re-evaluation of this potential hazard in the light of the present knowledge of the induction of graft versus host disease. Most of our factual information concerning graft versus host reactions comes from

  4. Navigating barriers: the challenge of directed secretion at the natural killer cell lytic immunological synapse.

    Science.gov (United States)

    Sanborn, Keri B; Orange, Jordan S

    2010-05-01

    Natural killer (NK) cells have an inherent ability to recognize and destroy a wide array of cells rendered abnormal by stress or disease. NK cells can kill a targeted cell by forming a tight interface-the lytic immunological synapse. This represents a dynamic molecular arrangement that over time progresses through a series of steps to ultimately deliver the contents of specialized organelles known as lytic granules. In order to mediate cytotoxicity, the NK cell faces the challenge of mobilizing the lytic granules, polarizing them to the targeted cell, facilitating their approximation to the NK cell membrane, and releasing their contents. This review is focused upon the final steps in accessing function through the lytic immunological synapse.

  5. Immunologic analyses of mouse cystathionase in normal and leukemic cells

    International Nuclear Information System (INIS)

    Bikel, I.; Faibes, D.; Uren, J.R.; Livingston, D.M.

    1978-01-01

    Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts

  6. Tumor Immunology meets…Immunology: Modified cancer cells as professional APC for priming naïve tumor-specific CD4+ T cells.

    Science.gov (United States)

    Bou Nasser Eddine, Farah; Ramia, Elise; Tosi, Giovanna; Forlani, Greta; Accolla, Roberto S

    2017-01-01

    Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer. Here we describe emerging new strategies to increase the TH cell recognition of tumor antigens. In particular, we review recent data indicating that tumor cells themselves can act as surrogate antigen presenting cells for triggering TH response and how these findings can help in constructing immunotherapeutic protocols for anti-cancer vaccine development.

  7. Immunological compatibility status of placenta-derived stem cells is mediated by scaffold 3D structure.

    Science.gov (United States)

    Azizian, Sara; Khatami, Fatemeh; Modaresifar, Khashayar; Mosaffa, Nariman; Peirovi, Habibollah; Tayebi, Lobat; Bahrami, Soheyl; Redl, Heinz; Niknejad, Hassan

    2018-02-23

    Placenta-derived amniotic epithelial cells (AECs), a great cell source for tissue engineering and stem cell therapy, are immunologically inert in their native state; however, immunological changes in these cells after culture and differentiation have challenged their applications. The aim of this study was to investigate the effect of 2D and 3D scaffolds on human lymphocyte antigens (HLA) expression by AECs. The effect of different preparation parameters including pre-freezing time and temperature was evaluated on 3D chitosan-gelatine scaffolds properties. Evaluation of MHC class I, HLA-DR and HLA-G expression in AECs after 7 d culture on 2D bed and 3D scaffold of chitosan-gelatine showed that culture of AECs on the 2D substrate up-regulated MHC class I and HLA-DR protein markers on AECs surface and down-regulated HLA-G protein. In contrast, 3D scaffold did not increase protein expression of MHC class I and HLA-DR. Moreover, HLA-G protein expression remained unchanged in 3D culture. These results confirm that 3D scaffold can remain AECs in their native immunological state and modification of physical properties of the scaffold is a key regulator of immunological markers at the gene and protein expression levels; a strategy which circumvents rejection challenge of amniotic stem cells to be translated into the clinic.

  8. T cell uptake for the use of boron neutron capture as an immunologic research tool

    International Nuclear Information System (INIS)

    Binello, E.; Mitchell, R.N.; Harling, O.K.

    2004-01-01

    An immunologic tool based on manipulation of the boron neutron capture reaction was previously proposed in the context of heart transplantation research to examine the temporal relationship between parenchymal rejection (representing immune cell infiltration) and transplantation-associated arteriosclerosis (characterized by progressive vascular occlusion). Critical to the development of this method is the uptake of boron by specific cells of the immune system, namely T cells, without adverse effects on cell function, which may be assessed by the ability of boron-loaded cells to produce IFNγ, a protein with substantial impact on rejection. This work presents the evaluation of two carboranyl thymidine analogs. Advantages of this type of boron compound are reduced risk of leakage and effective dose delivery based on their incorporation into cellular nuclear material. Results indicate that uptake of these boronated nucleosides is high with no adverse effects on cell function, thereby warranting the continued development of this technique that has potentially wide applicability in immunological models

  9. Immunologic glycosphingolipidomics and NKT cell development in mouse thymus

    DEFF Research Database (Denmark)

    Li, Yunsen; Thapa, Prakash; Hawke, David

    2009-01-01

    Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting...

  10. Innate immunological function of TH2 cells in vivo

    Science.gov (United States)

    Th2 cells produce IL-13 when stimulated by papain or house dust mites (HDM) and induce eosinophilic inflammation. This innate response of cells of the adaptive immune system is dependent on IL-33-, not T cell receptor-, based stimulation. While type 2 innate lymphoid cells (ILC2s) are the dominant ...

  11. Recovery of immune competence following sublethal X irradiation of young and old mice: a model for studying age-related loss of immunologic homeostasis

    International Nuclear Information System (INIS)

    Peterson, W.J.; Perkins, E.H.; Makinodan, T.

    1982-01-01

    Age-related alteration in lymphohematopoietic homeostasis was assessed kinetically by determining immunologic and stem-cell regenerating capacities of young (5-7 months), middle-aged (13 months), and old (23-24 months) C3H and C57BL/6 mice following their exposure to 500 R. Immunologic activities were based on the ability of spleen cells to respond to sheep erythrocytes, phytohemagglutinin, and bacterial lipopolysaccharide. Stem-cell activity was based on the ability of splenic and bone marrow cells to form colonies in vivo. Reflective of age-related homeostatic imbalance was alteration in the (a) time of recovery, (b) rate of regeneration, and (c) capacity of the regenerating system to overshoot the preirradition steady-state level. Most of the immunologic parameters showed a delay in the time of recovery in old mice. In contrast, the time of recovery of stem cells in old mice was equal to or faster than that in young mice. Furthermore, the magnitude of regeneration of stem cells was greater in old than young mice. These results suggest that recovery of immunologic activities in old mice is delayed partly because of the inability of their stem cells to rapidly generate immunocompetent progenies

  12. Immunologic targeting of FOXP3 in inflammatory breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Smita Nair

    Full Text Available The forkhead transcription factor FOXP3 is necessary for induction of regulatory T lymphocytes (Tregs and their immunosuppressive function. We have previously demonstrated that targeting Tregs by vaccination of mice with murine FOXP3 mRNA-transfected dendritic cells (DCs elicits FOXP3-specific T cell responses and enhances tumor immunity. It is clear that FOXP3 expression is not restricted to T-cell lineage and herein, using RT-PCR, flow cytometry, and western immunoblot we demonstrate for the first time that FOXP3 is expressed in inflammatory breast cancer (IBC cells, SUM149 (triple negative, ErbB1-activated and SUM190 (ErbB2-overexpressing. Importantly, FOXP3-specific T cells generated in vitro using human FOXP3 RNA-transfected DCs as stimulators efficiently lyse SUM149 cells. Interestingly, an isogenic model (rSUM149 derived from SUM149 with an enhanced anti-apoptotic phenotype was resistant to FOXP3-specific T cell mediated lysis. The MHC class I cellular processing mechanism was intact in both cell lines at the protein and transcription levels suggesting that the resistance to cytolysis by rSUM149 cells was not related to MHC class I expression or to the MHC class I antigen processing machinery in these cells. Our data suggest that FOXP3 may be an effective tumor target in IBC cells however increased anti-apoptotic signaling can lead to immune evasion.

  13. Effect of antigen on localization of immunologically specific B cells

    International Nuclear Information System (INIS)

    Ponzio, N.M.; Chapman, J.M.; Thorbecke, G.J.

    1976-01-01

    Studies were conducted to demonstrate homing of memory B cells to sites of antigen localization in lymph nodes, using functional criteria to detect local presence of memory cells at varying intervals after intravenous injection. Cell suspensions were prepared from spleens of donor mice injected with complete Freund's adjuvant. Recipient mice were injected with Escherichia coli endotoxin and immune or normal spleen cells and were gamma-irradiated. Results indicated that passively transferred unilateral B cell memory was established. The development over a period of several days of this difference between left and right lymph nodes suggests that recirculating memory B cells are being progressively selected by antigen in the lymph node, rather than that this difference is due to a specific exit of cells from the circulation towards the antigen

  14. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  15. Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

    Science.gov (United States)

    Roybal, Kole T; Lim, Wendell A

    2017-04-26

    The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

  16. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    International Nuclear Information System (INIS)

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%

  17. Biology and immunology of cancer stem(-like) cells in head and neck cancer.

    Science.gov (United States)

    Qian, Xu; Ma, Chenming; Nie, Xiaobo; Lu, Jianxin; Lenarz, Minoo; Kaufmann, Andreas M; Albers, Andreas E

    2015-09-01

    Immunological approaches against tumors including head and neck squamous cell carcinoma (HNSCC) have been investigated for about 50 years. Such immunotherapeutic treatments are still not sufficiently effective for therapy of HNSCC. Despite the existence of immunosurveillance tumor cells may escape from the host immune system by a variety of mechanisms. Recent findings have indicated that cancer stem(-like) cells (CSCs) in HNSCC have the ability to reconstitute the heterogeneity of the bulk tumor and contribute to immunosuppression and resistance to current therapies. With regard to the CSC model, future immunotherapy possibly in combination with other modes of treatment should target this subpopulation specifically to reduce local recurrence and metastasis. In this review, we will summarize recent research findings on immunological features of CSCs and the potential of immune targeting of CSCs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. From cell biology to immunology: Controlling metastatic progression of cancer via microRNA regulatory networks.

    Science.gov (United States)

    Park, Jae Hyon; Theodoratou, Evropi; Calin, George A; Shin, Jae Il

    2016-01-01

    Recently, the study of microRNAs has expanded our knowledge of the fundamental processes of cancer biology and the underlying mechanisms behind tumor metastasis. Extensive research in the fields of microRNA and its novel mechanisms of actions against various cancers has more recently led to the trial of a first cancer-targeted microRNA drug, MRX34. Yet, these microRNAs are mostly being studied and clinically trialed solely based on the understanding of their cell biologic effects, thus, neglecting the important immunologic effects that are sometimes opposite of the cell biologic effects. Here, we summarize both the cell biologic and immunologic effects of various microRNAs and discuss the importance of considering both effects before using them in clinical settings. We stress the importance of understanding the miRNA's effect on cancer metastasis from a "systems" perspective before developing a miRNA-targeted therapeutic in treating cancer metastasis.

  19. Innate Lymphoid Cells: a new paradigm in immunology

    Science.gov (United States)

    Eberl, Gérard; Colonna, Marco; Di Santo, James P.; McKenzie, Andrew N.J.

    2016-01-01

    Summary Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not express acquired antigen receptors or undergo clonal selection and expansion when stimulated. Instead, ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins termed cytokines that direct the developing immune response into one that is adapted to the original insult. The complex crosstalk between microenvironment, ILCs and adaptive immunity remains to be fully deciphered. Only by understanding these complex regulatory networks can the power of ILCs be controlled or unleashed to regulate or enhance immune responses in disease prevention and therapy. PMID:25999512

  20. Designing bovine T cell vaccines via reverse immunology

    DEFF Research Database (Denmark)

    Nene, Vishvanath; Svitek, Nicholas; Toye, Philip

    2012-01-01

    T cell responses contribute to immunity against many intracellular infections. There is, for example, strong evidence that major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) play an essential role in mediating immunity to East Coast fever (ECF), a fatal lymph...

  1. Designing bovine T-cell vaccines via reverse immunology

    Science.gov (United States)

    T-cell responses contribute to immunity against many intra-cellular infections. There is, for example, strong evidence that major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTLs) play an essential role in mediating immunity to East Coast fever (ECF), a fatal lymphop...

  2. Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.

    Science.gov (United States)

    Wang, Denong; Wu, Lisa; Liu, Xiaohe

    2017-01-01

    We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.

  3. The role of EMMPRIN in T cell biology and immunological diseases.

    Science.gov (United States)

    Hahn, Jennifer Nancy; Kaushik, Deepak Kumar; Yong, V Wee

    2015-07-01

    EMMPRIN (CD147), originally described as an inducer of the expression of MMPs, has gained attention in its involvement in various immunologic diseases, such that anti-EMMPRIN antibodies are considered as potential therapeutic medications. Given that MMPs are involved in the pathogenesis of various disease states, it is relevant that targeting an upstream inducer would make for an effective therapeutic strategy. Additionally, EMMPRIN is now appreciated to have multiple roles apart from MMP induction, including in cellular functions, such as migration, adhesion, invasion, energy metabolism, as well as T cell activation and proliferation. Here, we review what is known about EMMPRIN in numerous immunologic/inflammatory disease conditions with a particular focus on its complex roles in T cell biology. © Society for Leukocyte Biology.

  4. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.

    Science.gov (United States)

    Hartmann, Karin; Escribano, Luis; Grattan, Clive; Brockow, Knut; Carter, Melody C; Alvarez-Twose, Ivan; Matito, Almudena; Broesby-Olsen, Sigurd; Siebenhaar, Frank; Lange, Magdalena; Niedoszytko, Marek; Castells, Mariana; Oude Elberink, Joanna N G; Bonadonna, Patrizia; Zanotti, Roberta; Hornick, Jason L; Torrelo, Antonio; Grabbe, Jürgen; Rabenhorst, Anja; Nedoszytko, Boguslaw; Butterfield, Joseph H; Gotlib, Jason; Reiter, Andreas; Radia, Deepti; Hermine, Olivier; Sotlar, Karl; George, Tracy I; Kristensen, Thomas K; Kluin-Nelemans, Hanneke C; Yavuz, Selim; Hägglund, Hans; Sperr, Wolfgang R; Schwartz, Lawrence B; Triggiani, Massimo; Maurer, Marcus; Nilsson, Gunnar; Horny, Hans-Peter; Arock, Michel; Orfao, Alberto; Metcalfe, Dean D; Akin, Cem; Valent, Peter

    2016-01-01

    Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Bone marrow pre-B cells and the clonal anergy theory of immunologic tolerance.

    Science.gov (United States)

    Nossal, G J

    1987-03-01

    This review begins with a summary of a decade's research from the author's own laboratory which documents the fact that B lymphocytes can receive and store negative, down-regulatory signals from an encounter with antigen, and that the sensitivity to such negative signalling depends critically on maturational status, the most immature B cells being the most susceptible. The review then examines the relationship between these experimentally-induced models of immunologic tolerance, with the pre-B to B cell transition as the critical stage for examination, and the real-life phenomenon of self-tolerance. It makes the point that no repertoire-purging mechanism to ensure self-tolerance can afford to be too effective, for fear of purging too many useful cells, given the number and variability of self-antigens. The review then examines certain dilemmas posed by recent findings in cellular and molecular immunology. These include: 1) the preferential use of particular VH gene families by B cells at different stages of the differentiation process; 2) the apparent frequency of B lymphocytes with the potential for antiself-reactivity in the B cell repertoire; and 3) the existence of a new type of B cell, the Ly-1-positive B cell, with peculiar characteristics. These findings are considered within the particular contexts of pre-B-to-B cell transition and tolerance induction through clonal anergy mechanisms.

  6. Effect of UV-irradiation on immunological and histochemical markers of Langerhans cells in normal appearing skin of psoriatic patients

    International Nuclear Information System (INIS)

    Tjernlund, U.; Juhlin, L.

    1982-01-01

    A total of 12 patients with moderately severe psoriasis was treated with psoralen baths and/or ultraviolet radiation. Punch biopsies were taken for mimunological markers and shave biopsies for ATPase detection. As immunological marker immunosorbent purified antibodies against Ia antigens and monoclonal antigens against thymocyte antigens were used. The study showed that in the clinical relevant situation PUVA treatment had a more profound effect on the immunological markers of epidermal Langerhans cells than had light treatment without psoralens. With UV treatment without psoralens the ATPase activity of the Langerhans cells seemed to be more influenced than the immunological markers. (orig.)

  7. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

    Science.gov (United States)

    Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

  8. Ability of spleen cells from tumor bearing mice to transfer immunologic memory

    Energy Technology Data Exchange (ETDEWEB)

    Plavsic, B.; Jurin, M. (Zagreb Univ. (Yugoslavia)); Ugarkovic, B. (Institut Rudjer Boskovic, Zagreb (Yugoslavia))

    1983-01-01

    The ability of splenocytes from tumorous mice to transfer immunologic memory was tested. Three syngeneic experimental tumors from highly inbred strains were used; fibrosarcoma, lymphoma and Lewis lung carcinoma. Splenocytes from tumorous mice were collected after rejection of allogeneic skin which had been grafted at different stages of the tumor disease, and injected into lethally irradiated syngeneic recipients. These secondary hosts were grafted with the same allogeneic skin graft as their donors and the ability of cells transplanted from tumorous donors to transfer memory to allograft was tested. Tumorous mice seemed to have more memory cells (T lymphocytes) in their spleens than the controls.

  9. Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

    Science.gov (United States)

    Sackett, S D; Brown, M E; Tremmel, D M; Ellis, T; Burlingham, W J; Odorico, J S

    2016-04-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The relation between T-cell expression of LFA-1 and immunological memory

    DEFF Research Database (Denmark)

    Hviid, L; Odum, N; Theander, T G

    1993-01-01

    Antibodies against isotypes of the leucocyte common antigen (LCA, CD45) can be used to identify largely reciprocal subsets of human peripheral T cells, characterized by differential ability to respond to recall antigen in vitro. The transition from naive, unprimed T cells to memory cells capable...... of responding to recall stimulating has been associated with a switch in surface expression of CD45 from the CD45RA isotype to CD45RO. It has been proposed that this transition is accompanied by the coordinated up-regulation of a number of cell-surface molecules involved in cellular adhesion and/or activation......, including the leucocyte function-associated antigens (LFA). In the present study we have examined the expression of LFA-1 on subsets of human peripheral T cells, and related it to the expression of markers of cellular activation and CD45 isotypes, and thus to immunological memory. Our results suggest...

  11. Studies on the termination of immunological tolerance in the mouse thymus cell population after irradiation

    International Nuclear Information System (INIS)

    Amagai, Takashi

    1981-01-01

    Immunological tolerance in the mouse thymus cell population induced by the intravenous injection of deaggregated bovine gamma globulin was terminated by whole body irradiation. After irradiation, the weight of the thymus recovered biphasically, and the termination of tolerance occurred as early as in the first phase. Both Thy-1 antigen expression and helper activity of the thymus cell population in irradiated mice recovered in parallel with the recovery of the thymus weight. Sensitivity of the regenerating thymus cells to the tolerogen was not different from that of the normal thymus cells. The first phase of thymus regeneration may be caused by the proliferation and differentiation of relatively radioresistant and tolerogen insensitive precursors residing in the thymus. Tolerogen and/or immunogen reactive thymus cells may originate from the precursor. (author)

  12. 21st Nantes Actualités Transplantation: "When Stem Cells Meet Immunology".

    Science.gov (United States)

    Anegon, Ignacio; Nguyen, Tuan Huy

    2017-01-01

    "When Stem Cells Meet Immunology" has been the topic of the 21st annual "Nantes Actualités en Transplantation" meeting (June 9-10, 2016, Nantes, France). This meeting brought together pioneers and leading experts in the fields of stem cells, biomaterials and immunoregulation. Presentations covered multipotent (mesenchymal and hematopoietic) and pluripotent stem cells (embryonic and induced) for regenerative medicine of incurable diseases, immunotherapy and blood transfusions. An additional focus had been immune rejections and responses of allogeneic or autologous stem cells. Conversely, stem cells are also able to directly modulate the immune response through the production of immunoregulatory molecules. Moreover, stem cells may also provide an unlimited source of immune cells (DCs, NK cells, B cells, and T cells) that can operate as "super" immune cells, for example, through genetic engineering with chimeric antigen receptors.This meeting report puts presentations into an overall context highlighting new potential biomarkers for potency prediction of mesenchymal stem cell-derived and pluripotent stem cell-derived multicellular organoids. Finally, we propose future directions arising from the flourishing encounter of stem cell and immune biology.

  13. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems

    Directory of Open Access Journals (Sweden)

    Arico Maurizo

    2011-06-01

    Full Text Available Abstract Background Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs, this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK and invariant NKT (iNKT cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. Results NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked' with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. Conclusions These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system direct secretory lysosomes to

  14. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems.

    Science.gov (United States)

    Stinchcombe, Jane C; Salio, Mariolina; Cerundolo, Vincenzo; Pende, Daniela; Arico, Maurizo; Griffiths, Gillian M

    2011-06-28

    Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. Morphologically, the

  15. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  16. Influence of ionizing radiation on immune competent cells

    International Nuclear Information System (INIS)

    Sakhno, T.O.; Davidova, T.Yi.; Chumak, A.A.

    1997-01-01

    Stable injuries of immune-competent cells in patients with dose load higher than professional one are determined. Changes of metabolic profile, beside changes of surface membrane structures were observed

  17. Lack of correlation between immunologic markers and cell surface ultrastructure in the leukemic phase of lymphoproliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Golomb, Harvey M.; Simon, Deberah

    1977-01-01

    In a prospective study of malignant cells from 13 patients with the leukemic phase of lymphoproliferative diseases, we wished to determine whether any correlation between the immunologic markers and the cell surface ultrastructure. Five patients had chronic lymphocytic leukemia, four had malignant lymphomas, poorly differentiated lymphocytic type, two had the Sezary syndrome, and one each had acute prolymphocytic leukemia and acute lymphocytic leukemia. Cell separation and isolation was done at room temperature for all specimens. Immunologic markers tested for were surface immunoglobins, a B-cell property, and E-rosettes, a T-cell property. Three patients had T-cell diseases, 6 had B-cell diseases, and 4 were classified as ''null.'' All but one patient had moderate to large numbers of microvilli on their malignant cells. The single exception had a typical B-cell form of chronic lymphocytic leukemia. There appears to be no correlation between immunologic markers and cell surface ultrastructure; therefore, SEM appears not to be valuable in the diagnosis or classification of immunologic sub-types of certain lymphoproliferative diseases.

  18. Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Mark A.; Pfeiffer, Janet R. (University of New Mexico, Albuquerque, NM); Wilson, Bridget S. (University of New Mexico, Albuquerque, NM); Timlin, Jerilyn Ann; Thomas, James L. (University of New Mexico, Albuquerque, NM); Lidke, Keith A. (University of New Mexico, Albuquerque, NM); Spendier, Kathrin (University of New Mexico, Albuquerque, NM); Oliver, Janet M. (University of New Mexico, Albuquerque, NM); Carroll-Portillo, Amanda (University of New Mexico, Albuquerque, NM); Aaron, Jesse S.; Mirijanian, Dina T.; Carson, Bryan D.; Burns, Alan Richard; Rebeil, Roberto

    2009-10-01

    This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effort to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.

  19. The immunological effect of 8-methoxypsoralen and UVA treatment on murine T-cell leukemia

    International Nuclear Information System (INIS)

    Tingying Cheng; Fungwin Shen; Ronghwa Lin

    1996-01-01

    8-Methoxyproralen (8-MOP) plus long-wavelength UV radiation (UVA, 320-400 nm) have been used to treat various diseases such as cutaneous T-cell lymphoma, systemic scleroderma, rheumatoid arthritis and rejection of heart transplants. However, the immunological mechanism of this treatment remains unknown. In this report, we investigated the effect of 8-MOP/UVA on the modulation of the immunogenicity of a T-cell leukemia cell line (RL ''male'' 1 cells). The results demonstrated that the stimulator function of the in vitro 8-MOP/UVA-treated RL ''male'' 1 cells was enhanced in both RL ''male'' 1-specific allogeneic and syngeneic immune responses. Furthermore, the enhancement of the immunogenicity of the 8-MOP/UVA-treated RL ''male'' 1 cells was found to be strongly associated with the increase of intercellular adhesion molecule-1 expression on these 8-MOP/UVA-treated tumor cells. Therefore, our findings suggested that the alteration of the expression of the immune-related cell surface molecules might be an important effect of 8-MOP/UVA treatment on the elevation of the immunogenicity of the 8-MOP/UVA-treated tumor cells. (Author)

  20. The immunological effect of 8-methoxypsoralen and UVA treatment on murine T-cell leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Tingying Cheng; Fungwin Shen; Ronghwa Lin [National Taiwan Univ., Taipei (China)

    1996-09-01

    8-Methoxyproralen (8-MOP) plus long-wavelength UV radiation (UVA, 320-400 nm) have been used to treat various diseases such as cutaneous T-cell lymphoma, systemic scleroderma, rheumatoid arthritis and rejection of heart transplants. However, the immunological mechanism of this treatment remains unknown. In this report, we investigated the effect of 8-MOP/UVA on the modulation of the immunogenicity of a T-cell leukemia cell line (RL ``male`` 1 cells). The results demonstrated that the stimulator function of the in vitro 8-MOP/UVA-treated RL ``male`` 1 cells was enhanced in both RL ``male`` 1-specific allogeneic and syngeneic immune responses. Furthermore, the enhancement of the immunogenicity of the 8-MOP/UVA-treated RL ``male`` 1 cells was found to be strongly associated with the increase of intercellular adhesion molecule-1 expression on these 8-MOP/UVA-treated tumor cells. Therefore, our findings suggested that the alteration of the expression of the immune-related cell surface molecules might be an important effect of 8-MOP/UVA treatment on the elevation of the immunogenicity of the 8-MOP/UVA-treated tumor cells. (Author).

  1. Effect of Allium cepa and Allium sativum on some immunological cells in rats.

    Science.gov (United States)

    Mirabeau, Tatfeng Y; Samson, Enitan S

    2012-01-01

    Extracts of some spices have been reported to play a contributory role in enhancing immune function. We evaluated and compared the effect(s) of single and combined oral administration of fresh aqueous onion (Allium cepa) and garlic (Allium sativum) extracts at different concentrations on some immunological determinants in rats. CD₄ cells of the rats were estimated using Partec flow cytometric technique, while total and differential white blood cell (WBC) counts were estimated using the Sysmsex® automated haematology analyzing technique. Our findings revealed that, CD4 and total WBC counts were significantly increased (P≤0.05) in a dose-dependent manner in both onion (250mg/Kg/d: 349±11cell/ul and 2.75±0.15X10³cell/l; 500mg/Kg/d: 389±10cells/µl and 3.05±0.05 X10³cell/l; 750mg/Kg/d: 600±11cell/µl and 3.25±0.05X10³cells/l) and garlic (250mg/Kg/d: 410±10cell/ul and 2.85±0.15X10³cell/l; 500mg/Kg/d: 494±32cells/µl and 3.30±0.10 X10³cell/l; 750mg/Kg/d: 684±11cell/µl and 3.55±0.05X10³cells/l) treated rats when compared to the zero control (200±11cells/µl and 1.55±0.05X10³cells/l, respectively). Extract of garlic at 750mg/Kg/d had significantly increased the CD4 cells and total white cell count when compared to other concentrations (P≤0.05). However, no significant effect was observed on these parameters when extracts were combined (250mg/Kg/d: 252±21cell/µl and 1.80±0.10X10³cells/l; 500mg/Kg/d: 315±21cells/ul and 2.10±0.10X10³cells/l; 750mg/Kg/d: 368±10cells/µl and 2.35±0.05X10³cells/l, respectively), the differential WBC count showed a significant increase in the proportion of cell types (lymphocytes, neutophils and monocytes) (P≤0.05). The results from this study revealed the immune boosting capabilities of Allium cepa and Allium sativum, but underscored their synergistic activities.

  2. Intensive educational course in allergy and immunology.

    Science.gov (United States)

    Elizalde, A; Perez, E E; Sriaroon, P; Nguyen, D; Lockey, R F; Dorsey, M J

    2012-09-01

    A one-day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows-in-training. © 2012 John Wiley & Sons A/S.

  3. Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells.

    Science.gov (United States)

    Griffith, Thomas S; Brincks, Erik L; Gurung, Prajwal; Kucaba, Tamara A; Ferguson, Thomas A

    2011-01-15

    Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required Fas ligand-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by CD8(+) regulatory T cells. This study examined the mechanism by which these CD8(+) regulatory T cells mediate tolerance after AC injection of Ag. AC injection of Ag did not prime CD4(+) T cells and led to increased TRAIL expression by splenic CD8(+) T cells. Unlike wild-type mice, Trail(-/-) or Dr5(-/-) mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes of these mice. CD8(+) T cells from Trail(-/-) mice that were first injected via the AC with Ag were unable to transfer tolerance to naive recipient wild-type mice, but CD8(+) T cells from AC-injected wild-type or Dr5(-/-) mice could transfer tolerance. Importantly, the transferred wild-type (Trail(+/+)) CD8(+) T cells were also able to decrease the number of infiltrating inflammatory cells into the eye; however, Trail(-/-) CD8(+) T cells were unable to limit the inflammatory cell ingress. Together, our data suggest that "helpless" CD8(+) regulatory T cells generated after AC injection of Ag enforce systemic tolerance in a TRAIL-dependent manner to inhibit inflammation in the eye.

  4. Comparison of immunological properties of bone marrow stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro

    DEFF Research Database (Denmark)

    Niemeyer, Philipp; Kornacker, Martin; Mehlhorn, Alexander

    2007-01-01

    , the influence of osteogenic differentiation in vitro on the immunological characteristics of BMSCs and ASCs is the subject of this article. Before and after osteogenic induction, the influence of BMSCs and ASCs on the proliferative behavior of resting and activated allogenic peripheral blood mononuclear cells......Mesenchymal stem cells (MSCs) can be isolated from various tissues and represent an attractive cell population for tissue-engineering purposes. MSCs from bone marrow (bone marrow stromal cells [BMSCs]) are negative for immunologically relevant surface markers and inhibit proliferation of allogenic...... T cells in vitro. Therefore, BMSCs are said to be available for allogenic cell therapy. Although the immunological characteristics of BMSCs have been the subject of various investigations, those of stem cells isolated from adipose tissue (ASCs) have not been adequately described. In addition...

  5. Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation

    Directory of Open Access Journals (Sweden)

    Niloufar eSafinia

    2015-08-01

    Full Text Available Regulatory T cells (Tregs play an important role in immunoregulation and have been shown in animal models to promote transplantation tolerance and curb autoimmunity following their adoptive transfer. The safety and potential therapeutic efficacy of these cells has already been reported in Phase I trials of bone marrow transplantation and type I diabetes, the success of which has motivated the broadened application of these cells in solid organ transplantation. Despite major advances in the clinical translation of these cells, there are still key questions to be addressed to ensure that Tregs attest their reputation as ideal candidates for tolerance induction. In this review, we will discuss the unique traits of Tregs that have attracted such fame in the arena of tolerance induction. We will outline the protocols used for their ex vivo expansion and discuss the future directions of Treg cell therapy. In this regard, we will review the concept of Treg heterogeneity, the desire to isolate and expand a functionally superior Treg population and report on the effect of differing culture conditions. The relevance of Treg migratory capacity will also be discussed together with methods of in vivo visualization of the infused cells. Moreover, we will highlight key advances in the identification and expansion of antigen specific Tregs and discuss their significance for cell therapy application. We will also summarize the clinical parameters that are of importance, alongside cell manufacture, from the choice of immunosuppression regimens to the number of injections in order to direct the success of future efficacy trials of Treg cell therapy.Years of research in the field of tolerance have seen an accumulation of knowledge and expertise in the field of Treg biology. This perpetual progression has been the driving force behind the many successes to date and has put us now within touching distance of our ultimate success, immunological tolerance.

  6. Quantal concept of T-cell activation: adhesion domains as immunological synapses

    International Nuclear Information System (INIS)

    Sackmann, Erich

    2011-01-01

    Adhesion micro-domains (ADs) formed during encounters of lymphocytes with antigen-presenting cells (APC) mediate the genetic expression of quanta of cytokines interleukin-2 (IL-2). The IL-2-induced activation of IL-2 receptors promotes the stepwise progression of the T-cells through the cell cycle, hence their name, immunological synapses. The ADs form short-lived reaction centres controlling the recruitment of activators of the biochemical pathway (the kinases Lck and ZAP) while preventing the access of inhibitors (phosphatase CD45) through steric repulsion forces. CD45 acts as the generator of adhesion domains and, through its role as a spacer protein, also as the promoter of the reaction. In a second phase of T-cell-APC encounters, long-lived global reaction spaces (called supramolecular activation complexes (SMAC)) form by talin-mediated binding of the T-cell integrin (LFA-1) to the counter-receptor ICAM-1, resulting in the formation of ring-like tight adhesion zones (peripheral SMAC). The ADs move to the centre of the intercellular adhesion zone forming the central SMAC, which serve in the recycling of the AD. We propose that cell stimulation is triggered by integrating the effect evoked by the short-lived adhesion domains. Similar global reaction platforms are formed by killer cells to destruct APC. We present a testable mechanical model showing that global reaction spaces (SMAC or dome-like contacts between cytotoxic cells and APC) form by self-organization through delayed activation of the integrin-binding affinity and stabilization of the adhesion zones by F-actin recruitment. The mechanical stability and the polarization of the adhering T-cells are mediated by microtubule-actin cross-talk.

  7. A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections.

    Directory of Open Access Journals (Sweden)

    Gennady Bocharov

    Full Text Available Plasmacytoid dendritic cell (pDC-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mphis. These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 10(3 to 10(4 Mphis from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a 'sink' for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.

  8. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.

    Science.gov (United States)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-10-15

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.

  9. Immunological response induced by cryoablation against murine H22 hepatoma cell line in vivo.

    Science.gov (United States)

    Yang, Xueling; Li, Xiaoli; Guo, Zhi; Si, Tongguo; Yu, Haipeng; Xing, Wenge

    2018-02-01

    To describe immunological consequences induced by cryoablation against H22 cells in vivo. Adult BALB/c mice underwent subcutaneous implantation of H22 cells. All of them were assigned into three groups randomly: group A (false surgery), group B (cryoablation) and group C (cryoablation plus Freund's adjuvant). Animals were sacrificed 1, 2 and 3 weeks after treatment. Serum IFN-γ and IL-4, Th1/Th2 in spleens and cytotoxicity were detected. Compared with that of group A, (1) INF-γ of group B was higher, but IL-4 was lower; cryoablation plus Freund's adjuvant enhanced these effects. (2) Th1/Th2 rose significantly in both group B and group C. (3) Strong cytolytic activity against H22 cells of group B and group C was found on day 7, 14 and 21. Our study showed a marked shift toward Th1 and IFN-γ expression after cryoablation, with an immuno-stimulatory effect against murine H22 hepatoma Cell. Copyright © 2017. Published by Elsevier Inc.

  10. The varieties of immunological experience: of pathogens, stress, and dendritic cells.

    Science.gov (United States)

    Pulendran, Bali

    2015-01-01

    In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.

  11. In situ single molecule imaging of cell membranes: linking basic nanotechniques to cell biology, immunology and medicine

    Science.gov (United States)

    Pi, Jiang; Jin, Hua; Yang, Fen; Chen, Zheng W.; Cai, Jiye

    2014-10-01

    The cell membrane, which consists of a viscous phospholipid bilayer, different kinds of proteins and various nano/micrometer-sized domains, plays a very important role in ensuring the stability of the intracellular environment and the order of cellular signal transductions. Exploring the precise cell membrane structure and detailed functions of the biomolecules in a cell membrane would be helpful to understand the underlying mechanisms involved in cell membrane signal transductions, which could further benefit research into cell biology, immunology and medicine. The detection of membrane biomolecules at the single molecule level can provide some subtle information about the molecular structure and the functions of the cell membrane. In particular, information obtained about the molecular mechanisms and other information at the single molecule level are significantly different from that detected from a large amount of biomolecules at the large-scale through traditional techniques, and can thus provide a novel perspective for the study of cell membrane structures and functions. However, the precise investigations of membrane biomolecules prompts researchers to explore cell membranes at the single molecule level by the use of in situ imaging methods, as the exact conformation and functions of biomolecules are highly controlled by the native cellular environment. Recently, the in situ single molecule imaging of cell membranes has attracted increasing attention from cell biologists and immunologists. The size of biomolecules and their clusters on the cell surface are set at the nanoscale, which makes it mandatory to use high- and super-resolution imaging techniques to realize the in situ single molecule imaging of cell membranes. In the past few decades, some amazing imaging techniques and instruments with super resolution have been widely developed for molecule imaging, which can also be further employed for the in situ single molecule imaging of cell membranes. In

  12. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin and celeco......Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin...... and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN EliSpot. Secondary objec- tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten...

  13. Comparison of Th17 cells mediated immunological response among asthmatic children with or without allergic rhinitis.

    Science.gov (United States)

    Qing, Miao; Yongge, Liu; Wei, Xu; Yan, Wang; Zhen, Li; Yixin, Ren; Hui, Guan; Li, Xiang

    2018-03-31

    To investigate whether there were differences in Th17 cells mediated immunological responses among asthmatics with or without allergic rhinitis. A case-control comparison was conducted in a cohort of 67 children with asthma (AS), 50 children with allergic rhinitis (AR), 52 children with both AS and AR (ASR), 25 infectious rhinitis (IR), and 55 healthy controls (HC). The percentages of circulating Th17 cells were determined by flow cytometry. The Th2- and Th17-related cytokines in plasma and culture supernatants were measured by enzyme-linked immunosorbent assay. The effect of proinflammation cytokine IL-17E on Th2 cytokines production from human T helper (Th) lymphocytes was analyzed. (1) A inter-group comparison revealed that Th17 cells levels were highest in ASR group [(0.89% ± 0.27) %], following by AS group [(0.82 ± 0.29) %] and AR group[(0.78 ± 0.17) %] (Pimmunological characteristics among asthmatic children with or without allergic rhinitis.

  14. Immunological reactivity

    International Nuclear Information System (INIS)

    Shubik, V.M.

    1984-01-01

    Materials on comparative characteristics of state of some immunological parameters under the effect of toxic radioactive and non-radioactive chemical substances on organism of experimental animas as well as data on possible role of disclosed immunological changes are presented. Data on the possible role of immunological mechanisms in shortening life span and distortions of reproduction function are given

  15. Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution

    International Nuclear Information System (INIS)

    Tulunay, O.; Good, R.A.; Yunis, E.J.

    1975-01-01

    After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection

  16. The 5th EFIS Tatra Immunology Conference on 'Molecular Determinants of T Cell Immunity' Held in the High Tatra Mountains, Slovakia, September 7-11, 2002

    Czech Academy of Sciences Publication Activity Database

    Denzel, A.; Hořejší, Václav; Hayday, A.

    2003-01-01

    Roč. 86, č. 1 (2003), s. 1-6 ISSN 0165-2478 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : immunology * conference * T- cell Subject RIV: EC - Immunology Impact factor: 1.710, year: 2003

  17. Some notes on radiation immunology

    International Nuclear Information System (INIS)

    Sado, Toshihiko

    1977-01-01

    Immunological movement related to radiation immunology were reviewed. Basic items about cell mechanism of immunological reaction were explained, and then, relationship between immunity and radiation was given an outline. As to radiation effects on immunological lymphatic system, radiosensitivity of lymphocytes and immunological reaction, radiation effects on T and B cells, and radiosensitivity of lymphatic system, especially thymus were mentioned, and furthermore, delayed effects of radiation on immunological system were described. Radiation effects on relationship between bone marrow transplantation and genesis of reticulum cell tumor and delayed effects of radiation on them were mentioned, and genetic resistance against hematopoietic cell transplantation and its radiosensitivity were also described. Relationship between carcinogenesis due to radiation and immunity, and a state of specific immunological in an individual non-responsiveness having cancer, were also referred to. (Kanao, N.)

  18. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy

    International Nuclear Information System (INIS)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-01-01

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy. The online version of this article (doi:10.1186/s12885-015-1690-2) contains supplementary material, which is available to

  19. Mural granulosa cell gene expression associated with oocyte developmental competence

    Directory of Open Access Journals (Sweden)

    Jiang Jin-Yi

    2010-03-01

    Full Text Available Abstract Background Ovarian follicle development is a complex process. Paracrine interactions between somatic and germ cells are critical for normal follicular development and oocyte maturation. Studies have suggested that the health and function of the granulosa and cumulus cells may be reflective of the health status of the enclosed oocyte. The objective of the present study is to assess, using an in vivo immature rat model, gene expression profile in granulosa cells, which may be linked to the developmental competence of the oocyte. We hypothesized that expression of specific genes in granulosa cells may be correlated with the developmental competence of the oocyte. Methods Immature rats were injected with eCG and 24 h thereafter with anti-eCG antibody to induce follicular atresia or with pre-immune serum to stimulate follicle development. A high percentage (30-50%, normal developmental competence, NDC of oocytes from eCG/pre-immune serum group developed to term after embryo transfer compared to those from eCG/anti-eCG (0%, poor developmental competence, PDC. Gene expression profiles of mural granulosa cells from the above oocyte-collected follicles were assessed by Affymetrix rat whole genome array. Results The result showed that twelve genes were up-regulated, while one gene was down-regulated more than 1.5 folds in the NDC group compared with those in the PDC group. Gene ontology classification showed that the up-regulated genes included lysyl oxidase (Lox and nerve growth factor receptor associated protein 1 (Ngfrap1, which are important in the regulation of protein-lysine 6-oxidase activity, and in apoptosis induction, respectively. The down-regulated genes included glycoprotein-4-beta galactosyltransferase 2 (Ggbt2, which is involved in the regulation of extracellular matrix organization and biogenesis. Conclusions The data in the present study demonstrate a close association between specific gene expression in mural granulosa cells and

  20. Elucidating the immunological effects of 5-azacytidine treatment in patients with myelodysplastic syndrome and identifying new conditional ligands and T-cell epitopes of relevance in melanoma

    DEFF Research Database (Denmark)

    Frøsig, Thomas Mørch

    2015-01-01

    This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery...... frequently recognized by T cells from HLA-A2 patients. On contrary, in Paper II we wanted to investigate the protein Nodal as a novel immunological target. We took advantage of a T-cell epitope mapping platform in which HLA ligands are predicted by computer-based algorithms, further tested in the laboratory...... by an ELISA-based method and used for flow cytometry-based detection of specific T-cell responses by use of combinatorial encoded major histocompatibility (MHC) class I multimers. This procedure resulted in 127 (Paper I) and 32 (Paper II) confirmed HLA ligands, respectively, which we used for screening...

  1. T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.

    Science.gov (United States)

    Barcia, Carlos; Sanderson, Nicholas S R; Barrett, Robert J; Wawrowsky, Kolja; Kroeger, Kurt M; Puntel, Mariana; Liu, Chunyan; Castro, Maria G; Lowenstein, Pedro R

    2008-08-20

    Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown. Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes. Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV infection), anti

  2. T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.

    Directory of Open Access Journals (Sweden)

    Carlos Barcia

    2008-08-01

    Full Text Available Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown.Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes.Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV

  3. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  4. Immunological and histopathological changes in sheep affected with cutaneous squamous cell carcinoma and treated immunotherapeutically

    Directory of Open Access Journals (Sweden)

    Faten A. M. Abo-Aziza

    2017-09-01

    Full Text Available Background and Aim: Recently, it has been recorded unexpected percentage of cutaneous squamous cell carcinoma (cSCC in sheep. Despite the improvement in surgical treatment, the outcome of animals remains limited by metastatic relapse. Although antibodies for cancer treatment have been practiced for many decades, the use of this methodology in animals is deficient. This study aimed to establish cSCC therapy by tumor cell protein antibody (Ab1 or secondary antibody (Ab2 raised by two series of immunization in the same strain of rabbits. Materials and Methods: A total of 19 Ossimi sheep were used (14 sheep suffered from cSCC and 5 were apparently healthy. Each animal from control healthy group (n=5 and control cSCC (n=4 group was treated with a course of eight injections of normal globulins. Animals in the third (n=5 and the last (n=5 groups received a course of eight injections of Ab1and Ab2, respectively. Each tumor was measured before and after treatment. The eight injections were applied at 1st, 3rd, 5th, 7th, and 9th week and the remaining three injections were at 1 week interval. Tissue specimens and blood samples were taken for histological and immunological studies. Results: The obtained results revealed that injection of Ab1 might prevent the bad prognostic picture of polymorph infiltration without any criteria of regression % of tumor. Treatment with Ab2 showed regression of tumor size ranged between minimum of 8.99% and maximum of 78.12%, however, the measurements in most cases reached the maximum regression after the past two injections. In additions, infiltration of lymphocytes to tumor site, normalization of leukocytes picture and also increase of antibody titer were observed. Conclusion: This profile might confirm that Ab2 could act as an antigen and encourage us to use it as a tumor vaccine. Extensive studies are needed to isolate the idiotypic portion of Ab1 for raising Ab2 as an anti-idiotypic antibody to be used as tumor vaccine

  5. Role of mast cell- and non-mast cell-derived inflammatory mediators in immunologic induction of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    A.A.C. Albuquerque

    1997-07-01

    Full Text Available We have previously discovered a long-lasting enhancement of synaptic transmission in mammal autonomic ganglia caused by immunological activation of ganglionic mast cells. Subsequent to mast cell activation, lipid and peptide mediators are released which may modulate synaptic function. In this study we determined whether some mast cell-derived mediators, prostaglandin D2 (PGD2; 1.0 µM, platelet aggregating factor (PAF; 0.3 µM and U44619 (a thromboxane analogue; 1.0 µM, and also endothelin-1 (ET-1; 0.5 µM induce synaptic potentiation in the guinea pig superior cervical ganglion (SCG, and compared their effects on synaptic transmission with those induced by a sensitizing antigen, ovalbumin (OVA; 10 µg/ml. The experiments were carried out on SCGs isolated from adult male guinea pigs (200-250 g actively sensitized to OVA, maintained in oxygenated Locke solution at 37oC. Synaptic potentiation was measured through alterations of the integral of the post-ganglionic compound action potential (CAP. All agents tested caused long-term (LTP; duration ³30 min or short-term (STP; <30 min potentiation of synaptic efficacy, as measured by the increase in the integral of the post-ganglionic CAP. The magnitude of mediator-induced potentiation was never the same as the antigen-induced long-term potentiation (A-LTP. The agent that best mimicked the antigen was PGD2, which induced a 75% increase in CAP integral for LTP (antigen: 94% and a 34% increase for STP (antigen: 91%. PAF-, U44619-, and ET-1-induced increases in CAP integral ranged for LTP from 34 to 47%, and for STP from 0 to 26%. These results suggest that the agents investigated may participate in the induction of A-LTP

  6. Expression of Fgf23 in activated dendritic cells and macrophages in response to immunological stimuli in mice.

    Science.gov (United States)

    Masuda, Yuki; Ohta, Hiroya; Morita, Yumiko; Nakayama, Yoshiaki; Miyake, Ayumi; Itoh, Nobuyuki; Konishi, Morichika

    2015-01-01

    Fibroblast growth factors (Fgfs) are polypeptide growth factors with diverse biological activities. While several studies have revealed that Fgf23 plays important roles in the regulation of phosphate and vitamin D metabolism, the additional physiological roles of Fgf23 remain unclear. Although it is believed that osteoblasts/osteocytes are the main sources of Fgf23, we previously found that Fgf23 mRNA is also expressed in the mouse thymus, suggesting that it might be involved in the immune system. In this study we examined the potential roles of Fgf23 in immunological responses. Mouse serum Fgf23 levels were significantly increased following inoculation with Escherichia coli or Staphylococcus aureus or intraperitoneal injection of lipopolysaccharide. We also identified activated dendritic cells and macrophages that potentially contributed to increased serum Fgf23 levels. Nuclear factor-kappa B (NF-κB) signaling was essential for the induction of Fgf23 expression in dendritic cells in response to immunological stimuli. Moreover, we examined the effects of recombinant Fgf23 protein on immune cells in vitro. Fgfr1c, a potential receptor for Fgf23, was abundantly expressed in macrophages, suggesting that Fgf23 might be involved in signal transduction in these cells. Our data suggest that Fgf23 potentially increases the number in macrophages and induces expression of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine. Collectively, these data suggest that Fgf23 might be intimately involved in inflammatory processes.

  7. Different Immunological Phenotypes Associated with Preserved CD4+ T Cell Counts in HIV-Infected Controllers and Viremic Long Term Non-Progressors

    DEFF Research Database (Denmark)

    Gaardbo, Julie Christine; Hartling, Hans J; Ronit, Andreas

    2013-01-01

    HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell...

  8. Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV.

    Science.gov (United States)

    Liu, Dongfang; Tian, Shuo; Zhang, Kai; Xiong, Wei; Lubaki, Ndongala Michel; Chen, Zhiying; Han, Weidong

    2017-12-01

    Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CAR-modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.

  9. Immunologic effects of whole body ultraviolet (uv) irradiation. II. Defect in splenic adherent cell antigen presentation for stimulation of T cell proliferation

    International Nuclear Information System (INIS)

    Letvin, N.L.; Fox, I.J.; Greene, M.I.; Benacerraf, B.; Germain, R.N.

    1980-01-01

    Ultraviolet (uv) irradiation has been shown to alter many parameters of the immunologic reactivity of mice. The altered responsiveness of uv-irradiated mice, as measured by delayed-type hypersensitivity (DTH) and primary in vitro plaque-forming cell (PFC) responses to T-dependent antigens, has recently been correlated with a functional defect in the splenic adherent cell population of these animals. The present studies describe a model of this altered responsiveness, which allows further clarification of the effects of external uv irradiation on the splenic antigen-presenting cell (APC) in its interactions with T cells

  10. Immunological network activation by low-dose rate irradiation. Analysis of cell populations and cell surface molecules in whole body irradiated mice

    International Nuclear Information System (INIS)

    Ina, Yasuhiro; Sakai, Kazuo

    2003-01-01

    The effects of low-dose rate whole body irradiation on biodefense and immunological systems were investigated using female C57BL/6 (B6) mice. These B6 mice were exposed continuously to γ-rays from a 137 Cs source in the long-term low-dose rate irradiation facility at CRIEPI for 0 - 12 weeks at a dose rate of 0.95 mGy/hr. In the bone marrow, thymus, spleen, lymph nodes, and peripheral blood of the irradiated mice, changes in cell populations and cell surface molecules were examined. The cell surface functional molecules (CD3, CD4, CD8, CD19, CD45R/B220, ICAM-1, Fas, NK-1.1, CXCR4, and CCR5), and activation molecules (THAM, CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen, CTLA-4, CD30 ligand, and CD40 ligand) were analyzed by flow cytometry. The percentage of CD4 + T cells and cell surface CD8 molecule expressions on the CD8 + T cells increased significantly to 120-130% after 3 weeks of the irradiation, compared to non-irradiated control mice. On the other hand, the percentage of CD45R/B220 + CD40 + B cells, which is one of the immunological markers of inflammation, infection, tumor, and autoimmune disease, decreased significantly to 80-90% between the 3rd to 5th week of irradiation. There was no significant difference in other cell population rates and cell surface molecule expression. Furthermore, abnormal T cells bearing mutated T cell receptors induced by high-dose rate irradiation were not observed throughout this study. These results suggest that low-dose rate irradiation activates the immunological status of the whole body. (author)

  11. Assessment of the competing technologies to fuel cells in the stationary power and CHP markets

    Energy Technology Data Exchange (ETDEWEB)

    Pears, T.J.

    1999-07-01

    This report summarises the results of a study assessing the commercial technologies that are likely to compete with fuel cells in the fields of stationary power and cogeneration markets. The competing technologies examined include clean coal technologies, reciprocating engines, gas turbines, microturbines, and stirling engines. Energy and environmental legislation, and the ranking of the competing technologies are discussed. (UK)

  12. Comparison of Immunological Characteristics of Mesenchymal Stem Cells from the Periodontal Ligament, Umbilical Cord, and Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Jin-Hee Kim

    2018-01-01

    Full Text Available Mesenchymal stem cells (MSCs are of therapeutic importance in the fields of regenerative medicine and immunological diseases. Accordingly, studies evaluating MSCs for clinical applications are increasing. In this study, we characterized MSCs from the periodontal ligament, umbilical cord (UC-MSCs, and adipose tissue, which were relatively easy to obtain with limited ethical concerns regarding their acquisition, and compared their immunological characteristics. Among MSCs isolated from the three different tissues, UC-MSCs grew the fastest in vitro. The three types of MSCs were shown to inhibit proliferation of activated peripheral blood mononuclear cells (PBMCs to a similar degree, via the indoleamine 2,3-dioxygenase and cyclooxygenase-2 pathways. They were also shown to inhibit the proliferation of PBMCs using HLA-G, which was most prominent in UC-MSCs. Unlike the other two types of MSCs, UC-MSCs showed minimal expression of HLA-DR after activation, suggesting that they pose minimal risk of initiating an allogeneic immune response when administered in vivo. These characteristics, the ease of collection, and the minimal ethical concerns regarding their use suggest UC-MSCs to be suitable MSC therapeutic candidates.

  13. Selenium Pretreatment Alleviated LPS-Induced Immunological Stress Via Upregulation of Several Selenoprotein Encoding Genes in Murine RAW264.7 Cells.

    Science.gov (United States)

    Wang, Longqiong; Jing, Jinzhong; Yan, Hui; Tang, Jiayong; Jia, Gang; Liu, Guangmang; Chen, Xiaoling; Tian, Gang; Cai, Jingyi; Shang, Haiying; Zhao, Hua

    2018-04-18

    This study was conducted to profile selenoprotein encoding genes in mouse RAW264.7 cells upon lipopolysaccharide (LPS) challenge and integrate their roles into immunological regulation in response to selenium (Se) pretreatment. LPS was used to develop immunological stress in macrophages. Cells were pretreated with different levels of Se (0, 0.5, 1.0, 1.5, 2.0 μmol Se/L) for 2 h, followed by LPS (100 ng/mL) stimulation for another 3 h. The mRNA expression of 24 selenoprotein encoding genes and 9 inflammation-related genes were investigated. The results showed that LPS (100 ng/mL) effectively induced immunological stress in RAW264.7 cells with induced inflammation cytokines, IL-6 and TNF-α, mRNA expression, and cellular secretion. LPS increased (P immunological stress in RAW264.7 cells accompanied with the global downregulation of selenoprotein encoding genes and Se pretreatment alleviated immunological stress via upregulation of a subset of selenoprotein encoding genes.

  14. Pneumococcal Competence Coordination Relies on a Cell-Contact Sensing Mechanism.

    Directory of Open Access Journals (Sweden)

    Marc Prudhomme

    2016-06-01

    Full Text Available Bacteria have evolved various inducible genetic programs to face many types of stress that challenge their growth and survival. Competence is one such program. It enables genetic transformation, a major horizontal gene transfer process. Competence development in liquid cultures of Streptococcus pneumoniae is synchronized within the whole cell population. This collective behavior is known to depend on an exported signaling Competence Stimulating Peptide (CSP, whose action generates a positive feedback loop. However, it is unclear how this CSP-dependent population switch is coordinated. By monitoring spontaneous competence development in real time during growth of four distinct pneumococcal lineages, we have found that competence shift in the population relies on a self-activated cell fraction that arises via a growth time-dependent mechanism. We demonstrate that CSP remains bound to cells during this event, and conclude that the rate of competence development corresponds to the propagation of competence by contact between activated and quiescent cells. We validated this two-step cell-contact sensing mechanism by measuring competence development during co-cultivation of strains with altered capacity to produce or respond to CSP. Finally, we found that the membrane protein ComD retains the CSP, limiting its free diffusion in the medium. We propose that competence initiator cells originate stochastically in response to stress, to form a distinct subpopulation that then transmits the CSP by cell-cell contact.

  15. Immunologic proof of DNS irradiation damages and their repair in stationary yeast cells

    International Nuclear Information System (INIS)

    Waller, H.

    1980-08-01

    In rabbits an antiserum was produced by injecting UV-irradiated denaturated calf-thymus DNS; after inhibiting unspecific bindings, a specific serological reaction with UV-induced irradiation damages could be taken as present in this antiserum. By the ammonium sulphate precipitation as immunologic method of detection, after UV-irradiation the genesis of damages at certain sites in the DNS of different yeast lineages and their repair was observed. The elemination of UV-induced DNS damages was observed after an incubation in a nutrien medium, after photo-reactivation and after combining both therapeutic treatments. The following results were obtained: the detected DNS damage (number of induced dimeres/yeast genomes) had the same degree in the four yeast lineages. Apart from the excision-negative mutante 2094 for all yeast lineages a repair efficiency of 60% could be detected. All yeast lineages presented themselves as photographically to be reactivated; however, in all cases a DNS damage of 40 to 50% remained. The examinations for the specificity of antiserum against roentgenologically irradiated DNS led to the conclusion that the antibody population of the serum consisted mainly of immunoglobulines against unchanged DNS areas. A specific immunological reaction of only about 10% could be achieved. (orig./MG) [de

  16. Immunology studies

    International Nuclear Information System (INIS)

    Smith, D.M.; Baron, P.A.; Drake, G.A.; LaBauve, P.M.; London, J.E.; Wilson, J.S.

    1977-01-01

    The following studies were conducted in the field of immunology; a model system to determine toxic effects on the immune system using 3 H-uridine uptake by Feells of rats; and survival in lethally irradiatd mice receiving allogenic fetal liver and thymus

  17. Reproductive immunology

    DEFF Research Database (Denmark)

    Christiansen, Ole B

    2012-01-01

    pathological pregnancy are suggested to predispose to adaptive immunological processes against alloantigens on the trophoblast that may further increase the risk of pathological pregnancy outcome. The best documented adaptive immune reaction against fetal alloantigens is directed against male-specific minor...

  18. The immunological synapse

    DEFF Research Database (Denmark)

    Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten

    2003-01-01

    . A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...

  19. Basic and clinical immunology

    Science.gov (United States)

    Chinen, Javier; Shearer, William T.

    2003-01-01

    Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

  20. A baseline metabolomic signature is associated with immunological CD4+ T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients.

    Science.gov (United States)

    Rodríguez-Gallego, Esther; Gómez, Josep; Pacheco, Yolanda M; Peraire, Joaquim; Viladés, Consuelo; Beltrán-Debón, Raúl; Mallol, Roger; López-Dupla, Miguel; Veloso, Sergi; Alba, Verónica; Blanco, Julià; Cañellas, Nicolau; Rull, Anna; Leal, Manuel; Correig, Xavier; Domingo, Pere; Vidal, Francesc

    2018-03-13

    Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after antiretroviral therapy (ART) to envisage the underlying mechanistic pathways that influence the treatment response. This was a multicentre, prospective cohort study in ART-naive and a pre-ART low nadir (Immunological recovery was defined as reaching CD4 T-cell count at least 250 cells/μl after 36 months of virologically successful ART. We used univariate comparisons, Random Forest test and receiver-operating characteristic curves to identify and evaluate the predictive factors of immunological recovery after treatment. HIV-infected patients with a baseline metabolic pattern characterized by high levels of large high density lipoprotein (HDL) particles, HDL cholesterol and larger sizes of low density lipoprotein particles had a better immunological recovery after treatment. Conversely, patients with high ratios of non-HDL lipoprotein particles did not experience this full recovery. Medium very-low-density lipoprotein particles and glucose increased the classification power of the multivariate model despite not showing any significant differences between the two groups. In HIV-infected patients, a baseline healthier metabolomic profile is related to a better response to ART where the lipoprotein profile, mainly large HDL particles, may play a key role.

  1. Immunological and molecular biological identification of a true case of T-hairy cell leukaemia

    DEFF Research Database (Denmark)

    Demeter, J; Pálóczi, K; Földi, J

    1990-01-01

    A hairy cell leukaemia (HCL) patient is presented in whom the peripheral blood mononuclear cells (PBMCs) carried suppressor T-cell markers (CD3+, CD2+, CD8+/CD4-, CD38+). Analysis of genomic DNA of PBMNC showed the presence of a monoclonal population of T cells, the T-cell receptor (TCR) beta-cha...

  2. Immunology of Bee Venom.

    Science.gov (United States)

    Elieh Ali Komi, Daniel; Shafaghat, Farzaneh; Zwiener, Ricardo D

    2017-01-20

    Bee venom is a blend of biochemicals ranging from small peptides and enzymes to biogenic amines. It is capable of triggering severe immunologic reactions owing to its allergenic fraction. Venom components are presented to the T cells by antigen-presenting cells within the skin. These Th2 type T cells then release IL-4 and IL-13 which subsequently direct B cells to class switch to production of IgE. Generating venom-specific IgE and crosslinking FcεR1(s) on the surface of mast cells complete the sensitizing stage in allergic individuals who are most likely to experience severe and even fatal allergic reactions after being stung. Specific IgE for bee venom is a double-edged sword as it is a powerful mediator in triggering allergic events but is also applied successfully in diagnosis of the venom allergic patient. The healing capacity of bee venom has been rediscovered under laboratory-controlled conditions using animal models and cell cultures. The potential role of enzymatic fraction of bee venom including phospholipase A2 in the initiation and development of immune responses also has been studied in numerous research settings. Undoubtedly, having insights into immunologic interactions between bee venom components and innate/specific immune cells both locally and systematically will contribute to the development of immunologic strategies in specific and epitope-based immunotherapy especially in individuals with Hymenoptera venom allergy.

  3. Solving Immunology?

    Science.gov (United States)

    Vodovotz, Yoram; Xia, Ashley; Read, Elizabeth L; Bassaganya-Riera, Josep; Hafler, David A; Sontag, Eduardo; Wang, Jin; Tsang, John S; Day, Judy D; Kleinstein, Steven H; Butte, Atul J; Altman, Matthew C; Hammond, Ross; Sealfon, Stuart C

    2017-02-01

    Emergent responses of the immune system result from the integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for the systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology. Here, we present the perspectives that emerged from the National Institute of Allergy and Infectious Disease (NIAID) workshop 'Complex Systems Science, Modeling and Immunity' and subsequent discussions regarding the potential synergy of high-throughput data acquisition, data-driven modeling, and mechanistic modeling to define new mechanisms of immunological disease and to accelerate the translation of these insights into therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  5. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  6. The research on the influences of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis.

    Science.gov (United States)

    Sun, J-J; Fan, G-L; Wang, X-G; Xu, K

    2017-07-01

    To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49). We administered systemic vein chemotherapy for patients in the control group, and hyperthermal perfusion chemotherapy for the patients in the observation group in order to compare the subgroup levels of T lymphocytes, NK cells and immunoglobulin (IgG, IgA, and IgM) in the immune system of patients in both groups. We also assayed the circulating tumor cells (CTC) in the peripheral blood of patients in both groups using the cell search method, and compared the efficacy using response evaluation criteria in solid tumors and the survival rates of patients in both groups using the Kaplan-Meier method. After two treatment courses, the levels of CD3+, CD4+ and CD4+/CD8+ of the patients in the observation group were significantly higher than those of the control group, but the levels of CD8+ of patients in the observation group was lower than that in the control group (pfunctions of patients for the indirect anti-tumor effect, a significant decrease in CTC of patients, and a higher long-term survival rate have been achieved in the treatment with hyperthermal perfusion chemotherapy combined with immunologic therapy for the advanced colorectal cancer patients with liver metastasis. Thus, it can serve as the preferable drug for the treatment of advanced colorectal cancer with liver metastasis.

  7. Evaluating the Role of Immunological Cells (Tissue Eosinophils and Mast Cells) in Progression of Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Saxena, S; Singh, A; Singh, P; Sundaragiri, K S; Sankhla, B; Bhargava, A

    2018-04-01

    Mast cells and eosinophils are increased in oral squamous cell carcinoma. The significance of such an association has been variably thought to be either a potential diagnostic tool for stromal invasion or as a prognostic indicator. The aim of the study was to study the mast cells and eosinophils between normal oral mucosa, leukoplakia and oral squamous cell carcinoma and to study the significance of mast cells in the progression of the lesion. A retrospective study was done on archival tissue received from January 2015 to December 2015, in the Department of Oral Pathology, RUHS College of Dental Sciences, Jaipur, Rajasthan, India. Seventy (70) cases were studied (30 cases each of leukoplakia and carcinoma and 10 cases of control group), sections were stained with toluidine blue solution to reveal mast cells. Eosinophils were studied in Haematoxylin & Eosin stained sections. Mast cell density significantly increased from: normal mucosa to oral leukoplakia to carcinoma, suggesting a role of the mast cells in the development of these lesions. The higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion. The assessment of these could become, in the future, useful for therapeutic approaches in this subset of the patient.

  8. CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation1,2

    Science.gov (United States)

    Thauland, Timothy J.; Koguchi, Yoshinobu; Dustin, Michael L.; Parker, David C.

    2014-01-01

    Regulatory T cells (Tregs) are essential for tolerance to self and environmental antigens, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naïve CD4 T cell-DC interactions. Here, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down, but maintain a highly polarized and motile phenotype after recognizing antigen in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or ‘kinapse’. However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking antibodies, we show that, while CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of antigen. Together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals. PMID:25355918

  9. Assessment of centrifugation using for accelerated immunological microarray analysis for blood cells investigation

    Directory of Open Access Journals (Sweden)

    A. V. Shishkin

    2011-01-01

    Full Text Available Phase of incubation microarray with cell suspension is prolonged when cells are investigated. It takes from 20 to 60 min if cell sedimentation on the surface of microarray is the result of gravity . Decrease of this stage duration is possible due to centrifugation. In th is article influence of centrifugation on results of analysis is considered. Changes of morphological description of cells are estimated when they a re precipitatedwith different acceleration. Also availability of centrifugation using when it is necessary to obtain the high density of cell binding in test regions of microarray if cells concentration in sample is small is demonstrated.

  10. Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966.

    Science.gov (United States)

    Hanibuchi, M; Yano, S; Nishioka, Y; Yanagawa, H; Miki, T; Sone, S

    2000-01-01

    serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells. Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype. These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological circumvention of multiple-organ metastases of refractory SCLC.

  11. Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b1

    Science.gov (United States)

    Doherty, Melissa; Osborne, Douglas G.; Browning, Diana L.; Parker, David C.; Wetzel, Scott A.

    2010-01-01

    CD4+ T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with antigen in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study we anergized primary murine CD4+ T cells by incubation of costimulation-deficient, transfected fibroblast APC. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic cSMAC and pSMAC domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the pSMAC and the cSMAC of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance and/or induction. PMID:20207996

  12. PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse.

    Science.gov (United States)

    Huang, Yu; Chen, Zhiying; Jang, Joon Hee; Baig, Mirza S; Bertolet, Grant; Schroeder, Casey; Huang, Shengjian; Hu, Qian; Zhao, Yong; Lewis, Dorothy E; Qin, Lidong; Zhu, Michael Xi; Liu, Dongfang

    2018-04-18

    The inhibitory receptor programmed cell death protein 1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic viral infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. We sought to determine the effect of PD-1 signaling on NK cells. PD-1 was overexpressed in CD16-KHYG-1 (a human NK cell line with both antibody-dependent cellular cytotoxicity through CD16 and natural cytotoxicity through NKG2D) cells and stimulated by exposing the cells to NK-sensitive target cells expressing programmed death ligand 1 (PD-L1). PD-1 engagement by PD-L1 specifically blocked NK cell-mediated cytotoxicity without interfering with the conjugation between NK cells and target cells. Further examination showed that PD-1 signaling blocked lytic granule polarization in NK cells, which was accompanied by failure of integrin-linked kinase, a key molecule in the integrin outside-in signaling pathway, to accumulate in the immunological synapse after NK-target cell conjugation. Our results suggest that NK cell cytotoxicity is inhibited by PD-1 engagement, which blocks lytic granule polarization to the NK cell immunological synapse with concomitant impairment of integrin outside-in signaling. This study provides novel mechanistic insights into how PD-1 inhibition disrupts NK cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. The Immunological Impact of Chemotherapy on the Tumor Microenvironment of Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Takakura, Hiroaki; Domae, Shohei; Ono, Toshiro; Sasaki, Akira

    2017-06-01

     Anticancer drugs induce cell-cycle arrest and apoptosis not only in tumor cells, but also in immune cells. However, many preclinical and clinical findings show that some chemotherapeutic agents can improve the antitumor efficacy of immunotherapy. We immunohistochemically analyzed the degree of immune cell infiltration and the relevance of programmed cell death 1 ligand-1 (PD-L1) expression in surgically resected oral squamous cell carcinoma (OSCC) specimens from patients who had undergone pretreatment with certain chemotherapies and other patients without pretreatment. We divided the patients into the group of neoadjuvant chemotherapy (NAC) patients (n=8) and the nNAC (without NAC) patient group (n=10). We observed that NAC induced infiltrations of CD4, CD8 T cells and CD56 NK cells into the tumor microenvironment. Decreased numbers of Tregs and PD-1-positive cells were observed in the NAC group. No significant difference was observed in the degree of immune-cell infiltration between the patient groups except for CD56 NK cells in the stroma and PD-1 cells in cancer nests. Eighty percent of the nNAC specimens showed intermediate-to-strong PD-L1 protein expression, whereas 75% of the NAC specimens showed down-regulation of the PD-L1 protein, indicating the effectiveness of the chemotherapeutic treatment before surgery.

  14. Mesenchymal Stem Cells from Human Amniotic Membrane and Umbilical Cord Can Diminish Immunological Response in an in vitro Allograft Model.

    Science.gov (United States)

    Dabrowski, Filip A; Burdzinska, Anna; Kulesza, Agnieszka; Chlebus, Marcin; Kaleta, Beata; Borysowski, Jan; Zolocinska, Aleksandra; Paczek, Leszek; Wielgos, Miroslaw

    2017-01-01

    Mesenchymal stem cells (MSCs) are gaining rising interest in gynecology and obstetrics. MSCs immunomodulatory properties are suitable enough to reduce perinatal morbidity caused by inflammation in premature neonates. The aim of this study was to evaluate and compare the ability to inhibit allo-activated lymphocytes proliferation by MSCs derived from different sources: amniotic membrane (AM), umbilical cord (UC) and adipose tissue (AT). MSCs were isolated from AM (n = 7) and UC (n = 6) and AT (n = 6) of healthy women. Cells were characterized by flow cytometry and differentiation assay. To evaluate the potential of fetal and adult MSCs to diminish immunological response, mixed lymphocytes reaction (MLR) was performed. Amnion and UC-derived cells displayed typical MSCs characteristics. Addition of MSCs to MLR significantly inhibited the proliferation of stimulated lymphocytes. The effect was observed regardless of the MSCs type used (p < 0.01 in all groups). Comparative analysis revealed no significant differences in this action between tested MSCs types. Additionally, no type of MSCs significantly stimulated allogeneic lymphocytes. The results prove the immunosuppressive capacities of fetal-derived MSCs in vitro. In the future, they may be potentially used to treat premature newborn as well as in immunomodulation in post-transplant therapy. © 2016 S. Karger AG, Basel.

  15. Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

    Science.gov (United States)

    Ottobrini, Luisa; Biasin, Mara; Borelli, Manuela; Lucignani, Giovanni; Trabattoni, Daria; Clerici, Mario

    2016-01-01

    Introduction Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies. Matherials & Methods We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation. Results Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer. PMID:26795765

  16. MreB-Dependent Inhibition of Cell Elongation during the Escape from Competence in Bacillus subtilis.

    Science.gov (United States)

    Mirouze, Nicolas; Ferret, Cécile; Yao, Zhizhong; Chastanet, Arnaud; Carballido-López, Rut

    2015-06-01

    During bacterial exponential growth, the morphogenetic actin-like MreB proteins form membrane-associated assemblies that move processively following trajectories perpendicular to the long axis of the cell. Such MreB structures are thought to scaffold and restrict the movement of peptidoglycan synthesizing machineries, thereby coordinating sidewall elongation. In Bacillus subtilis, this function is performed by the redundant action of three MreB isoforms, namely MreB, Mbl and MreBH. mreB and mbl are highly transcribed from vegetative promoters. We have found that their expression is maximal at the end of exponential phase, and rapidly decreases to a low basal level upon entering stationary phase. However, in cells developing genetic competence, a stationary phase physiological adaptation, expression of mreB was specifically reactivated by the central competence regulator ComK. In competent cells, MreB was found in complex with several competence proteins by in vitro pull-down assays. In addition, it co-localized with the polar clusters formed by the late competence peripheral protein ComGA, in a ComGA-dependent manner. ComGA has been shown to be essential for the inhibition of cell elongation characteristic of cells escaping the competence state. We show here that the pathway controlling this elongation inhibition also involves MreB. Our findings suggest that ComGA sequesters MreB to prevent cell elongation and therefore the escape from competence.

  17. MreB-Dependent Inhibition of Cell Elongation during the Escape from Competence in Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Nicolas Mirouze

    2015-06-01

    Full Text Available During bacterial exponential growth, the morphogenetic actin-like MreB proteins form membrane-associated assemblies that move processively following trajectories perpendicular to the long axis of the cell. Such MreB structures are thought to scaffold and restrict the movement of peptidoglycan synthesizing machineries, thereby coordinating sidewall elongation. In Bacillus subtilis, this function is performed by the redundant action of three MreB isoforms, namely MreB, Mbl and MreBH. mreB and mbl are highly transcribed from vegetative promoters. We have found that their expression is maximal at the end of exponential phase, and rapidly decreases to a low basal level upon entering stationary phase. However, in cells developing genetic competence, a stationary phase physiological adaptation, expression of mreB was specifically reactivated by the central competence regulator ComK. In competent cells, MreB was found in complex with several competence proteins by in vitro pull-down assays. In addition, it co-localized with the polar clusters formed by the late competence peripheral protein ComGA, in a ComGA-dependent manner. ComGA has been shown to be essential for the inhibition of cell elongation characteristic of cells escaping the competence state. We show here that the pathway controlling this elongation inhibition also involves MreB. Our findings suggest that ComGA sequesters MreB to prevent cell elongation and therefore the escape from competence.

  18. Psoralen/UV inactivation of HIV-1-infected cells for use in cytologic and immunologic procedures

    International Nuclear Information System (INIS)

    Watson, A.J.; Klaniecki, J.; Hanson, C.V.

    1990-01-01

    A rapid procedure for the inactivation of HIV-1-infected cells using psoralen and ultraviolet (UV) light is described. Exposure of HIV-1-infected cells to 5 micrograms/ml psoralen followed by UV irradiation (320-380 nm) for 5 minutes yields cells that are noninfectious as assessed by extended infectivity assays. The psoralen/UV inactivation procedure described is effective with cells chronically or acutely infected with HIV-1 and is unaffected by cell densities up to 12 x 10(6)/ml. At 5 micrograms/ml psoralen does little damage to cellular permeability as shown by the ability of treated cells to exclude trypan blue and propidium iodide. Psoralen/UV treatment of HIV-1-infected cells does not cause a significant decrease in the reactivity of HIV-1 core and envelope antigens or cellular antigens to monoclonal antibodies. Experiments are presented demonstrating the use of these cells for flow cytometry studies and for cell surface labeling using the lactoperoxidase 125 I iodination procedure

  19. Detection of the immunologic rejection after xeno-islet transplantation: a study by MR imaging enhanced with superparamagnetic iron oxide marking CD4+ T cell antibody

    International Nuclear Information System (INIS)

    Nie Wei; Tang Yiya; Rong Pengfei; Ye Bin; Ye Zheng; Tong Qiongjuan; Wang Wei

    2008-01-01

    Objective: To evaluate the feasibility of the diagnosis of the early immunologic rejection after xeno-islet transplantation by MR imaging enhanced with superparamagnetic iron oxide (SPIO) marking CD4 + T cell antibody. Methods: Two thousand neonatal porcine islets (NPI)were transplanted under the left renal capsule of BALB/C nude mice. When the grafts could be observed by MRI, 10 7 human PBMC was intraperitoneal injected to nude mouse models to reconstitute the human immunologic system, 20 mice were reconstituted. Before and 3,7,14 days after reconstitution of human immunologic system on BALB/C nude mice, MRI imaging was performed half an hour after intravenous injection of nano-immunomagnetic beads via vena caudatis to observe the grafts' MRI signal. BALB/C nude mice were sacrificed after MRI scanning immediately, the histopathologic examination was assessed on grafts, the results were compared with MRI results. And calculate the sensitivity, specificity, Youden index number and coincidence of the MRI for immunologic rejection. Results: Grafts can be observed by MRI 3 weeks after islet cell transplantation (before immunologic rejection modeling), there is no abnormal MRI signal detected in nude mice' graft region after microbeads injected. Seven days after building of immunologic rejection model, MRI hypo-signal in graft site is shown in the T 2 WI sequence after nano-bioprober injected. Histopathologic assessments were employed on grafts in nude mice immediately (HE and immunohistochemistry staining), the results shown that there are a lot of T lymphocyts infiltrated in graft region, implying the occurrence of immunologic rejection. And the sensitivity, specificity, Youden index number and coincidence is: (72.96±0.24)%, 100%, 0.73±0.24, (88.46±0.13)% respectively. The correct Kappa between the MRI and the imunohistochemistry staining was 0.76. Conclusion: The cellular immunological rejection to xeno-islet grarts can be assessed with nano-bioprobe with anti-CD4

  20. Membrane prteins of herpes simplex infected cells. Immunological and biochemical studies

    NARCIS (Netherlands)

    Welling-Wester, Sijtske

    1981-01-01

    As a consequence of infection with herpes simplex virus (HSV), cells exhibit a number of alterations. One of these is expressed as a change in the polypeptide composition of the surface of the infected cells. In this study several methods used for the isolation of these polypeptides expressed on the

  1. Immunological challenges associated with artificial skin grafts: available solutions and stem cells in future design of synthetic skin.

    Science.gov (United States)

    Dixit, Saurabh; Baganizi, Dieudonné R; Sahu, Rajnish; Dosunmu, Ejowke; Chaudhari, Atul; Vig, Komal; Pillai, Shreekumar R; Singh, Shree R; Dennis, Vida A

    2017-01-01

    The repair or replacement of damaged skins is still an important, challenging public health problem. Immune acceptance and long-term survival of skin grafts represent the major problem to overcome in grafting given that in most situations autografts cannot be used. The emergence of artificial skin substitutes provides alternative treatment with the capacity to reduce the dependency on the increasing demand of cadaver skin grafts. Over the years, considerable research efforts have focused on strategies for skin repair or permanent skin graft transplantations. Available skin substitutes include pre- or post-transplantation treatments of donor cells, stem cell-based therapies, and skin equivalents composed of bio-engineered acellular or cellular skin substitutes. However, skin substitutes are still prone to immunological rejection, and as such, there is currently no skin substitute available to overcome this phenomenon. This review focuses on the mechanisms of skin rejection and tolerance induction and outlines in detail current available strategies and alternatives that may allow achieving full-thickness skin replacement and repair.

  2. Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).

    Science.gov (United States)

    Yazdani, Reza; Sharifi, Mehri; Shirvan, Aylar Saba; Azizi, Gholamreza; Ganjalikhani-Hakemi, Mazdak

    2015-01-01

    Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells.

    Science.gov (United States)

    Voos, Patrick; Fuck, Sebastian; Weipert, Fabian; Babel, Laura; Tandl, Dominique; Meckel, Tobias; Hehlgans, Stephanie; Fournier, Claudia; Moroni, Anna; Rödel, Franz; Thiel, Gerhard

    2018-01-01

    Impairment or stimulation of the immune system by ionizing radiation (IR) impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL) to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens. These responses include oscillations of cytosolic Ca 2+ , an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca 2+ sensitive K + channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca 2+ buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca 2+ -dependent immune activation and radiation-induced cell cycle arrest. Furthermore, on a functional level, Jurkat and PBL cell adhesion to endothelial cells was increased upon radiation exposure and was highly dependent on an upregulation of integrin beta-1 expression and clustering. In conclusion, we here report that IR impacts on immune activation and functional properties of T-lymphocytes that may have implications in both toxic effects and treatment response to combined radiation and immune therapy in cancer patients.

  4. Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Patrick Voos

    2018-04-01

    Full Text Available Impairment or stimulation of the immune system by ionizing radiation (IR impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens. These responses include oscillations of cytosolic Ca2+, an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca2+ sensitive K+ channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca2+ buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca2+-dependent immune activation and radiation-induced cell cycle arrest. Furthermore, on a functional level, Jurkat and PBL cell adhesion to endothelial cells was increased upon radiation exposure and was highly dependent on an upregulation of integrin beta-1 expression and clustering. In conclusion, we here report that IR impacts on immune activation and functional properties of T-lymphocytes that may have implications in both toxic effects and treatment response to combined radiation and immune therapy in cancer patients.

  5. The up side of decidual natural killer cells: new developments in immunology of pregnancy.

    Science.gov (United States)

    Jabrane-Ferrat, Nabila; Siewiera, Johan

    2014-04-01

    Early phases of human pregnancy are associated with the accumulation of a unique subset of natural killer (NK) cells in the maternal decidua. Decidual NK (dNK) cells that are devoid of cytotoxicity play a pivotal role in successful pregnancy. By secreting large amounts of cytokines/chemokines and angiogenic factors, dNK cells participate in all steps of placentation including trophoblast invasion into the maternal endometrium and vascular remodelling. In this review, we summarize some of dNK cell features and discuss more recent exciting data that challenge the conventional view of these cells. Our new data demonstrate that dNK cells undergo fine tuning or even subvert their classical inhibitory machinery and turn into a real defence force in order to prevent the spread of viruses to fetal tissue. Today it is not clear how these phenotypic and functional adaptations impact cellular cross-talk at the fetal-maternal interface and tissue homeostasis. Ultimately, precise understanding of the molecular mechanisms that govern dNK cell plasticity during congenital human cytomegalovirus infection should lead to the design of more robust strategies to reverse immune escape during viral infection and cancer. © 2013 John Wiley & Sons Ltd.

  6. Cosmos-1989 immunology studies

    Science.gov (United States)

    Sonnenfeld, Gerald

    1991-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.

  7. Hematology and immunology studies

    Science.gov (United States)

    Kimzey, S. L.

    1977-01-01

    A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.

  8. Unwanted Immunology

    Directory of Open Access Journals (Sweden)

    M.V. Supotnytskyi

    2016-04-01

    Full Text Available The paper considers the role of antigenic imprin­ting phenomena and antibody-dependent enhancement of infection in epidemic, infectious and postvaccinal processes. Based on published experimental data, it is shown that both phenomena are directly related to the laws of development and course of epide­mics, the pathogenesis of infectious diseases and safe use of vaccines. Their ignoring by researchers has led to failures in the design of vaccines against HIV/AIDS, dengue fever, influenza, malaria, hemorrhagic fever and encephalitis. These data show that, without taking into account the two phenomena, the further development of immunology and epidemiology in the direction of breakthrough discoveries in there areas of science are impossible.

  9. Human-induced pluripotent stem cell-derived macrophages and their immunological function in response to tuberculosis infection.

    Science.gov (United States)

    Hong, Danping; Ding, Jiongyan; Li, Ouyang; He, Quan; Ke, Minxia; Zhu, Mengyi; Liu, Lili; Ou, Wen-Bin; He, Yulong; Wu, Yuehong

    2018-02-26

    Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control. iPS-Mφ were characterized by using morphology, Giemsa staining, nonspecific esterase staining (α-NAE), phagocytosis, and surface phenotype. Additionally, after treatment with Bacillus Calmette-Guérin (BCG) for 24 h, cell apoptosis was detected by using an Annexin V-FITC Apoptosis Detection assay. The production of nitric oxide (NO), expression of tumor necrosis factor alpha (TNF-α), activity of apoptosis-related protein cysteine-3 (Caspase-3) and expression of B-cell lymphoma-2 (Bcl-2) were analyzed. With respect to morphology, surface phenotype, and function, the iPS-Mφ closely resembled their counterparts generated in vitro from a human monocyte cell line. iPS-Mφ exhibited the typically morphological characteristics of macrophages, such as round, oval, fusiform and irregular characteristics. The cells were Giemsa-stained-positive, α-NAE-positive, and possessed phagocytic ability. iPS-Mφ express high levels of CD14, CD11b, CD40, CD68, and major histocompatibility complex II (MHC-II). Moreover, with regard to the apoptotic rate, the production of NO, expression of TNF-α, and activity of Caspase-3 and Bcl-2, iPS-Mφ closely resemble that of their counterparts generated in vitro from human monocyte cell line in response to BCG infection. The rate of apoptosis of BCG-treated iPS-Mφ was 37.77 ± 7.94% compared to that of the untreated group at 4.97 ± 1.60% (P immunological function in response to Bacillus Calmette

  10. Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors

    Directory of Open Access Journals (Sweden)

    Shanawaz Mohammed Ghouse

    2018-01-01

    Full Text Available Summary: High numbers of mast cells populate the stroma of many types of neoplasms, including human papilloma virus-induced benign and malignant tumors in man and mouse. Equipped with numerous pattern recognition receptors and capable of executing important pro-inflammatory responses, mast cells are considered innate sentinels that significantly impact tumor biology. Mast cells were reported to promote human papilloma virus (HPV-induced epithelial hyperproliferation and neo-angiogenesis in an HPV-driven mouse model of skin cancer. We analyzed HPV-induced epithelial hyperplasia and squamous cell carcinoma formation, as well as growth of tumors inoculated into the dermis, in mice lacking skin mast cells. Unexpectedly, the absence of mast cells had no effect on HPV-induced epithelial growth or angiogenesis, on growth kinetics of inoculated tumors, or on the immunological tumor micro-milieu. Thus, the conspicuous recruitment of mast cells into tumor tissues cannot necessarily be equated with important mast cell functions in tumor growth. : Mast cells accumulate in high numbers in many human tumors, and they are widely viewed as important promoters of tumor growth. Ghouse et al. show that growth, angiogenesis, and the immunological micro-milieu of tumors growing in mice genetically deficient for mast cells are unchanged compared to control tumors. Keywords: mast cells, HPV-induced skin cancer, tumor angiogenesis, tumor micro-milieu

  11. Immunological evaluation of polystyrene and poly(ether imide) cell culture inserts with different roughness.

    Science.gov (United States)

    Roch, Toralf; Krüger, Anne; Kratz, Karl; Ma, Nan; Jung, Friedrich; Lendlein, Andreas

    2012-01-01

    For the successful clinical and biological application of polymers, their interaction with cells, tissues, and body fluids has to be well characterized. In order to investigate how the physical, chemical, and mechanical properties of candidate biomaterials influence cell behaviours, the testing sample is usually placed in commercially available cell culture plates. Thus, not only the testing sample itself but also the culture dish material might influence the cell behaviour. Therefore, an insert system was created to exclude this influence and allow investigations of the testing material solely. In this study micropatterned inserts prepared from polystyrene (PS) as well as from poly(ether imide) (PEI) with three different roughness levels of i) Rq = 0.29 μm (PS) and 0.23 μm (PEI); ii) Rq = 3.47 μm (PS) and 3.92 μm (PEI); and iii) Rq = 22.16 μm [corrected] (PS) and 22.65 μm (PEI) were explored with regard of their immuno-compatibility including the determination of potential contaminations with endotoxins or other microbial products. The endotoxin levels of the inserts were determined to be less than 0.07 EU/mL, which is well below the U.S. Food and Drug Administration limit of 0.5 EU/mL and the survival of murine macrophages cultured in the inserts was not impaired. Activation of early immune mechanisms such as complement activation and the generation of reactive oxygen species could not be observed. All tested materials had no influence on the cytokine secretion from cells of whole human blood. The investigated inserts were immuno-compatible and apparently free of contaminations with microbial products. The roughness of the inserts had no stimulatory or inhibitory effect on early immune mechanisms. Conclusively, the 24-well plate insert systems introduced in this study allow investigating the interactions of tailored surface properties such as roughness with many other cell types, without the disadvantage of the standard commercially available culture

  12. Regenerative immunology: the immunological reaction to biomaterials.

    Science.gov (United States)

    Cravedi, Paolo; Farouk, Samira; Angeletti, Andrea; Edgar, Lauren; Tamburrini, Riccardo; Duisit, Jerome; Perin, Laura; Orlando, Giuseppe

    2017-12-01

    Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression-free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials-both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes. This review will succinctly discuss progress in the understanding of immunological characteristics and behavior of different scaffolds currently under development, with emphasis on the extracellular matrix scaffolds obtained decellularized animal or human organs which seem to provide the ideal template for bioengineering purposes. © 2017 Steunstichting ESOT.

  13. Adoptively transferred dendritic cells restore primary cell-mediated inflammatory competence to acutely malnourished weanling mice.

    Science.gov (United States)

    Hillyer, Lyn; Whitley, Charlene; Olver, Amy; Webster, Michelle; Steevels, Tessa; Woodward, Bill

    2008-02-01

    Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in each dietary group received a simultaneous injection of 10(6) syngeneic dendritic cells (JAWS II). All mice were challenged with the immunizing antigen in the right hind footpad on day 13, and the 24-hour delayed hypersensitivity response was assessed as percentage increase in footpad thickness. The low-protein diet reduced the inflammatory immune response, but JAWS cells, which exhibited immature phenotypic and functional characteristics, increased the response of both the malnourished group and the controls. By contrast, i.p. injection of 10(6) syngeneic T cells did not influence the inflammatory immune response of mice subjected to the low-protein protocol. Antigen-presenting cell numbers limited primary inflammatory cell-mediated competence in this model of wasting malnutrition, an outcome that challenges the prevailing multifactorial model of malnutrition-associated immune depression. Thus, a new dendritic cell-centered perspective emerges regarding the cellular mechanism underlying immune depression in acute pediatric protein and energy deficit.

  14. Targeting dendritic cells through gold nanoparticles: A review on the cellular uptake and subsequent immunological properties.

    Science.gov (United States)

    Ahmad, Suhana; Zamry, Anes Ateqah; Tan, Hern-Tze Tina; Wong, Kah Keng; Lim, JitKang; Mohamud, Rohimah

    2017-11-01

    Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity. In this review, we describe the synthesis and physiochemical properties of gold NPs as well as the importance of gold NPs in immunotherapies through their actions on human DCs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Systemic immunological tolerance to ocular antigens is mediated by TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD8+ T cells*

    OpenAIRE

    Griffith, Thomas S.; Brincks, Erik L.; Gurung, Prajwal; Kucaba, Tamara A.; Ferguson, Thomas A.

    2010-01-01

    Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required FasL-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by C...

  16. Clinical and Immunological Features of Opsoclonus-Myoclonus Syndrome in the Era of Neuronal Cell Surface Antibodies.

    Science.gov (United States)

    Armangué, Thaís; Sabater, Lidia; Torres-Vega, Estefanía; Martínez-Hernández, Eugenia; Ariño, Helena; Petit-Pedrol, Mar; Planagumà, Jesús; Bataller, Luis; Dalmau, Josep; Graus, Francesc

    2016-04-01

    Most studies on opsoclonus-myoclonus syndrome (OMS) in adults are based on small case series before the era of neuronal cell surface antibody discovery. To report the clinical and immunological features of idiopathic OMS (I-OMS) and paraneoplastic OMS (P-OMS), the occurrence of antibodies to cell surface antigens, and the discovery of a novel cell surface epitope. Retrospective cohort study and laboratory investigations of 114 adult patients with OMS at a center for autoimmune neurological disorders done between January 2013 and September 2015. Review of clinical records. Immunohistochemistry on rat brain and cultured neurons as well as cell-based assays were used to identify known autoantibodies. Immunoprecipitation and mass spectrometry were used to characterize novel antigens. Of the 114 patients (62 [54%] female; median age, 45 years; interquartile range, 32-60 years), 45 (39%) had P-OMS and 69 (61%) had I-OMS. In patients with P-OMS, the associated tumors included lung cancer (n = 19), breast cancer (n = 10), other cancers (n = 5), and ovarian teratoma (n = 8); 3 additional patients without detectable cancer were considered to have P-OMS because they had positive results for onconeuronal antibodies. Patients with I-OMS, compared with those who had P-OMS, were younger (median age, 38 [interquartile range, 31-50] vs 54 [interquartile range, 45-65] years; P OMS with lung cancer (21% vs 5% in patients with OMS without lung cancer; P = .02); however, a similar frequency of glycine receptor antibodies was found in patients with lung cancer without OMS (13 of 65 patients [20%]). A novel cell surface epitope, human natural killer 1 (HNK-1), was the target of the antibodies in 3 patients with lung cancer and P-OMS. Patients with I-OMS responded better to treatment and had fewer relapses than those with P-OMS. Older age and encephalopathy, significantly associated with P-OMS, are clinical clues suggesting an underlying tumor. Glycine receptor antibodies occur

  17. Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with high-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response.

    Science.gov (United States)

    Ridolfi, Laura; de Rosa, Francesco; Ridolfi, Ruggero; Gentili, Giorgia; Valmorri, Linda; Scarpi, Emanuela; Parisi, Elisabetta; Romeo, Antonino; Guidoboni, Massimo

    2014-09-23

    Tumor cells killed by radiation therapy (RT) are a potentially good source of antigens for dendritic cell (DC) uptake and presentation to T-cells. RT upregulates cell death receptors such as Fas/CD95 and MHC-I, induces the expression of co-stimulatory molecules on tumor cells, and promotes production of pro-inflammatory cytokines. High-dose interleukin-2 (HD-IL-2) bolus has been shown to obtain objective response rates ranging from 15% to 17% in patients with metastatic melanoma or renal cell carcinoma (RCC), with 6% to 8% of cases experiencing a durable complete response. However, HD-IL-2 is also associated with severe side-effects; if it is to remain a component of the curative treatment strategy in patients with metastatic melanoma or RCC, its therapeutic efficacy must be improved and patients who are most likely to benefit from treatment must be identified a priori. We designed a clinical study combining immunomodulating RT and HD-IL-2 to evaluate their clinical and immunological efficacy and to explore the predictive and prognostic value of 1) tumor-specific immune response and 2) serum levels of proangiogenic cytokines. The primary endpoint of this proof-of-principle phase II study is immune response. Secondary endpoints are the identification of biomarkers potentially predictive of response, toxicity, response rate and overall survival. Three daily doses of booster radiotherapy (XRT) at 6-12 Gy will be administered to at least one metastatic field on days -3 to -1 before the first and third cycle. Treatment with IL-2 (dose 18 MIU/m2/day by continuous IV infusion for 72 hours) will start on day +1 and will be repeated every 3 weeks for up to 4 cycles and then every 4 weeks for a further 2 cycles. Immune response against tumor antigens expressed by melanoma and/or RCC will be evaluated during treatment. Circulating immune effectors and regulators, e.g. cytotoxic T lymphocytes and regulatory T cells, as well as serum levels of proangiogenic

  18. Antibody response against Betaferon® in immune tolerant mice: involvement of marginal zone B-cells and CD4+ T-cells and apparent lack of immunological memory.

    Science.gov (United States)

    Sauerborn, Melody; van Beers, Miranda M C; Jiskoot, Wim; Kijanka, Grzegorz M; Boon, Louis; Schellekens, Huub; Brinks, Vera

    2013-01-01

    The immunological processes underlying immunogenicity of recombinant human therapeutics are poorly understood. Using an immune tolerant mouse model we previously demonstrated that aggregates are a major trigger of the antidrug antibody (ADA) response against recombinant human interferon beta (rhIFNβ) products including Betaferon®, and that immunological memory seems to be lacking after a rechallenge with non-aggregated rhIFNβ. The apparent absence of immunological memory indicates a CD4+ T-cell independent (Tind) immune response underlying ADA formation against Betaferon®. This hypothesis was tested. Using the immune tolerant mouse model we first validated that rechallenge with highly aggregated rhIFNβ (Betaferon®) does not lead to a subsequent fast increase in ADA titers, suggesting a lack of immunological memory. Next we assessed whether Betaferon® could act as Tind antigen by inactivation of marginal zone (MZ) B-cells during treatment. MZ B-cells are major effector cells involved in a Tind immune response. In a following experiment we depleted the mice from CD4+ T-cells to test their involvement in the ADA response against Betaferon®. Inactivation of MZ B-cells at the start of Betaferon® treatment drastically lowered ADA levels, suggesting a Tind immune response. However, persistent depletion of CD4+ T-cells before and during Betaferon® treatment abolished the ADA response in almost all mice. The immune response against rhIFNβ in immune tolerant mice is neither a T-cell independent nor a classical T-cell dependent immune response. Further studies are needed to confirm absence of immunological memory (cells).

  19. Immunological aspects of adult T-cell leukemia/lymphoma (ATLL), a possible neoplasm of regulatory T-cells

    OpenAIRE

    Yamada, Yasuaki; Kamihira, Shimeru

    2008-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a distinct disease caused by the first discovered human oncogenic retrovirus, human T-cell leukemia virus type-1 (HTLV-1). The peculiarity of this disease is not only in its causative agent HTLV-1 but also in the character of leukemia cells. ATLL cells express the mature helper/inducer T-cell antigens, CD2, CD3, CD4 and CD5 but usually lacking CD8. Despite CD4 expression, it has long been known that ATLL cells exhibit strong immunosuppressive activity ...

  20. Immunology in Pittsburgh.

    Science.gov (United States)

    Finn, Olivera J; Salter, Russell D

    2006-01-01

    The University of Pittsburgh School of Medicine has a long tradition of excellence in immunology research and training. Faculty, students, and postdoctoral fellows walk through hallways that are pictorial reminders of the days when Dr. Jonas Salk worked here to develop the polio vaccine, or when Dr. Niels Jerne chaired the Microbiology Department and worked on perfecting the Jerne Plaque Assay for antibody-producing cells. Colleagues and postdoctoral fellows of Professor Salk are still on the faculty of the University of Pittsburgh Medical School as are graduate students of Professor Jerne. A modern research building, the 17 story high Biomedical Science Tower, is a vivid reminder of the day when Dr. Thomas Starzl arrived in Pittsburgh and started building the most prominent solid-organ-transplant program in the world. The immunology research that developed around the problem of graft rejection and tolerance induction trained numerous outstanding students and fellows. Almost 20 yr ago, the University of Pittsburgh founded the University of Pittsburgh Cancer Institute (UPCI) with the renowned immunologist Dr. Ronald Herberman at its helm. This started a number of new research initiatives in cancer immunology and immunotherapy. A large number of outstanding young investigators, as well as several well-established tumor immunologists, were recruited to Pittsburgh at that time.

  1. Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons

    DEFF Research Database (Denmark)

    Kragsnaes, Maja Skov; Fredberg, Ulrich; Stribolt, Katrine

    2014-01-01

    BACKGROUND: Limited data exist on the presence and function of immune-competent cells in chronic tendinopathic tendons and their potential role in inflammation and tissue healing as well as in predicting long-term outcome. PURPOSE: To quantify subtypes of immune-competent cells in biopsy specimens...... immunohistochemically by quantifying the presence of macrophages (CD68-PGM1(+), CD68-KP1(+)), hemosiderophages (Perls blue), T lymphocytes (CD2(+), CD3(+), CD4(+), CD7(+), CD8(+)), B lymphocytes (CD20(+)), natural killer cells (CD56(+)), mast cells (NaSDCl(+)), Schwann cells (S100(+)), and endothelial cells (CD34......(+)) using a stereological technique. A follow-up examination was conducted more than 4 years (range, 4-9 years) after the biopsy procedure to evaluate the long-term presence of Achilles tendon symptoms. RESULTS: Macrophages, T lymphocytes, mast cells, and natural killer cells were observed in the majority...

  2. Plasmacytoid dendritic cells and type I interferon in the immunological response against warts.

    Science.gov (United States)

    Saadeh, D; Kurban, M; Abbas, O

    2017-12-01

    Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), and are involved in the pathogenesis of several cutaneous infectious (especially viral), inflammatory/autoimmune and neoplastic entities. Their role in the pathogenesis and regression of human papilloma virus (HPV)-induced skin lesions has not been well studied. To investigate pDC occurrence and activity in HPV-induced skin lesions, including inflamed and uninflamed warts as well as epidermodysplasia verruciformis (EDV)-associated lesions. In total 20 inflamed and 20 uninflamed HPV-induced skin lesions (including 7 EDV lesions) were retrieved from our database, and the tissue was immunohistochemically tested for pDC occurrence and activity using anti-BDCA-2 and anti-MxA antibodies, respectively. pDCs were present in all 20 inflamed warts and absent from all 20 uninflamed cases. MxA expression was also diffuse and strong in 75% (15/20) inflamed warts, but not in any of the uninflamed warts. pDCs constitute a central component of the inflammatory host response in inflamed warts, possibly contributing to their regression through production of type I interferons. © 2017 British Association of Dermatologists.

  3. Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bordon, Victoria; Gennery, Andrew R; Slatter, Mary A; Vandecruys, Els; Laureys, Genevieve; Veys, Paul; Qasim, Waseem; Waseem, Qasim; Friedrich, Wilhelm; Wulfraat, Nico M; Scherer, Franziska; Cant, Andrew J; Fischer, Alain; Cavazzana-Calvo, Marina; Cavazanna-Calvo, Marina; Bredius, Robbert G M; Notarangelo, Luigi D; Mazzolari, Evelina; Neven, Benedicte; Güngör, Tayfun; Tayfun, Güngör

    2010-07-08

    Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.

  4. Cancer immunotherapy and immunological memory.

    Science.gov (United States)

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

    Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

  5. Comparative immune phenotypic analysis of cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in immune-competent individuals: proportional representation of CD8+ T-cells but not FoxP3+ Regulatory T-cells is associated with disease stage.

    Directory of Open Access Journals (Sweden)

    Andrew Freeman

    Full Text Available Squamous Cell Carcinoma (SCC is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can develop from premalignant lesions including Intraepidermal Carcinoma (IEC. Notably, while SCC regression is rare, IEC typically regresses in response to immune modifying topical treatments, however the underlying immunological reasons for these differential responses remain unclear. This study aimed to define whether IEC and SCC are associated with distinct immune profiles. We investigated the immune cell infiltrate of photo-damaged skin, IEC, and SCC tissue using 10-colour flow cytometry following fresh lesion digest. We found that IEC lesions contain higher percentages of CD3+ T-cells than photo-damaged skin, however, the abundance of CD3-CD56+ Natural Killer (NK cells, CD11c+HLA-DR+ conventional Dendritic Cells (cDC, BDCA-2+HLA-DR+ plasmacytoid DC (pDC, FoxP3+ Regulatory T-cells (T-reg, Vα24+Vβ11+ invariant NKT-cells, and γδ Tcells did not alter with disease stage. Within the total T-cell population, high percentages of CD4+ T-cells were associated with SCC, yet CD8+ T-cells were less abundant in SCC compared with IEC. Our study demonstrates that while IEC lesions contain a higher proportion of T-cells than SCC lesions in general, SCC lesions specifically display a lower abundance of CD8+ T-cells than IEC. We propose that differences in CD8+ T-cell abundance contribute critically to the different capacity of SCC and IEC to regress in response to immune modifying topical treatments. Our study also suggests that a high ratio of CD4+ T-cells to CD8+ T-cells may be a immunological diagnostic indicator of late-stage SCC development in immune-competent patients.

  6. HIV-infected viremic long-term non-progressors and controllers display different immunological mechanisms for preserved CD4+cell counts

    DEFF Research Database (Denmark)

    Gaardbo, J; Ronit, A; Hartling, H

    2012-01-01

    of viral replication cannot explain non-progression in LTNP. Therefore we hypothesized that the immunological mechanism responsible for preserved CD4 counts in LTNP is different from that in VC. Methods: 69 treatment naïve HIV-infected patients were included in a cross-sectional study. A total of 14 LTNP...... ratio in LTNP compared to VC were found (3.8 vs. 5.5, P=0.068) while ratios in LTNP and PR were similar (4.0, P>0.05). Conclusion: LTNP displayed high levels of immune activation, apoptotic cells and reduced Th17/Treg ratio compared to VC, while LTNP were similar to PR. Thus, the immunological mechanism...... responsible for preserved CD4 counts in LTNP is still unclear but seems to be different from that in VC....

  7. The Reorientation of T-Cell Polarity and Inhibition of Immunological Synapse Formation by CD46 Involves Its Recruitment to Lipid Rafts

    Directory of Open Access Journals (Sweden)

    Mandy J. Ludford-Menting

    2011-01-01

    Full Text Available Many infectious agents utilize CD46 for infection of human cells, and therapeutic applications of CD46-binding viruses are now being explored. Besides mediating internalization to enable infection, binding to CD46 can directly alter immune function. In particular, ligation of CD46 by antibodies or by measles virus can prevent activation of T cells by altering T-cell polarity and consequently preventing the formation of an immunological synapse. Here, we define a mechanism by which CD46 reorients T-cell polarity to prevent T-cell receptor signaling in response to antigen presentation. We show that CD46 associates with lipid rafts upon ligation, and that this reduces recruitment of both lipid rafts and the microtubule organizing centre to the site of receptor cross-linking. These data combined indicate that polarization of T cells towards the site of CD46 ligation prevents formation of an immunological synapse, and this is associated with the ability of CD46 to recruit lipid rafts away from the site of TCR ligation.

  8. An immunologic portrait of cancer

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2011-08-01

    Full Text Available Abstract The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns commonly observed during the inflammatory response against pathogens, which leads to elimination of infected cells. As these signatures are observed in growing cancers, they are not sufficient to entirely clear the organism of neoplastic cells but they sustain, as in chronic infections, a self-perpetuating inflammatory process. Yet, several studies determined an association between this inflammatory status and a favorable natural history of the disease or a better responsiveness to cancer immune therapy. Moreover, these signatures overlap with those observed during immune-mediated cancer rejection and, more broadly, immune-mediated tissue-specific destruction in other immune pathologies. Thus, a discussion concerning this cancer phenotype is warranted as it remains unknown why it occurs in immune competent hosts. It also remains uncertain whether a genetically determined response of the host to its own cancer, the genetic makeup of the neoplastic process or a combination of both drives the inflammatory process. Here we reflect on commonalities and discrepancies among studies and on the genetic or somatic conditions that may cause this schism in cancer behavior.

  9. Nurses' competences in the critical care of children undergoing hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Marianna Ferreira

    2017-11-01

    Full Text Available This is a descriptive study, with qualitative data analysis, in order to identify and analyze the experiences and competencies required by nurses in the care of transplanted child, who demand critical care. Nine nurses were interviewed. We analyzed the data according to the procedures for qualitative content analysis, and then we elaborated the following themes: Critical care to the transplanted child: a double challenge for the nurse; Nurses' competences for the care towards the critically ill child submitted to hematopoietic stem cell transplantation (HSCT. The identified competencies based on scientific knowledge, skills and natural abilities and relate to specific knowledge about pediatric HSCT; technical-scientific, interactive and communication skills; management of material resources and equipment; emotional control, empathy and leadership. Such competences help in the construction of a specific profile for the care offered to this clientele, with a view to therapeutic success.

  10. Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

    Science.gov (United States)

    Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

    2014-06-01

    The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

  11. T cell differentiation stages identified by molecular and immunologic analysis of the T cell receptor complex in childhood lymphoblastic leukemia.

    Science.gov (United States)

    Mirro, J; Kitchingman, G; Behm, F G; Murphy, S B; Goorha, R M

    1987-03-01

    T cell differentiation was investigated by determining the relationship of T cell receptor (Ti) gene rearrangement and transcription to the expression of surface and cytoplasmic T3 antigen using blast cells from five children with acute lymphoblastic leukemia of thymic origin. Patterns of monoclonal antibody (MoAb) reactivity indicated that these cases were representative of the three recognized stages (I, II, III) of human thymocyte development. The T3 antigen, which becomes linked to the Ti to form a functional T cell receptor complex on mature thymocytes, was expressed on the cell surface in two cases (stage III). However, in the remaining three cases that were surface T3 negative (stages I and II), large amounts of T3 were identified in the cytoplasm by immunoperoxidase staining and flow cytometry. Leukemic blasts from all five patients showed rearranged genes encoding the beta-chain portion of the Ti heterodimer. RNA transcripts of Ti beta-chain genes were also evident in lymphoblasts from all five cases, but transcripts coding for the alpha-chain portion of Ti were found only in cases that expressed T3 on the cell surface. Thus the absence of surface T3 (and presumably Ti) coincides with the absence of Ti alpha-chain RNA, suggesting that transcription of alpha-chain genes is a critical regulatory event in the surface expression of the Ti-T3 complex. Leukemic T cells that rearrange and express Ti beta-chain genes but lack Ti alpha-chain messenger RNA (mRNA) may represent a stage of differentiation analogous to pre-B cells, where heavy-chain immunoglobulin (Ig) genes are rearranged and expressed but light-chain Ig genes are not expressed.

  12. Germ Cells are Made Semiotically Competent During Evolution

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2016-01-01

    Germ cells are cross-roads of development and evolution. They define the origin of every new generation and, at the same time, represent the biological end-product of any mature organism. Germ cells are endowed with the following capacities: (1) to store a self-descriptive program, (2......) to accumulate a protein-synthesizing machinery (ribosomes), and (3) to incorporate enough nourishment to sustain embryonic development (yolk). To accomplish this goal, germ cells do not simply unfold a pre-determined program or realize a sole instructive role. On the contrary, due to the complexity...... milieu and experience the compatibility of selected developmental sequences. The question of which signaling pathways are activated at each developmental stage does not result from a strictly predetermined program instructing germ cell stemness. Rather, each developmental sequence is an open...

  13. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

    Science.gov (United States)

    Mallone, R; Mannering, S I; Brooks-Worrell, B M; Durinovic-Belló, I; Cilio, C M; Wong, F S; Schloot, N C

    2011-01-01

    Autoimmune T cell responses directed against insulin-producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

  14. Divergent regeneration-competent cells adopt a common mechanism for callus initiation in angiosperms.

    Science.gov (United States)

    Hu, Bo; Zhang, Guifang; Liu, Wu; Shi, Jianmin; Wang, Hua; Qi, Meifang; Li, Jiqin; Qin, Peng; Ruan, Ying; Huang, Hai; Zhang, Yijing; Xu, Lin

    2017-06-01

    In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice ( Oryza sativa ) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration-competent cells to initiate callus, whereas the cells all adopt WUSCHEL-RELATED HOMEOBOX 11 ( WOX11 ) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration-competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.

  15. Virtual Immunology: Software for Teaching Basic Immunology

    Science.gov (United States)

    Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

    2013-01-01

    As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…

  16. Immunological self, nonself discrimination

    DEFF Research Database (Denmark)

    Guillet, J G; Lai, M Z; Briner, T J

    1987-01-01

    The ability of immunodominant peptides derived from several antigen systems to compete with each other for T cell activation was studied. Only peptides restricted by a given transplantation antigen are mutually competitive. There is a correlation between haplotype restriction, ability to bind to ...

  17. Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice.

    Science.gov (United States)

    Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U

    2018-01-01

    In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN

  18. CCL8 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of CCL8.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...

  19. Immunological consideration for some aspects of radiology

    International Nuclear Information System (INIS)

    Makidono, Atsushi; Makidono, Tohoru; Yoshimoto, Kiichiro.

    1978-01-01

    What immunology should be in radiology was considered from the modern immunological and radioimmunological point of view. In order to evaluate an immunological response to radiation at a cellular level, radiosensitivities of macrophage, T-cell, and B-cell were selectively described from a modern immunological stand point. On the basis of this knowledge, radioimmunology was explained; and in clinical field, diagnosis and treatment of malignant tumor, radiotherapy for suppressing immuno-lymphatic system, and reactivators for making the treatment effective were described. Immunoreaction in homo-transplantation of organs, relationship between radiation and auto-immunization, and relationship between carcinogenesis of radiation and immunity were explained so that the way of considering immunology in radiology will be summarized. (Ueda, J.)

  20. [Immunological theory of senescence].

    Science.gov (United States)

    Drela, Nadzieja

    2014-01-01

    Senescence can result from decreased potential of the immune system to respond to foreign and self antigens. The most common effect is the inhibition to destroy dying and cancer cells and the decrease of the immune response to pathogens. Aging is closely related to inflammatory phenotype, which facilitate the development of age-related diseases. The mammal immune system is highly organized and adapted to react to a wide range of antigens. According to the immunological theory, the causative agents of senescence are multilevel changes of development and functions of immune cells. Some of changes can be beneficial for the maintenance of homeostasis and lifespan in continuously changing endogenous environment and immune history of the organism.

  1. Immunology of breast milk.

    Science.gov (United States)

    Palmeira, Patricia; Carneiro-Sampaio, Magda

    2016-09-01

    In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA) antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk's immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant's ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant's secretory IgA production is insignificant.

  2. Immunology of breast milk

    Directory of Open Access Journals (Sweden)

    Patricia Palmeira

    Full Text Available Summary In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk’s immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant’s ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant’s secretory IgA production is insignificant.

  3. Virtual immunology: software for teaching basic immunology.

    Science.gov (United States)

    Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

    2013-01-01

    As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available free of charge in Portuguese and English, which can be used by teachers and students in physiology, immunology, and cellular biology classes. We discuss the development of the initial two modules: "Organs and Lymphoid Tissues" and "Inflammation" and the use of interactive activities to provide microscopic and macroscopic understanding in immunology. Students, both graduate and undergraduate, were questioned along with university level professors about the quality of the software and intuitiveness of use, facility of navigation, and aesthetic organization using a Likert scale. An overwhelmingly satisfactory result was obtained with both students and immunology teachers. Programs such as "Virtual Immunology" are offering more interactive, multimedia approaches to complex scientific principles that increase student motivation, interest, and comprehension. © 2013 by The International Union of Biochemistry and Molecular Biology.

  4. Replication-competent human adenovirus 11p vectors can propagate in Vero cells

    International Nuclear Information System (INIS)

    Gokumakulapalle, Madhuri; Mei, Ya-Fang

    2016-01-01

    The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

  5. Replication-competent human adenovirus 11p vectors can propagate in Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Gokumakulapalle, Madhuri; Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

    2016-08-15

    The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

  6. Immunological quality and performance of tumor vessel-targeting CAR-T cells prepared by mRNA-EP for clinical research.

    Science.gov (United States)

    Inoo, Kanako; Inagaki, Ryo; Fujiwara, Kento; Sasawatari, Shigemi; Kamigaki, Takashi; Nakagawa, Shinsaku; Okada, Naoki

    2016-01-01

    We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6-12 hours after mRNA-EP. Triple transfer of murine anti-VEGFR2 CAR-T cells into B16BL6 tumor-bearing mice demonstrated an antitumor effect comparable to that for the single transfer of CAR-T cells engineered with retroviral vector. The mRNA-EP did not cause any damage or defects to human T-cell characteristics, as determined by viability, growth, and phenotypic parameters. Additionally, two kinds of human anti-VEGFR2 CAR-T cells, which expressed different CAR construction, differentiated to effector phase with cytokine secretion and cytotoxic activity in antigen-specific manner. These results indicate that our anti-VEGFR2 CAR-T cells prepared by mRNA-EP have the potential in terms of quality and performance to offer the prospect of safety and efficacy in clinical research as cellular medicine.

  7. Consortium biology in immunology: the perspective from the Immunological Genome Project.

    Science.gov (United States)

    Benoist, Christophe; Lanier, Lewis; Merad, Miriam; Mathis, Diane

    2012-10-01

    Although the field has a long collaborative tradition, immunology has made less use than genetics of 'consortium biology', wherein groups of investigators together tackle large integrated questions or problems. However, immunology is naturally suited to large-scale integrative and systems-level approaches, owing to the multicellular and adaptive nature of the cells it encompasses. Here, we discuss the value and drawbacks of this organization of research, in the context of the long-running 'big science' debate, and consider the opportunities that may exist for the immunology community. We position this analysis in light of our own experience, both positive and negative, as participants of the Immunological Genome Project.

  8. Comparison of immunological characteristics of peripheral, splenic and tonsilar naïve B cells by differential gene expression meta-analyses.

    Science.gov (United States)

    Chokeshai-u-saha, Kaj; Lepoivre, Cyrille; Grieco, Luca; Nguyen, Catherine; Ruxrungtham, Kiat

    2012-12-01

    Naïve B cells isolated from peripheral blood, spleen and tonsil are commonly used in human B cell studies. However, little has been written about their possible variations in immunological properties. This study compared differential gene expression in human naive B subsets by meta-analysis using expression data available in Gene Expression Onimbus (GEO). Gene expression files of the Affymetrix Human Genome U133A Array (Affymetrix) were downloaded to collect 21 total array data samples of peripheral naïve B cells (n=10), splenic naïve B cells (n=2), tonsilar naïve B cells (n=3), peripheral memory B cells (n=4) and splenic memory B cells (n=2). Prior to differential gene expression analyses, data were normalized in order to reduce non-biological variation among the datasets. Comparisons of peripheral naive B cells with their splenic and tonsilar counterparts showed remarkable differences in terms of gene expression (29 and 202 genes, respectively). However, only minor differences were detected between splenic and tonsilar naive B cells (10 genes), consistent with the clustering results classifying both of them as lymphoid naive B cells. Differential gene expression results also implied higher stimulating states of lymphoid naive B cells when compared with peripheral blood naive B cells. These included enhanced expressions of CD27, CR2, EGR1, GADD45B, ICAM1, ICOSLG, IGHA, IL6, MMP9, SAMSN1, SMAD7, TNFAIP3, but reduced HLA-DOB expression. Our findings suggest that results generated from peripheral naive B cells may not always be applicable to the biological activities of other lymphoid naïve B cells. Nonetheless, further biological study is warranted.

  9. Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells

    Energy Technology Data Exchange (ETDEWEB)

    Mukai, Atsushi [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Kurisaki, Tomohiro [Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Sato, Satoshi B. [Research Center for Low Temperature and Material Sciences, Kyoto University, Yoshida-honmachi, Kyoto 606-8501 (Japan); Kobayashi, Toshihide [Lipid Biology Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351-0198 (Japan); Kondoh, Gen [Laboratory of Animal Experiments for Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Hashimoto, Naohiro, E-mail: nao@nils.go.jp [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan)

    2009-10-15

    Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, {beta}-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.

  10. Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells

    International Nuclear Information System (INIS)

    Mukai, Atsushi; Kurisaki, Tomohiro; Sato, Satoshi B.; Kobayashi, Toshihide; Kondoh, Gen; Hashimoto, Naohiro

    2009-01-01

    Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, β-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.

  11. Systemic immunological tolerance to ocular antigens is mediated by TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD8+ T cells*

    Science.gov (United States)

    Griffith, Thomas S.; Brincks, Erik L.; Gurung, Prajwal; Kucaba, Tamara A.; Ferguson, Thomas A.

    2010-01-01

    Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required FasL-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by CD8+ regulatory T cells. The present study examined the mechanism by which these CD8+ regulatory T cells mediate tolerance after AC injection of Ag. AC injection of Ag did not prime CD4+ T cells, and led to increased TRAIL expression by splenic CD8+ T cells. Unlike wildtype mice, Trail−/− or Dr5−/− mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes of these mice. CD8+ T cells from Trail−/− mice that were first injected AC with Ag were unable to transfer tolerance to naïve recipient wildtype mice, but CD8+ T cells from AC-injected wildtype or Dr5−/− mice could transfer tolerance. Importantly, the transferred wildtype (Trail+/+) CD8+ T cells were also able to decrease the number of infiltrating inflammatory cells into the eye; however, Trail−/− CD8+ T cells were unable to limit the inflammatory cell ingress. Together, our data suggest that “helpless” CD8+ regulatory T cells generated after AC injection of Ag enforce systemic tolerance in a TRAIL-dependent manner to inhibit inflammation in the eye. PMID:21169546

  12. Germline competence of mouse ES and iPS cell lines: Chimera technologies and genetic background.

    Science.gov (United States)

    Carstea, Ana Claudia; Pirity, Melinda K; Dinnyes, Andras

    2009-12-31

    In mice, gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics. This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression ("knock-out"), or to introduce mutant or modified alleles at the locus of interest ("knock-in"). The efficacy of producing live, transgenic mice challenges our understanding of this complex process, and of the factors which influence germline competence of embryonic stem cell lines. Increasingly, evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell (ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability. Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential. There are a number of options for generating chimeras from ES cells (ES chimera mice); however, each method has its advantages and disadvantages. Recent developments in induced pluripotent stem (iPS) cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies. The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines. The most recent methods for generating specifically ES and iPS chimera mice, including the advantages and disadvantages of each method are also discussed.

  13. Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats

    Science.gov (United States)

    WANG, HONGWU; QIU, XIAOYAN; NI, PING; QIU, XUERONG; LIN, XIAOBO; WU, WEIZHAO; XIE, LICHUN; LIN, LIMIN; MIN, JUAN; LAI, XIULAN; CHEN, YUNBIN; HO, GUYU; MA, LIAN

    2014-01-01

    Islet transplantation involves the transplantation of pancreatic islets from the pancreas of a donor to another individual. It has proven to be an effective method for the treatment of type 1 diabetes. However, islet transplantation is hampered by immune rejection, as well as the shortage of donor islets. Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (HUMSCs) are an ideal cell source for use in transplantation due to their biological characteristics and their use does not provoke any ethical issues. In this study, we investigated the immunological characteristics of HUMSCs and their effects on lymphocyte proliferation and the secretion of interferon (IFN)-γ, and explored whether direct cell-to-cell interactions and soluble factors, such as IFN-γ were important for balancing HUMSC-mediated immune regulation. We transplanted HUMSCs into diabetic rats to investigate whether these cells can colonize in vivo and differentiate into pancreatic β-cells, and whether the hyperglycemia of diabetic rats can be improved by transplantation. Our results revealed that HUMSCs did not stimulate the proliferation of lymphocytes and did not induce allogeneic or xenogeneic immune cell responses. qRT-PCR demonstrated that the HUMSCs produced an immunosuppressive isoform of human leukocyte antigen (HLA-I) and did not express HLA-DR. Flow cytometry revealed that the HUMSCs did not express immune response-related surface antigens such as, CD40, CD40L, CD80 and CD86. IFN-γ secretion by human peripheral blood lymphocytes was reduced when the cells were co-cultured with HUMSCs. These results suggest that HUMSCs are tolerated by the host in an allogeneic transplant. We transplanted HUMSCs into diabetic rats, and the cells survived in the liver and pancreas. Hyperglycemia of the diabetic rats was improved and the destruction of pancreatic cells was partly repaired by HUMSC transplantation. Hyperglycemic improvement may be related to the immunomodulatory effects of

  14. Competence Classification of Cumulus and Granulosa Cell Transcriptome in Embryos Matched by Morphology and Female Age.

    Directory of Open Access Journals (Sweden)

    Rehannah Borup

    Full Text Available By focussing on differences in the mural granulosa cell (MGC and cumulus cell (CC transcriptomes from follicles resulting in competent (live birth and non-competent (no pregnancy oocytes the study aims on defining a competence classifier expression profile in the two cellular compartments.A case-control study.University based facilities for clinical services and research.MGC and CC samples from 60 women undergoing IVF treatment following the long GnRH-agonist protocol were collected. Samples from 16 oocytes where live birth was achieved and 16 age- and embryo morphology matched incompetent oocytes were included in the study.MGC and CC were isolated immediately after oocyte retrieval. From the 16 competent and non-competent follicles, mRNA was extracted and expression profile generated on the Human Gene 1.0 ST Affymetrix array. Live birth prediction analysis using machine learning algorithms (support vector machines with performance estimation by leave-one-out cross validation and independent validation on an external data set.We defined a signature of 30 genes expressed in CC predictive of live birth. This live birth prediction model had an accuracy of 81%, a sensitivity of 0.83, a specificity of 0.80, a positive predictive value of 0.77, and a negative predictive value of 0.86. Receiver operating characteristic analysis found an area under the curve of 0.86, significantly greater than random chance. When applied on 3 external data sets with the end-point outcome measure of blastocyst formation, the signature resulted in 62%, 75% and 88% accuracy, respectively. The genes in the classifier are primarily connected to apoptosis and involvement in formation of extracellular matrix. We were not able to define a robust MGC classifier signature that could classify live birth with accuracy above random chance level.We have developed a cumulus cell classifier, which showed a promising performance on external data. This suggests that the gene signature at

  15. Freeze-thaw lysates of Plasmodium falciparum-infected red blood cells induce differentiation of functionally competent regulatory T cells from memory T cells.

    Science.gov (United States)

    Finney, Olivia C; Lawrence, Emma; Gray, Alice P; Njie, Madi; Riley, Eleanor M; Walther, Michael

    2012-07-01

    In addition to naturally occurring regulatory T (nTreg) cells derived from the thymus, functionally competent Treg cells can be induced in vitro from peripheral blood lymphocytes in response to TCR stimulation with cytokine costimulation. Using these artificial stimulation conditions, both naïve as well as memory CD4(+) T cells can be converted into induced Treg (iTreg) cells, but the cellular origin of such iTreg cells in vivo or in response to more physiologic stimulation with pathogen-derived antigens is less clear. Here, we demonstrate that a freeze/thaw lysate of Plasmodium falciparum schizont extract (PfSE) can induce functionally competent Treg cells from peripheral lymphocytes in a time- and dose-dependent manner without the addition of exogenous costimulatory factors. The PfSE-mediated induction of Treg cells required the presence of nTreg cells in the starting culture. Further experiments mixing either memory or naïve T cells with antigen presenting cells and CFSE-labeled Treg cells identified CD4(+) CD45RO(+) CD25(-) memory T cells rather than Treg cells as the primary source of PfSE-induced Treg cells. Taken together, these data suggest that in the presence of nTreg cells, PfSE induces memory T cells to convert into iTreg cells that subsequently expand alongside PfSE-induced effector T cells. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. A roadmap towards personalized immunology

    DEFF Research Database (Denmark)

    Delhalle, Sylvie; Bode, Sebastian F N; Balling, Rudi

    2018-01-01

    Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tu......-communicable inflammatory diseases such as autoimmune diseases or allergies. We provide a roadmap and highlight experimental, clinical, computational analysis, data management, ethical and regulatory issues to accelerate the implementation of personalized immunology....

  17. REST controls self-renewal and tumorigenic competence of human glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Luciano Conti

    Full Text Available The Repressor Element 1 Silencing Transcription factor (REST/NRSF is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets.

  18. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  19. Communication, the centrosome and the immunological synapse.

    Science.gov (United States)

    Stinchcombe, Jane C; Griffiths, Gillian M

    2014-09-05

    Recent findings on the behaviour of the centrosome at the immunological synapse suggest a critical role for centrosome polarization in controlling the communication between immune cells required to generate an effective immune response. The features observed at the immunological synapse show parallels to centrosome (basal body) polarization seen in cilia and flagella, and the cellular communication that is now known to occur at all of these sites.

  20. Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.

    Science.gov (United States)

    Maddur, Mohan S; Stephen-Victor, Emmanuel; Das, Mrinmoy; Prakhar, Praveen; Sharma, Varun K; Singh, Vikas; Rabin, Magalie; Trinath, Jamma; Balaji, Kithiganahalli N; Bolgert, Francis; Vallat, Jean-Michel; Magy, Laurent; Kaveri, Srini V; Bayry, Jagadeesh

    2017-03-20

    Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (T reg ) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with T reg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and T reg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. T reg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. T reg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. T reg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

  1. Immunological quality and performance of tumor vessel-targeting CAR-T cells prepared by mRNA-EP for clinical research

    Directory of Open Access Journals (Sweden)

    Kanako Inoo

    2016-01-01

    Full Text Available We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR specific for vascular endothelial growth factor receptor 2 (VEGFR2, demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6–12 hours after mRNA-EP. Triple transfer of murine anti-VEGFR2 CAR-T cells into B16BL6 tumor-bearing mice demonstrated an antitumor effect comparable to that for the single transfer of CAR-T cells engineered with retroviral vector. The mRNA-EP did not cause any damage or defects to human T-cell characteristics, as determined by viability, growth, and phenotypic parameters. Additionally, two kinds of human anti-VEGFR2 CAR-T cells, which expressed different CAR construction, differentiated to effector phase with cytokine secretion and cytotoxic activity in antigen-specific manner. These results indicate that our anti-VEGFR2 CAR-T cells prepared by mRNA-EP have the potential in terms of quality and performance to offer the prospect of safety and efficacy in clinical research as cellular medicine.

  2. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors.

    Science.gov (United States)

    Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

    2014-03-01

    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

  3. Immunology of Gut Mucosal Vaccines

    Science.gov (United States)

    Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

    2011-01-01

    Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

  4. [Medical knowledge in immunological security of red blood cells transfusion in Tunisia: evaluation of a CD-ROM of auto-learning].

    Science.gov (United States)

    Ben Salah, N; El Borgi, W; Aounallah Skhiri, H; Ben Lakhal, F; Mouelhi, H; Zoueri, B; Gouider, E; Hafsia, R

    2013-09-01

    In Tunisia, red blood cells (RBC) transfusion joins in a statutory frame but remains subject to failures because of the misunderstanding of legislation and regulations. Our purpose is to estimate the knowledge of the medical staff in the immunological safety of RBC transfusion before and after reading an auto-education CD-ROM. It is a study of evaluation of an intervention. Eighty physicians participated to the study. The evaluation was done using an anonymous questionnaire, containing seven questions with multiple choices (QMC) relating to several items. The rate of good answers (RGA) calculated by questions and by items took into account the impact of the CD-ROM on the improvement of the answers after reading. The global average mark is 2.9/7. The RGA to questions varies from 22.5 % to 76.3%. All participants answered correctly to more than 50% of all items. Two answered correctly to all items. Among the participants, 31.3% answered to all "important" items, concerning ABO blood groups compatibility and ultimate bedside test. The rate of participation to the final evaluation was 83%. The impact of the CD-ROM was important and statistically significant. In the final evaluation, the global mark raised from 2.9 to 5.8/7, 31.5% (vs 2%) answered correctly all the questions and 95.5% (vs 31.3%) answered correctly all "important" items. This study revealed a misunderstanding of the doctors in immunological safety of RBC transfusions. Auto-teaching by CD-ROM was efficient. An improvement of the knowledge by continuous training is necessary in our country. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Development of radiation immunology

    International Nuclear Information System (INIS)

    Xie Yi; Dang Bingrong; Bing Tao; Zhang Hong; Li Wenjian; Liu Bing

    2005-01-01

    Radiation immunology as a new subject has made a great progress in recent years, especially in the radiation hormesis. At the same time, the research of radiobiological effect on heavy ions has played an important role in the cancer therapy, especially on the radiation immunology of heavy ions in the outer space. In this review, the authors summarized the status and development of radiation-immunology, and try to find out some better ways which can increase efficient killing on tumours, but reduce the damages on normal tissues. (authors)

  6. Using distributed fuel cells to compete with established utilities under rules permitting retail wheeling

    International Nuclear Information System (INIS)

    Miller, D.A.; Mathur, A.

    1996-01-01

    Regulatory reform in the electricity industry clearly has many implications for the corporate structure of electric utilities, the pricing of energy products and services, and the quality of service received by customers. But it also has implications for the selection of energy generating technologies. The rise of the cogenerator and independent power producer has been a major force in the expanded use of combined-cycle power plants and their technological advancement. The next stage of increased deregulation, retail wheeling, must also lead to further technological change, because the economic climate determines the operational characteristics required of new generating resources. This paper discusses the use of distributed fuel cells to compete with established utilities in areas where retail wheeling has been instituted. It will cover in detail the unique advantages of the technology under this industry configuration. The paper will pay particular attention to the operational and design characteristics of fuel cells that will provide companies the flexibility they require to compete successfully. Finally, the paper will discuss the implications for the use of distributed fuel cells of alternative retail wheeling implementation schemes

  7. Essential Neuroscience in Immunology.

    Science.gov (United States)

    Chavan, Sangeeta S; Tracey, Kevin J

    2017-05-01

    The field of immunology is principally focused on the molecular mechanisms by which hematopoietic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with the identification of several other reflexes regulating discrete immune functions. As outlined in this review, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first-in-class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoietic and neural responses to infection and injury. Copyright © 2017 by The American Association of Immunologists, Inc.

  8. Roitt's essential immunology

    National Research Council Canada - National Science Library

    Delves, Peter J; Roitt, Ivan M

    2011-01-01

    ... of the immune system, the hallmark easy-reading style of Roitt's Essential Immunology clearly explains the key principles needed by medical and health sciences students, from the basis of immunity to clinical applications...

  9. Immunologic manifestations of autophagy

    DEFF Research Database (Denmark)

    Deretic, Vojo; Kimura, Tomonori; Timmins, Graham

    2015-01-01

    The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique...... immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes...... the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy....

  10. Effects of feed-borne Fusarium mycotoxins with or without yeast cell wall adsorbent on organ weight, serum biochemistry, and immunological parameters of broiler chickens.

    Science.gov (United States)

    Li, Z; Yang, Z B; Yang, W R; Wang, S J; Jiang, S Z; Wu, Y B

    2012-10-01

    The objectives of the present study were to investigate the toxicity of feed-borne Fusarium mycotoxins on organ weight, serum biochemistry, and immunological parameters of broiler chickens and to evaluate the efficacy of yeast cell wall adsorbent in preventing mycotoxin-induced adverse effects. In total, 300 one-day-old vaccinated (Marek's disease and infectious bronchitis) Arbor Acres broiler chickens (mixed sex) were randomly divided into 3 treatments (5 repetitions per treatment) and fed basal diet and naturally contaminated diets with or without yeast cell wall adsorbent. Treatments were control, naturally contaminated diet (NCD; aflatoxin, 102.08 mg/kg; zearalenone, 281.92 mg/kg; fumonisin, 5,874.38 mg/kg; deoxynivalenol, 2,038.96 mg/kg), and NCD + 2 g/kg of yeast cell wall adsorbent (NCDD). The test included 2 phases: d 0-21 and d 22-42. At 42 d, broilers fed contaminated diets without yeast cell wall adsorbent had higher (P effect on the relative weight of the liver and spleen at 21 d, relative weight of the bursa of Fabricius and thymus at 42 d, antibody titers of Newcastle disease at both 28 d and 42 d, and splenic mRNA expression of IL-1β, IL-6, and IFN-γ at 42 d. It is suggested that feeding a naturally contaminated diet for 42 d might result in a deleterious effect in broiler chickens, and addition of 2 g/kg of yeast cell wall enterosorbent can partly neutralize the detrimental effects of the naturally contaminated feed.

  11. Diversity in immunological synapse structure

    Science.gov (United States)

    Thauland, Timothy J; Parker, David C

    2010-01-01

    Immunological synapses (ISs) are formed at the T cell–antigen-presenting cell (APC) interface during antigen recognition, and play a central role in T-cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T-cell receptor (TCR)–peptide major histocompatibility complex (pMHC) interactions. Although the structure of these ‘classical’ ISs has been the subject of intense study, non-classical ISs have also been observed under a variety of conditions. Multifocal ISs, characterized by adhesion molecules dispersed among numerous small accumulations of TCR–pMHC, and motile ‘immunological kinapses’ have both been described. In this review, we discuss the conditions under which non-classical ISs are formed. Specifically, we explore the profound effect that the phenotypes of both T cells and APCs have on IS structure. We also comment on the role that IS structure may play in T-cell function. PMID:21039474

  12. Local immunological mechanisms of sublingual immunotherapy.

    Science.gov (United States)

    Allam, Jean-Pierre; Novak, Natalija

    2011-12-01

    To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective. To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response. Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.

  13. Immunological targeting of cytomegalovirus for glioblastoma therapy

    OpenAIRE

    Nair, Smita K; Sampson, John H; Mitchell, Duane A

    2014-01-01

    Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM.

  14. Long-term engraftment, graft-vs.-host disease, and immunologic reconstitution after experimental transplantation of allogeneic peripheral blood cells from G-CSF-treated donors.

    Science.gov (United States)

    Pan, L; Bressler, S; Cooke, K R; Krenger, W; Karandikar, M; Ferrara, J L

    1996-10-01

    Peripheral blood cells (PBPC) are an alternative source of bone marrow for allogeneic transplantation. Reports from recent clinical trials granulocyte colony-stimulating factor (G-CSF)-mobilized PBPC for allogeneic transplantation show incidence and severity of graft-vs.-host disease (GVHD) similar to those observed in conventional bone marrow transplantation (BMT), despite the presence of 10- to 20-fold more T cell in the PBPC inoculum. In the present study, we examined the effects of pretreatment of donors with G-CSF on GVHD, long-term engraftment, and lymphocyte reconstitution in a murine parent-->F1 model (B6.Ly-5a-->B6d2F1) using splenocytes as a source of peripheral progenitor cells. Recipients of splenocytes from G-CSF-treated donors experienced less mortality from acute GVHD and showed sustained weight gain by day 100 after transplantation. At that time, there was no histological evidence od GVHD in either liver or gut. Recipients of splenocytes from G-CSF-treated donors showed complete donor engraftment within 1 month, which was sustained until the end of the observation period. In contrast, recipients of T cell-depleted splenocytes showed slower donor engraftment and persistent donor/host chimerism. In addition, lymphocyte phenotype and function in mice receiving splenocytes from G-CSF-treated donors was significantly restored by day 100 after transplantation. Thus, the use of G-CSF-mobilized PBPC may provide significant advantages to conventional BMT by reducing GVHD without impairing long-term engraftment and immunologic reconstruction.

  15. Evaluation of porcine stem cells competence for somatic cell nuclear transfer and production of cloned animals

    DEFF Research Database (Denmark)

    Secher, Jan; Liu, Ying; Petkov, Stoyan

    2017-01-01

    Porcine somatic cell nuclear transfer (SCNT) has been used extensively to create genetically modified pigs, but the efficiency of the methodology is still low. It has been hypothesized that pluripotent or multipotent stem cells might result in increased SCNT efficacy as these cells are closer than...... somatic cells to the epigenetic state found in the blastomeres and therefore need less reprogramming. Our group has worked with porcine SCNT during the last 20 years and here we describe our experience with SCNT of 3 different stem cell lines. The porcine stem cells used were: Induced pluripotent stem...... cells (iPSCs) created by lentiviral doxycycline-dependent reprogramming and cultered with a GSK3β- and MEK-inhibitor (2i) and leukemia inhibitor factor (LIF) (2i LIF DOX-iPSCs), iPSCs created by a plasmid-based reprogramming and cultured with 2i and fibroblast growth factor (FGF) (2i FGF Pl...

  16. Long Noncoding RNA HOTAIR Controls Cell Cycle by Functioning as a Competing Endogenous RNA in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kewei Ren

    2016-12-01

    Full Text Available Recent studies have shown that long noncoding RNAs (lncRNAs play pivotal roles in the initiation and progression of cancer, including esophageal squamous cell carcinoma (ESCC. The lncRNA HOX transcript antisense RNA (HOTAIR was reported to be dysregulated and correlated with the progression of ESCC. However, the biological role and the underlying mechanism of HOTAIR in the development of ESCC remain unclear. Herein, we found that HOTAIR was aberrantly upregulated in ESCC cells and that HOTAIR depletion inhibited proliferation and led to G1 cell cycle arrest in ESCC cells. Besides, we found that HOTAIR acted as an endogenous sponge to downregulate miR-1 expression by directly binding to miR-1. Furthermore, HOTAIR overturned the effect of miR-1 on the proliferation and cell cycle profile in ESCC cells, which involved the derepression of cyclin D1 (CCND1 expression, a target of miR-1. Taken together, our study elucidated a novel HOTAIR /miR-1/CCND1 regulatory axis in which HOTAIR acted as a competing endogenous RNA by sponging miR-1 and upregulated CCND1 expression, thereby facilitating the tumorigenesis of ESCC. Investigation of this lncRNA/miRNA/mRNA pathway may contribute to a better understanding of ESCC pathogenesis and facilitate the development of lncRNA-directed therapy against this disease.

  17. Consortium biology in immunology: the perspective from the Immunological Genome Project.

    OpenAIRE

    Benoist, C; Lanier, L; Merad, M; Mathis, D; Immunological Genome Project,

    2012-01-01

    Although the field has a long collaborative tradition, immunology has made less use than genetics of 'consortium biology', wherein groups of investigators together tackle large integrated questions or problems. However, immunology is naturally suited to large-scale integrative and systems-level approaches, owing to the multicellular and adaptive nature of the cells it encompasses. Here, we discuss the value and drawbacks of this organization of research, in the context of the long-running 'bi...

  18. Competence is Competence

    DEFF Research Database (Denmark)

    Bramming, Pia

    2004-01-01

    The article will address competence, its' diffusion, application, and the consequence of this application within the field of Human Resource Management (HRM). The concept competence-in-practice will be presented and in conclusion the article will consider implications and possibilities...... of competence-in-practice as an alternative approach to Competence Development within Human Resource Management....

  19. Microparticle-Mediated Delivery of BMP4 for Generation of Meiosis-Competent Germ Cells from Embryonic Stem Cells.

    Science.gov (United States)

    Esfandiari, Fereshteh; Ashtiani, Mohammad Kazemi; Sharifi-Tabar, Mehdi; Saber, Maryam; Daemi, Hamed; Ghanian, Mohammad Hossein; Shahverdi, Abdolhossein; Baharvand, Hossein

    2017-03-01

    Producing meiosis-competent germ cells (GCs) from embryonic stem cells (ESCs) is essential for developing advanced therapies for infertility. Here, a novel approach is presented for generation of GCs from ESCs. In this regard, microparticles (MPs) have been developed from alginate sulfate loaded with bone morphogenetic protein 4 (BMP4). The results here show that BMP4 release from alginate sulfate MPs is significantly retarded by the sulfated groups compared to neat alginate. Then, BMP4-laden MPs are incorporated within the aggregates during differentiation of GCs from ESCs. It is observed that BMP4-laden MPs increase GC differentiation from ESCs at least twofold compared to the conventional soluble delivery method. Interestingly, following meiosis induction, Dazl, an intrinsic factor that enables GCs to enter meiosis, and two essential meiosis genes (Stra8 and Smc1b) are upregulated significantly in MP-induced aggregates compared to aggregates, which are formed by the conventional method. Together, these data show that controlled delivery of BMP4 during ESC differentiation into GC establish meiosis-competent GCs which can serve as an attractive GC source for reproductive medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Localization of functional memory B cells at sites of antigen localization and its relationship to local aspects of immunological memory

    International Nuclear Information System (INIS)

    Ponzio, N.M.; Baine, Y.; Thorbecke, G.J.

    1980-01-01

    Experiments are described which have been designed to test whether antigen in a draining lymph node can mediate local accumulation of passively transferred antigen-specific memory B cells, using recipients whose own immune response is inhibited via γ-irradiation or by injection of cyclophosphamide. (Auth.)

  1. Generation of competent bone marrow-derived antigen presenting cells from the deer mouse (Peromyscus maniculatus

    Directory of Open Access Journals (Sweden)

    Farrell Regina M

    2004-09-01

    Full Text Available Abstract Background Human infections with Sin Nombre virus (SNV and related New World hantaviruses often lead to hantavirus cardiopulmonary syndrome (HCPS, a sometimes fatal illness. Lungs of patients who die from HCPS exhibit cytokine-producing mononuclear infiltrates and pronounced pulmonary inflammation. Deer mice (Peromyscus maniculatus are the principal natural hosts of SNV, in which the virus establishes life-long persistence without conspicuous pathology. Little is known about the mechanisms SNV employs to evade the immune response of deer mice, and experimental examination of this question has been difficult because of a lack of methodologies for examining such responses during infection. One such deficiency is our inability to characterize T cell responses because susceptible syngeneic deer mice are not available. Results To solve this problem, we have developed an in vitro method of expanding and generating competent antigen presenting cells (APC from deer mouse bone marrow using commercially-available house mouse (Mus musculus granulocyte-macrophage colony stimulating factor. These cells are capable of processing and presenting soluble protein to antigen-specific autologous helper T cells in vitro. Inclusion of antigen-specific deer mouse antibody augments T cell stimulation, presumably through Fc receptor-mediated endocytosis. Conclusions The use of these APC has allowed us to dramatically expand deer mouse helper T cells in culture and should permit extensive characterization of T cell epitopes. Considering the evolutionary divergence between deer mice and house mice, it is probable that this method will be useful to other investigators using unconventional models of rodent-borne diseases.

  2. The interplay between surfaces and soluble factors define the immunologic and angiogenic properties of myeloid dendritic cells

    Directory of Open Access Journals (Sweden)

    Mansfield Kristen

    2011-06-01

    Full Text Available Abstract Background Dendritic cells (DCs are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. Interestingly, microenvironment conditions such as those present in tumor settings might induce a DC phenotype that is poorly immunogenic and with the capability of promoting angiogenesis. We hypothesize that this plasticity may be caused not only by the action of specific cytokines or growth factors but also by the properties of the surfaces with which they interact, such as extracellular matrix (ECM components. Results Herewith we studied the effect of different surfaces and soluble factors on the biology of DCs. To accomplish this, we cultured murine myeloid(m DCs on surfaces coated with fibronectin, collagen I, gelatin, and Matrigel using poly-D-lysine and polystyrene as non-biological surfaces. Further, we cultured these cells in the presence of regular DC medium (RPMI 10% FBS or commercially available endothelial medium (EGM-2. We determined that mDCs could be kept in culture up to 3 weeks in these conditions, but only in the presence of GM-CSF. We were able to determine that long-term DC cultures produce an array of angiogenic factors, and that some of these cultures still retain the capability to induce T cell responses. Conclusions Altogether these data indicate that in order to design DC-based vaccines or treatments focused on changing the phenotype of DCs associated with diseases such as cancer or atherosclerosis, it becomes necessary to fully investigate the microenvironment in which these cells are present or will be delivered.

  3. Development of a replication-competent lentivirus assay for dendritic cell-targeting lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Daniel C Farley

    Full Text Available It is a current regulatory requirement to demonstrate absence of detectable replication-competent lentivirus (RCL in lentiviral vector products prior to use in clinical trials. Immune Design previously described an HIV-1-based integration-deficient lentiviral vector for use in cancer immunotherapy (VP02. VP02 is enveloped with E1001, a modified Sindbis virus glycoprotein which targets dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN expressed on dendritic cells in vivo. Vector enveloped with E1001 does not transduce T-cell lines used in standard HIV-1-based RCL assays, making current RCL testing formats unsuitable for testing VP02. We therefore developed a novel assay to test for RCL in clinical lots of VP02. This assay, which utilizes a murine leukemia positive control virus and a 293F cell line expressing the E1001 receptor DC-SIGN, meets a series of evaluation criteria defined in collaboration with US regulatory authorities and demonstrates the ability of the assay format to amplify and detect a hypothetical RCL derived from VP02 vector components. This assay was qualified and used to test six independent GMP production lots of VP02, in which no RCL was detected. We propose that the evaluation criteria used to rationally design this novel method should be considered when developing an RCL assay for any lentiviral vector.

  4. In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors.

    Directory of Open Access Journals (Sweden)

    Matteo Vecellio

    Full Text Available Adult human cardiac mesenchymal-like stromal cells (CStC represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS in the presence of 5 µM all-trans Retinoic Acid (ATRA, 5 µM Phenyl Butyrate (PB, and 200 µM diethylenetriamine/nitric oxide (DETA/NO, to create a novel epigenetically active cocktail (EpiC. Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and α-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors.

  5. Systems Theory in Immunology

    CERN Document Server

    Doria, Gino; Koch, Giorgio; Strom, Roberto

    1979-01-01

    This volume collects the contributions presented at the "Working Conference on System Theory in Immunology", held in Rome, May 1978. The aim of the Conference was to bring together immunologists on one side and experts in system theory and applied mathematics on the other, in order to identify problems of common interest and to establish a network of joint effort toward their solution. The methodologies of system theory for processing experimental data and for describing dynamical phenomena could indeed contribute significantly to the under­ standing of basic immunological facts. Conversely, the complexity of experimental results and of interpretative models should stimulate mathematicians to formulate new problems and to design appropriate procedures of analysis. The multitude of scientific publications in theoretical biology, appeared in recent years, confirms this trend and calls for extensive interaction between mat- matics and immunology. The material of this volume is divided into five sections, along ...

  6. Morphological and immunological criteria of minimal residual disease detection in children with B-cell precursors acute lymphoblastic leukemia

    Science.gov (United States)

    Beznos, O. A.; Grivtsova, L. Yu; Popa, A. V.; Shervashidze, M. A.; Serebtyakova, I. N.; Tupitsyn, N. N.; Selchuk, V. U.; Grebennikova, O. P.; Titova, G. V.

    2018-01-01

    One of the key factors of prognosis and risk stratification in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is minimal residual disease (MRD). Identification of MRD on the day 15th is one of the most significant in prognosis of the disease. We compared data of a morphological and flow cytometry results of assessment of a bone marrow (BM) at the day 15th of induction chemotherapy in children with BCP-ALL.

  7. Isolation of IL-12p70-competent human monocyte-derived dendritic cells

    DEFF Research Database (Denmark)

    Søndergaard, Jonas Nørskov; Pedersen, Susanne Brix

    2012-01-01

    that moDCs generated under standard conditions develop into two subsets based on CD1a-expression with the CD1a+ moDCs being the main IL-12p70 producers. This has however not been generally accepted, which we show here because the subset described as CD1a-negative does express CD1a, but at a lower level...... is not available to many laboratories and has incompatibility with clinical settings, a more widely useable technique is warranted. Therefore we tested if magnetic-activated cell sorting is useful for the purpose, and show that it is possible to isolate IL-12p70-competent CD1a-hi moDCs to a...

  8. Immunologic mechanism at infertility

    OpenAIRE

    Aydın, İlknur; Erci, Behice

    2006-01-01

    Infertility has been serious problem for couples that want to have a child. It is estimated that %10-15 of marriages are involuntary childless; that is, there is the serious problem of infertility. In more than 40% of infertility couples that is the reason of their infertility was unknown. In those couples, probably immunological factors were found to be responsible for the infertility. In the article, it was aimed to review the immunologic causes of male and female infertility in the light o...

  9. Immunologic lung disease

    International Nuclear Information System (INIS)

    Harman, E.M.

    1985-01-01

    The term immunologic lung disease comprises a broad spectrum of disease. The authors have covered a few entities in which recent studies have been particularly helpful in elucidating pathophysiology though not in uncovering the inciting cause. Common to all of these entities is the problem of finding appropriate methods of defining disease activity and response to treatment. As exemplified by the improved outlook for Goodpasture's syndrome with elucidation of its underlying immunopathology, it is likely that better understanding of the immunologic basis of sarcoid and interstitial disease may be helpful in planning more effective treatment strategies. 44 references

  10. Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM2.5 organic extract from Puerto Rico

    International Nuclear Information System (INIS)

    Fuentes-Mattei, Enrique; Rivera, Evasomary; Gioda, Adriana; Sanchez-Rivera, Diana; Roman-Velazquez, Felix R.; Jimenez-Velez, Braulio D.

    2010-01-01

    Fine particulate air pollutants, mainly their organic fraction, have been demonstrated to be associated with cardiovascular and respiratory health problems. Puerto Rico has been reported to have the highest prevalence of pulmonary diseases (e.g., asthma) in the United States. The aim of this study was to assess, for the first time, the immunological response of human bronchial epithelial cells (BEAS-2B) to organic extracts isolated from airborne particulate matter (PM 2.5 ) in Puerto Rico. Organic extracts from PM 2.5 collected throughout an 8-month period (2000-2001) were pooled (composite) in order to perform chemical analysis and biological activity testing. BEAS-2B cells were exposed to PM 2.5 organic extract to assess cytotoxicity, levels of cytokines and relative gene expression of MHC-II, hPXR and CYP3A5. Our findings show that organic PM 2.5 consist of toxic as well as bioactive components that can regulate the secretion of cytokines in BEAS-2B, which could modulate inflammatory response in the lung. Trace element analyses confirmed the presence of metals in organic extracts highlighting the relative high abundance of Cu and Zn in polar organic extracts. Polar organic extracts exhibited dose-dependant toxicity and were found to significantly induce the release of interleukin 6 (IL-6), IL-1β and IL-7 while significantly inhibiting the secretion of IL-8, G-CSF and MCP-1. Moreover, MHC-II transcriptional activity was up-regulated after 24 h of exposure, whereas PXR and CYP3A5 were down-regulated. This research provides a new insight into the effects of PM 2.5 organic fractions on specific effectors and their possible role in the development of respiratory inflammatory diseases in Puerto Rico.

  11. Allergoid-specific T-cell reaction as a measure of the immunological response to specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine.

    Science.gov (United States)

    von Baehr, V; Hermes, A; von Baehr, R; Scherf, H P; Volk, H D; Fischer von Weikersthal-Drachenberg, K J; Woroniecki, S

    2005-01-01

    Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper cells. In order to improve safety, SIT vaccines are often formulated with allergoids (chemically modified allergens). Interaction between T-cells and allergoids is necessary to influence cellular cytokine expression. There have been few reports on identification the early cellular effects of SIT. Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4-shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant, monophosphoryl lipid A (MPL). Fourteen grass-allergic patients served as untreated controls. Using the peripheral blood mononuclear cells of these patients, an optimized lymphocyte transformation test (LTT) was employed to monitor the in vitro proliferative response of T-cells to an allergoid challenge (solubilised Pollinex Quattro) before the first and last injection and then 2 and 20 weeks after the final injection. Control challenges utilised preparations of a similar pollen vaccine without the adjuvant MPL and a tree pollen vaccine with and without MPL. The LTT showed increased LTT stimulation indices (SI) in 17/20 SIT patients when the solublised vaccine preparation was used as a challenge before the last injection and 2 weeks after, in comparison to pre-treatment levels. Twenty weeks after therapy, the SI decreased to baseline level. A vaccine challenge without MPL gave lower SI levels. A challenge of a clinically inappropriate tree allergoid vaccine gave no response, and a nontreated group also showed no response. Following a short-course SIT adjuvated with MPL, challenges of allergoids were shown to activate allergen-specific T cells in vitro. There was an additional stimulating effect when the challenge was in combination with MPL. There were no non-specific effects of MPL, shown by the tree allergoid/MPL control. The timing of the response was closely correlated to the

  12. G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

    Science.gov (United States)

    Grivtsova, L. Yu; Melkova, K. N.; Kupryshkina, N. A.; Vorotnikov, I. K.; Grigoryeva, T. A.; Selchuk, V. Yu; Grebennikova, O. P.; Titova, G. V.; Tupitsyn, N. N.

    2018-01-01

    60 samples of G-CSF-primed bone marrow (39 cancer patients and 21 healthy donors) to be used for transplantation to cancer patients were analyzed and compared by main characteristics with historical control and 13 bone marrow samples from control patient with mastopathy. Basing on morphological and multicolor flow cytometry findings certain characteristics of G-CSF-primed bone marrow were discovered, such as a significant increase in blast count in cancer patients as compared to donors and control patients (p<0.037), a higher neutrophil maturation index (p<0.001) and a lower percentage of mature lymphocytes (p<0.008) as compared to the control group. Among lymphocyte populations G-CSF-priming was associated with a significant increase in the total of mature CD3+ T-cells and CD8+ T-killers (p<0.0001) and a decrease in CD56+CD3- and/or CD16+CD3- NK-cells (p<0.006) both in cancer patients and healthy donors in comparison with the controls.

  13. Cell envelope of Bordetella pertussis: immunological and biochemical analyses and characterization of a major outer membrane porin protein

    International Nuclear Information System (INIS)

    Armstrong, S.K.

    1986-01-01

    Surface molecules of Bordetella pertussis which may be important in metabolism, pathogenesis, and immunity to whooping cough were examined using cell fractionation and 125 I cell surface labeling. Antigenic envelope proteins were examined by immunofluorescence microscopy and Western blotting procedures using monoclonal antibodies and convalescent sera. A surface protein with a high M/sub r/, missing in a mutant lacking the filamentous hemagglutinin, was identified in virulent Bordetella pertussis but was absent in virulent B. pertussis strains. At least three envelope proteins were found only in virulent B. pertussis strains and were absent or diminished in avirulent and most phenotypically modulated strains. Transposon-induced mutants unable to produce hemolysin, dermonecrotic toxin, pertussis toxin, and filamentous hemagglutinin also lacked these three envelope proteins, confirming that virulence-associated envelope proteins were genetically regulated with other virulence-associated traits. Two dimensional gel electrophoresis revealed at least five heat modifiable proteins which migrated as higher or lower M/sub r/ moieties if solubilized at 25 0 C instead of 100 0 C

  14. Relationship between DNA repair and cell recovery: Importance of competing biochemical and metabolic processes

    International Nuclear Information System (INIS)

    Van Ankeren, S.C.; Wheeler, K.T.; Kansas Univ., Lawrence

    1985-01-01

    The relationship between the inhibition of repair of radiation-induced DNA damage and the inhibition of recovery from radiation-induced potentially lethal damage (PLD) by hypertonic treatment was compared in 9L/Ro rat brain tumor cells. Fed plateau phase cultures were γ-irradiated with 1500 rad and then immediately treated for 20 min with a 37 0 C isotonic (0.15 M) or hypertonic (0.50 M) salt solution. The kinetics of repair of radiation-induced DNA damage as assayed using alkaline filter elution were compared to those of recovery from radiation-induced PLD as assayed by colony formation. hypertonic treatment of unirradiated cells produced neither DNA damage nor cell kill. Post-irradiation hypertonic treatment inhibited both DNA repair and PLD recovery, while post-irradiation istonic treatment inhibited neither phenomenon. However, by 2 h after irradiation, the amount of DNA damage remaining after a 20 min hypertonic treatment was equivalent to that remaining after a 20 min isotonic treatment. In contrast, cell survival after hypertonic treatment remained 2 logs lower than after isotonic treatment even at times up to 24 h. These results suggest that the repair of radiation-induced DNA damage per per se is not causally related to recovery from radiation-induced PLD. However, the data are consistent with the time of DNA repair as an important parameter in determining cell survival and, therefore, tend to support the hypothesis that imbalances in sets of competing biochemical or metabolic processes determine survival rather than the presence of a single class of unrepaired DNA lesions. (orig.)

  15. Mechanical compliance and immunological compatibility of fixative-free decellularized/cryopreserved human pericardium.

    Directory of Open Access Journals (Sweden)

    Maria Cristina Vinci

    Full Text Available BACKGROUND: The pericardial tissue is commonly used to produce bio-prosthetic cardiac valves and patches in cardiac surgery. The procedures adopted to prepare this tissue consist in treatment with aldehydes, which do not prevent post-graft tissue calcification due to incomplete xeno-antigens removal. The adoption of fixative-free decellularization protocols has been therefore suggested to overcome this limitation. Although promising, the decellularized pericardium has not yet used in clinics, due to the absence of proofs indicating that the decellularization and cryopreservation procedures can effectively preserve the mechanical properties and the immunologic compatibility of the tissue. PRINCIPAL FINDINGS: The aim of the present work was to validate a procedure to prepare decellularized/cryopreserved human pericardium which may be implemented into cardiovascular homograft tissue Banks. The method employed to decellularize the tissue completely removed the cells without affecting ECM structure; furthermore, uniaxial tensile loading tests revealed an equivalent resistance of the decellularized tissue to strain, before and after the cryopreservation, in comparison with the fresh tissue. Finally, immunological compatibility, showed a minimized host immune cells invasion and low levels of systemic inflammation, as assessed by tissue transplantation into immune-competent mice. CONCLUSIONS: Our results indicate, for the first time, that fixative-free decellularized pericardium from cadaveric tissue donors can be banked according to Tissue Repository-approved procedures without compromising its mechanical properties and immunological tolerance. This tissue can be therefore treated as a safe homograft for cardiac surgery.

  16. Impact of the B Cell Growth Factor APRIL on the Qualitative and Immunological Characteristics of Atherosclerotic Plaques.

    Science.gov (United States)

    Bernelot Moens, Sophie J; van Leuven, Sander I; Zheng, Kang H; Havik, Stefan R; Versloot, Miranda V; van Duivenvoorde, Leonie M; Hahne, Michael; Stroes, Erik S G; Baeten, Dominique L; Hamers, Anouk A J

    2016-01-01

    Studies on the role of B lymphocytes in atherosclerosis development, have yielded contradictory results. Whereas B lymphocyte-deficiency aggravates atherosclerosis in mice; depletion of mature B lymphocytes reduces atherosclerosis. These observations led to the notion that distinct B lymphocyte subsets have different roles. B1a lymphocytes exert an atheroprotective effect, which has been attributed to secretion of IgM, which can be deposited in atherosclerotic lesions thereby reducing necrotic core formation. Tumor necrosis factor (TNF)-family member 'A Proliferation-Inducing Ligand' (APRIL, also known as TNFSF13) was previously shown to increase serum IgM levels in a murine model. In this study, we investigated the effect of APRIL overexpression on advanced lesion formation and composition, IgM production and B cell phenotype. We crossed APRIL transgenic (APRIL-Tg) mice with ApoE knockout (ApoE-/-) mice. After a 12-week Western Type Diet, ApoE-/-APRIL-Tg mice and ApoE-/- littermates showed similar increases in body weight and lipid levels. Histologic evaluation showed no differences in lesion size, stage or necrotic area. However, smooth muscle cell (α-actin stain) content was increased in ApoE-/-APRIL-Tg mice, implying more stable lesions. In addition, increases in both plaque IgM deposition and plasma IgM levels were found in ApoE-/-APRIL-Tg mice compared with ApoE-/- mice. Flow cytometry revealed a concomitant increase in peritoneal B1a lymphocytes in ApoE-/-APRIL-Tg mice. This study shows that ApoE-/-APRIL-Tg mice have increased oxLDL-specific serum IgM levels, potentially mediated via an increase in B1a lymphocytes. Although no differences in lesion size were found, transgenic ApoE-/-APRIL-Tg mice do show potential plaque stabilizing features in advanced atherosclerotic lesions.

  17. p53-competent cells and p53-deficient cells display different susceptibility to oxygen functionalized graphene cytotoxicity and genotoxicity.

    Science.gov (United States)

    Petibone, Dayton M; Mustafa, Thikra; Bourdo, Shawn E; Lafont, Andersen; Ding, Wei; Karmakar, Alokita; Nima, Zeid A; Watanabe, Fumiya; Casciano, Daniel; Morris, Suzanne M; Dobrovolsky, Vasily N; Biris, Alexandru S

    2017-11-01

    Due to the distinctive physical, electrical, and chemical properties of graphene nanomaterials, numerous efforts pursuing graphene-based biomedical and industrial applications are underway. Oxidation of pristine graphene surfaces mitigates its otherwise hydrophobic characteristic thereby improving its biocompatibility and functionality. Yet, the potential widespread use of oxidized graphene derivatives raises concern about adverse impacts on human health. The p53 tumor suppressor protein maintains cellular and genetic stability after toxic exposures. Here, we show that p53 functional status correlates with oxygen functionalized graphene (f-G) cytotoxicity and genotoxicity in vitro. The f-G exposed p53-competent cells, but not p53-deficient cells, initiated G 0 /G 1 phase cell cycle arrest, suppressed reactive oxygen species, and entered apoptosis. There was p53-dependent f-G genotoxicity evident as increased structural chromosome damage, but not increased gene mutation or chromatin loss. In conclusion, the cytotoxic and genotoxic potential for f-G in exposed cells was dependent on the p53 functional status. These findings have broad implications for the safe and effective implementation of oxidized graphene derivatives into biomedical and industrial applications. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  18. Oral Microbiology and Immunology

    DEFF Research Database (Denmark)

    Dahlén, Gunnar; Fiehn, Nils-Erik; Olsen, Ingar

    , dental assistants and trainees may find it a useful source of reference. The contents are based on general microbiology and immunology. Oral microbiology is given particular attention, with examples relevant to oral infectious diseases. Each chapter opens with a relatively short pre-reading section...

  19. Immunology & Human Health.

    Science.gov (United States)

    Dawson, Jeffrey R.; And Others

    This monograph was designed for the high school biology curriculum. The first section reviews the major areas of importance in immunology. Section three contains six instructional activities for the high school classroom and the second section contains teacher's materials for those activities. The activities address for students some of the major…

  20. T-cell tropism of simian T-cell leukaemia virus type 1 and cytokine profiles in relation to proviral load and immunological changes during chronic infection of naturally infected mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Souquière, Sandrine; Mouinga-Ondeme, Augustin; Makuwa, Maria; Beggio, Paola; Radaelli, Antonia; De Giuli Morghen, Carlo; Mortreux, Franck; Kazanji, Mirdad

    2009-08-01

    Although a wide variety of non-human primates are susceptible to simian T-cell leukaemia virus type 1 (STLV-1), little is known about the virological or molecular determinants of natural STLV-1 infection. We determined STLV-1 virus tropism in vivo and its relation to the immune response by evaluating cytokine production and T-cell subsets in naturally infected and uninfected mandrills. With real-time PCR methods, we found that STLV-1 in mandrills infects both CD4(+) and CD8(+) T cells; however, proviral loads were significantly higher (P = 0.01) in CD4(+) than in CD8(+) cells (mean STLV-1 copies number per 100 cells (+/- SD) was 7.8 +/- 8 in CD4(+) T cells and 3.9 +/- 4.5 in CD8(+) T cells). After culture, STLV-1 provirus was detected in enriched CD4(+) but not in enriched CD8(+) T cells. After 6 months of culture, STLV-1-transformed cell lines expressing CD3(+), CD4(+) and HLADR(+) were established, and STLV-1 proteins and tax/rex mRNA were detected. In STLV-1 infected monkeys, there was a correlation between high proviral load and elevated levels of interleukin (IL)-2, IL-6, IL-10, interferon-gamma and tumour necrosis factor-alpha. The two monkeys with the highest STLV-1 proviral load had activated CD4(+)HLADR(+) and CD8(+)HLADR(+) T-cell subsets and a high percentage of CD25(+) in CD4(+) and CD8(+) T cells. Our study provides the first cellular, immunological and virological characterization of natural STLV-1 infection in mandrills and shows that they are an appropriate animal model for further physiopathological studies of the natural history of human T-cell leukaemia viruses.

  1. IP-I0 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of IP-10.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...

  2. Haematological and immunological effect of coadministration of ...

    African Journals Online (AJOL)

    This study evaluated the effect of co-administration of extracts of Vernonia amygdalina Del. (VA) and Azadirachta indica Linn.(AI) on haemapoietic and immunological indices of normal and diabetic rats. White blood cells which were non-significantly decreased (p>0.05) in diabetic control rats relative to the normal control, ...

  3. TRAIL causes deletions at the HPRT and TK1 loci of clonogenically competent cells

    Energy Technology Data Exchange (ETDEWEB)

    Miles, Mark A.; Shekhar, Tanmay M. [Department of Biochemistry and Genetics, La Trobe University, Bundoora, Victoria (Australia); La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria (Australia); Hall, Nathan E. [La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria (Australia); Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative, Melbourne, Victoria (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry and Genetics, La Trobe University, Bundoora, Victoria (Australia); La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria (Australia)

    2016-05-15

    Highlights: • Treatment with TRAIL or EMS provokes mutations in clonogenically viable TK6 cells. • TRAIL is 2–5-fold less mutagenic than an equivalently lethal concentration of EMS. • EMS mainly causes transition mutations at the HPRT and TK1 loci of TK6 cells. • Most loss-of-function HPRT or TK1 mutations caused by TRAIL treatment are deletions. - Abstract: When chemotherapy and radiotherapy are effective, they function by inducing DNA damage in cancerous cells, which respond by undergoing apoptosis. Some adverse effects can result from collateral destruction of non-cancerous cells, via the same mechanism. Therapy-related cancers, a particularly serious adverse effect of anti-cancer treatments, develop due to oncogenic mutations created in non-cancerous cells by the DNA damaging therapies used to eliminate the original cancer. Physiologically achievable concentrations of direct apoptosis inducing anti-cancer drugs that target Bcl-2 and IAP proteins possess negligible mutagenic activity, however death receptor agonists like TRAIL/Apo2L can provoke mutations in surviving cells, probably via caspase-mediated activation of the nuclease CAD. In this study we compared the types of mutations sustained in the HPRT and TK1 loci of clonogenically competent cells following treatment with TRAIL or the alkylating agent ethyl methanesulfonate (EMS). As expected, the loss-of-function mutations in the HPRT or TK1 loci triggered by exposure to EMS were almost all transitions. In contrast, only a minority of the mutations identified in TRAIL-treated clones lacking HPRT or TK1 activity were substitutions. Almost three quarters of the TRAIL-induced mutations were partial or complete deletions of the HPRT or TK1 genes, consistent with sub-lethal TRAIL treatment provoking double strand breaks, which may be mis-repaired by non-homologous end joining (NHEJ). Mis-repair of double-strand breaks following exposure to chemotherapy drugs has been implicated in the pathogenesis of

  4. TRAIL causes deletions at the HPRT and TK1 loci of clonogenically competent cells

    International Nuclear Information System (INIS)

    Miles, Mark A.; Shekhar, Tanmay M.; Hall, Nathan E.; Hawkins, Christine J.

    2016-01-01

    Highlights: • Treatment with TRAIL or EMS provokes mutations in clonogenically viable TK6 cells. • TRAIL is 2–5-fold less mutagenic than an equivalently lethal concentration of EMS. • EMS mainly causes transition mutations at the HPRT and TK1 loci of TK6 cells. • Most loss-of-function HPRT or TK1 mutations caused by TRAIL treatment are deletions. - Abstract: When chemotherapy and radiotherapy are effective, they function by inducing DNA damage in cancerous cells, which respond by undergoing apoptosis. Some adverse effects can result from collateral destruction of non-cancerous cells, via the same mechanism. Therapy-related cancers, a particularly serious adverse effect of anti-cancer treatments, develop due to oncogenic mutations created in non-cancerous cells by the DNA damaging therapies used to eliminate the original cancer. Physiologically achievable concentrations of direct apoptosis inducing anti-cancer drugs that target Bcl-2 and IAP proteins possess negligible mutagenic activity, however death receptor agonists like TRAIL/Apo2L can provoke mutations in surviving cells, probably via caspase-mediated activation of the nuclease CAD. In this study we compared the types of mutations sustained in the HPRT and TK1 loci of clonogenically competent cells following treatment with TRAIL or the alkylating agent ethyl methanesulfonate (EMS). As expected, the loss-of-function mutations in the HPRT or TK1 loci triggered by exposure to EMS were almost all transitions. In contrast, only a minority of the mutations identified in TRAIL-treated clones lacking HPRT or TK1 activity were substitutions. Almost three quarters of the TRAIL-induced mutations were partial or complete deletions of the HPRT or TK1 genes, consistent with sub-lethal TRAIL treatment provoking double strand breaks, which may be mis-repaired by non-homologous end joining (NHEJ). Mis-repair of double-strand breaks following exposure to chemotherapy drugs has been implicated in the pathogenesis of

  5. A CREB-MPP7-AMOT Regulatory Axis Controls Muscle Stem Cell Expansion and Self-Renewal Competence

    Directory of Open Access Journals (Sweden)

    Lydia Li

    2017-10-01

    Full Text Available Summary: Skeletal muscle regeneration requires resident muscle stem cells, termed satellite cells (SCs. SCs are largely quiescent during homeostasis yet become activated upon injury to supply myonuclei and self-renewed SCs. Molecular mechanisms underlying the competence of SCs to proliferate and self-renew in response to injury remain unclear. Here, we show that CREB activity establishes proliferative potential during SC quiescence. SCs with inhibited CREB activity remain quiescent and positioned in their niche, but upon injury, they cannot enter or maintain a proliferative state for expansion and self-renewal. We demonstrate mechanistically that Mpp7 is a CREB target and its functional mediator. MPP7 loss affects the level and sub-cellular localization of AMOT and YAP1 in quiescent SCs. Furthermore, MPP7 and AMOT are required for YAP1 nuclear accumulation, and the three are individually required for a proliferative state in myoblasts. We propose that the CREB-MPP7-AMOT-YAP1 axis establishes the competence of quiescent SCs to expand and self-renew, thereby preserving stem cell function. : Satellite cells are quiescent muscle stem cells that have the ability to regenerate muscles after injury. Li and Fan reveal an MPP7-AMOT-YAP1 regulatory axis that acts downstream of CREB to instill satellite cell competence. They also show how this regulatory axis prepares satellite cells for robust muscle regeneration after injury.

  6. Modulation of Immunological Pathways in Autistic and Neurotypical Lymphoblastoid Cell Lines by the Enteric Microbiome Metabolite Propionic Acid.

    Science.gov (United States)

    Frye, Richard E; Nankova, Bistra; Bhattacharyya, Sudeepa; Rose, Shannon; Bennuri, Sirish C; MacFabe, Derrick F

    2017-01-01

    Propionic acid (PPA) is a ubiquitous short-chain fatty acid which is a fermentation product of the enteric microbiome and present or added to many foods. While PPA has beneficial effects, it is also associated with human disorders, including autism spectrum disorders (ASDs). We previously demonstrated that PPA modulates mitochondrial dysfunction differentially in subsets of lymphoblastoid cell lines (LCLs) derived from patients with ASD. Specifically, PPA significantly increases mitochondrial function in LCLs that have mitochondrial dysfunction at baseline [individuals with autistic disorder with atypical mitochondrial function (AD-A) LCLs] as compared to ASD LCLs with normal mitochondrial function [individuals with autistic disorder with normal mitochondrial function (AD-N) LCLs] and control (CNT) LCLs. PPA at 1 mM was found to have a minimal effect on expression of immune genes in CNT and AD-N LCLs. However, as hypothesized, Panther analysis demonstrated that 1 mM PPA exposure at 24 or 48 h resulted in significant activation of the immune system genes in AD-A LCLs. When the effect of PPA on ASD LCLs were compared to the CNT LCLs, both ASD groups demonstrated immune pathway activation, although the AD-A LCLs demonstrate a wider activation of immune genes. Ingenuity Pathway Analysis identified several immune-related pathways as key Canonical Pathways that were differentially regulated, specifically human leukocyte antigen expression and immunoglobulin production genes were upregulated. These data demonstrate that the enteric microbiome metabolite PPA can evoke atypical immune activation in LCLs with an underlying abnormal metabolic state. As PPA, as well as enteric bacteria which produce PPA, have been implicated in a wide variety of diseases which have components of immune dysfunction, including ASD, diabetes, obesity, and inflammatory diseases, insight into this metabolic modulator may have wide applications for both health and disease.

  7. Health and safety of competing fuel options for fuel cells in the road transport sector

    Energy Technology Data Exchange (ETDEWEB)

    Green, E.; Short, S.; Stutt, E.; Wickramatillake, H.; Harrison, P.

    2000-07-01

    This report presents a critical analysis of the health and safety issues surrounding competing transport fuel options, including those for possible future fuel-cell powered vehicles. The fuels considered in this report are gasoline (unleaded and reformulated), diesel, hydrogen (H{sub 2}), methanol, natural gas and liquefied petroleum gas (LPG). The analysis presented here is based on available information in peer-reviewed, published papers and other sources such as government department or research laboratory reports and websites. An overall evaluation of the fuels in terms of their toxicity and health effects, environmental fate, and fire and explosion safety aspects is presented. The report is based on current knowledge and makes no assumptions as to how fuels may change in the future if they are to be used in fuel-cell vehicles. The report identifies the hazards of the fuels but does not estimate the risks likely to be associated with their eventual use in fuel-cell vehicles. The focus is on the fuels themselves and not their exhaust or reaction products. sNo assessment has been made of the environmental effects data for the fuels. Broad environmental considerations such as ozone forming potential and also global warming are not considered. Basic information on environmental fate is included to provide an understanding of migratory pathways, environmental compartmentalisation and potential routes of human exposure. Other factors such as economics, government incentives or disincentives and public attitudes may have a bearing on which of the fuels are considered most appropriate for future fuel-cell vehicles; these factors are not considered in any detail in this report. (Author)

  8. [Immunological background and pathomechanisms of food allergies].

    Science.gov (United States)

    Schülke, Stefan; Scheurer, Stephan

    2016-06-01

    Recent advances in immunology have greatly improved our understanding of the pathomechanisms of food allergies. Food allergies are caused and maintained by complex interactions of the innate and adaptive immune system involving antigen-presenting cells (APC), T cells, group 2 innate lymphoid cells (ILC2), epithelial cells (EC) and effectors cells. Additionally, epigenetic factors, the intestinal microbiome and nutritional factors modulating the gastrointestinal lymphatic tissue probably have a significant impact on allergy development. However, why certain individuals develop tolerance while others mount allergic responses, the factors defining the allergenicity of food proteins, as well as the immunological mechanisms triggering allergy development have yet to be analyzed in detail.

  9. Comparative anatomy of phagocytic and immunological synapses

    Directory of Open Access Journals (Sweden)

    Florence eNiedergang

    2016-01-01

    Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

  10. Identification of mononuclear cells in human blood. II. Evaluation of morphological and immunological aspects of native and formaldehyde-fixed cell populations

    NARCIS (Netherlands)

    Schuit, H.R.E.; Hijmans, W.

    1980-01-01

    The presence of surface-associated immunoglobulins and Fc receptors on mononuclear cells from normal human blood waas investigated by the direct immunofluorescence technique combined with phase-contrast microscopy. Formaldehyde-fixed cells were compared to unfixed cells and to cells preincubated at

  11. A roadmap towards personalized immunology.

    Science.gov (United States)

    Delhalle, Sylvie; Bode, Sebastian F N; Balling, Rudi; Ollert, Markus; He, Feng Q

    2018-01-01

    Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions. There is still a long way ahead on translating our capability to identify potentially targetable personalized biomarkers into effective personalized therapy in immune-centralized diseases. Here, we discuss the recent advances and successful applications in "Omics" data utilization and network analysis on patients' samples of clinical trials and studies, as well as the major challenges and strategies towards personalized stratification and treatment for infectious or non-communicable inflammatory diseases such as autoimmune diseases or allergies. We provide a roadmap and highlight experimental, clinical, computational analysis, data management, ethical and regulatory issues to accelerate the implementation of personalized immunology.

  12. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

    OpenAIRE

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2011-01-01

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends o...

  13. Immunological Deregulation in Classic Hodgkin Lymphoma

    Science.gov (United States)

    Romano, Alessandra; Vetro, Calogero; Caocci, Giovanni; Greco, Marianna; Parrinello, Nunziatina Laura; Di Raimondo, Francesco; La Nasa, Giorgio

    2014-01-01

    Classic Hodgkin Lymphoma (cHL) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in regulatory T cells signaling, expansion of myeloid derived suppressor cells, HLA-G signaling and natural killer cells dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in cHL with translational implications. PMID:24959336

  14. The immunology of smallpox vaccines

    Science.gov (United States)

    Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

    2010-01-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

  15. Approach to a case of multiple irregular red cell antibodies in a liver transplant recipient: Need for developing competence.

    Science.gov (United States)

    Dara, Ravi C; Tiwari, Aseem K; Pandey, Prashant; Arora, Dinesh

    2015-01-01

    Liver transplant procedure acts as a challenge for transfusion services in terms of specialized blood components, serologic problems, and immunologic effects of transfusion. Red cell alloimmunization in patients awaiting a liver transplant complicate the process by undue delay or unavailability of compatible red blood cell units. Compatible blood units can be provided by well-equipped immunohematology laboratory, which has expertise in resolving these serological problems. This report illustrates resolution of a case with multiple alloantibodies using standard techniques, particularly rare antisera. Our case re-emphasizes the need for universal antibody screening in all patients as part of pretransfusion testing, which helps to identify atypical antibodies and plan for appropriate transfusion support well in time. We recommend that the centers, especially the ones that perform complex procedures like solid organ transplants and hematological transplants should have the necessary immunohematological reagents including rare antisera to resolve complex cases of multiple antibodies as illustrated in this case.

  16. Approach to a case of multiple irregular red cell antibodies in a liver transplant recipient: Need for developing competence

    Directory of Open Access Journals (Sweden)

    Ravi C Dara

    2015-01-01

    Full Text Available Liver transplant procedure acts as a challenge for transfusion services in terms of specialized blood components, serologic problems, and immunologic effects of transfusion. Red cell alloimmunization in patients awaiting a liver transplant complicate the process by undue delay or unavailability of compatible red blood cell units. Compatible blood units can be provided by well-equipped immunohematology laboratory, which has expertise in resolving these serological problems. This report illustrates resolution of a case with multiple alloantibodies using standard techniques, particularly rare antisera. Our case re-emphasizes the need for universal antibody screening in all patients as part of pretransfusion testing, which helps to identify atypical antibodies and plan for appropriate transfusion support well in time. We recommend that the centers, especially the ones that perform complex procedures like solid organ transplants and hematological transplants should have the necessary immunohematological reagents including rare antisera to resolve complex cases of multiple antibodies as illustrated in this case.

  17. A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion

    DEFF Research Database (Denmark)

    Faassen, A E; Schrager, J A; Klein, D J

    1992-01-01

    The metastatic spread of tumor cells occurs through a complex series of events, one of which involves the adhesion of tumor cells to extracellular matrix (ECM) components. Multiple interactions between cell surface receptors of an adherent tumor cell and the surrounding ECM contribute to cell...... collagen could also be inhibited by removing cell surface chondroitin sulfate with chondroitinase. In contrast, type I collagen-mediated melanoma cell adhesion and spreading were not affected by either beta-D-xyloside or chondroitinase treatments. These results suggest that mouse melanoma CSPG...... was shown to be mediated, at least in part, by chondroitin sulfate. Additionally we have determined that mouse melanoma CSPG is composed of a 110-kD core protein that is recognized by anti-CD44 antibodies on Western blots. Collectively, our data suggests that interactions between a cell surface CD44-related...

  18. Immunology of the eye

    OpenAIRE

    Weronika Ratajczak; Beata Tokarz-Deptuła; Wiesław Deptuła

    2018-01-01

    The eye is an organ of sight characterized by unusual immunological properties, resulting from its anatomical structure and physiology, as well as the presence of specific elements that, through the mechanisms of innate and adaptive immunity, provide homeostasis of the eyeball. This article reviews the defensive elements of individual eye structures: conjunctiva, cornea, lacrimal gland, anterior chamber of the eye, uvea, retina and eye-associated lymphoid tissue (EALT), where we distinguish a...

  19. Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia.

    Science.gov (United States)

    Yirdaw, Kesetebirhan Delele; Hattingh, Susan

    2015-01-01

    Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk

  20. Immunology and Epidemiology

    CERN Document Server

    Hraba, Tomáš

    1986-01-01

    In February 1985 a small international meeting of scientists took place at the recreation resort of the Polish Academy of Sci­ ences in Mogilany, near Cracow, Poland. The initiative for holding the workshop came from a working meeting on mathematical immunology and related topics at the International Institute for Applied Sys­ tems Analysis in Laxenburg, Austria, in November 1983. In addition to representatives of IIASA, delegates of the IIASA National Member Organizations (NMO) of Czechoslovakia, Italy, and the soviet Union took part in that working meeting. The participants came to the conclusion that IIASA could play an important role in facilitating the development of research in this field. The first step that they recommended to I IASA was to organize a workshop on mathematical immunology. The purpose of the workshop was to review the progress that has been made in applying mathematics to problems in immunology and to explore ways in which further progress might be achieved, especially by more efficie...

  1. Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.

    Science.gov (United States)

    Cummins, Nathan W; Rizza, Stacey; Litzow, Mark R; Hua, Stephane; Lee, Guinevere Q; Einkauf, Kevin; Chun, Tae-Wook; Rhame, Frank; Baker, Jason V; Busch, Michael P; Chomont, Nicolas; Dean, Patrick G; Fromentin, Rémi; Haase, Ashley T; Hampton, Dylan; Keating, Sheila M; Lada, Steven M; Lee, Tzong-Hae; Natesampillai, Sekar; Richman, Douglas D; Schacker, Timothy W; Wietgrefe, Stephen; Yu, Xu G; Yao, Joseph D; Zeuli, John; Lichterfeld, Mathias; Badley, Andrew D

    2017-11-01

    Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

  2. Non-invasive bioluminescence imaging to monitor the immunological control of a plasmablastic lymphoma-like B cell neoplasia after hematopoietic cell transplantation.

    Directory of Open Access Journals (Sweden)

    Martin Chopra

    Full Text Available To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Igha(tm1(MycJanz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Igha(tm1(MycJanz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies.

  3. The role of the thymus for maturation of transferred bursa cells into immuno-competent B cells in chickens treated with cyclophosphamide

    International Nuclear Information System (INIS)

    Hirota, Y.; Bito, Y.

    1978-01-01

    Chickens injected with cyclophosphamide and X-ray irradiated in the newly hatched period were immunized with a mixture of sheep red blood cells, Brucella abortus and Salmonella pullorum at 4, 5 and 6 weeks of age, and were examined for serum antibody titres, serum immunoglobulin concentration and bursal and splenic structures at 7 weeks of age. The neonatal treatments suppressed completely or almost completely antibody responses, immunoglobulin production and formation of bursal follicles and splenic germinal centres. The transplantation of bursa cells into the chickens immunologically impaired by the treatments restored these functions and structures. In contrast, the transfer of bursa cells into chickens thymectomized, cyclophosphamide-treated and X-ray irradiated did not result in efficient restoration of the bursa-dependent immune system; 10-day-old bursa cells hardly restore the system, although 4-week-old bursa cells did so slightly. The chickens thymectomized, cyclophosphamide-treated, X-ray irradiated and re-populated with 10-day-old bursa cells were examined for the existence of functional B cells with the use of a syngeneic cell transfer system. The experiments verified that immunocompetent B cells had not developed in the chickens thus treated. (author)

  4. Germ cell transplantation using sexually competent fish: an approach for rapid propagation of endangered and valuable germlines.

    Directory of Open Access Journals (Sweden)

    Sullip K Majhi

    Full Text Available The transplantation of germ cells into adult recipient gonads is a tool with wide applications in animal breeding and conservation of valuable and/or endangered species; it also provides a means for basic studies involving germ cell (GC proliferation and differentiation. Here we describe the establishment of a working model for xenogeneic germ cell transplantation (GCT in sexually competent fish. Spermatogonial cells isolated from juveniles of one species, the pejerrey Odontesthes bonariensis (Atherinopsidae, were surgically transplanted into the gonads of sexually mature Patagonian pejerrey O. hatcheri, which have been partially depleted of endogenous GCs by a combination of Busulfan (40 mg/kg and high water temperature (25 degrees C treatments. The observation of the donor cells' behavior showed that transplanted spermatogonial cells were able to recolonize the recipients' gonads and resume spermatogenesis within 6 months from the GCT. The presence of donor-derived gametes was confirmed by PCR in 20% of the surrogate O. hatcheri fathers at 6 months and crosses with O. bonariensis mothers produced hybrids and pure O. bonariensis, with donor-derived germline transmission rates of 1.2-13.3%. These findings indicate that transplantation of spermatogonial cells into sexually competent fish can shorten considerably the production time of donor-derived gametes and offspring and could play a vital role in germline conservation and propagation of valued and/or endangered fish species.

  5. Reprogramming of rabbit induced pluripotent stem cells toward epiblast and chimeric competency using Krüppel-like factors

    Directory of Open Access Journals (Sweden)

    Yann Tapponnier

    2017-10-01

    Full Text Available Rabbit induced pluripotent stem cells (rbiPSCs possess the characteristic features of primed pluripotency as defined in rodents and primates. In the present study, we reprogrammed rbiPSCs using human Krüppel-like factors (KLFs 2 and 4 and cultured them in a medium supplemented with fetal calf serum and leukemia inhibitory factor. These cells (designated rbEKA were propagated by enzymatic dissociation for at least 30 passages, during which they maintained a normal karyotype. This new culturing protocol resulted in transcriptional and epigenetic reconfiguration, as substantiated by the expression of transcription factors and the presence of histone modifications associated with naïve pluripotency. Furthermore, microarray analysis of rbiPSCs, rbEKA cells, rabbit ICM cells, and rabbit epiblast showed that the global gene expression profile of the reprogrammed rbiPSCs was more similar to that of rabbit ICM and epiblast cells. Injection of rbEKA cells into 8-cell stage rabbit embryos resulted in extensive colonization of ICM in 9% early-blastocysts (E3.5, epiblast in 10% mid-blastocysts (E4.5, and embryonic disk in 1.4% pre-gastrulae (E6. Thus, these results indicate that KLF2 and KLF4 triggered the conversion of rbiPSCs into epiblast-like, embryo colonization-competent PSCs. Our results highlight some of the requirements to achieve bona fide chimeric competency.

  6. Immunological studies in the acquired immunodeficiency syndrome. II. Active suppression or intrinsic defect--investigated by mixing AIDS cells with HLA-DR identical normal cells

    DEFF Research Database (Denmark)

    Hofmann, B; Ødum, Niels; Jakobsen, B K

    1986-01-01

    The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls...... with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset...

  7. An investigation into the activation and deactivation of chlorinated hydrocarbons to genotoxins in metabolically competent human cells.

    Science.gov (United States)

    Doherty, A T; Ellard, S; Parry, E M; Parry, J M

    1996-05-01

    We have investigated the induction of micronuclei by 15 chlorinated hydrocarbons in the cytochalasin B-blocked micronucleus assay utilizing genetically engineered cell lines. The human lymphoblastoid cell line AHH-1, with native cytochrome CYP1A1 activity, the MCL-5 cell line, which stably expresses cDNAs encoding human CYP1A2, 2A6, 3A4, 2E1 and microsomal epoxide hydrolase, and the h2E1 cell line, containing a cDNA for CYP2E1, were used in this study. We have demonstrated the induction of kinetochore-positive micronuclei by two chlorinated solvents, 2,3-dichlorobutane and 1,1, 2-trichloroethane, in the metabolically competent cell lines MCL-5 and h2E1. The MCL-5 and h2E1 cell lines have in addition shown the capacity to produce metabolites in the presence of methylene chloride, carbon tetrachloride, 1,2,3-trichloropropane, tetrachloroethylene, toluene and n-hexane, wich yield elevated micronucleus frequencies compared with the parental cell line AHH-1. Hexachloroethane failed to induce micronuclei in any of the cell lines and 1,2-dichloroethane and 1-chlorohexane induced micronuclei without the requirement for metabolic activation in all three cell lines. The MCL-5 cell line exhibited reduced micronucleus frequencies compared with the AHH-1 and h2E1 cell lines following exposure to 1,2-dichloroethylene, 1,3-dichloropropane, 1,1, 1-trichloroethane and 1,2,3-trichloropropane. The methodology used has shown the ability of metabolically competent cell lines expressing cDNAs encoding the cytochrome P450 isoenzymes to metabolize halogenated hydrocarbons to genotoxic species, including both clastogens and aneugens. The biotransformation of chemicals to aneugenic species has not previously been demonstrated.

  8. Immunology taught by rats

    OpenAIRE

    Klenerman, P; Barnes, EJ

    2017-01-01

    Immunology may be best taught by viruses, and possibly by humans, but the rats of New York City surprisingly also have plenty to offer. A survey published in 2014 of the pathogens carried by rats trapped in houses and parks in Manhattan identified a huge burden of infectious agents in these animals, including several novel viruses. Among these are Norway rat hepaciviruses (NrHVs), which belong to the same family as hepatitis C virus (HCV). NrHVs were found in rat livers, raising the possibili...

  9. Mucosal immunology and virology

    National Research Council Canada - National Science Library

    Tyring, Stephen

    2006-01-01

    .... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

  10. Differential toxicity of heterocyclic aromatic amines and their mixture in metabolically competent HepaRG cells

    International Nuclear Information System (INIS)

    Dumont, Julie; Josse, Rozenn; Lambert, Carine; Antherieu, Sebastien; Le Hegarat, Ludovic; Aninat, Caroline; Robin, Marie-Anne; Guguen-Guillouzo, Christiane

    2010-01-01

    Human exposure to heterocyclic aromatic amines (HAA) usually occurs through mixtures rather than individual compounds. However, the toxic effects and related mechanisms of co-exposure to HAA in humans remain unknown. We compared the effects of two of the most common HAA, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), individually or in combination, in the metabolically competent human hepatoma HepaRG cells. Various endpoints were measured including cytotoxicity, apoptosis, oxidative stress and DNA damage by the comet assay. Moreover, the effects of PhIP and/or MeIQx on mRNA expression and activities of enzymes involved in their activation and detoxification pathways were evaluated. After a 24 h treatment, PhIP and MeIQx, individually and in combination, exerted differential effects on apoptosis, oxidative stress, DNA damage and cytochrome P450 (CYP) activities. Only PhIP induced DNA damage. It was also a stronger inducer of CYP1A1 and CYP1B1 expression and activity than MeIQx. In contrast, only MeIQx exposure resulted in a significant induction of CYP1A2 activity. The combination of PhIP with MeIQx induced an oxidative stress and showed synergistic effects on apoptosis. However, PhIP-induced genotoxicity was abolished by a co-exposure with MeIQx. Such an inhibitory effect could be explained by a significant decrease in CYP1A2 activity which is responsible for PhIP genotoxicity. Our findings highlight the need to investigate interactions between HAA when assessing risks for human health and provide new insights in the mechanisms of interaction between PhIP and MeIQx.

  11. Immunological memory: What's in a name?

    Science.gov (United States)

    Pradeu, Thomas; Du Pasquier, Louis

    2018-05-01

    Immunological memory is one of the core topics of contemporary immunology. Yet there are many discussions about what this concept precisely means, which components of the immune system display it, and in which phyla it exists. Recent years have seen the multiplication of claims that immunological memory can be found in "innate" immune cells and in many phyla beyond vertebrates (including invertebrates, plants, but also bacteria and archaea), as well as the multiplication of concepts to account for these phenomena, such as "innate immune memory" or "trained immunity". The aim of this critical review is to analyze these recent claims and concepts, and to distinguish ideas that have often been misleadingly associated, such as memory, adaptive immunity, and specificity. We argue that immunological memory is a gradual and multidimensional phenomenon, irreducible to any simple dichotomy, and we show why adopting this new view matters from an experimental and therapeutic point of view. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals.

    Science.gov (United States)

    Banga, Riddhima; Procopio, Francesco A; Ruggiero, Alessandra; Noto, Alessandra; Ohmiti, Khalid; Cavassini, Matthias; Corpataux, Jean-Marc; Paxton, William A; Pollakis, Georgios; Perreau, Matthieu

    2018-01-01

    We recently demonstrated that lymph nodes (LNs) PD-1 + /T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investigated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1 + CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1 + CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment containing inducible replication competent virus in treated aviremic HIV-infected individuals.

  13. An analysis of an immunological effect in the cases of osteogenic sarcoma treated with massive radiotherapy

    International Nuclear Information System (INIS)

    Fukushima, Hiroshi; Itami, Yasuto; Akamatsu, Noriya; Matsuura, Koichi; Aoki, Haruhito

    1978-01-01

    Changes in immunological competence of 16 patients with osteogenic sarcoma treated with long-term radiotherapy with massive doses were investigated. The irradiation dose ranged from 7600 to 24200 rad with a mean dose of 13000 rad, and the irradiation term ranged from 7 to 24 weeks. The treatment with linac was performed except one case treated with tele-cobalt. The number of lymphocytes in peripheral blood decreased during the irradiation, but a tendency to recover appeared within about 6 months after discontinuance of the irradiation. The number of T cells showed the same change as that of lymphocytes during and after the irradiation. In cases fairly progressed, decreases of lymphocytes and T cells during the irradiation were small as compared to those in cases poorly progressed. A tendency to recover was marked, in the former cases. The effect of the irradiation on B cells was small in comparison with that on T cells. The difference by prognosis was not recognized. The numbers of lymphocytes and T cells and juvenile rate of lymphocytes by PHA in cases which progressed satisfactory over 3 years showed high values after the finish of the irradiation as compared to those in cases in which the time after the irradiation was short. The prognosis in the PPD negative cases and the cases whose PPD changed to negative was clearly unfavorable in comparison with that in the cases in which PPD was positive before to after the irradiation. The above-mentioned results suggested a relationship between an appearance of metastasis to the lung and changes in immunological competence, and these were interesting findings showing a treatment principle for patients with osteogenic sarcoma and an expectation of prognosis. (Tsunoda, M.)

  14. Effect of intratracheally instilled depleted uranium on immunological function of rats

    International Nuclear Information System (INIS)

    You Hanhu; Yang Zhihua; Cao Zhenshan; Zhu Maoxiang; Liu Xingrong

    2004-01-01

    Objective: To study immunological effects of depleted uranium in rats. Methods: Wistar rats were exposed to depleted uranium by single intratracheal instillation. Body weight and peripheral blood cells were measured weekly and immunological functions were evaluated by weight coefficient of immune organs, plague forming cells of splenocytes, total and subpopulation counts of lymphocytes in thymus. Results: Early after administration, body weight decreased and red blood cells as well as platelets reduced while white blood cells increased, which returned to normal within 1 or 2 months. Immunological functions of splenocytes and thymocytes were affected dose-dependently by depleted uranium. Conclusion: Depleted uranium induces immunological dysfunction in rats. (authors)

  15. Advances in clinical immunology in 2015.

    Science.gov (United States)

    Chinen, Javier; Notarangelo, Luigi D; Shearer, William T

    2016-12-01

    Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Immunology of Yersinia pestis Infection.

    Science.gov (United States)

    Bi, Yujing

    2016-01-01

    As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

  17. Immunological effects of irradiation: waiting for a model

    International Nuclear Information System (INIS)

    Doria, G.

    1979-01-01

    Decreased resistance to pathogens, is an effect of ionizing radiations, is largely mediated by impairment of the specific immune response. It has been established that the antibody response is depressed when the antigen is injected shortly before or immediately after irradiation. Recovery of the response in animals immunized after sublethal irradiation starts after about 1 week and may be complete 2 months after irradiation. If animals are immunized a few or several days before radiation exposure, some parameters of the antibody response are unaffected while others may display lower or higher values than normal, depending on the nature and physical form of the antigen. Recent studies have described the effects of whole-body irradiation on antibody ability. Since this antibody property affects the stability of immune complexes and, therefore, the antibody's ability to neutralize viruses and toxins, affinity was felt to be of importance to counteract infections in irradiated animals. Antibody affinity was found up to 20 times greater in irradiated than in control mice when antigen was injected 1 to 5 days before or 2 hr to 8 weeks after a sublethal dose of x-rays. Recovery profiles of mitotic responses of spleen cells to PHA, ConA, or LPS suggest that the enhancement of antibody affinity in irradiated mice could result from a relative lack of suppressor T cells. Dysfunctions of the immune system of irradiated animals can be attributed to alterations of the populations of immunologically competent cells. Unlike auxiliary cells, lymphocytes are extremely sensitive to ionizing radiations. Subpopulations of T and B lymphocytes appear to have different radiosensitivities and to develop with different efficiencies in irradiated animals. B cells seem to be more radiosensitive and to recover faster than T cells

  18. Immunology of age-related macular degeneration

    Science.gov (United States)

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  19. THE IMMUNOLOGICAL CHARACTERISTIC OF RA PATIENTS WITH ANAEMIA

    Directory of Open Access Journals (Sweden)

    A. E. Sizikov

    2014-07-01

    Full Text Available Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

  20. Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

    Science.gov (United States)

    Blanc, Pascal; Moro-Sibilot, Ludovic; Barthly, Lucas; Jagot, Ferdinand; This, Sébastien; de Bernard, Simon; Buffat, Laurent; Dussurgey, Sébastien; Colisson, Renaud; Hobeika, Elias; Fest, Thierry; Taillardet, Morgan; Thaunat, Olivier; Sicard, Antoine; Mondière, Paul; Genestier, Laurent; Nutt, Stephen L.; Defrance, Thierry

    2016-01-01

    Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG+ counterparts do not. Antigen boost modifies the gene expression profile of IgM+ plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge. PMID:27924814

  1. [Sporulation or competence development? A genetic regulatory network model of cell-fate determination in Bacillus subtilis].

    Science.gov (United States)

    Lu, Zhenghui; Zhou, Yuling; Zhang, Xiaozhou; Zhang, Guimin

    2015-11-01

    Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.

  2. Enhancement of immunological activity after mild hyperthermia

    International Nuclear Information System (INIS)

    Noguchi, Kenichi; Hasegawa, Takeo; Takahashi, Tohru

    2002-01-01

    At present, hyperthermia is clinically very important as interdisciplinary therapeutic method, and studies are being performed on combined effects with surgical treatment, radiotherapy, chemotherapy and gene therapy for the treatment of malignant tumors. We evaluated the effects of hyperthermia under temperature of 42.5C and demonstrated that the activation of immunological response is increased and anti-tumor effect cabn be obtained in this studies. We used animals were C3H mice (male,7W) bearing SCC-VII tumor on femur skin. Then, the mice were divided to 10 mice in each group, and only femur region was immersed in warm water for thermal treatment. Also we measured the tumor growth, changes of blood cell fraction and NK cell activity. The results of the present study confirmed: (1) Anti-tumor effect can be given by thermal treatment at relatively mild temperature (mild temperature at 39C-42C); (2) The increase of neutrophils is dependent on the quantity of heat added; (3) Immunological response of monocytes and lymphocytes is associated with it; (4) Activity of the immunological potency as a whole such as activation of NK cells was also confirmed

  3. Ideernes epidemiologi og kulturens immunologi

    DEFF Research Database (Denmark)

    Sørensen, Jesper

    2007-01-01

    , suggested by Sperber, is extended by an ‘immunology of cultural systems’. In addition to the selective forces described by Sperber and Boyer, the immunological approach argues that the relative success of new representations is largely dependent on how well they fit already existing cultural models...

  4. Immunology for rheumatology residents: working toward a Canadian national curriculum consensus.

    Science.gov (United States)

    Chow, Shirley L; Herman-Kideckel, Sari; Mahendira, Dharini; McDonald-Blumer, Heather

    2015-01-01

    Immunologic mechanisms play an integral role in understanding the pathogenesis and management of rheumatic conditions. Currently, there is limited access to formal instruction in immunology for rheumatology trainees across Canada. The aims of this study were (1) to describe current immunology curricula among adult rheumatology training programs across Canada and (2) to compare the perceived learning needs of rheumatology trainees from the perspective of program directors and trainees to help develop a focused nationwide immunology curriculum. Rheumatology trainees and program directors from adult rheumatology programs across Canada completed an online questionnaire and were asked to rank a comprehensive list of immunology topics. A modified Delphi approach was implemented to obtain consensus on immunology topics. Only 42% of program directors and 31% of trainees felt the current method of teaching immunology was effective. Results illustrate concordance between program directors and trainees for the highest-ranked immunology topics including innate immunity, adaptive immunity, and cells and tissues of the immune system. However, there was discordance among other topics, such as diagnostic laboratory immunology and therapeutics. There is a need to improve immunology teaching in rheumatology training programs. Results show high concordance between the basic immunology topics. This study provides the groundwork for development of future immunology curricula.

  5. Immunological properties of gold nanoparticles.

    Science.gov (United States)

    Dykman, Lev A; Khlebtsov, Nikolai G

    2017-03-01

    In the past decade, gold nanoparticles have attracted strong interest from the nanobiotechnological community owing to the significant progress made in robust and easy-to-make synthesis technologies, in surface functionalization, and in promising biomedical applications. These include bioimaging, gene diagnostics, analytical sensing, photothermal treatment of tumors, and targeted delivery of various biomolecular and chemical cargos. For the last-named application, gold nanoparticles should be properly fabricated to deliver the cargo into the targeted cells through effective endocytosis. In this review, we discuss recent progress in understanding the selective penetration of gold nanoparticles into immune cells. The interaction of gold nanoparticles with immune cell receptors is discussed. As distinct from other published reviews, we present a summary of the immunological properties of gold nanoparticles. This review also summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo . For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Thus, this review presents a detailed analysis of data on interaction of gold nanoparticles with immune cells. Emphasis is placed on the systematization of data over production of antibodies by using gold nanoparticles and adjuvant properties of gold nanoparticles. Specifically, we start our discussion with current data on interaction of various gold nanoparticles with immune cells. The next section describes existing technologies to improve production of antibodies in vivo by using gold nanoparticles conjugated with specific ligands. Finally, we describe what is known about adjuvant properties of bare gold or functionalized nanoparticles. In the Conclusion section, we present a short summary of reported data and some challenges and perspectives.

  6. Kinetics and clonality of immunological memory in humans.

    Science.gov (United States)

    Beverley, Peter C L

    2004-10-01

    T-cell immunological memory consists largely of clones of proliferating lymphocytes maintained by antigenic stimulation and the survival and proliferative effects of cytokines. The duration of survival of memory clones in humans is determine by the Hayflick limit on the number of cell divisions, the rate of cycling of memory cells and factors that control erosion of telomeres, including mechanisms that control telomerase.

  7. Overcoming immunological barriers in regenerative medicine.

    Science.gov (United States)

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2014-08-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists.

  8. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics

    Science.gov (United States)

    Hosmane, Nina N.; Kwon, Kyungyoon J.; Bruner, Katherine M.; Capoferri, Adam A.; Rosenbloom, Daniel I.S.; Keele, Brandon F.; Ho, Ya-Chi

    2017-01-01

    A latent reservoir for HIV-1 in resting CD4+ T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure. PMID:28341641

  9. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics.

    Science.gov (United States)

    Hosmane, Nina N; Kwon, Kyungyoon J; Bruner, Katherine M; Capoferri, Adam A; Beg, Subul; Rosenbloom, Daniel I S; Keele, Brandon F; Ho, Ya-Chi; Siliciano, Janet D; Siliciano, Robert F

    2017-04-03

    A latent reservoir for HIV-1 in resting CD4 + T lymphocytes precludes cure. Mechanisms underlying reservoir stability are unclear. Recent studies suggest an unexpected degree of infected cell proliferation in vivo. T cell activation drives proliferation but also reverses latency, resulting in productive infection that generally leads to cell death. In this study, we show that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. Thus, assays relying on one round of activation underestimate reservoir size. Sequencing of independent clonal isolates of replication-competent virus revealed that 57% had env sequences identical to other isolates from the same patient. Identity was confirmed by full-genome sequencing and was not attributable to limited viral diversity. Phylogenetic and statistical analysis suggested that identical sequences arose from in vivo proliferation of infected cells, rather than infection of multiple cells by a dominant viral species. The possibility that much of the reservoir arises by cell proliferation presents challenges to cure. © 2017 Hosmane et al.

  10. Transforming growth factor type β can act as a potent competence factor for AKR-2B cells

    International Nuclear Information System (INIS)

    Goustin, A.S.; Nuttall, G.A.; Leof, E.B.; Ranganathan, G.; Moses, H.L.

    1987-01-01

    Transforming growth factor type β (TGFβ) is a pleiotropic regulator of cell growth with specific high-affinity cell-surface receptors on a large number of cells; its mechanism of action, however, is poorly defined. In this report, the authors utilized the mouse fibroblast line AKR-2B to explore the question of the temporal requirements during the cell cycle in regard to both the growth inhibitory and the growth stimulatory action of TGFβ. The results indicate that AKR-2B cells are most sensitive to the inhibitory action of TGFβ during early to mid-G 1 . In addition, TGFβ need be present only briefly in order to exert its inhibitory effect on EGF-induced DNA synthesis. Likewise, the stimulatory effect of TGFβ in the absence of EGF requires only an equally brief exposure to TGFβ. Use of homogeneous 125 I-labeled TGFβ in a cell-binding assay demonstrates that TGFβ bound to cell-surface receptors can readily exchange into the culture medium, helping to rule out the possibility that persistent receptor-bound TGFβ is the source of a continuous stimulus. The data indicate that TGFβ exposure induces a stable state in the cell similar to but distinct from the state of competence induced by platelet-derived growth factor (PDGF)

  11. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  12. Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation

    DEFF Research Database (Denmark)

    Fritzsche, Marco; Fernandes, Ricardo A.; Chang, Veronica T.

    2017-01-01

    optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse...

  13. The sea urchin Paracentrotus lividus immunological response to chemical pollution exposure: The case of lindane.

    Science.gov (United States)

    Stabili, Loredana; Pagliara, Patrizia

    2015-09-01

    In the marine environment organochlorine insecticides can be broadly detected in water, sediments, and biota. These pollutants may have major ecological consequences since they may affect marine organisms and endanger organismal growth, reproduction or survival. In this study we investigated the modification of some sea urchin immunological parameters in response to subchronic lindane (γ-HCH) exposure. Adult specimens of the sea urchin Paracentrotus lividus were exposed to two different concentrations (0.1 and 0.5 mg L(-1)) of lindane. After 24 and 48h of treatment, we examined the lindane influence on coelomocytes vitality and enumeration as well on some humoral parameters. Our results showed that the presence of the pesticide affected both cellular and humoral components of the immune system. In particular, P. lividus coelomocytes vitality did not change but a decrease of the total cell number and an increase of the red cells was recorded. Haemolytic and lysozyme-like activities as well as antibacterial activity on Vibrio alginolyticus of treated animals decreased. Sea urchin immunological competence modifications might represent a tool for monitoring disease susceptibility thus providing biological criteria for the implementation of water quality standards to protect marine organisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Immunological methods for gentamicin determination

    International Nuclear Information System (INIS)

    Krugers Dagneauz, P.G.L.C.; Olthuis, F.M.F.G.

    1979-01-01

    For immunoassay, an antibody against the substance to the determined, the pure substance itself, and a labelled form or derivative of the substance are required. The principles and problems of the preparation of antibodies are discussed, some methods for the preparation of derivatives labelled with radioactive tracers or enzymes are reviewed, and homologous enzyme-immunological determination of gentamicin is discussed in detail. A comparison is mae of three radio-immunological determination methods, and the most suitable radio-immunological method is compared with two microbiological techniques. The results are found to be comparable. (Auth.)

  15. Systems immunology: just getting started.

    Science.gov (United States)

    Davis, Mark M; Tato, Cristina M; Furman, David

    2017-06-20

    Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated.

  16. Understanding ageing: Biomedical and bioengineering approaches, the immunologic view

    Directory of Open Access Journals (Sweden)

    Vasto Sonya

    2008-09-01

    Full Text Available Abstract During the past century, humans have gained more years of average life expectancy than in the last 10,000 years; we are now living in a rapidly ageing world. The sharp rise in life expectancy, coupled to a steady decline in birth rates in all developed countries, has led to an unprecedented demographic revolution characterized by an explosive growth in the number and proportion of older people. Ageing is a complex process that negatively impacts the development of the immune system and its ability to function. Progressive changes in the T and B cell systems over the life span have a major impact on the capacity to respond to immune challenge. These cumulative age-associated changes in immune competence are termed Immunosenescence: some immunological parameters are commonly notably reduced in the elderly and, reciprocally good function is tightly correlated to health status. Hence, a better understanding of Immunosenescence and the development of new strategies to counteract it are essential for improving the quality of life of the elderly population.

  17. [Autoimmune hepatitis: Immunological diagnosis].

    Science.gov (United States)

    Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim

    2017-11-01

    Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Systems immunology: just getting started

    OpenAIRE

    Davis, Mark M; Tato, Cristina M; Furman, David

    2017-01-01

    Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immun...

  19. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development.

    Science.gov (United States)

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2012-01-15

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends on pancreas developmental stage. Using temporal genetic labeling approaches we examined the dynamic of endocrine progenitor differentiation and explored the plasticity of Neurog3-induced cells throughout development. We found that Neurog3(+) progenitors develop into hormone-expressing cells in a fast process taking less then 10h. Furthermore, fate-mapping studies in heterozygote (Neurog3(CreERT/+)) and Neurog3-deficient (Neurog3(CreERT/CreERT)) embryos revealed that Neurog3-induced cells have different potential over time. At the early bud stage, failed endocrine progenitors can adopt acinar or ductal fate, whereas later in the branching pancreas they do not contribute to the acinar lineage but Neurog3-deficient cells eventually differentiate into duct cells. Thus these results provide evidence that the plasticity of Neurog3-induced cells becomes restricted during development. Furthermore these data suggest that during the secondary transition, endocrine progenitor cells arise from bipotent precursors already committed to the duct/endocrine lineages and not from domain of cells having distinct potentialities. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Interspecies somatic cell nucleus transfer with porcine oocytes as recipients: A novel bioassay system for assessing the competence of canine somatic cells to develop into embryos.

    Science.gov (United States)

    Sugimura, S; Narita, K; Yamashiro, H; Sugawara, A; Shoji, T; Terashita, Y; Nishimori, K; Konno, T; Yoshida, M; Sato, E

    2009-09-01

    Interspecies somatic cell nucleus transfer (iSCNT) could be a useful bioassay system for assessing the ability of mammalian somatic cells to develop into embryos. To examine this possibility, we performed canine iSCNT using porcine oocytes, allowed to mature in vitro, as recipients. Canine fibroblasts from the tail tips and dewclaws of a female poodle (Fp) and a male poodle (Mp) were used as donors. We demonstrated that the use of porcine oocytes induced blastocyst formation in the iSCNT embryos cultured in porcine zygote medium-3. In Fp and Mp, the rate of blastocyst formation from cleaved embryos (Fp: 6.3% vs. 22.4%; and Mp: 26.1% vs. 52.4%) and the number of cells at the blastocyst stage (Fp: 30.7 vs. 60.0; and Mp: 27.2 vs. 40.1) were higher in the embryos derived from dewclaw cells than in those derived from tail-tip cells (Ptip cells of Fp. Only blastocysts derived from dewclaw cells of Mp developed outgrowths. However, outgrowth formation was retrieved in the embryos derived from dewclaw cells of Fp by aggregation at the 4-cell stage. We inferred that iSCNT performed using porcine oocytes as recipients could represent a novel bioassay system for evaluating the developmental competence of canine somatic cells.

  1. Lessons from reproductive immunology for other fields of immunology and clinical approaches.

    Science.gov (United States)

    Markert, Udo R; Fitzgerald, Justine S; Seyfarth, Lydia; Heinzelmann, Joana; Varosi, Frauke; Voigt, Sandra; Schleussner, Ekkehard; Seewald, Hans-Joachim

    2005-01-01

    Reproduction is indispensable to evolution and, thus, life. Nonetheless, it overcomes common rules known to established life. Immunology of reproduction, and especially the tolerance of two genetically distinct organisms and their fruitful symbiosis, is one of the most imposing paradox of life. Mechanisms, which are physiologically used for induction of said tolerance, are frequently abused by pathogens or tumors intending to escape the host's immune response. Understanding the regulation of immune responses in pregnancy and the invasion of allogeneic fetus-derived trophoblast cells into the decidua may lead to new therapeutic concepts. In transplantation, knowledge concerning local physiological immunotolerance may be useful for the development of new therapies, which do not require a general immune suppression of the patient. In immunological disorders, such as autoimmune diseases or allergies, immune deviations occur which are either prevented during pregnancy or have parallels to pregnancy. Vice versa, lessons from other fields of immunology may also offer new notions for the comprehension of reproductive immunology and may lead to new therapies for the treatment of pregnancy-related problems.

  2. Immunological studies relating to the climate

    International Nuclear Information System (INIS)

    Ballester, J.M.; Cruz, C.; Inclan, G.; Maclas, C.; Suarez, L.; Rivero, R.; Borres, I.M.; Ustariz, C.; Del Valle, L.; Villegas, R.; Martinez, E.; Rorrajero, I.; Guevara, V.; Leon, A.; Paz, L.; Pelaez, J.C.; Roque, M.C.

    1993-01-01

    In order to know the effects of ultra-violet radiations on the integrity of their immunological system, a hematologic and immunological study was carried out in 30 clinically healthy children aged between 10 and 15; 15 of each sex, who come from a region in Bielorussia that was affected by the Chernobyl nuclear accident, and who received medical and recreational services at the 'Jose Marti' Pioneers'City, located Tarara Beach (Havana, Cuba) from July 9,1990 to August 27,1990. Data from the initial evaluations upon their arrival in Cuba were compared whit the final results before their return to Bielorussia, in the following variables: haemoglobin, leucocytes, platelets, absolute counts of lymphocytes and neutrophylous polymorphonuclears, levels of sericeus of Igs G, A, M, and E sericas and (CH50), as well as the presence of circulating immuno complexes; besides spot-forming cellular clusters (spontaneous, active, and medial by the receptor Fc in neutrophylous) and the cells identified with monoclonal antibodies against CD2, CD3, CD8 and CD4/CD8 quotient. Cutaneous response to antigen and lymphoblastic transformation in the presence of PHA and PwN were also assessed. Results of this research allow to infer that the adequate and monitored position against ultra-violet rays from the solar radiation in children exposed to low doses of ionizing irradiation does not deteriorate the human immunological system, and do favor its regulation and normal performance

  3. Panel 5: Microbiology and Immunology Panel

    Science.gov (United States)

    Murphy, Timothy F.; Chonmaitree, Tasnee; Barenkamp, Stephen; Kyd, Jennelle; Nokso-Koivisto, Johanna; Patel, Janak A.; Heikkinen, Terho; Yamanaka, Noboru; Ogra, Pearay; Swords, W. Edward; Sih, Tania; Pettigrew, Melinda M.

    2014-01-01

    Objective The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Conclusion Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. Implications for Practice The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media. PMID:23536533

  4. IMMUNOLOGICAL MECHANISMS OF APOPTOSIS IN PLACENTAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    D. I. Sokolov

    2008-01-01

    Full Text Available Abstract. In present review, the data are considered that concern a role of immunological mechanisms controlling the events of apoptosis at different stages of development of placenta. Intensity of apoptotic process in human placenta is progressively increasing in the course of pregnancy, until delivery act. The processes of apoptosis induction and its prevention in placental cells are inseparably linked to development of placenta and formation of vascular system, as controlled by trophoblast cells, as well as by maternal fetal immune cells. T-lymphocytes, natural killer cells, NKT-cells and macrophages that perform surveillance over the processes of angiogenesis and apoptosis in placental tissue, thus providing its normal development and functioning.

  5. (Na+ + K+)-ATPase and plasma membrane polarity of intestinal epithelial cells: Presence of a brush border antigen in the distal large intestine that is immunologically related to beta subunit

    Energy Technology Data Exchange (ETDEWEB)

    Marxer, A.; Stieger, B.; Quaroni, A.; Kashgarian, M.; Hauri, H.P. (Univ. of Basel (Switzerland))

    1989-09-01

    The previously produced monoclonal antibody IEC 1/48 against cultured rat intestinal crypt cells was extensively characterized and found to be directed against the beta subunit of (Na+ + K+)-ATPase as assessed by immunological and enzymatic criteria. Under nondenaturing conditions the antibody precipitated the alpha-beta enzyme complex (98,000 and 48,000 Mr). This probe, together with the monoclonal antibody C 62.4 against the alpha subunit was used to localize (Na+ + K+)-ATPase in epithelial cells along the rat intestinal tract by immunofluorescence and immunoelectron microscopy. Both antibodies exclusively labeled the basolateral membrane of small intestine and proximal colon epithelial cells. However, in the distal colon, IEC 1/48, but not C 62.4, also labeled the brush border membrane. The cross-reacting beta-subunit-like antigen on the apical cell pole was tightly associated with isolated brush borders but was apparently devoid of (Na+ + K+)-ATPase activity. Subcellular fractionation of colonocytes in conjunction with limited proteolysis and surface radioiodination of intestinal segments suggested that the cross-reacting antigen in the brush border may be very similar to the beta subunit. The results support the notion that in the small intestine and proximal colon the enzyme subunits are exclusively targeted to the basolateral membrane while in the distal colon nonassembled beta subunit or a beta-subunit-like protein is also transported to the apical cell pole.

  6. The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Mai [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Kitaguchi, Tetsuya [Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABOIS), Waseda University, 11 Biopolis Way, 05-01/02 Helios, Singapore 138667 (Singapore); Numano, Rika [The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tennpaku-cho, Toyohashi, Aichi 441-8580 (Japan); Ikematsu, Kazuya [Forensic Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kakeyama, Masaki [Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Murata, Masayuki; Sato, Ken [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Tsuboi, Takashi, E-mail: takatsuboi@bio.c.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer Regulation of exocytosis by Rho GTPase Cdc42. Black-Right-Pointing-Pointer Cdc42 increases the number of fusion events from newly recruited vesicles. Black-Right-Pointing-Pointer Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott-Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

  7. The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

    International Nuclear Information System (INIS)

    Sato, Mai; Kitaguchi, Tetsuya; Numano, Rika; Ikematsu, Kazuya; Kakeyama, Masaki; Murata, Masayuki; Sato, Ken; Tsuboi, Takashi

    2012-01-01

    Highlights: ► Regulation of exocytosis by Rho GTPase Cdc42. ► Cdc42 increases the number of fusion events from newly recruited vesicles. ► Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott–Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

  8. Role of immunological surveillance in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Sado, Toshihiko

    2003-01-01

    The immune system is known to be highly susceptible to various physical, chemical, and biological insults. The studies on the immediate and long-term effects of radiation on immune system of mice indicated very clearly that there was a dose-dependent reduction in the number of T and B cells, depression of antibody and cytotoxic T cell responses as well as proliferative responses of spleen cells to T and B cell mitogens shortly after irradiation, but they all recovered to the control level within a few months. Immunosuppression observed shortly after irradiation had little influence on the development of radiogenic tumors. The effects of radiation on the incidence of Friend leukemia virus (FLV)-induced leukemias are examined by using young adult B6C3F 1 male mice which are normally resistant to FLV-induced leukemogenesis. There was a clear threshold dose of 2 Gy below which the development of FLV induced leukemias was not observed but after exposure to >3 Gy high incidence of leukemias was observed. Fractionated, weekly exposure of young C57BL strain mice to 1.6 Gy of X-rays for four successive weeks causes most of the exposed mice to develop thymic lymphomas between 3 and 10 months. However, when the exposed mice are grafted with bone marrow cells from normal donors, the development of thymic lymphomas on the exposed mice is greatly inhibited. There was a clear dose response relationship between the number of bone marrow cells injected and the inhibition of the development of thymic lymphomas. It now appears clear that T cell-mediated immunological surveillance against newly arising neoplasms conceived by Thomas and Burnet does not hold true anymore in the original form, although virus-infected host cells and other host cells expressing altered-self' markers on their cell surfaces are constantly monitored by the immunological surveillance mechanism. A surveillance function against newly arising neoplasms may be a property of surrounding normal tissue cells rather

  9. Membrane fusion-competent virus-like proteoliposomes and proteinaceous supported bilayers made directly from cell plasma membranes.

    Science.gov (United States)

    Costello, Deirdre A; Hsia, Chih-Yun; Millet, Jean K; Porri, Teresa; Daniel, Susan

    2013-05-28

    Virus-like particles are useful materials for studying virus-host interactions in a safe manner. However, the standard production of pseudovirus based on the vesicular stomatitis virus (VSV) backbone is an intricate procedure that requires trained laboratory personnel. In this work, a new strategy for creating virus-like proteoliposomes (VLPLs) and virus-like supported bilayers (VLSBs) is presented. This strategy uses a cell blebbing technique to induce the formation of nanoscale vesicles from the plasma membrane of BHK cells expressing the hemagglutinin (HA) fusion protein of influenza X-31. These vesicles and supported bilayers contain HA and are used to carry out single particle membrane fusion events, monitored using total internal reflection fluorescence microscopy. The results of these studies show that the VLPLs and VLSBs contain HA proteins that are fully competent to carry out membrane fusion, including the formation of a fusion pore and the release of fluorophores loaded into vesicles. This new strategy for creating spherical and planar geometry virus-like membranes has many potential applications. VLPLs could be used to study fusion proteins of virulent viruses in a safe manner, or they could be used as therapeutic delivery particles to transport beneficial proteins coexpressed in the cells to a target cell. VLSBs could facilitate high throughput screening of antiviral drugs or pathogen-host cell interactions.

  10. Immunologically active biomaterials for cancer therapy.

    Science.gov (United States)

    Ali, Omar A; Mooney, David J

    2011-01-01

    Our understanding of immunological regulation has progressed tremendously alongside the development of materials science, and at their intersection emerges the possibility to employ immunologically active biomaterials for cancer immunotherapy. Strong and sustained anticancer, immune responses are required to clear large tumor burdens in patients, but current approaches for immunotherapy are formulated as products for delivery in bolus, which may be indiscriminate and/or shortlived. Multifunctional biomaterial particles are now being developed to target and sustain antigen and adjuvant delivery to dendritic cells in vivo, and these have the potential to direct and prolong antigen-specific T cell responses. Three-dimensional immune cell niches are also being developed to regulate the recruitment, activation and deployment of immune cells in situ to promote potent antitumor responses. Recent studies demonstrate that materials with immune targeting and stimulatory capabilities can enhance the magnitude and duration of immune responses to cancer antigens, and preclinical results utilizing material-based immunotherapy in tumor models show a strong therapeutic benefit, justifying translation to and future testing in the clinic.

  11. MicroRNA and protein profiling of brain metastasis competent cell-derived exosomes.

    Directory of Open Access Journals (Sweden)

    Laura Camacho

    Full Text Available Exosomes are small membrane vesicles released by most cell types including tumor cells. The intercellular exchange of proteins and genetic material via exosomes is a potentially effective approach for cell-to-cell communication and it may perform multiple functions aiding to tumor survival and metastasis. We investigated microRNA and protein profiles of brain metastatic (BM versus non-brain metastatic (non-BM cell-derived exosomes. We studied the cargo of exosomes isolated from brain-tropic 70W, MDA-MB-231BR, and circulating tumor cell brain metastasis-selected markers (CTC1BMSM variants, and compared them with parental non-BM MeWo, MDA-MB-231P and CTC1P cells, respectively. By performing microRNA PCR array we identified one up-regulated (miR-210 and two down-regulated miRNAs (miR-19a and miR-29c in BM versus non-BM exosomes. Second, we analyzed the proteomic content of cells and exosomes isolated from these six cell lines, and detected high expression of proteins implicated in cell communication, cell cycle, and in key cancer invasion and metastasis pathways. Third, we show that BM cell-derived exosomes can be internalized by non-BM cells and that they effectively transport their cargo into cells, resulting in increased cell adhesive and invasive potencies. These results provide a strong rationale for additional investigations of exosomal proteins and miRNAs towards more profound understandings of exosome roles in brain metastasis biogenesis, and for the discovery and application of non-invasive biomarkers for new therapies combating brain metastasis.

  12. Advances in asthma, allergy and immunology series 2004: basic and clinical immunology.

    Science.gov (United States)

    Chinen, Javier; Shearer, William T

    2004-08-01

    This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.

  13. Wild immunology assessed by multidimensional mass cytometry.

    Science.gov (United States)

    Japp, Alberto Sada; Hoffmann, Kerstin; Schlickeiser, Stephan; Glauben, Rainer; Nikolaou, Christos; Maecker, Holden T; Braun, Julian; Matzmohr, Nadine; Sawitzki, Birgit; Siegmund, Britta; Radbruch, Andreas; Volk, Hans-Dieter; Frentsch, Marco; Kunkel, Desiree; Thiel, Andreas

    2017-01-01

    A great part of our knowledge on mammalian immunology has been established in laboratory settings. The use of inbred mouse strains enabled controlled studies of immune cell and molecule functions in defined settings. These studies were usually performed in specific-pathogen free (SPF) environments providing standardized conditions. In contrast, mammalians including humans living in their natural habitat are continuously facing pathogen encounters throughout their life. The influences of environmental conditions on the signatures of the immune system and on experimental outcomes are yet not well defined. Thus, the transferability of results obtained in current experimental systems to the physiological human situation has always been a matter of debate. Studies elucidating the diversity of "wild immunology" imprintings in detail and comparing it with those of "clean" lab mice are sparse. Here, we applied multidimensional mass cytometry to dissect phenotypic and functional differences between distinct groups of laboratory and pet shop mice as a source for "wild mice". For this purpose, we developed a 31-antibody panel for murine leukocyte subsets identification and a 35-antibody panel assessing various cytokines. Established murine leukocyte populations were easily identified and diverse immune signatures indicative of numerous pathogen encounters were classified particularly in pet shop mice and to a lesser extent in quarantine and non-SPF mice as compared to SPF mice. In addition, unsupervised analysis identified distinct clusters that associated strongly with the degree of pathogenic priming, including increased frequencies of activated NK cells and antigen-experienced B- and T-cell subsets. Our study unravels the complexity of immune signatures altered under physiological pathogen challenges and highlights the importance of carefully adapting laboratory settings for immunological studies in mice, including drug and therapy testing. © 2016 International Society

  14. Immunological Evasion in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Roxana Magaña-Maldonado

    2016-01-01

    Full Text Available Glioblastoma is the most aggressive tumor in Central Nervous System in adults. Among its features, modulation of immune system stands out. Although immune system is capable of detecting and eliminating tumor cells mainly by cytotoxic T and NK cells, tumor microenvironment suppresses an effective response through recruitment of modulator cells such as regulatory T cells, monocyte-derived suppressor cells, M2 macrophages, and microglia as well as secretion of immunomodulators including IL-6, IL-10, CSF-1, TGF-β, and CCL2. Other mechanisms that induce immunosuppression include enzymes as indolamine 2,3-dioxygenase. For this reason it is important to develop new therapies that avoid this immune evasion to promote an effective response against glioblastoma.

  15. The immunological synapse: a focal point for endocytosis and exocytosis.

    Science.gov (United States)

    Griffiths, Gillian M; Tsun, Andy; Stinchcombe, Jane C

    2010-05-03

    There are many different cells in the immune system. To mount an effective immune response, they need to communicate with each other. One way in which this is done is by the formation of immunological synapses between cells. Recent developments show that the immune synapse serves as a focal point for exocytosis and endocytosis, directed by centrosomal docking at the plasma membrane. In this respect, formation of the immunological synapse bears striking similarities to cilia formation and cytokinesis. These intriguing observations suggest that the centrosome may play a conserved role in designating a specialized area of membrane for localized endocytosis and exocytosis.

  16. Immunology of the Uterine and Vaginal Mucosae.

    Science.gov (United States)

    Zhou, Jordan Z; Way, Sing Sing; Chen, Kang

    2018-04-01

    Along with the maintenance of symbiotic mutualism with commensal microbes and protection against invasive infections common to all mucosal barrier tissues, female reproductive tissues have additional, unique tasks that include dynamic cyclic cellular turnover in menstruation and immunological tolerance to genetically foreign fetal antigens in pregnancy. Here we review current knowledge on distinct features of the immune cells in female reproductive tissue with regard to antimicrobial host defense and adaptations to accommodate the fetus during pregnancy. Outstanding areas for future research to obtain new functional insights on this enigmatic mucosal barrier are also highlighted. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Bone marrow transplantation immunology

    International Nuclear Information System (INIS)

    Trentin, J.J.; Kiessling, R.; Wigzell, H.; Gallagher, M.T.; Datta, S.K.; Kulkarni, S.S.

    1977-01-01

    Tests were made to determine whether genetic resistance (GR) to bone marrow transplantation represents a natural lymphoma-leukemia defense mechanism, as follows: (C57 x AKR) F 1 hybrid mice show GR to C57 parental bone marrow cells, but not to AKR parental bone marrow cells (C3H x AKR) F 1 hybrids show no GR to bone marrow transplantation from either parental strain. However, transplantation of AKR lymphoma cells into lethally irradiated ''resistant'' (C57 x AKR) F 1 and ''nonresistant'' (C3H x AKR) F 1 hybrids produced lymphomatous spleen colonies in ''nonresistant'' hybrids but not in ''resistant'' hybrids. Thus ''resistant'' (C57 x AKR) F 1 hybrids can recognize and reject AKR lymphoma cells, but not normal AKR bone marrow cells. A normal biologic role of leukemia-lymphoma surveillance was postulated for genetic resistance to marrow transplantation, directed at antigens which, like TL, are expressed on normal hemopoietic cells of some strains, but only on leukemic cells of other strains

  18. The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice

    Science.gov (United States)

    Manuel, Martine; Martynoga, Ben; Yu, Tian; West, John D.; Mason, John O.; Price, David J.

    2010-01-01

    Summary Foxg1 is required for development of the ventral telencephalon in the embryonic mammalian forebrain. Although one existing hypothesis suggests that failed ventral telencephalic development in the absence of Foxg1 is due to reduced production of the morphogens sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8), the possibility that telencephalic cells lacking Foxg1 are intrinsically incompetent to generate the ventral telencephalon has remained untested. We examined the ability of Foxg1−/− telencephalic cells to respond to Shh and Fgf8 by examining the expression of genes whose activation requires Shh or Fgf8 in vivo and by testing their responses to Shh and Fgf8 in culture. We found that many elements of the Shh and Fgf8 signalling pathways continue to function in the absence of Foxg1 but, nevertheless, we were unable to elicit normal responses of key ventral telencephalic marker genes in Foxg1−/− telencephalic tissue following a range of in vivo and in vitro manipulations. We explored the development of Foxg1−/− cells in Foxg1−/− Foxg1+/+ chimeric embryos that contained ventral telencephalon created by normally patterned wild-type cells. We found that Foxg1−/− cells contributed to the chimeric ventral telencephalon, but that they retained abnormal specification, expressing dorsal rather than ventral telencephalic markers. These findings indicate that, in addition to regulating the production of ventralising signals, Foxg1 acts cell-autonomously in the telencephalon to ensure that cells develop the competence to adopt ventral identities. PMID:20081193

  19. Novel immunological strategies for islet transplantation.

    Science.gov (United States)

    Tezza, Sara; Ben Nasr, Moufida; Vergani, Andrea; Valderrama Vasquez, Alessandro; Maestroni, Anna; Abdi, Reza; Secchi, Antonio; Fiorina, Paolo

    2015-08-01

    Islet transplantation has been demonstrated to improve glycometabolic control, to reduce hypoglycemic episodes and to halt the progression of diabetic complications. However, the exhaustion of islet function and the side effects related to chronic immunosuppression limit the spread of this technique. Consequently, new immunoregulatory protocols have been developed, with the aim to avoid the use of a life-time immunosuppression. Several approaches have been tested in preclinical models, and some are now under clinical evaluation. The development of new small molecules and new monoclonal or polyclonal antibodies is continuous and raises the possibility of targeting new costimulatory pathways or depleting particular cell types. The use of stem cells and regulatory T cells is underway to take advantage of their immunological properties and to induce tolerance. Xenograft islet transplantation, although having severe problems in terms of immunological compatibility, could theoretically provide an unlimited source of donors; using pigs carrying human immune antigens has showed indeed promising results. A completely different approach, the use of encapsulated islets, has been developed; synthetic structures are used to hide islet alloantigen from the immune system, thus preserving islet endocrine function. Once one of these strategies is demonstrated safe and effective, it will be possible to establish clinical islet transplantation as a treatment for patients with type 1 diabetes long before the onset of diabetic-related complications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Performance of immunological response in predicting virological failure.

    Science.gov (United States)

    Ingole, Nayana; Mehta, Preeti; Pazare, Amar; Paranjpe, Supriya; Sarkate, Purva

    2013-03-01

    In HIV-infected individuals on antiretroviral therapy (ART), the decision on when to switch from first-line to second-line therapy is dictated by treatment failure, and this can be measured in three ways: clinically, immunologically, and virologically. While viral load (VL) decreases and CD4 cell increases typically occur together after starting ART, discordant responses may be seen. Hence the current study was designed to determine the immunological and virological response to ART and to evaluate the utility of immunological response to predict virological failure. All treatment-naive HIV-positive individuals aged >18 years who were eligible for ART were enrolled and assessed at baseline, 6 months, and 12 months clinically and by CD4 cell count and viral load estimations. The patients were categorized as showing concordant favorable (CF), immunological only (IO), virological only (VO), and concordant unfavorable responses (CU). The efficiency of immunological failure to predict virological failure was analyzed across various levels of virological failure (VL>50, >500, and >5,000 copies/ml). At 6 months, 87(79.81%), 7(5.5%), 13 (11.92%), and 2 (1.83%) patients and at 12 months 61(69.3%), 9(10.2%), 16 (18.2%), and 2 (2.3%) patients had CF, IO, VO, and CU responses, respectively. Immunological failure criteria had a very low sensitivity (11.1-40%) and positive predictive value (8.3-25%) to predict virological failure. Immunological criteria do not accurately predict virological failure resulting in significant misclassification of therapeutic responses. There is an urgent need for inclusion of viral load testing in the initiation and monitoring of ART.

  1. Immunology of Psoriasis

    Science.gov (United States)

    Lowes, Michelle A.; Suárez-Fariñas, Mayte; Krueger, James G.

    2014-01-01

    The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases. PMID:24655295

  2. Oligopeptide antigens of the angiotensin lineage compete for presentation by paraformaldehyde-treated accessory cells to T cells

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1986-01-01

    series are highly susceptible to proteolytic destruction in cultures containing prefixed accessory cells. The proteases responsible for the destruction of these peptides are apparently located in the plasma membrane of accessory cells. These enzymes represent a methodologic problem in studies...

  3. Breaking Immunological Tolerance through OX40 (CD134

    Directory of Open Access Journals (Sweden)

    Pratima Bansal-Pakala

    2001-01-01

    Full Text Available Immunological tolerance represents a mechanism by which cells of the host remain protected from the immune system. Breaking of immunological tolerance can result in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis. The reasons for tolerance breaking down and autoimmune processes arising are largely unknown but of obvious interest for therapeutic intervention of these diseases. Although reversal of the tolerant state is generally unwanted, there are instances where this may be of benefit to the host. In particular, one way a cancerous cell escapes being targeted by the immune system is through tolerance mechanisms that in effect turn off the reactivity of T lymphocytes that can respond to tumor-associated peptides. Thus tolerance represents a major obstacle in developing effective immunotherapy against tumors. The molecules that are involved in regulating immunological tolerance are then of interest as they may be great targets for positively or negatively manipulating the tolerance process.

  4. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    Science.gov (United States)

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Effect of radiation on the expression of tumor-associated antigens of human lung adenocarcinoma cells. Immunological study using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Hareyama, Masato

    1988-12-01

    We studied the effects of irradiation on the expression of a tumor-associated antigen (YH206 antigen) of cultured human lung adenocarcinoma A549 cells by using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. YH206 antigen is preferentially expressed on adenocarcinoma cells. Irradiation of A549 cells remarkably increased the expression of YH206 antigen on the cell surface and the level of the antigen in the culture supernatant as well as in the cell lysate, whereas it significantly affected the expression of HLA (MHC-class I) antigen on the same cells. The expression of HLA antigen on the cell was also increased after treatment of the cells with interferon-..gamma... In an additional experiment, cells were stained simultaneously for surface antigens (fluorescein coupled antibodies) and for DNA content (propidium iodide), and then dual parameter measurements were performed by flow cytometry to analyse the relationship between antigen levels and the cell cycle. YH206 antigen and HLA antigen increased more in the S and G/sub 2//M phases of the cell cycle than in G/sub 0//G/sub 1/. The expression of YH206 antigen was enhanced in the S and G/sub 2//M phases by irradiation, whereas the expression of HLA antigen was enhanced in each phase of the cell cycle with irradiation or IFN. These results suggest that irradiation plays a key role in the change of the expression of certain tumor-associated antigens.

  6. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Juliane Brun

    Full Text Available The use of mesenchymal stromal cells (MSCs differentiated toward a smooth muscle cell (SMC phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2, transgelin (TAGLN, calponin (CNN1, and smooth muscle myosin heavy chain (SM-MHC; MYH11 according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion

  7. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Science.gov (United States)

    Brun, Juliane; Lutz, Katrin A; Neumayer, Katharina M H; Klein, Gerd; Seeger, Tanja; Uynuk-Ool, Tatiana; Wörgötter, Katharina; Schmid, Sandra; Kraushaar, Udo; Guenther, Elke; Rolauffs, Bernd; Aicher, Wilhelm K; Hart, Melanie L

    2015-01-01

    The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel

  8. Effector/memory CD8+ T cells synergize with co-stimulation competent macrophages to trigger autoimmune peripheral neuropathy.

    Science.gov (United States)

    Yang, Mu; Shi, Xiang Qun; Peyret, Corentin; Oladiran, Oladayo; Wu, Sonia; Chambon, Julien; Fournier, Sylvie; Zhang, Ji

    2018-04-05

    Autoimmune peripheral neuropathy (APN) such as Guillain Barre Syndrome (GBS) is a debilitating illness and sometimes life threatening. The molecular and cellular mechanisms remain elusive but exposure to environmental factors including viral/bacterial infection and injury is highly associated with disease incidence. We demonstrated previously that both male and female B7.2 (CD86) transgenic L31 and L31/CD4KO mice develop spontaneous APN. Here we further reveal that CD8 + T cells in these mice exhibit an effector/memory phenotype, which bears a resemblance to the CD8 + T cell response following persistent cytomegalovirus (CMV) infection in humans and mice, whilst CMV has been considered as one of the most relevant pathogens in APN development. These activated, peripheral myelin Ag specific CD8 + T cells are required for the disease initiation. While an injury to a peripheral nerve results in Wallerian degeneration in control littermates, the same injury accelerates the development of APN in other non-injured nerves of L31 mice which have a predisposed inflammatory background consisting of effector/memory CD8 + T (CD8 + T EM ) cells. However, CD8 + T EM cells alone are not sufficient. A certain threshold of B7.2 expression on nerve macrophages is an additional requisite. Our findings reveal that indeed, the synergism between CD8 + T EM cells and co-stimulation competent macrophages is crucial in inducing autoimmune-mediated peripheral neuropathy. The identification of decisive molecular/cellular players connecting environmental triggers and the occurrence of APN provides opportunities to prevent disease onset, reduce relapses and develop new therapeutic strategies. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  9. Citizens unite for computational immunology!

    Science.gov (United States)

    Belden, Orrin S; Baker, Sarah Catherine; Baker, Brian M

    2015-07-01

    Recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for such 'crowdsourcing' efforts in immunology. Tools for developing applications, new funding opportunities, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real - it is time to jump in! Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Immunology update: topics in basic and clinically applied reproductive immunology.

    Science.gov (United States)

    Hunt, J S

    1996-05-01

    A postgraduate course covering basic and clinical reproductive immunology was held in Philadelphia, PA, U.S.A., on March 19, 1996, in conjunction with the annual meeting of the Society for Gynecological Investigation. The course was organized and chaired by Joseph A. Hill.

  11. Immunologic roles of hyaluronan.

    Science.gov (United States)

    Mummert, Mark E

    2005-01-01

    Hyaluronan (HA), a large glycosaminoglycan composed of D-N-acetylglucosamine and D-glucuronic acid, is expressed in virtually all tissues and has long been considered to serve as a structural component or filling material in the tissue interstitium (Filler Theory). This idea was revised with the discovery of HA-binding proteins that introduced the concept that HA may also serve as an adhesive substrate for cellular trafficking (Adhesion Theory). Most recently, it has been shown that HA fragments can deliver maturational signals to dendritic cells (DCs) and high molecular weight HA polymers can deliver costimulatory signals to T-cells (Signaling Theory). Thus, HA may represent an important component of the immune system. Recently, we have evaluated the impact of HA on Langerhans cell (LC) maturation and migration using a novel peptide inhibitor of HA function, termed Pep-1 (GAHWQFNALTVR). As skin-specific members of the DC family, LCs are crucial for the initiation of cutaneous immune responses. Local injections of Pep-1 prevented hapten-induced LC migration from the epidermis, providing the first experimental evidence that HA facilitates their emigration. Moreover, Pep-1 also significantly inhibited the hapten-induced maturation of LCs in vivo as assessed by cell morphology, costimulatory molecule expression, and their ability to induce proliferation of allogeneic T-cells. HA therefore has dual functionality to facilitate LC migration and maturation, the two critical events for the initiation of adaptive immune responses. Finally, we have observed that DC-dependent, antigen-specific T-cell proliferation and cytokine secretion is blocked by Pep-1. These results have revealed a previously unrecognized role for HA in antigen presentation. Thus, far from an inert structural biopolymer, HA represents a multifunctional carbohydrate mediator of immune processes.

  12. Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

    International Nuclear Information System (INIS)

    Shu, S.; Fonseca, L.S.; Hunter, J.T.; Rapp, H.J.

    1983-01-01

    The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity

  13. Maximal frustration as an immunological principle.

    Science.gov (United States)

    de Abreu, F Vistulo; Mostardinha, P

    2009-03-06

    A fundamental problem in immunology is that of understanding how the immune system selects promptly which cells to kill without harming the body. This problem poses an apparent paradox. Strong reactivity against pathogens seems incompatible with perfect tolerance towards self. We propose a different view on cellular reactivity to overcome this paradox: effector functions should be seen as the outcome of cellular decisions which can be in conflict with other cells' decisions. We argue that if cellular systems are frustrated, then extensive cross-reactivity among the elements in the system can decrease the reactivity of the system as a whole and induce perfect tolerance. Using numerical and mathematical analyses, we discuss two simple models that perform optimal pathogenic detection with no autoimmunity if cells are maximally frustrated. This study strongly suggests that a principle of maximal frustration could be used to build artificial immune systems. It would be interesting to test this principle in the real adaptive immune system.

  14. Teacher competencies

    OpenAIRE

    Svatošová, Kateřina

    2012-01-01

    This diploma thesis deals with adult teacher competencies. It describes current situation in adult education and it focuses on measuring quality level of teacher competencies. There is given the main overview of adult education specifics. These are the prerequisites for defining adult teacher competencies. There is given specific adult teacher competencies and related roles which are generally based on teacher's activities during educational courses. Next part describes present conception of ...

  15. Advances in transplantation immunology.

    Science.gov (United States)

    Morris, P J

    1987-09-01

    Although there have been dramatic advances in clinical organ transplantation over the past 20 years, rejection, both acute and chronic, and the complications of immunosuppression remain major problems. Nevertheless as our understanding of the immune response to a vascularized organ allograft develops, so too will our ability to develop more specific immunosuppression. In any strategy for more specific immunosuppression compatibility for the major histocompatibility complex of antigens (HLA in man) is likely to be important. Monoclonal antibodies to T cell subpopulations, or even to T cells specifically activated by the graft, provide methods of suppressing the immune response at a more specific level. The recognition that stable grafts are maintained, at least in experimental rodent models, by T suppressor cells may allow development of precise methods of inducing the generation of such cells in clinical practice. The induction of tolerance in the adult animal can be achieved in a number of ways, the most promising of which for clinical application, is antigen pretreatment. If tolerance could be achieved in clinical practice within the not too distant future, then this would represent the attainment of the ultimate goal of transplantation.

  16. Advances in mechanisms of asthma, allergy, and immunology in 2010.

    Science.gov (United States)

    Broide, David H; Finkelman, Fred; Bochner, Bruce S; Rothenberg, Marc E

    2011-03-01

    2010 was marked by rapid progress in our understanding of the cellular and molecular mechanisms involved in the pathogenesis of allergic inflammation and asthma. Studies published in the Journal of Allergy and Clinical Immunology described advances in our knowledge of cells associated with allergic inflammation (mast cells, eosinophils, dendritic cells, and T cells), as well as IgE, cytokines, receptors, signaling molecules, and pathways. Studies used animal models, as well as human cells and tissues, to advance our understanding of mechanisms of asthma, eosinophilic esophagitis, food allergy, anaphylaxis and immediate hypersensitivity, mast cells and their disorders, atopic dermatitis, nasal polyposis, and hypereosinophilic syndromes. Additional studies provided novel information about the induction and regulation of allergic inflammation and the genetic contribution to allergic inflammation. Critical features of these studies and their potential effects on human atopic disorders are summarized here. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  17. AAOHN Competencies.

    Science.gov (United States)

    2015-11-01

    The AAOHN Competency document is one of the core documents that define occupational health nursing practice. This article provides a description of the process used to update the competencies, as well as a description of the new competencies. © 2015 The Author(s).

  18. Quality in radio-immunology

    International Nuclear Information System (INIS)

    Hegesippe, Michel

    1982-01-01

    The author outlines the technique of radio-immunological analysis (RIA) which is now widely used for neo-natal detection of congenital hyperthyroidism. He describes the methods and controls that are called for - as regards the specificity of doses, the sensitivity and reliability of the separation technique - to guarantee the quality of RIA and the validity of its results [fr

  19. Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete for the HSC niche?

    Science.gov (United States)

    Noll, J E; Williams, S A; Purton, L E; Zannettino, A C W

    2012-09-14

    In the adult mammal, normal haematopoiesis occurs predominantly in the bone marrow, where primitive haematopoietic stem cells (HSC) and their progeny reside in specialised microenvironments. The bone marrow microenvironment contains specific anatomical areas (termed niches) that are highly specialised for the development of certain blood cell types, for example HSCs. The HSC niche provides important cell-cell interactions and signalling molecules that regulate HSC self-renewal and differentiation processes. These same signals and interactions are also important in the progression of haematological malignancies, such as multiple myeloma (MM). This review provides an overview of the bone marrow microenvironment and its involvement in normal, physiological HSC maintenance and plasma cell growth throughout MM disease progression.

  20. Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

    NARCIS (Netherlands)

    Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Steingrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, José A. M.; Miedema, Frank

    2008-01-01

    It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

  1. Restoration of the CD4 T cell compartment after long-term highly active Antiretroviral therapy without phenotypical signs of accelerated immunological aging

    NARCIS (Netherlands)

    Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Stemgrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, Jose A. M.; Miedema, Frank

    2008-01-01

    It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

  2. HIV-infected viremic long-term non-progressors and controllers display different immunological mechanisms for preserved CD4+cell counts

    DEFF Research Database (Denmark)

    Gaardbo, J; Ronit, A; Hartling, H

    2012-01-01

    161+), and regulatory T cells (Tregs, CD4+CD25+CD127lowFoxP3+) were evaluated using flow cytometry. For statistics Kruskal-Wallis test followed by Mann-Whitney U test were used. Data are given as medians. Summary of results: LTNP had higher frequency of activated CD4+ and CD8+cells compared to VC (3...

  3. Identification of CD8(+) T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lelic, A.; Parsons, R.

    2010-01-01

    bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell...

  4. Experimental photoimmunology: immunologic ramifications of UV-induced carcinogenesis

    International Nuclear Information System (INIS)

    Daynes, R.A.; Bernhard, E.J.; Gurish, M.F.; Lynch, D.H.

    1981-01-01

    The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet light (UVL) exposure has clearly shown that the direct mutagenic effects of UVL is only one of the components involved in this process. In spite of the fact that overt carcinogenesis is only one of the many effects produced by UV light, most hypotheses as to the mechanism by which UVL can cause the mutations necessary to achieve the transformed phenotype have focused on the direct effects of UVL on DNA and the generation of carcinogenic compounds. Investigations during the last 5 yr, however, have clearly demonstrated that immunologic factors are also critically important in the pathogenesis of UV-induced skin cancers. A complete understanding of UV-carcinogenesis must therefore consider the mechanisms which allow the transformed cell to evade immunologic rejection by the host in addition to those aspects which deal with conversion of a normal cell to a cancer cell. It is the object of this review to provide both a historical account of the work which established the immunologic consequences of chronic UVL exposure and the results of recent experiments designed to investigate the kinetics and mechanisms by which UVL affects the immunologic apparatus. In addition, a hypothetical model is presented to explain the sequence of events which ultimately lead to the emergence of the suppressor T-cells which regulate antitumor immune responses

  5. The lymphopenic mouse in immunology: from patron to pariah.

    Science.gov (United States)

    Singh, Nevil J; Schwartz, Ronald H

    2006-12-01

    A recent surge of interest in the behavior of T and B cells in lymphopenic model systems has resurrected a certain cynicism about the validity of using such models to answer important immunological questions. Here we discuss this skepticism in a broader historical context.

  6. Polish scientists in fish immunology: a short history : review

    NARCIS (Netherlands)

    Muiswinkel, van W.B.; Pilarczyk, A.

    2015-01-01

    This review describes the role played by Polish scientists in the field of fish immunology and vaccination starting around 1900. In the early days, most publications were dealing with a description of relevant cells and organs in fish. Functional studies (phagocytosis, antibody response) came later

  7. Single cell analysis of gene expression patterns of competence development and initiation of sporulation in Bacillus subtilis grown on chemically defined media

    NARCIS (Netherlands)

    Veening, J. -W.; Smits, W. K.; Hamoen, L. W.; Kuipers, O. P.

    Aim: Understanding the basis for the heterogeneous (or bistable) expression patterns of competence development and sporulation in Bacillus subtilis. Methods and Results: Using flow cytometric analyses of various promoter-GFP fusions, we have determined the single-cell gene expression patterns of

  8. Immunological Responses to Total Hip Arthroplasty.

    Science.gov (United States)

    Man, Kenny; Jiang, Lin-Hua; Foster, Richard; Yang, Xuebin B

    2017-08-01

    The use of total hip arthroplasties (THA) has been continuously rising to meet the demands of the increasingly ageing population. To date, this procedure has been highly successful in relieving pain and restoring the functionality of patients' joints, and has significantly improved their quality of life. However, these implants are expected to eventually fail after 15-25 years in situ due to slow progressive inflammatory responses at the bone-implant interface. Such inflammatory responses are primarily mediated by immune cells such as macrophages, triggered by implant wear particles. As a result, aseptic loosening is the main cause for revision surgery over the mid and long-term and is responsible for more than 70% of hip revisions. In some patients with a metal-on-metal (MoM) implant, metallic implant wear particles can give rise to metal sensitivity. Therefore, engineering biomaterials, which are immunologically inert or support the healing process, require an in-depth understanding of the host inflammatory and wound-healing response to implanted materials. This review discusses the immunological response initiated by biomaterials extensively used in THA, ultra-high-molecular-weight polyethylene (UHMWPE), cobalt chromium (CoCr), and alumina ceramics. The biological responses of these biomaterials in bulk and particulate forms are also discussed. In conclusion, the immunological responses to bulk and particulate biomaterials vary greatly depending on the implant material types, the size of particulate and its volume, and where the response to bulk forms of differing biomaterials are relatively acute and similar, while wear particles can initiate a variety of responses such as osteolysis, metal sensitivity, and so on.

  9. A new era in veterinary immunology

    NARCIS (Netherlands)

    Halliwell, R.E.W.; Goudswaard, J.

    1979-01-01

    The importance of the creation of a new international journal of “Veterinary Immunology and Immunopathology” is apparent following the emergence of veterinary immunology as an identifiable discipline and the vital part played by investigations of animal models of immunological diseases of

  10. 42 CFR 493.921 - Diagnostic immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

  11. 42 CFR 493.927 - General immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual program...

  12. IMMUNOLOGY OF TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    Federica Bozzano

    2014-04-01

    Full Text Available MTB ranks as the first worldwide pathogen latently infecting one third of the population and the second leading cause of death from a single infectious agent, after the human immunodeficiency virus (HIV. The development of vigorous and apparently appropriate immune response upon infection with M.tuberculosis in humans and experimental animals conflict with failure to eradicate the pathogen itself and with its ability to undergo clinical latency from which it may exit. From a clinical standpoint, our views on MTB infection may take advantage from updating the overall perspective, that has quite changed over the last decade, following remarkable advances in our understanding of the manipulation of the immune system by M.tuberculosis and of the role of innate components of the immune response, including macrophages, neutrophils, dendritic cells and NK cells in the initial spread of MTB and in its exit from latency. Scope of this review is to highlight the the major mechanisms of MTB escape from immune control and to provide a supplementary translational perspective for the interpretation of innate immune mechanisms with particular impact on clinical aspects.

  13. Induction and characterization of a replication competent cervid endogenous gammaretrovirus (CrERV) from mule deer cells.

    Science.gov (United States)

    Fábryová, Helena; Hron, Tomáš; Kabíčková, Hana; Poss, Mary; Elleder, Daniel

    2015-11-01

    Endogenous retroviruses (ERVs) were acquired during evolution of their host organisms after infection and mendelian inheritance in the germline by their exogenous counterparts. The ERVs can spread in the host genome and in some cases they affect the host phenotype. The cervid endogenous gammaretrovirus (CrERV) is one of only a few well-defined examples of evolutionarily recent invasion of mammalian genome by retroviruses. Thousands of insertionally polymorphic CrERV integration sites have been detected in wild ranging mule deer (Odocoileus hemionus) host populations. Here, we describe for the first time induction of replication competent CrERV by cocultivation of deer and human cells. We characterize the physical properties and tropism of the induced virus. The genomic sequence of the induced virus is phylogenetically related to the evolutionarily young endogenous CrERVs described so far. We also describe the level of replication block of CrERV on deer cells and its capacity to establish superinfection interference. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Immunological condition in population living near Semipalatinsk tests site

    International Nuclear Information System (INIS)

    Satow, Yukio; Ueda, Masafumi.

    1992-01-01

    This is the brief introduction of the immunological survey at Pavlodar, Kazakhstan SSR, a 300 km away from the Semipalatinsk test site, originally reported by Beysembaev E.A.,Valivach M.N. (Course of Clinical Immunology in Pavlodar Dzerzhynsky str., 166), Molochanov N.E. (Pavlodar Regional Hospital), Kazakav, V.M. (Radiologist Lab. of Regional Sanitary and Epidemiology Station), Ounusov B.A. and Osorodnikova O.P. (Clinical Immunology Centre in Pavlodar). The comparative investigations on (1) 150 preschool age children in Pavlodar before and 6 months after the cessation of nuclear tests, (2) 25 children suffering from frequent respiratory infections before the cessation and 25 analogous children after the cessation, and (3) 69 children (age 1 - 7) and 70 adults (age 28 - 58) inhabitants of Maysky district, where radioactivity is especially high, and 50 children and 50 adults of Pavlodar inhabitants, are reported. Erythrocyte rosette-forming cells, immunoglobulins G, A, and M, etc. are tested. (A.Y.)

  15. From two competing oscillators to one coupled-clock pacemaker cell system

    Science.gov (United States)

    Yaniv, Yael; Lakatta, Edward G.; Maltsev, Victor A.

    2015-01-01

    At the beginning of this century, debates regarding “what are the main control mechanisms that ignite the action potential (AP) in heart pacemaker cells” dominated the electrophysiology field. The original theory which prevailed for over 50 years had advocated that the ensemble of surface membrane ion channels (i.e., “M-clock”) is sufficient to ignite rhythmic APs. However, more recent experimental evidence in a variety of mammals has shown that the sarcoplasmic reticulum (SR) acts as a “Ca2+-clock” rhythmically discharges diastolic local Ca2+ releases (LCRs) beneath the cell surface membrane. LCRs activate an inward current (likely that of the Na+/Ca2+ exchanger) that prompts the surface membrane “M-clock” to ignite an AP. Theoretical and experimental evidence has mounted to indicate that this clock “crosstalk” operates on a beat-to-beat basis and determines both the AP firing rate and rhythm. Our review is focused on the evolution of experimental definition and numerical modeling of the coupled-clock concept, on how mechanisms intrinsic to pacemaker cell determine both the heart rate and rhythm, and on future directions to develop further the coupled-clock pacemaker cell concept. PMID:25741284

  16. HIV As Trojan Exosome: Immunological Paradox Explained?

    Science.gov (United States)

    Hildreth, James E K

    2017-01-01

    The HIV pandemic is still a major global challenge, despite the widespread availability of antiretroviral drugs. An effective vaccine would be the ideal approach to bringing the pandemic to an end. However, developing an effective HIV vaccine has proven to be an elusive goal. Three major human HIV vaccine trials revealed a strong trend toward greater risk of infection among vaccine recipients versus controls. A similar observation was made in a macaque SIV vaccine study. The mechanism explaining this phenomenon is not known. Here, a model is presented that may explain the troubling results of vaccine studies and an immunological paradox of HIV pathogenesis: preferential infection of HIV-specific T cells. The central hypothesis of this perspective is that as "Trojan exosomes" HIV particles can directly activate HIV-specific T cells enhancing their susceptibility to infection. Understanding the biology of HIV as an exosome may provide insights that enable novel approaches to vaccine development.

  17. Characterization of a new cell-bound alpha-amylase in Bacillus subtilis 168 Marburg that is only immunologically related to the exocellular alpha-amylase.

    OpenAIRE

    Haddaoui, E; Petit-Glatron, M F; Chambert, R

    1995-01-01

    Immunoblot analysis of Bacillus subtilis cell extracts with polyclonal antibodies, raised against purified exocellular alpha-amylase, revealed one protein species of 82,000 Da. This protein was found even in cells in which the amyE gene, encoding exocellular alpha-amylase, was disrupted. Isolated from the membrane fraction, the 82,000-M(r) protein displayed an alpha-amylase activity in vitro.

  18. In vitro studies: The role of immunological cells in Indonesian thin tail sheep in the killing of the liver fluke, Fasciola

    Directory of Open Access Journals (Sweden)

    S.E Estuningsih

    2002-06-01

    Full Text Available Previous studies have shown that Indonesian Thin Tail (ET sheep exhibit high resistance to challenge with Fasciola gigantica when compared with Merino sheep, and this resistance is expressed in early infection. In order to study the role of the immune system in this resistance to ET sheep, in vitro studies were undertaken in the laboratory. In vitro study to confirm the ability of immune cells from ET sheep in the killing of F. gigantica larvae has been done by incubating immune cells and F. gigantica larvae together with immune sera or normal sera. The viability of the larvae was observed over a period 3 days incubation by observing their motility. The results showed that the cells isolated from F. gigantica- challenged ET sheep in the presence of immune sera from ET were able to kill 70% of the larvae. In contrast, cells from infected Merino were unable to kill a significant number of F. gigantica using the same sera source. It seems that the cytotoxicity was dependent on the presence of immune sera and ET peritoneal cells, suggesting the potential role of an antibody-dependent cell cytotoxic (ADCC mechanism in the resistant ET sheep.

  19. A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.

    Science.gov (United States)

    Aljurayyan, A N; Sharma, R; Upile, N; Beer, H; Vaughan, C; Xie, C; Achar, P; Ahmed, M S; McNamara, P S; Gordon, S B; Zhang, Q

    2016-08-01

    T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    . Material and Methods: The SRD molecules were isolated from Lymphatic Systems of animals that were irradiated with high doses of irradiation and had a clinical and laboratory picture of the Cerebral Acute Radia-tion Syndrome, Cardiovascular Acute Radiation Syndrome, Gastrointestinal Acute Radiation Syndrome, and Hematological Acute Radiation Syndrome. Our classification of radiation tox-ins includes 4 major groups: 1.SRD-1, Cerebrovascular neurotoxic Radiation Toxins (CvARS); 2.SRD-2, Cardiovascular Radiation Toxins(CrARS); 3.SRD-3,Gastrointestinal neurotoxic Ra-diation Toxins (GiARS); 4.SRD-4, Hematopietic Radiation Toxins (HpARS). Radiation tox-ins possess both toxic and immunological properties. But mechanisms of immune-toxicity by which radiation toxins stimulate development of the ARS are poorly understood. We have studied lethal toxicity of radiation toxins and an ability of specific antibodies to neutralize toxic activity of radiation toxins by specific antibodies. Results: The Blocking Antiradiation Antibodies induce an immunologically specific effect and inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity. Antiradiation Antibodies prevent the radiation induced cytolysis of selected groups of cells that are sensitive to radiation. The Blocking Antiradiation Antibodies are immunologically specific and can be produced by immunization with the different radiation toxins isolated from irradiated mam-mals. We propose that Specific Antiradiation Antibodies targeted against the radiation induced Toxins. Specific Antiradiation Antibodies neutralize toxic properties of radiation toxins. Anti-radiation Antibodies in different phases of the Acute Radiation Syndromes can compete with cytotoxic lymphocytes and prevent cytolysis mediated by cytotoxic lymphocytes. Conclusions: Immunological inhibition of cytotoxic and neurotoxic properties of Specific Radiation Toxins are significant factors for improving

  1. Characteristic of the immunological state of Chernobyl accident clean-up workers in a late period after the accident

    International Nuclear Information System (INIS)

    Kurjane, N.; Zvagule, T.; Curbakova, E.; Bruvere, R.; Romanova, T.; Sitova, O; Hagina, E.; Socnevs, A.

    2001-01-01

    No differences in the number of immunologically competent cells and other immunological variables were found among the clean-up workers, depending on the time they were in Chernobyl. However, a statistically significant reduction in the number of CD3+, CD4+, CD16+ and CD19+, decrease in the levels of IgG and suppression of APH and the phagocytic activity of neutrophils with a simultaneous increase in the levels of IgA and C3d was found in all clean-up workers when compared to controls. In a small group of clean-up workers, the levels of some plasma cytokines were detected. A statistically significant increase in IL-6 levels was found in the clean-up workers when compared to controls. The irradiation received by the Chernobyl accident clean-up workers was large enough to cause disturbances in the function of cells and organ systems through immune system disorders with a resultant weakening of the body response and adaptation mechanisms. (authors)

  2. A subpopulation of smooth muscle cells, derived from melanocyte-competent precursors, prevents patent ductus arteriosus.

    Directory of Open Access Journals (Sweden)

    Ichiro Yajima

    Full Text Available BACKGROUND: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA, a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2 and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes.

  3. A Subpopulation of Smooth Muscle Cells, Derived from Melanocyte-Competent Precursors, Prevents Patent Ductus Arteriosus

    Science.gov (United States)

    Puig, Isabel; Champeval, Delphine; Kumasaka, Mayuko; Belloir, Elodie; Bonaventure, Jacky; Mark, Manuel; Yamamoto, Hiroaki; Taketo, Mark M.; Choquet, Philippe; Etchevers, Heather C.; Beermann, Friedrich; Delmas, Véronique; Monassier, Laurent; Larue, Lionel

    2013-01-01

    Background Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes. PMID:23382837

  4. Physical properties of ordered mesoporous SBA-15 silica as immunological adjuvant

    Science.gov (United States)

    Mariano-Neto, F.; Matos, J. R.; Cides da Silva, L. C.; Carvalho, L. V.; Scaramuzzi, K.; Sant'Anna, O. A.; Oliveira, C. P.; Fantini, M. C. A.

    2014-10-01

    This work reports a detailed analysis of the ordered mesoporous SBA-15 silica synthesis procedure that provides a matrix with mean pore diameter around 10 nm. The encapsulation of bovine serum albumin (BSA) by four different methods allowed the determination of the best imbibition condition, which is keeping the mixture under rest and solvent evaporation. Simulation of the in situ SAXS scattered intensity of the BSA release in potassium buffer solution, gastrointestinal fluids revealed a slow evolution of BSA content, independent of the media. Proton induced x-ray emission results obtained in calcined mouse organs revealed that silica is only present in the spleen after 35 days and is completely eliminated from all mouse organs after 10 weeks. Biological studies showed that Santa Barbara Amorphous-15 is an effective adjuvant when compared to the traditional Al(OH)3, and is non-toxic to mice, rats, dogs and even cells, such as macrophages and dendritic cells. Recent studies showed that the immunological response is improved by enhancing the inflammatory response and the recruitment of immune competent cells to the site of injection as by the oral route and, most importantly, by increasing the number of phagocytes of a particulate antigen by antigen presenting cells. This research is under the scope of the International Patent WO 07030901, IN248654,ZA2008/02277, KR 1089400, MX297263, JP5091863, CN101287491B.

  5. Current status of immunologic studies in human lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gross, R.L.

    1978-06-01

    Several aspects of the immunology of human malignancy are reviewed, with particular emphasis on relevant findings in lung cancer. The existence of tumor-specific cell-mediated immune responses in patients with cancer has been demonstrated in numerous tumor types. Of more relevance in clinical situations is the association of generalized immunologic depression with malignancy. In the vast majority of cases, progressive declines in both tumor-specific and nonspecific immunologic parameters are observed with advancing disease. The approach to the immunologic evaluation of cancer patients and the potential usefulness of this approach to the diagnosis, prognosis, management, and assessment of therapeutic response are discussed. Evidence aimed at elucidating the mechanism of immunosuppression in malignancy, such as serum-blocking factors, immunoregulatory alpha globulins, and suppressor cells, is presented. Finally, emphasis is placed on the various forms of immunotherapy, including both specific active methods such as tumor cell or tumor antigen vaccines and nonspecific active immunotherapy involving agents like Bacillus Calmette-Guerin and levamisole. Early results from clinical immunotherapeutic trials are discussed.

  6. Immunologic assessment of patients with pulmonary metaplasia and neoplasia

    International Nuclear Information System (INIS)

    Gross, R.L.; Saccomanno, G.; Smith, D.M.; Saunders, R.; Thomas, R.G.

    1979-01-01

    Immune profiles have been obtained on 206 individuals including 57 controls, 50 lung cancer patients, and 99 uranium miners with well-defined sputum cytologies ranging from normal to carcinoma in situ. Little effect of smoking, uranium mining or a combination of mining plus smoking on immune function was observed if sputum cytology was normal. In heavy smokers there was a suggestion that total T cells are increased while T cell function is slightly depressed. Immunologic abnormalities were noted in the moderate atypia group where 40% had one or more abnormal immunologic parameters. Immunologic abnormalities were detected in 68 to 70 patients with marked atypia, carcinoma in situ, or invasive carcinoma. Further sequential study of the uranium miner population is necessary to define more precisely the predictive value of immunologic testing, and the role of early identification of high risk individuals in the early institution of definitive therapy, such as surgery or immunotherapy. Long-term prospective analysis of this population may also provide the answer to the question of whether alterations in immune function precede, or result from the appearance of cells committed to the development of neoplasia

  7. [Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

    Science.gov (United States)

    Vlieger, A M; van den Hoogen, F H; Brinkman, D M; van Laar, J M; Schipperus, M; Kruize, A A; Wulffraat, N M

    2000-08-12

    The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

  8. Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy.

    Science.gov (United States)

    Lyrio, Eloah C D; Campos-Souza, Ivy C; Corrêa, Luiz C D; Lechuga, Guilherme C; Verícimo, Maurício; Castro, Helena C; Bourguignon, Saulo C; Côrte-Real, Suzana; Ratcliffe, Norman; Declercq, Wim; Santos, Dilvani O

    2015-07-01

    Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae affecting the skin and peripheral nerves. Despite M. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during M. leprae infection is poorly understood. Conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and ELISA were used to study the in vitro interaction of M. leprae with the HaCaT human keratinocyte cell line. Keratinocytes uptake of M. leprae is described, and modulation of the surface expression of CD80 and CD209, cathelicidin expression and TNF-α and IL-1β production of human keratinocytes are compared with dendritic cells and macrophages during M. leprae interaction. This study demonstrated that M. leprae interaction with human keratinocytes enhanced expression of cathelicidin and greatly increased TNF-α production. The highest spontaneous expression of cathelicidin was by dendritic cells which are less susceptible to M. leprae infection. In contrast, keratinocytes displayed low spontaneous cathelicidin expression and were more susceptible to M. leprae infection than dendritic cells. The results show, for the first time, an active role for keratinocytes during infection by irradiated whole cells of M. leprae and the effect of vitamin D on this process. They also suggest that therapies which target cathelicidin modulation may provide novel approaches for treatment of leprosy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Schistosoma mansoni Phosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

    OpenAIRE

    Asahi, Hiroko; Osman, Ahmed; Cook, Rosemary M.; LoVerde, Philip T.; Stadecker, Miguel J.

    2000-01-01

    In schistosomiasis mansoni, hepatic granulomatous inflammation surrounding parasite eggs is mediated by CD4+ T helper (Th) cells sensitized to schistosomal egg antigens (SEA). We previously showed that a prominent lymphoproliferative response of CD4+ Th cells from schistosome-infected C57BL/6 (BL/6) mice was directed against a 62-kDa component of SEA. A partial amino acid sequence of the 62-kDa component was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinas...

  10. Immunological aspects of the investigation in the effect of external UV-irradiation and UV-irradiated bioliquids of the Langerhans cell

    International Nuclear Information System (INIS)

    Volyanskij, Yu.L.; Marchuk, L.M.; Telepneva, L.G.

    1989-01-01

    The origin and role of the Langerhans cell are considered in the immune response of the organism, as well as in a number of human diseases. It is noted that the antigen-presenting function of this macrophage suffers when taking glucocorticosteroid preparations, at AIDS and large doses of ultraviolet radiation. Therefore, the investigation of the effect of UV-irradiated blood reinfusion on the Langerhans cell will help to determine the possibilities of UV-irradiated blood therapy in treating a wide range of diseases, including AIDS, in the transplantation of organs and tissues. 163 refs.; 2 figs

  11. IMMUNOLOGICAL MECHANISMS OF LOCAL INFLAMMATION

    Directory of Open Access Journals (Sweden)

    V. A. Chereshnev

    2011-01-01

    Full Text Available Abstract.  The  lecture  presents  current  data,  as  well  as  authors’  view  to  the  issue  of  immune  system involvement into inflammation. General physiological principles of immune system functioning are considered in details. Immunological mechanisms of local inflammation and participation of immune system components are analyzed with regard of protective/adaptive reactions in inflammatory foci. Original formulations of basic concepts are presented from the viewpoint of pathophysiology, immunopathology and clinical immunology, as being applied to the issues discussed. (Med. Immunol., 2011, vol. 13, N 6, pp 557-568

  12. Timespacing competence

    DEFF Research Database (Denmark)

    Laursen, Helle Pia; Mogensen, Naja Dahlstrup

    2016-01-01

    -generated activity My linguistic world 2014, they are invited to map and talk about their lived experiences as multiple language users seen in the light of place and movement. By demythifying themselves and their linguistic worlds, the children also raise important questions about the notion of linguistic competence....... By perceiving competences from a subjective child perspective, we learn how children do what we call timespacing competence. On that basis, we suggest paying attention to how children themselves timespace competence by focusing (more consistently) on the subjective, social, spatial and temporal dimensions...

  13. Unique ζ-chain motifs mediate a direct TCR-actin linkage critical for immunological synapse formation and T-cell activation.

    Science.gov (United States)

    Klieger, Yair; Almogi-Hazan, Osnat; Ish-Shalom, Eliran; Pato, Aviad; Pauker, Maor H; Barda-Saad, Mira; Wang, Lynn; Baniyash, Michal

    2014-01-01

    TCR-mediated activation induces receptor microclusters that evolve to a defined immune synapse (IS). Many studies showed that actin polymerization and remodeling, which create a scaffold critical to IS formation and stabilization, are TCR mediated. However, the mechanisms controlling simultaneous TCR and actin dynamic rearrangement in the IS are yet not fully understood. Herein, we identify two novel TCR ζ-chain motifs, mediating the TCR's direct interaction with actin and inducing actin bundling. While T cells expressing the ζ-chain mutated in these motifs lack cytoskeleton (actin) associated (cska)-TCRs, they express normal levels of non-cska and surface TCRs as cells expressing wild-type ζ-chain. However, such mutant cells are unable to display activation-dependent TCR clustering, IS formation, expression of CD25/CD69 activation markers, or produce/secrete cytokine, effects also seen in the corresponding APCs. We are the first to show a direct TCR-actin linkage, providing the missing gap linking between TCR-mediated Ag recognition, specific cytoskeleton orientation toward the T-cell-APC interacting pole and long-lived IS maintenance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A.

    Science.gov (United States)

    Williams, C M; Coleman, J W

    1995-10-01

    We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Unstimulated PMC expressed detectable mRNA for TNF-alpha but not for the other four cytokines. Incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10(-6) M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-alpha. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs.

  15. Historical overview of immunological tolerance.

    Science.gov (United States)

    Schwartz, Ronald H

    2012-04-01

    A fundamental property of the immune system is its ability to mediate self-defense with a minimal amount of collateral damage to the host. The system uses several different mechanisms to achieve this goal, which is collectively referred to as the "process of immunological tolerance." This article provides an introductory historical overview to these various mechanisms, which are discussed in greater detail throughout this collection, and then briefly describes what happens when this process fails, a state referred to as "autoimmunity."

  16. A comparison study of children with sickle cell disease and their non-diseased siblings on hopelessness, depression, and perceived competence.

    Science.gov (United States)

    Lee, E J; Phoenix, D; Brown, W; Jackson, B S

    1997-01-01

    The purpose of this comparison study was to explore the extent to which hopelessness and self-perceptions of competence are associated with depression in a community population of children with sickle cell disease compared to their non-diseased siblings. Subjects were African-American children drawn randomly from the case management programme at the L.D. Barksdale Sickle Cell Anemia Foundation. Depression scores were higher for the non-diseased siblings. The children with sickle cell disease scored lower on the perceived physical competence scale. Recommendations for practice include increasing hope, improving relationships, monitoring depression in patients and their siblings, and monitoring perceptions of cognitive, social, physical, and general self-worth.

  17. IMMUNOLOGICAL ASPECTS OF OBESITY

    Directory of Open Access Journals (Sweden)

    Z. R. Gusova

    2015-01-01

    Full Text Available Background: At present, convincing data on the role of immune system in pathophysiology of obesity are lacking, which makes it necessary to investigate this issue. Aim: To assess metabolic status and characteristics of immune system in patients with overweight and morbid obesity.Materials and methods: One hundred and ninety two patients with overweight and advanced obesity (mean body mass index (BMI 36.8 ± 7.3 kg/m. aged from 19 to 55 years were recruited in to the study. Depending on the grade of obesity, the patients were divided into two groups. Group 1 included 84 overweight patients (BMI 27.65 ± 0.17 kg/m., group 2 included 88 patients with obesity grade III (BMI 44.03 ± 0.44 kg/m.. The groups were comparable as to their age and gender. The control group comprised 20 otherwise healthy subjects with normal body weight. Assessments included parameters of carbohydrate and lipid metabolism, hemodynamic parameters, immune status including cytokine profile.Results: In patients of both groups abnormalities in carbohydrate and lipid metabolism were found, together with changes of hemodynamic parameters which were more advanced with higher degree of obesity. These parameters demonstrated that obesity promotes manifestation of metabolic syndrome. There was remarkable imbalance in pro-inflammatory cytokines. Patients with obesity grade III had a statistically significant (р = 0.05 increase in their serum levels of tumor necrosis factor-α (6.32 ± 0.49 vs 2.14 ± 0.25, interleukin (IL-4 (7.56 ± 0.44 vs 1.44 ± 0.10, IL-6 (5.39 ± 0.89 vs 2.02 ± 0.16, IL-17 (2.74 ± 0.29 vs 0.59 ± 0.20 both in basal and stimulated conditions, compared to those in patients with overweight and control patients.Conclusion: The study showed that imbalance in immune system increases with an increase of obesity grade. This imbalance implies lymphocyte maturation and differentiation, higher cytotoxicity of immunocompetent cells, over expression of receptors both to

  18. Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

    Science.gov (United States)

    Jallet, Corinne; Jacob, Yves; Bahloul, Chokri; Drings, Astrid; Desmezieres, Emmanuel; Tordo, Noël; Perrin, Pierre

    1999-01-01

    The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH2 half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another GT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6). PMID:9847325

  19. APOPTOSIS RATE IN CUMULUS CELLS AS POSSIBLE MOLECULAR BIOMARKER FOR OOCYTE COMPETENCE.

    Directory of Open Access Journals (Sweden)

    Liana Bosco

    2017-04-01

    Full Text Available Several lines of evidence showed that apoptosis rate of cumulus cells in oocytes derived by assisted reproductive technologies could be used as an indicator of fertilizing gamete quality. Aim of the study was to investigate the effects of three different ovarian stimulation protocols on the biological and clinical outcome in hyporesponder patients. Collected data showed a higher significant rate of DNA fragmentation index (DFI in U group (patients treated with Highly Purified human Menopausal Gonadotrophin than in P group (treated with recombinant human Follicle Stimulating Hormone (r-hFSH combined with recombinant human Luteinizing Hormone (r-hLH. Both groups R (treated with r-hFSH alone and P showed a significant increase in collected and fertilized oocytes number, embryo quality number. This study showed that combined r-hFSH/r-hLH therapy could represent the best pharmacological strategy for controlled ovarian stimulation and suggests to use DFI as a biomarker of ovarian function in hyporesponder patients.

  20. Selection of SARS-Coronavirus-specific B cell epitopes by phage peptide library screening and evaluation of the immunological effect of epitope-based peptides on mice

    International Nuclear Information System (INIS)

    Yu Hua; Jiang Lifang; Fang Danyun; Yan Huijun; Zhou Jingjiao; Zhou Junmei; Liang Yu; Gao Yang; Zhao, Wei; Long Beiguo

    2007-01-01

    Antibodies to SARS-Coronavirus (SARS-CoV)-specific B cell epitopes might recognize the pathogen and interrupt its adherence to and penetration of host cells. Hence, these epitopes could be useful for diagnosis and as vaccine constituents. Using the phage-displayed peptide library screening method and purified Fab fragments of immunoglobulin G (IgG Fab) from normal human sera and convalescent sera from SARS-CoV-infected patients as targets, 11 B cell epitopes of SARS-CoV spike glycoprotein (S protein) and membrane protein (M protein) were screened. After a bioinformatics tool was used to analyze these epitopes, four epitope-based S protein dodecapeptides corresponding to the predominant epitopes were chosen for synthesis. Their antigenic specificities and immunogenicities were studied in vitro and in vivo. Flow cytometry and ELISPOT analysis of lymphocytes as well as a serologic analysis of antibody showed that these peptides could trigger a rapid, highly effective, and relatively safe immune response in BALB/c mice. These findings might aid development of SARS diagnostics and vaccines. Moreover, the role of S and M proteins as important surface antigens is confirmed

  1. Autoreactive lymphocytes in thyroid disorders. 2. Comparison of anti-thyroglobulin antibody production by plaque-forming cell, radio-immunological and enzyme-linked immunosorbent assays

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, J; Feldt-Rasmussen, U; Siersbaek-Nielsen, K; Hoeier-Madsen, M; Larsen, F; Husby, S

    1986-01-01

    Blood mononuclear cells (MNC) from 9 randomly selected patients with autoimmune thyroiditis were stimulated in vitro with pokeweed mitogen (PWM), a polyclonal B lymphocyte activator. The secretion of immunoglobulins (Ig) and anti-thyroglobulin antibodies (TgAb) was assayed by means of haemolytic plaque-forming cell (PFC) assays, radioimmune assay (RIA) and enzyme-linked immunosorbent assays (ELISA). Total Ig and TgAb production was maximal using MNC cultured at 1.0 x 10/sup 6//ml as estimated by PFC, RIA and ELISA. The Ig and TgAb production as measured by RIA and ELISA was 1.5 - 3 times higher after 12 days' culture compared to 6 days' culture. Ig and TgAb production measured by PFC-assays at day 6 correlated positively to the results obtained by RIA and ELISA at day 12. PWM-induced TgAb secretion correlated positively to TgAb titres in serum. As judged by PFC, TgAb production was found in 8/9 patients; about 5% (range 0 - 7.9%) of the total PWM-stimulated IgG-secreting cells were involved in TgAb secretion. TgAb production as measured by ELISA and RIA was found in 6/9 patients. By reference to an affinity-purified human TgAb preparation, the TgAb secretion was about 0.7% (range 0 - 21.3%) of the total PWM-induced IgG secretion.

  2. Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months

    DEFF Research Database (Denmark)

    Katzenstein, T.; Ullum, H.; Røge, B.T.

    2003-01-01

    OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of

  3. Advances in basic and clinical immunology in 2016.

    Science.gov (United States)

    Chinen, Javier; Badran, Yousef R; Geha, Raif S; Chou, Janet S; Fried, Ari J

    2017-10-01

    Advances in basic immunology in 2016 included studies that further characterized the role of different proteins in the differentiation of effector T and B cells, including cytokines and proteins involved in the actin cytoskeleton. Regulation of granule formation and secretion in cytotoxic cells was also further described by examining patients with familial hemophagocytic lymphohistiocytosis. The role of prenylation in patients with mevalonate kinase deficiency leading to inflammation has been established. We reviewed advances in clinical immunology, as well as new approaches of whole-genome sequencing and genes newly reported to be associated with immunodeficiency, such as linker of activation of T cells (LAT); B-cell CLL/lymphoma 11B (BCL11B); RGD, leucine-rich repeat, tropomodulin domain, and proline-rich domain-containing protein (RLTPR); moesin; and Janus kinase 1 (JAK1). Trials of hematopoietic stem cell transplantation and gene therapy for primary immunodeficiency have had relative success; the use of autologous virus-specific cytotoxic T cells has proved effective as well. New medications are being explored, such as pioglitazone, which is under study for its role in enhancing the oxidative burst in patients with chronic granulomatous disease. Development of vaccines for HIV infection continues to provide insight into the immune response against a virus with an extraordinary mutation rate. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. [Value of immunologic phenotyping of acute leukemias in children].

    Science.gov (United States)

    Vannier, J P; Bene, M C

    1989-10-01

    Immunologic typing has demonstrated considerable heterogeneity among the acute leukemias. The most significant recent advance has been development of monoclonal antibody techniques. Some markers identified using these techniques seem to be specific for a given stage of maturation of one lymphoid or myeloid cell line. Most acute lymphoblastic leukemias (ALLs) are malignant proliferations whose differentiation appears to have become 'stuck' at one stage of maturation. Results of immunologic typing correlate well with the other clinical and biological data. For prognostic purposes, several patterns can be identified. Among B line ALLs, four varieties have been differentiated, i.e., CD10 negative ALLs, common ALLs, pre-B ALLs, and B ALLs. T ALLs include a broad spectrum of heterogeneous proliferations whose immunologic classification is made difficult by the large number of phenotypes encountered. Among acute myeloblastic leukemias (AMLs), some highly undifferentiated forms have been recognized, by means of immunologic typing, as originating in one of the myeloid cell lines. However, the nosologic and prognostic significance of these studies is less obvious than in ALLs.

  5. Adjudicative Competence

    Science.gov (United States)

    Dawes, Sharron E.; Palmer, Barton W.; Jeste, Dilip V.

    2008-01-01

    Purpose of review Although the basic standards of adjudicative competence were specified by the U.S. Supreme Court in 1960, there remain a number of complex conceptual and practical issues in interpreting and applying these standards. In this report we provide a brief overview regarding the general concept of adjudicative competence and its assessment, as well as some highlights of recent empirical studies on this topic. Findings Most adjudicative competence assessments are conducted by psychiatrists or psychologists. There are no universal certification requirements, but some states are moving toward required certification of forensic expertise for those conducting such assessments. Recent data indicate inconsistencies in application of the existing standards even among forensic experts, but the recent publication of consensus guidelines may foster improvements in this arena. There are also ongoing efforts to develop and validate structured instruments to aid competency evaluations. Telemedicine-based competency interviews may facilitate evaluation by those with specific expertise for evaluation of complex cases. There is also interest in empirical development of educational methods to enhance adjudicative competence. Summary Adjudicative competence may be difficult to measure accurately, but the assessments and tools available are advancing. More research is needed on methods of enhancing decisional capacity among those with impaired competence. PMID:18650693

  6. Outsourcing competence

    NARCIS (Netherlands)

    Bergstra, J.; Delen, G.; van Vlijmen, B.

    2011-01-01

    The topic of this paper, competences needed for outsourcing, is organized by first providing a generic competence scheme, which is subsequently instantiated to the area of sourcing and outsourcing. Sourcing and outsourcing are positioned as different areas of activity, neither one of which is

  7. Competence Building

    DEFF Research Database (Denmark)

    Borrás, Susana; Edquist, Charles

    The main question that guides this paper is how governments are focusing (and must focus) on competence building (education and training) when designing and implementing innovation policies. With this approach, the paper aims at filling the gap between the existing literature on competences...... on the one hand, and the real world of innovation policy-making on the other, typically not speaking to each other. With this purpose in mind, this paper discusses the role of competences and competence-building in the innovation process from a perspective of innovation systems; it examines how governments...... and public agencies in different countries and different times have actually approached the issue of building, maintaining and using competences in their innovation systems; it examines what are the critical and most important issues at stake from the point of view of innovation policy, looking particularly...

  8. Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors

    Directory of Open Access Journals (Sweden)

    Catherine M. Crosby

    2017-02-01

    Full Text Available Most adenovirus (Ad vectors are E1 gene deleted replication defective (RD-Ad vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed “single cycle” Ad (SC-Ad vectors. SC-Ads amplify transgene expression and generated markedly stronger and more persistent immune responses than RD-Ad as expected. However, they also unexpectedly generated stronger immune responses than RC-Ad vectors. To explore the basis of this potency here, we compared gene expression and the cellular responses to infection to these vectors in vitro and in vivo. In vitro, in primary human lung epithelial cells, SC- and RC-Ad amplified their genomes more than 400-fold relative to RD-Ad with higher replication by SC-Ad. This replication translated into higher green fluorescent protein (GFP expression for 48 h by SC- and RC-Ad than by RD-Ad. In vitro, in the absence of an immune system, RD-Ad expression became higher by 72 h coincident with cell death mediated by SC- and RC-Ad and release of transgene product from the dying cells. When the vectors were compared in human THP-1 Lucia- interferon-stimulated gene (ISG cells, which are a human monocyte cell line that have been modified to quantify ISG activity, RC-Ad6 provoked significantly stronger ISG responses than RD- or SC-Ad. In mice, intravenous or intranasal injection produced up to 100-fold genome replication. Under these in vivo conditions in the presence of the immune system, luciferase expression by RC and SC-Ad was markedly higher than that by RD-Ad. In

  9. Immunologic Quality Improvement of Racing Pigeon Squabs Through Induction of Cropmilk Using Probiotic Lactobacillus SP.

    OpenAIRE

    Irianto, Agus; Budiyanto, B Heru

    2004-01-01

    Probiotic is live microbial cells supplementation that has beneficial effect to the host. Feeding adult pigeons (Columba livia) with food supplemented with probiotic, Lactobacillus sp., at concentration 106,108, and 1010 cells g-1 respectively have been done in order to improve the immunologic quality of the squabs. Immunologic response namely the number and activity of kidney’s macrophage were examined. Also, the pathologic signs which developed following artificial infection by intramuscula...

  10. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    Science.gov (United States)

    Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

    2017-01-01

    HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

  11. CsSCL1 is differentially regulated upon maturation in chestnut microshoots and is specifically expressed in rooting-competent cells.

    Science.gov (United States)

    Vielba, Jesús M; Díaz-Sala, Carmen; Ferro, Enrique; Rico, Saleta; Lamprecht, María; Abarca, Dolores; Ballester, Antonio; Sánchez, Conchi

    2011-10-01

    The Castanea sativa SCL1 gene (CsSCL1) has previously been shown to be induced by auxin during adventitious root (AR) formation in rooting-competent microshoots. However, its expression has not previously been analyzed in rooting-incompetent shoots. This study focuses on the regulation of CsSCL1 during maturation and the role of the gene in the formation of AR. The expression of CsSCL1 in rooting-incompetent microshoots and other tissues was investigated by quantitative reverse transcriptase--polymerase chain reaction. The analysis was complemented by in situ hybridization of the basal segments of rooting-competent and --incompetent microshoots during AR induction, as well as in AR and lateral roots. It was found that CsSCL1 is upregulated by auxin in a cell-type- and phase-dependent manner during the induction of AR. In root-forming shoots, CsSCL1 mRNA was specifically located in the cambial zone and derivative cells, which are rooting-competent cells, whereas in rooting-incompetent shoots the hybridization signal was more diffuse and evenly distributed through the phloem and parenchyma. CsSCL1 expression was also detected in lateral roots and axillary buds. The different CsSCL1 expression patterns in rooting-competent and -incompetent microshoots, together with the specific location of transcripts in cell types involved in root meristem initiation and in the root primordia of AR and lateral roots, indicate an important role for the gene in determining whether certain cells will enter the root differentiation pathway and its involvement in meristem maintenance.

  12. Immunological study in A-bomb survivors

    International Nuclear Information System (INIS)

    Imamura, Nobutaka

    1994-01-01

    This study examined peripheral T and B lymphocytes using monoclonal antibodies in twin A-bomb survivors and myelodysplastic syndrome (MDS) patients in the exposed and non-exposed groups. The subjects were 10 persons (9 exposed ones and 1 non-exposed one), collected from 6 pairs of twins (in the twin group); 8 MDS patients in the exposed group; and 4 MDS patients in the non-exposed group. In the twin group, an increase in CD4-positive helper/inducer T cells and a decrease in CD8-positive suppressor/cytotoxic T cells were definitely observed. This tended to be noticeable in persons exposed nearer the hypocenter. Furthermore, the twin group had a higher ratio of CD4 to CD8. Immunological findings reflecting B cell abnormalities were not found in this group. In all MDS patients in both the exposed and non-exposed groups, refractory anemia (Hb of 10.0 g/dl or less) were observed. Some of the patients in the exposed group had an increase of T4 (CD4) + T cells, a decrease of T8(CD8) + T cells, a decrease of B-1(CD20) + B cells, and an increase of TQ-1 + cells. Double-fluorescence staining revealed an increase in T4(CD4) + 2H4(CD45RA) + cells in patients with primary acquired refractory anemia. The ratio of CD4 to CD8 in all MDS patients, except for one patient, was normal or increased. Furthermore, neither RAS nor p53 oncogenes were observed in the MDS group. (N.K.)

  13. Immunological pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Seung Hoon Lee

    2018-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD and ulcerative colitis (UC. The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17 cells and innate lymphoid cells (ILCs are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

  14. Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer

    DEFF Research Database (Denmark)

    Konge, Lars; Vilmann, P; Clementsen, P

    2012-01-01

    Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliabilit...... and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC....

  15. IMMUNOLOGICAL MECHANISMS OF LOCAL INFLAMMATION

    OpenAIRE

    V. A. Chereshnev; M. V. Chereshneva

    2011-01-01

    Abstract.  The  lecture  presents  current  data,  as  well  as  authors’  view  to  the  issue  of  immune  system involvement into inflammation. General physiological principles of immune system functioning are considered in details. Immunological mechanisms of local inflammation and participation of immune system components are analyzed with regard of protective/adaptive reactions in inflammatory foci. Original formulations of basic concepts are presented from the viewpoint of pathophysiol...

  16. Effects of ground thyme and probiotic supplements in diets on broiler performance, blood biochemistry and immunological response to sheep red blood cells

    Directory of Open Access Journals (Sweden)

    Seyed A. Hosseini

    2013-03-01

    Full Text Available A trial was conducted to study the effects of the aromatic plant thyme, a commercial probiotic (Protexin and avilamycin on broiler performance, blood biochemical parameters and also the antibody response to sheep red blood cells. A total of 750 broilers were assigned into five replicate groups for each of five dietary treatments, namely; control (C, 2.5 mg/kg avilamycin (AB, 0.1 g/kg commercial probiotic (P, 5 g/kg ground thyme (T1, and 7.5 g/kg ground thyme (T2. In general, body weight, feed consumption and feed conversion ratio were not affected by dietary treatments compared to the control birds (P>0.05. Birds fed the P supplemented treatment had the greatest serum protein levels (P<0.001 and highest albumin levels (P<0.001 when compared with control birds, while the birds fed T2 had the lowest (P<0.001. Dietary supplementation reduced (P<0.001 cholesterol and triglyceride concentration in serum of broilers, with the effect were more noticeable by P supplements. Moreover, blood calcium and phosphorus concentrations were higher (P<0.001 in birds fed the P-supplemented diet compared to the birds fed the control diets. This study suggests that probiotic supplementation in particular, and to an intermediate extent ground thyme supplementation in diets of broiler, resulted in chicks with favorably improved blood biochemical parameters and mineral utilization, compared to the birds fed diets supplemented with avilamycin or without any supplementation.

  17. Some advances in radiation immunology

    International Nuclear Information System (INIS)

    Liu Shuzheng

    1985-01-01

    This paper is an overview of some of the recent advances in the study of radiation effects on immunity with special emphasis on the relation between radiation immunology and radiation carcinogenesis. The first part of the paper discusses the radiosensitivity of lymphocytes, emphasizing the heterogeneity of the lymphocyte population, the relative radiosensitivity of different lymphocyte subpopulations and their subsets, and the effect of the state of activation on lymphocyte radiosensitivity. The second part deals with the essentials of the theory of immunological surveillance, the specific and nonspecific components of anti-tumor immunity, and the effects of radiation on them. The last part of the paper is concerned with the phenomenon of radiation-induced augmentation of the immune response and the expression of radiation hormesis in the immune system with brief descriptions of some of the data from the author's laboratory. The need for a more sophisticated study of the possible hormetic effects of low level radiation on the immune system and other defense and adaptive functions of the body is stressed

  18. The Basel Institute for Immunology.

    Science.gov (United States)

    Melchers, Fritz

    2012-01-01

    At the Centennial Exhibition of the Nobel Prize, the Nobel Foundation called it one of the ten cradles of creativity. The journal Nature likened its ideals to those of the French revolution--Liberté, Egalité, Fraternité--and called it a paradise devoted to the science of immune systems: the Basel Institute for Immunology (BII). Founded by Roche in 1968, inaugurated in 1971, and closed in 2000, it was home to almost 450 scientific members, over 1,000 scientific visitors, and nearly 100 scientific advisors from more than 30 countries who worked in complete academic freedom and without commercial motives on over 3,500 projects, publishing more than 3,200 scientific papers, almost all of them on the structure and functions of immune systems of different species. This review contains a first collection of historical facts and dates that describe the background of the exceptionally successful performance and the strong scientific impact of the institute on the field of immunology.

  19. [Immunological Markers in Organ Transplantation].

    Science.gov (United States)

    Beckmann, J H; Heits, N; Braun, F; Becker, T

    2017-04-01

    The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

  20. 21 CFR 866.5040 - Albumin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. An albumin immunological test system is a device that consists of...

  1. Advances in mechanisms of asthma, allergy, and immunology in 2011.

    Science.gov (United States)

    Boyce, Joshua A; Bochner, Bruce; Finkelman, Fred D; Rothenberg, Marc E

    2012-02-01

    2011 was marked by rapid progress in the identification of basic mechanisms of allergic disease and the translation of these mechanisms into human cell systems. Studies published in the Journal of Allergy and Clinical Immunology this year provided new insights into the molecular determinants of allergenicity, as well as the environmental, cellular, and genetic factors involved in sensitization to allergens. Several articles focused on mechanisms of allergen immunotherapy and the development of novel strategies to achieve tolerance to allergens. Additional studies identified substantial contributions from T(H)17-type cells and cytokines to human disease pathogenesis. Finally, new therapeutic applications of anti-IgE were identified. The highlights of these studies and their potential clinical implications are summarized in this review. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. Therapeutic Effects of Bee Venom on Immunological and Neurological Diseases.

    Science.gov (United States)

    Hwang, Deok-Sang; Kim, Sun Kwang; Bae, Hyunsu

    2015-06-29

    Bee Venom (BV) has long been used in Korea to relieve pain symptoms and to treat inflammatory diseases, such as rheumatoid arthritis. The underlying mechanisms of the anti-inflammatory and analgesic actions of BV have been proved to some extent. Additionally, recent clinical and experimental studies have demonstrated that BV and BV-derived active components are applicable to a wide range of immunological and neurodegenerative diseases, including autoimmune diseases and Parkinson's disease. These effects of BV are known to be mediated by modulating immune cells in the periphery, and glial cells and neurons in the central nervous system. This review will introduce the scientific evidence of the therapeutic effects of BV and its components on several immunological and neurological diseases, and describe their detailed mechanisms involved in regulating various immune responses and pathological changes in glia and neurons.

  3. Immunological disturbances and their role in treatment for cervical carcinoma

    International Nuclear Information System (INIS)

    Grinevich, Yu.A.; Dzyubko, N.Ya.; Kokhanevich, E.V.

    1983-01-01

    The study is concerned with immunologic status (cell-mediated and humoral immunity) as a factor influencing the choice of scheme of treatment for carcinoma of cervix uteri. The indexes of immunocompetence should be taken into account in planning the differential treatment of precancer and early forms of carcinoma of cervix uteri. Radiation treatment exerts an immunosuppressive effect. However, immunologic indexes are not affected considerably by laser destruction or surgery. Cryodestruction has a beneficial effect on cell-mediated immunity. Considering these effects as well as the long-term results of different orocedures of treatment, laser coagulation, cryogenic destruction or diathermoconization should be recommended for management of carcinoma in situ of cervix uteri, and extensive extirpation of the uterus, unattended by radiation, for Tla

  4. Recognition of higher order patterns in proteins: immunologic kernels.

    Directory of Open Access Journals (Sweden)

    Robert D Bremel

    Full Text Available By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximately thirty amino acids each bounded by cathepsin cleavage sites and each comprising B-cell linear epitopes, MHC-I and MHC-II binding peptides. Such "immunologic kernel" peptides comprise all signals necessary for adaptive immunologic cognition, response and recall. The patterns described indicate a higher order spatial integration that forms a symbolic logic coordinating the adaptive immune system.

  5. Historical links between toxinology and immunology.

    Science.gov (United States)

    Cavaillon, Jean-Marc

    2018-04-01

    Research on bacterial toxins is closely linked to the birth of immunology. Our understanding of the interaction of bacterial protein toxins with immune cells has helped to decipher immunopathology, develop preventive and curative treatments for infections, and propose anti-cancer immunotherapies. The link started when Behring and Kitasato demonstrated that serotherapy was effective against 'the strangling angel', namely diphtheria, and its dreadful toxin discovered by Roux and Yersin. The antitoxin treatment helped to save thousands of children. Glenny demonstrated the efficacy of the secondary immune response compared to the primary one. Ramon described anatoxins that allowed the elaboration of effective vaccines and discovered the use of adjuvant to boost the antibody response. Similar approaches were later made for the tetanus toxin. Studying antitoxin antibodies Ehrlich demonstrated, for the first time, the transfer of immunity from mother to newborns. In 1989 Marrack and Kappler coined the concept of 'superantigens' to characterize protein toxins that induce T-lymphocyte proliferation, and cytokine release by both T-lymphocytes and antigen presenting cells. More recently, immunotoxins have been designed to kill cancer cells targeted by either specific antibodies or cytokines. Finally, the action of IgE antibodies against toxins may explain their persistence through evolution despite their side effect in allergy.

  6. Immunological and Psychological Benefits of Aromatherapy Massage

    Science.gov (United States)

    2005-01-01

    This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs), white blood cells (WBCs), neutrophils, peripheral blood lymphocytes (PBLs), CD4+, CD8+ and CD16+ lymphocytes, CD4+/CD8+ ratio, hematocrit, humoral parameters including serum interferon-γ and interleukin-6, salivary secretory immunoglobulin A (IgA). Psychological measures including the State–Trait Anxiety Inventory (STAI) questionnaire and the Self-rating Depression Scale (SDS) between recipients (n = 11) of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P aromatherapy and carrier massage, no difference between the aromatherapy and control massage was observed for STAI and SDS. Aromatherapy, in contrast to control massage, did not significantly reduce RBC count or hematocrit. However, aromatherapy massage showed a significant (P > 0.05) increase in PBLs, possibly due to an increase in CD8+ and CD16+ lymphocytes, which had significantly increased post-treatment (P aromatherapy massage could be beneficial in disease states that require augmentation of CD8+ lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients. PMID:15937558

  7. Immunologic methods for monitoring carcinogen exposure

    Science.gov (United States)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  8. Immunological and Psychological Benefits of Aromatherapy Massage

    Directory of Open Access Journals (Sweden)

    Hiroko Kuriyama

    2005-01-01

    Full Text Available This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs, white blood cells (WBCs, neutrophils, peripheral blood lymphocytes (PBLs, CD4+, CD8+ and CD16+ lymphocytes, CD4+/CD8+ ratio, hematocrit, humoral parameters including serum interferon-γ and interleukin-6, salivary secretory immunoglobulin A (IgA. Psychological measures including the State–Trait Anxiety Inventory (STAI questionnaire and the Self-rating Depression Scale (SDS between recipients (n = 11 of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P 0.05 increase in PBLs, possibly due to an increase in CD8+ and CD16+ lymphocytes, which had significantly increased post-treatment (P < 0.01. Consequently, the CD4+/CD8+ ratio decreased significantly (P < 0.01. The paucity of such differences after carrier oil massage suggests that aromatherapy massage could be beneficial in disease states that require augmentation of CD8+ lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients.

  9. Immunological functioning in Alzheimer's disease: differential effects of relative left versus right temporoparietal dysfunction.

    Science.gov (United States)

    Foster, Paul S; Roosa, Katelyn M; Williams, Megan R; Witt, John C; Heilman, Kenneth M; Drago, Valeria

    2013-10-15

    The cerebral hemispheres are differentially involved in regulating immunological functioning and the neuropathology associated with Alzheimer's disease (AD) is asymmetrical. Thus, subgroups of AD patients may exhibit different patterns of immunological dysfunction. We explored this possibility in a group of AD patients and found that patients with low white blood cell counts and low lymphocyte numbers exhibited better performance on tests of right temporoparietal functioning. Also, a significant positive relationship exists between lymph numbers and performance on a test of left temporoparietal functioning. Thus, some AD patients have greater immunological dysfunction based on relative left versus right temporoparietal functioning. © 2013.

  10. The ninth international veterinary immunology symposium

    Science.gov (United States)

    This Introduction to the special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August, 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune...

  11. Hematology and immunology studies - The second manned Skylab mission

    Science.gov (United States)

    Kimzey, S. L.; Johnson, P. C.; Ritzman, S. E.; Mengel, C. E.

    1976-01-01

    The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.

  12. Immunologic parameters of ultraviolet carcinogenesis

    International Nuclear Information System (INIS)

    Kripke, M.L.; Fisher, M.S.

    1976-01-01

    Skin tumors induced in mice by uv light are usually immunologically rejected by normal syngeneic recipients. We evaluated, the immune status of primary hosts against these highly antigenic tumors immediately after surgical removal of the primary tumor. All primary hosts were susceptible to challenge with their autochthonous tumors, though most of these were rejected by untreated control mice. Primary hosts were also susceptible to challenge with isografts of antigenically dissimilar uv-induced neoplasms. The susceptibility of the primary hosts to tumor challenge was probably induced by chronic exposure to uv light, since uv-irradiated non-tumor-bearing mice were also susceptible to challenge with these tumors. Although uv-treated mice were unable to reject these syngeneic tumors, they could reject skin and tumor allografts. Further, uv irradiation did not interfere with the second-set rejection of syngeneic uv-induced tumors in mice that were specifically immunized before uv treatment

  13. Surgical competence.

    Science.gov (United States)

    Patil, Nivritti G; Cheng, Stephen W K; Wong, John

    2003-08-01

    Recent high-profile cases have heightened the need for a formal structure to monitor achievement and maintenance of surgical competence. Logbooks, morbidity and mortality meetings, videos and direct observation of operations using a checklist, motion analysis devices, and virtual reality simulators are effective tools for teaching and evaluating surgical skills. As the operating theater is also a place for training, there must be protocols and guidelines, including mandatory standards for supervision, to ensure that patient care is not compromised. Patients appreciate frank communication and honesty from surgeons regarding their expertise and level of competence. To ensure that surgical competence is maintained and keeps pace with technologic advances, professional registration bodies have been promoting programs for recertification. They evaluate performance in practice, professional standing, and commitment to ongoing education.

  14. Etiology and immunology of infectious bronchitis virus

    Directory of Open Access Journals (Sweden)

    LF Caron

    2010-06-01

    Full Text Available Infectious bronchitis virus (IBV of chickens is currently one of the main diseases associated with respiratory syndrome in domestic poultry, as well as with losses related to egg production. The etiological agent is a coronavirus, which presents structural differences in the field, mainly in the S1 spike protein. The immune response against this virus is complicated by the few similarities among serotypes. Environmental and management factors, as well as the high mutation rate of the virus, render it difficult to control the disease and compromise the efficacy of the available vaccines. Bird immune system capacity to respond to challenges depend on the integrity of the mucosae, as an innate compartment, and on the generation of humoral and cell-mediated adaptive responses, and may affect the health status of breeding stocks in the medium run. Vaccination of day-old chicks in the hatchery on aims at eliciting immune responses, particularly cell-mediated responses that are essential when birds are first challenged. Humoral response (IgY and IgA are also important for virus clearance in subsequent challenges. The presence of antibodies against the S1 spike protein in 3- to 4-week-old birds is important both in broilers and for immunological memory in layers and breeders.

  15. Understanding Immunology via Engineering Design: The Role of Mathematical Prototyping

    Science.gov (United States)

    Klinke, David J.; Wang, Qing

    2012-01-01

    A major challenge in immunology is how to translate data into knowledge given the inherent complexity and dynamics of human physiology. Both the physiology and engineering communities have rich histories in applying computational approaches to translate data obtained from complex systems into knowledge of system behavior. However, there are some differences in how disciplines approach problems. By referring to mathematical models as mathematical prototypes, we aim to highlight aspects related to the process (i.e., prototyping) rather than the product (i.e., the model). The objective of this paper is to review how two related engineering concepts, specifically prototyping and “fitness for use,” can be applied to overcome the pressing challenge in translating data into improved knowledge of basic immunology that can be used to improve therapies for disease. These concepts are illustrated using two immunology-related examples. The prototypes presented focus on the beta cell mass at the onset of type 1 diabetes and the dynamics of dendritic cells in the lung. This paper is intended to illustrate some of the nuances associated with applying mathematical modeling to improve understanding of the dynamics of disease progression in humans. PMID:22973412

  16. Pediatric allergy and immunology in Turkey.

    Science.gov (United States)

    Celik, Gülfem; Bakirtas, Arzu; Sackesen, Cansin; Reisli, Ismail; Tuncer, Ayfer

    2011-06-01

    Allergic diseases constitute a significant health problem in Turkey. According to a recent multicenter study, which used the ISAAC questionnaire, the mean prevalence of wheezing, rhinoconjunctivitis, and eczema in 10-yr-old school children during the past year was 15.8%, 23.5%, and 8.1%, respectively. A healthcare level system, regulated by Ministry of Health, is available in Turkey. Pediatric allergists and pediatric immunologists provide patient care at the tertiary level. Currently, 48 centers deliver care for allergic and immunologic diseases in children. There are 136 pediatric and 61 adult allergists/immunologists. Although the number of allergy/clinical immunology specialists is limited, these centers are capable of delivering many of the procedures required for the proper management and diagnosis of allergy/immunology. Pediatric allergy and/or immunology is a subspecialty lasting 3 yr and follows a 4-yr pediatric specialist training. Fellow training involves gaining knowledge in basic and clinical allergy and immunology as well as the performance and interpretation of laboratory procedures in the field of allergy and clinical immunology. The Turkish National Society of Allergy and Clinical Immunology (TNSACI) was officially established in 1989 and currently has 356 members. The society organizes a national congress annually and winter schools for fellowship training as well as training courses for patients and their relatives. TNSACI also has a strong representation in European Academy of Allergy and Clinical Immunology (EAACI) and European Society for Immunodeficiencies (ESID) through its participation in the executive committee, consensus reports, and initiatives in the diagnosis of allergic and immunologic diseases of children. The 30th Congress of the EAACI is also due to be held in Istanbul, Turkey, between June 11 and 15, 2011. © 2011 John Wiley & Sons A/S.

  17. A competing risk model of first failure site after definitive (chemo) radiation therapy for locally advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M

    2018-01-01

    INTRODUCTION: The aim of the study was to build a model of first failure site and lesion specific failure probability after definitive chemo-radiotherapy for inoperable non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 251 patients receiving definitive chemo......-regional failure, multivariable logistic regression was applied to assess risk of each lesion being first site of failure. The two models were used in combination to predict lesion failure probability accounting for competing events. RESULTS: Adenocarcinoma had a lower hazard ratio (HR) of loco-regional (LR...

  18. Haematological and immunological indicators for radiation exposure

    International Nuclear Information System (INIS)

    Dehos, A.

    1990-01-01

    It is examined if haematological and immunological parameters can be used as biological indicators for radiation exposure. Additional criteria for biological indicators, apart from the dose dependence of the effect, are listed here. The state of the art concerning the development of haematological and immunological indicators is discussed. Several haematological indicators are currently used in diagnosis when excess radiation exposure has occurred (e.g., after the Chernobyl accident). However, further research work has to be done in the field of immunological indicators. (orig.) [de

  19. Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum

    Science.gov (United States)

    Biesold, Susanne E.; Ritz, Daniel; Gloza-Rausch, Florian; Wollny, Robert; Drexler, Jan Felix; Corman, Victor M.; Kalko, Elisabeth K. V.; Oppong, Samuel; Drosten, Christian; Müller, Marcel A.

    2011-01-01

    Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs. PMID:22140523

  20. Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets

    Directory of Open Access Journals (Sweden)

    Ieva Saulite

    2016-01-01

    Full Text Available Sézary syndrome (SS, an aggressive form of erythrodermic pruritic cutaneous T cell lymphoma (CTCL, from an immunological perspective characterized by increased Th2 cytokine levels, elevated serum IgE and impaired cellular immunity. Not only the clinical appearance but also the hallmark immunological characteristics of SS often share striking similarities with acute flares of atopic dermatitis (AD, a common benign chronic inflammatory skin disease. Given the overlap of several immunological features, the application of similar or even identical therapeutic approaches in certain stages of both diseases may come into consideration. The aim of this review is to compare currently accepted immunological aspects and possible therapeutic targets in AD and SS.

  1. Anti-tumor response with immunologically modified carbon nanotubes and phototherapy

    Science.gov (United States)

    Acquaviva, Joseph T.; Zhou, Feifan; Boarman, Ellen; Chen, Wei R.

    2013-02-01

    While successes of different cancer therapies have been achieved in various degrees a systemic immune response is needed to effectively treat late-stage, metastatic cancers, and to establish long-term tumor resistance in the patients. A novel method for combating metastatic cancers has been developed using immunologically modified carbon nanotubes in conjunction with phototherapy. Glycated chitosan (GC) is a potent immunological adjuvant capable of increasing host immune responses, including antigen presentation by activation of dendritic cells (DCs) and causing T cell proliferation. GC is also an effective surfactant for nanomaterials. By combining single-walled carbon nanotubes (SWNTs) and GC, immunologically modified carbon nanotubes (SWNT-GC) were constructed. The SWNT-GC suspension retains the enhanced light absorption properties in the near infrared (NIR) region and the ability to enter cells, which are characteristic of SWNTs. The SWNT-GC also retains the immunological properties of GC. Cellular SWNT-GC treatments increased macrophage activity, DC activation and T cell proliferation. When cellular SWNT-GC was irradiated with a laser of an appropriate wavelength, these immune activities could be enhanced. The combination of laser irradiation and SWNT-GC induced cellular toxicity in targeted tumor cells, leading to a systemic antitumor response. Immunologically modified carbon nanotubes in conjunction with phototherapy is a novel and promising method to produce a systemic immune response for the treatment of metastatic cancers.

  2. IMMUNOLOGICAL ASPECTS OF ENDOMETRIAL DISEASE

    Directory of Open Access Journals (Sweden)

    B. A. Slobodyanyuk

    2015-01-01

    Full Text Available Background: Immunological processes involving peritoneal macrophages could play a critical role in pathophysiology of external genital endometriosis.Aim: To assess levels of MCP-1, RANTES, and C-reactive protein and to identify their correlations with endometriosis.Materials and methods: Seventy two patients were evaluated: 26 healthy controls and 46 with endometriosis. Patients were divided into groups as follows: 17 with superficial endometriosis, 18 with endometriomas and 11 with deep infiltrative endometriosis. All patients underwent a laparoscopy during the proliferative phase of the cycle; levels of peritoneal and serum MCP-1, RANTES and C-reactive protein were measured using standard ELISA assays.Results: There were positive correlations between serum MCP-1 (p = 0.03 and C-reactive protein(p = 0.045 and severity of endometriosis, that could indicate malfunctioning of peritoneal macrophages in advanced stages of endometriosis. Conclusion: MCP-1 and C-reactive protein levels in peripheral blood can be used as markers of endometriosis activity.

  3. Immunological responses to parasitic arthropods.

    Science.gov (United States)

    Baron, R W; Weintraub, J

    1987-03-01

    Parasitic arthropods are responsible for enormous economic losses to livestock producers throughout the world. These production losses may range from simple irritation caused by biting and non-biting flies to deaths and/or damage to carcass, fleece, or skin resulting from attack by myiasis flies. The estimated costs of these losses are colossal but even these usually include only direct losses and ignore those associated with pesticide application. In the USA alone (in 1976), these losses were conservatively estimated at more than 650 million US dollars. The long term use of chemical control measures for these pests has resulted in many serious problems including residues in meat and milk products, rapid development of insecticide resistance, the destruction of non-target organisms, environmental pollution, and mortality and morbidity of livestock. These concerns have prompted researchers to seek alternative methods of arthropod control, including the artificial induction of immunity. In this review, R. W. Baron and J. Weintraub discuss several examples of ectoparasites that can induce immunological resistance in the host, including Sarcoptes and Demodex mites, the sheep ked (Melophagus ovinus), Anopluran lice and myiasis-causing flies such as Hypoderma.

  4. Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.

    LENUS (Irish Health Repository)

    Tinago, Willard

    2014-01-01

    Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+\\/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+\\/CD8+ ratio have not been well described.

  5. BELFAST nonagenarians: nature or nurture? Immunological, cardiovascular and genetic factors

    Directory of Open Access Journals (Sweden)

    Rea I M

    2010-05-01

    Full Text Available Abstract Nonagenarians are the fastest growing sector of populations across Western European and the developed world. They are some of the oldest members of our societies and survivors of their generation and may help us understand how to age not only longer, but better. The Belfast Longevity Group enlisted the help of 500 community-living, mobile, mentally competent, 'elite' nonagenarians, as part of an ongoing study of ageing. We assessed some immunological, cardiovascular, nutritional and genetic factors and some aspects of their interaction in this group of 'oldest old'. Here we present some of the evidence related to genetic and nutritional factors which seem to be important for good quality ageing in nonagenarians from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST.

  6. Towards integrating extracellular matrix and immunological pathways.

    Science.gov (United States)

    Boyd, David F; Thomas, Paul G

    2017-10-01

    The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM. We highlight studies that have taken an integrative approach to studying immune responses in the context of the ECM and studies that use novel proteomic strategies. Finally, we discuss research challenges relevant to the integration of immune and ECM networks and propose experimental and translational approaches to resolve these issues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effects of sulekang capsule in enhancement of resistance to radiation and regulating immunological function in mice

    International Nuclear Information System (INIS)

    Zhao Naikun; Zhou Ouliang; Du Weixia

    1990-01-01

    The effects of Sulekang capsule in enhancing the resistance to radiation and regulating the immunological function in mice were described. The results show that Sulekang capsule may lengthen the survival time (p 60 Co gamma rays. The experimental results of ANAE reaction show that the activety of T cells of normal or exposed mice may be enhanced by Sulekang capsule, which can control the decrease of both ANAE-positive cells and T cells in exposed mice. So it may enhance the immunological function on exposed animals

  8. Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy

    DEFF Research Database (Denmark)

    Gaardbo, J.C.; Nielsen, S.D.; Vedel, S.J.

    2008-01-01

    Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechan......(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients....

  9. Recovery of immune competence following sublethal irradiation: the role of the mouse strains, thymic function and aging

    International Nuclear Information System (INIS)

    Peterson, W.J.

    1976-01-01

    The bone marrow, thymus and lymphohematopoietic microenvironments are determining factors in recovery of immune competence following sublethal irradiation. Because of age-related degenerative changes in all of these parameters it was anticipated that immune competence of irradiated old mice would show an altered pattern of recovery. Therefore, three age groups (3-7, 15, and 23-34-months) of C57BL/6J mice were treated with either 250R, 500R or 600R. At various intervals thereafter their spleen cells were assessed for recovery of humoral and cell-mediated immunologic activity and for thymus derived (T-), bone marrow derived (B-) and stem-cell compartments. Two age groups (3-7 and 23-months) of C3H/Anf Cum mice were also treated with the two highest doses or irradiation and their spleen cells tested only for recovery of T- and B-cell compartments. The results showed that recovery of immune competence following 250R was independent of age

  10. Multiscale modelling in immunology: a review.

    Science.gov (United States)

    Cappuccio, Antonio; Tieri, Paolo; Castiglione, Filippo

    2016-05-01

    One of the greatest challenges in biomedicine is to get a unified view of observations made from the molecular up to the organism scale. Towards this goal, multiscale models have been highly instrumental in contexts such as the cardiovascular field, angiogenesis, neurosciences and tumour biology. More recently, such models are becoming an increasingly important resource to address immunological questions as well. Systematic mining of the literature in multiscale modelling led us to identify three main fields of immunological applications: host-virus interactions, inflammatory diseases and their treatment and development of multiscale simulation platforms for immunological research and for educational purposes. Here, we review the current developments in these directions, which illustrate that multiscale models can consistently integrate immunological data generated at several scales, and can be used to describe and optimize therapeutic treatments of complex immune diseases. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. Modeling-Enabled Systems Nutritional Immunology

    Science.gov (United States)

    Verma, Meghna; Hontecillas, Raquel; Abedi, Vida; Leber, Andrew; Tubau-Juni, Nuria; Philipson, Casandra; Carbo, Adria; Bassaganya-Riera, Josep

    2016-01-01

    This review highlights the fundamental role of nutrition in the maintenance of health, the immune response, and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition, and the immune system interact to delineate health and disease. The review sets an unconventional path to apply complex science methodologies to nutritional immunology research, discovery, and development through “use cases” centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, which include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism. PMID:26909350

  12. Modeling-Enabled Systems Nutritional Immunology

    Directory of Open Access Journals (Sweden)

    Meghna eVerma

    2016-02-01

    Full Text Available This review highlights the fundamental role of nutrition in the maintenance of health, the immune response and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition and the immune system interact to delineate health and disease. The review sets an unconventional path to applying complex science methodologies to nutritional immunology research, discovery and development through ‘use cases’ centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, that include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism.

  13. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 13, No 1 (2015) >. Log in or Register to get access to full text downloads.

  14. Clinical immunology - Autoimmunity in the Netherlands

    NARCIS (Netherlands)

    Tervaert, Jan Willem Cohen; Kallenberg, Cees G. M.

    2014-01-01

    Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking

  15. Biosensors in immunology: the story so far

    NARCIS (Netherlands)

    Pathak, S.S.; Savelkoul, H.F.J.

    1997-01-01

    Optical biosensors are finding a range of applications in immunology. They enable biomolecular interactions to be characterized in real time without the need to label reactants, and, because individual binding steps can be visualized, are particularly suited to complex assays

  16. The pluripotent history of immunology. A review

    Directory of Open Access Journals (Sweden)

    Neeraja Sankaran

    2012-09-01

    Full Text Available The historiography of immunology since 1999 is reviewed, in part as a response to claims by historians such as Thomas Söderqvist the field was still immature at the time (Söderqvist & Stillwell 1999. First addressed are the difficulties, past and present, surrounding the disciplinary definition of immunology, which is followed by a commentary on the recent scholarship devoted to the concept of the immune self. The new literature on broad immunological topics is examined and assessed, and specific charges leveled against the paucity of certain types of histories, e.g. biographical and institutional histories, are evaluated. In conclusion, there are compelling indications that the history of immunology has moved past the initial tentative stages identified in the earlier reviews to become a bustling, pluripotent discipline, much like the subject of its scrutiny, and that it continues to develop in many new and exciting directions.

  17. Cancer immunology and colorectal cancer recurrence

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca

    -, č. 3 (2011), s. 1421-1431 ISSN 1945-0524 R&D Projects: GA AV ČR IAA500200917 Institutional research plan: CEZ:AV0Z50200510 Keywords : colorectal cancer * inflammation * tumor Subject RIV: EC - Immunology

  18. American College of Allergy, Asthma & Immunology

    Science.gov (United States)

    ... Care Professionals Find an Allergist American College of Allergy, Asthma, and Immunology Seeking Relief? Find an Allergist ... shots? View All Postings Ask the Allergist Index Allergy & Asthma News Let it snow, but don’t ...

  19. American Academy of Allergy, Asthma, and Immunology

    Science.gov (United States)

    ... reasons to celebrate its journals. Learn More about the American Academy Of Allergy, Asthma & Immunology Life Spectrum of Asthma Meeting School-based Asthma Management Program – (SAMPRO TM ) This central resource focuses on ...

  20. IMMUNOLOGICAL REACTIVITY IN CHILDREN WITH CHRONIC GLOMERULONEPHRITIS

    Directory of Open Access Journals (Sweden)

    R. O. Beglarov

    2018-01-01

    Full Text Available Purpose. The purpose is to study the state of immunological reactivity in children with chronic glomerulonephritis.Patients and methods. 288 children with chronic glomerulonephritis were examined, of which boys accounted for 64.6%, girls — 35.4%. The mean age was 10.63 ± 3.88 years. Children are divided into 3 groups: Group I — 104 children with nephrotic form, Group II — 96 children with hematuric form, Group III — 88 children with mixed form. In the serum are identifi ed: CD3 +, CD4 +, CD8 +, CD16/56 +, CD19 +, CD95 + -subpopulations of lymphocytes; IgA, M, G; cytokines — IL-1β, IL-8, TNF-α, IFN-α, IL-4 and IL-10; the level of circulating immune complexes, the test for the reduction of nitrous tetrazolium (HST test, the phagocytic index and the phagocytic activity of neutrophils.Results. Immunological reactivity in children with chronic glomerulonephritis is characterized by a statistically significant increase in T-helpers (by 36.2% and 41.9% in nephrotic and mixed forms, apoptosis marker (by 50.5%, 51.7% and 65.4% respectively, in children with nephrotic, hematuric and mixed forms, parameters of humoral immunity, the level of circulating immune complexes (2.4, 2.2 and 2.6 times, respectively, in nephrotic, hematuric and mixed forms, p < 0.05, pro-inflammatory cytokines and decreased T-killers, B cells and phagocytic activity. At the same time, the degree of expression of immunoglobulin changes was higher with nephrotic (IgA 2.1 times, IgM 2.2 times, IgG 1.7 times, p < 0.05 and mixed forms (IgA 2.0 times, IgM 1.8 times, IgG 1.6 times, p < 0.05 with chronic glomerulonephritis. The level of TNF-α in children with a hematuric form exceeded the control ones by 3.9 times (p < 0.01, with the nephrotic and mixed form in 4.2 (p < 0.01 and 4.3 times (p < 0.01 respectively. The level of IL-1β and IL-8 was higher in nephrotic form in 2.0 and 1.5 times (p < 0.05, with hematuric — in 1.8 and 1.4 times (p < 0.05, at mixed — in 2

  1. Immunologic, hemodynamic, and adrenal incompetence in cirrhosis

    DEFF Research Database (Denmark)

    Risør, Louise Madeleine; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    dysfunction, but is not responsive to volume expansion. Recent research indicates that development of hepatic nephropathy represents a continuous spectrum of functional and structural dysfunction and may be precipitated by the inherent immunologic, adrenal, and hemodynamic incompetence in cirrhosis. New...... research explores several new markers of renal dysfunction that may replace serum creatinine in the future and give new insight on the hepatic nephropathy. Our understanding of the pathophysiological mechanisms causing the immunologic, adrenal, and hemodynamic incompetence, and the impact on renal...

  2. Effect of Yikangning on immunological function in mice

    International Nuclear Information System (INIS)

    Hou Fangyu; Xu Xiaoyi; Shi Yulu; Sheng Xuecheng; Zhao Liyan

    2001-01-01

    Objective: To investigate the effect of Yikangning oral liquid on immunological function in mice. Methods: 3 H-TdR incorporation was used to detect the lymphocyte transformation rate for Con A and LPS. Results: The drug increased the lymphocyte transformation rate in mice with lowed immunological function. Conclusion: Yikangning enhances immunological function in mice with lowered immunological function

  3. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yoo, Young-Choon [Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Hwang, Young-Jeong [Division of Food Science, International University of Korea, Jinju 660-759 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-{alpha} and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX (P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

  4. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    International Nuclear Information System (INIS)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

    2009-01-01

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX (P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

  5. A role for Waldeyer's ring in immunological response to allergens.

    Science.gov (United States)

    Masieri, Simonetta; Trabattoni, Daria; Incorvaia, Cristoforo; De Luca, Maria Cristina; Dell'Albani, Ilaria; Leo, Gualtiero; Frati, Franco

    2014-02-01

    Adenoids, tubal tonsil, palatine tonsil, and lingual tonsil are immunological organs included in the Waldeyer's ring, the basic function of which is the antibody production to common environmental antigens. Adenoidal hypertrophy (AH) is a major medical issue in children, and adenoidectomy is still the most used treatment worldwide. The response of adenoids to allergens is a good model to evaluate their immunological function. This report assessed the immunological changes in adenoid tissues from children with allergic rhinitis (AR) undergoing sublingual immunotherapy (SLIT). Adenoid samples from 16 children (seven males, nine females, mean age 7.12 years) with AH and clinical indication to adenoidectomy were collected. Of them, five children were not allergic and 11 had house dust mite and grass pollen-induced AR. Among allergic children, in four AR was treated by antihistamines while in seven AR was treated by high-dose SLIT during 4-6 months. The evaluation addressed the T helper 1 (Th1), Th2, and Th3 cells by performing a PCR array on mRNA extracted from adenoid samples. In non-allergic children, a typical Th1 pattern was found. SLIT induced a strong down-regulation of genes involved in Th2 and Th1 activation and function. In particular, in SLIT-treated allergic children IL-4, CCR2, CCR3, and PTGDR2 (Th2 related genes) and CD28, IL-2, and INHA (Th1 related genes) expression was reduced, compared with children treated with antihistamines. These preliminary findings warrant investigation in trials including larger numbers of patients, but indicate that hypertrophic adenoids of allergic children have the typical response to the specific allergen administered by SLIT. This should suggest that one should reconsider the immunological role of adenoids.

  6. Orchestrating cytoskeleton and intracellular vesicle traffic to build functional immunological synapses.

    Science.gov (United States)

    Soares, Helena; Lasserre, Rémi; Alcover, Andrés

    2013-11-01

    Immunological synapses are specialized cell-cell contacts formed between T lymphocytes and antigen-presenting cells. They are induced upon antigen recognition and are crucial for T-cell activation and effector functions. The generation and function of immunological synapses depend on an active T-cell polarization process, which results from a finely orchestrated crosstalk between the antigen receptor signal transduction machinery, the actin and microtubule cytoskeletons, and controlled vesicle traffic. Although we understand how some of these particular events are regulated, we still lack knowledge on how these multiple cellular elements are harmonized to ensure appropriate T-cell responses. We discuss here our view on how T-cell receptor signal transduction initially commands cytoskeletal and vesicle traffic polarization, which in turn sets the immunological synapse molecular design that regulates T-cell activation. We also discuss how the human immunodeficiency virus (HIV-1) hijacks some of these processes impairing immunological synapse generation and function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

    Science.gov (United States)

    ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

    2018-06-20

    Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

  8. Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV Vulnerable to Clearance by CD8 T Cells

    Directory of Open Access Journals (Sweden)

    Julia A. Sung

    2017-09-01

    Full Text Available Latently human immunodeficiency virus (HIV-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA. The LCA is a quantitative viral outgrowth assay (QVOA that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from VOR exposed resting CD4 T cells following addition of immune effectors for a discrete period. Take home message: VOR exposure leads to sufficient production of viral protein on the cell surface, creating a window of vulnerability within this latent reservoir in antiretroviral therapy (ART-suppressed HIV-infected individuals that allows the clearance of latently infected cells by an array of effector mechanisms.

  9. Moleculer nutritional immunology and cancer

    OpenAIRE

    Rüksan Çehreli

    2018-01-01

    The immune system composed of cells that are sensitive to a series of surrounding factors and forming an integrated network. During the last decade a significant increase in the number of studies demonstrated that diet components released from adipocytes and metabolic pathways, affected the immune system and highly contributed to the human health.T-cells are significantly affected by nutrition. Decrease in glucose uptake and metabolism, cytokine synthesis, T-cell proliferation and survival in...

  10. Developmental Competence of Buffalo (Bubalus bubalis) Pluripotent Embryonic Stem Cells Over Different Homologous Feeder Layers and the Comparative Evaluation with Various Extracellular Matrices.

    Science.gov (United States)

    Sharma, Manjinder; Dubey, Pawan K; Kumar, Rajesh; Nath, Amar; Kumar, G Sai; Sharma, G Taru

    2013-05-01

    Use of somatic cells as a feeder layer to maintain the embryonic stem cells (ESCs) in undifferentiated state limits the stem cell research design, since experimental data may result from a combined ESCs and feeder cell response to various stimuli. Therefore, present study was designed to evaluate the developmental competence of the buffalo ESCs over different homogenous feeders and compare with various extracellular matrices using different concentrations of LIF. Inner cell masses (ICMs) of in vitro hatched blastocysts were cultured onto homologous feeders viz. fetal fibroblast, granulosa and oviductal cell feeder layers and synthetic matrices viz. fibronectin, collagen type I and matrigel in culture medium. Developmental efficiency was found higher for ESCs cultured on fetal fibroblast and granulosa layers (83.33%) followed by fibronectin (77.78%) at 30 ng LIF. Oviductal feeder was found to be the least efficient feeder showing only 11.11% undifferentiated primary ESC colonies at 30 ng LIF. However, neither feeder layer nor synthetic matrix could support the development of primary colonies at 10 ng LIF. Expression of SSEA- 4, TRA-1-60 and Oct-4 were found positive in ESC colonies from all the feeders and synthetic matrices with 20 ng and 30 ng LIF. Fetal fibroblast and granulosa cell while, amongst synthetic matrices, fibronectin were found to be equally efficient to support the growth and maintenance of ESCs pluripotency with 30 ng LIF. This well-defined culture conditions may provide an animal model for culturing human embryonic stem cells in the xeno-free or feeder-free conditions for future clinical applications.

  11. SPECIAL ISSUE VETERINARY IMMUNOLOGY IMMUNOPATHOLOGY: PROCEEDINGS 8TH INTERNATIONAL VETERINARY IMMUNOLOGY SYMPOSIUM

    Science.gov (United States)

    This is the Special Issue of Vet. Immunol. Immunopathol. that summarizes the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto, Brazil. The 8 th IVIS highlighted the importance of veterinary immunology for animal health, vaccinology, reproducti...

  12. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

    Science.gov (United States)

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank

    2017-01-01

    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868

  13. Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer.

    Science.gov (United States)

    Konge, L; Vilmann, P; Clementsen, P; Annema, J T; Ringsted, C

    2012-10-01

    Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliability and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC. A total of 30 patients with proven or suspected NSCLC underwent EUS - FNA for mediastinal staging by three trainees and three experienced physicians. Their performances were assessed prospectively by three experts in EUS under direct observation and again 2 months later in a blinded fashion using digital video-recordings. Based on the assessments, intra-rater reliability, inter-rater reliability, and construct validity were explored. The intra-rater reliability was good (Cronbach's α = 0.80), but comparison of results based on direct observations and blinded video-recordings indicated a significant bias favoring consultants (P = 0.022). Inter-rater reliability was very good (Cronbach's α = 0.93). However, one rater assessing five procedures or two raters each assessing four procedures were necessary to secure a generalizability coefficient of 0.80. The assessment tool demonstrated construct validity by discriminating between trainees and experienced physicians (P = 0.034). Competency in mediastinal staging of NSCLC using EUS and EUS - FNA can be assessed in a reliable and valid way using the EUSAT assessment tool. Measuring and defining competency and training requirements could improve EUS quality and benefit patient care. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Immunological mechanisms of sublingual allergen-specific immunotherapy.

    Science.gov (United States)

    Novak, Natalija; Bieber, T; Allam, J-P

    2011-06-01

    Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT. © 2011 John Wiley & Sons A/S.

  15. Case immunologically disturbed by thorotrast-induced hepatoma

    Energy Technology Data Exchange (ETDEWEB)

    Boku, S; Kato, M; Okuyama, T; Masuzawa, Manabu; Matsuo, S [National Osaka Hospital (Japan)

    1980-10-01

    A case, 57 years old man, with thorotrast-induced hepatocellular carcinoma was reported. Thorium deposits in the reticuloendothelial tissues have the hazardous radiation effects on those tissues forever. In this case, the mean thorium amount in the spleen was 28.4% and the mean activity ratio of Ac-228 to Th-232 was 0.948. These values were much different from those reported by Kato in 1968. The ratio of T-cell to T.B. population decreased and PPD and PHA intradermal skin test were negative. Plasma cells in bone marrow increased and IgG was 4 g/dl. In these immunological studies it was supposed that T-cell function was impaired and B-cell function, especially IgG fraction was stimulated.

  16. Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras

    International Nuclear Information System (INIS)

    Rueedi, E.S.; Sykes, M.; Ildstad, S.T.; Chester, C.H.; Althage, A.; Hengartner, H.; Sachs, D.H.; Zinkernagel, R.M.

    1989-01-01

    Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells

  17. Immunological effects of hypomethylating agents.

    Science.gov (United States)

    Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

    2017-08-01

    Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

  18. Pediatric allergy and immunology in Israel.

    Science.gov (United States)

    Geller-Bernstein, Carmi; Etzioni, Amos

    2013-03-01

    After the geographic and sociodemographic settings as well as the health care in Israel are briefly described, the scope of pediatric allergy and immunology in Israel is presented. This includes specific disorders commonly encountered, the environment that induces symptoms, the specialists who treat them, and the common challenges of patients, parents, doctors, and allied health personnel who collaborate to manage the maladies and patient care. Allergies usually affect some overall 15-20% of the pediatric population. The main allergens are inhaled, ingested, or injected (insects stings). Generally, the incidence of the various allergens affecting children in Israel, is similar to other parts of the Western world. Owing to the high consanguinity rate in the Israeli population, the prevalence of the various immunodeficiency conditions (in the adaptive as well as the innate system) is higher than that reported worldwide. Pediatric allergists/immunologists also treat autoimmune disorders affecting the pediatric group. Pediatric allergy and clinical immunology are not separate specialties. The 25 specialists who treat children with allergic/immunologic diseases have undergone a basic training in Pediatrics. They also received an additional 2-yr training in allergy and clinical immunology and then have to pass the board examinations. They work mainly in pediatric allergy units, in several hospitals that are affiliated to the five medical schools in the country. Aside from clinical work, most of the centers are also heavily involved in clinical and basic research in allergy and immunology. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  19. Liver immunology and its role in inflammation and homeostasis.

    Science.gov (United States)

    Robinson, Mark W; Harmon, Cathal; O'Farrelly, Cliona

    2016-05-01

    The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

  20. Disturbances of immunological homeostasis induced by radioactive iodine agents

    International Nuclear Information System (INIS)

    Anokhin, Yu.N.; Norets, T.A.

    1986-01-01

    (CBAxC57B1/6)F 1 mice were injected with 125 I and 131 I-sodium iodide at a dose of 5.74x10 4 Bq/g. For a long time after such treatment the animals manifested an increased level of spleen cells humoral immune response to a foreign antigen (sheep erythrocytes). The autoreactivity of spleen and lymph node lymphocytes to autologous erythrocytes was also elevated. At the same time the selective migration of 51 Cr-labeled spleen lymphocytes to the peripheral lymphoid organs was suppressed. The use of a model system of adoptive cell transfer revealed an increase in the functional activity of cells suppressing a humoral response in mice treated with radiopharmaceuticals. The most pronounced disturbances of immunological reactivity in mice took place 6 mos. after the beginning of the experiment. The results obtained indicated that mechanisms of immune response regulation played a certain role in disturbances of immunological homeostasis induced by radioactive iodine agents

  1. Cancer immunology and canine malignant melanoma: A comparative review.

    Science.gov (United States)

    Atherton, Matthew J; Morris, Joanna S; McDermott, Mark R; Lichty, Brian D

    2016-01-01

    Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A roadmap towards personalized immunology

    OpenAIRE

    Delhalle, Sylvie; Bode, Sebastian F. N.; Balling, Rudi; Ollert, Markus; He, Feng Q.

    2018-01-01

    Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions. There is still a long way ahead on translating our capability to ...

  3. Comparison of dengue virus type 2-specific small RNAs from RNA interference-competent and -incompetent mosquito cells.

    Directory of Open Access Journals (Sweden)

    Jaclyn C Scott

    2010-10-01

    Full Text Available The exogenous RNA interference (RNAi pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (siRNAs are key components of this pathway. Understanding the biogenesis of siRNAs in mosquitoes could have important ramifications in using RNAi to control arbovirus transmission. Using deep sequencing technology, we characterized dengue virus type 2 (DENV2-specific small RNAs produced during infection of Aedes aegypti mosquitoes and A. aegypti Aag2 cell cultures and compared them to those produced in the C6/36 Aedes albopictus cell line. We show that the size and mixed polarity of virus-specific small RNAs from DENV-infected A. aegypti cells indicate that they are products of Dicer-2 (Dcr2 cleavage of long dsRNA, whereas C6/36 cells generate DENV2-specific small RNAs that are longer and predominantly positive polarity, suggesting that they originate from a different small RNA pathway. Examination of virus-specific small RNAs after infection of the two mosquito cell lines with the insect-only flavivirus cell fusing agent virus (CFAV corroborated these findings. An in vitro assay also showed that Aag2 A. aegypti cells are capable of siRNA production, while C6/36 A. albopictus cells exhibit inefficient Dcr2 cleavage of long dsRNA. Defective expression or function of Dcr2, the key initiator of the RNAi pathway, might explain the comparatively robust growth of arthropod-borne viruses in the C6/36 cell line, which has been used frequently as a surrogate for studying molecular interactions between arboviruses and cells of their mosquito hosts.

  4. Endolymphatic radionuclide therapy (ERT) in malignant melanomas and its immunological side effects

    International Nuclear Information System (INIS)

    Richter, G.; Heidenbluth, I.; Heidelbach, U.

    1982-01-01

    Doses of some thousands Gy affecting the retroperitoneal lymph nodes, but hardly causing reduction of subjective well-being, are interesting as to the endolymphatic instillation of 32 P tri-n-octylphosphate as an additional prophylactic therapy in operated stage 1 melanomas of the extremities. A real proof for its utility, however, has been missed till now, not only in our hitherto controlled 46 patients but also in the literature. On the other hand we found a significant lymphopenia for more than 1 year and reduced percentages of stimulated lymphocytes and rosette forming cells for 3 months. Compared to 3 control groups (melanomas before treatment, effect of operation and anaesthesia, patients without immunological alterations) these immunological changes proved to be caused by the ERT itself. They suggest a limitation of ERT to melanomas with a high likelihood of separating tumor cells or micrometastases as well as further immunological follow-up checks. (author)

  5. Immunological and biological properties of recombinant Lol p 1.

    Science.gov (United States)

    Boutin, Y; Lamontagne, P; Boulanger, J; Brunet, C; Hébert, J

    1997-03-01

    Current forms of allergy diagnosis and therapies are based on the use of natural allergenic extracts. Despite strong evidence that higher therapeutic efficacy may be achieved with purified allergens, the purification of multiple allergic components from extracts is a fastidious and sometimes an impossible task. However, the use of recombinant allergens may be an alternative to overcome this problem. In this study, we compared the immunological properties of recombinant (r) Lol p 1 with those of the natural protein. We cloned directly the gene encoding Lol p 1 from genomic DNA of ryegrass pollen. This gene was subcloned into the expression vector pMAL-c and expressed as fusion protein. Subsequently, rLol p 1 was cleaved from maltose-binding protein using factor Xa. Using binding inhibition and proliferative assays, we assessed the immunological properties of the recombinant allergens. The capacity of rLol p 1 to trigger basophil histamine release and to elicit a skin reaction was also assessed and compared to those of its natural counterpart. We found that the Lol p 1 gene has no introns since we amplified this gene directly from genomic DNA. We demonstrated that the binding sites of anti-Lol p 1 monoclonal antibody, specific human IgG and IgE antibody are well conserved on rLol p 1 as no difference in the binding inhibition profile was observed when using either natural or recombinant protein. At the T-cell level, rLol p 1 elicited a T-cell response in mice comparable to that observed with the natural protein. In addition, we demonstrated that the biological characteristics of rLol p 1 were comparable to those of the natural counterpart, in that rLol p 1 elicited a skin wheal reaction and induced basophil histamine release in grass-allergic patients only. The data indicate that natural Lol p 1 and rLol p 1 shared identical immunological and biological properties.

  6. Immunological profile of silent brain infarction and lacunar stroke.

    Directory of Open Access Journals (Sweden)

    Paola Sarchielli

    Full Text Available Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI. However, the immunological profile of SBI has been scarcely investigated. In the context of a national research project named SILENCE, aimed at investigating clinical, biochemical and pathogenic features of SBI, we have measured the plasma profile of some inflammatory-related molecules in SBI patients (n = 21, patients with recent lacunar infarcts (LI, n = 28 and healthy controls (n = 31, consecutively enrolled in four Italian centres. A panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1, growth factors (SCF, SCGFb, HGF, IL3, immunoglobulin-type adhesion molecules (ICAM1, VCAM1, proinflammatory cytokines (IL18, INFa2, MIF, IL12p40, cell surface receptors on T-cells (IL2Ra, and inductors of apoptosis (TRAIL was assessed in plasma samples by Luminex xMAP™ technology. Immunological parameters were compared using non-parametric statistics and performance to distinguish SBI and LI was evaluated by receiver operating characteristic (ROC analysis. Plasma levels of ICAM1 were significantly higher in both SBI and LI patients as compared to controls (SBI≥LI>Ctrl. A different trend was observed for IL16 (SBICtrl, SCF (LICtrl and SCGFb (SBI>LICtrl and IL18 when compared to LI patients (Ctrl≤SBI>LI. All the other immunological markers did not significantly differ among groups. According to ROC analysis, the best predictor for SBI condition was the chemokine MIG (AUC = 0.84, sensitivity 86%, specificity 77%, while SCF had the best performance in distinguishing LI patients (AUC = 0.84, sensitivity 86%, specificity 68%. These results confirm the involvement of inflammatory processes in cerebrovascular disorders, particularly in SBI, a very common age-related condition. The differences in plasma profile of inflammatory molecules may underlie different pathological mechanisms in SBI and LI patients.

  7. A Competing Risk Model of First Failure Site after Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M; Kjær, Andreas; Langer, Seppo W; Aznar, Marianne C; Persson, Gitte F; Bentzen, Søren M

    2018-04-01

    The aim of the study was to build a model of first failure site- and lesion-specific failure probability after definitive chemoradiotherapy for inoperable NSCLC. We retrospectively analyzed 251 patients receiving definitive chemoradiotherapy for NSCLC at a single institution between 2009 and 2015. All patients were scanned by fludeoxyglucose positron emission tomography/computed tomography for radiotherapy planning. Clinical patient data and fludeoxyglucose positron emission tomography standardized uptake values from primary tumor and nodal lesions were analyzed by using multivariate cause-specific Cox regression. In patients experiencing locoregional failure, multivariable logistic regression was applied to assess risk of each lesion being the first site of failure. The two models were used in combination to predict probability of lesion failure accounting for competing events. Adenocarcinoma had a lower hazard ratio (HR) of locoregional failure than squamous cell carcinoma (HR = 0.45, 95% confidence interval [CI]: 0.26-0.76, p = 0.003). Distant failures were more common in the adenocarcinoma group (HR = 2.21, 95% CI: 1.41-3.48, p failure showed that primary tumors were more likely to fail than lymph nodes (OR = 12.8, 95% CI: 5.10-32.17, p failure (OR = 1.26 per unit increase, 95% CI: 1.12-1.40, p failure site-specific competing risk model based on patient- and lesion-level characteristics. Failure patterns differed between adenocarcinoma and squamous cell carcinoma, illustrating the limitation of aggregating them into NSCLC. Failure site-specific models add complementary information to conventional prognostic models. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  8. Comparison of Different Vitrification Procedures on Developmental Competence of Mouse Germinal Vesicle Oocytes in the Presence or Absence of Cumulus Cells

    Directory of Open Access Journals (Sweden)

    Mojdeh Salehnia

    2009-01-01

    Full Text Available Background: An evaluation of the developmental competence of vitrified mouse germinal vesicle(GV oocytes with various equilibration and vitrification times; in the presence or absence ofcumulus cells and by comparison between the cryotop method and straws was performed.Materials and Methods: Mouse GV oocytes were considered in cumulus-denuded oocytes(CDOs and cumulus-oocyte complexes (COCs groups. Their survival and developmental rateswere studied in the following experiments: (I exposure to different equilibration times (0, 3 and5 minutes and vitrification (1, 3 and 5 minutes without plunging in LN2 as toxicity tests, (IIoocytes were vitrified using straws followed by exposure to equilibration solution for 0, 3 and 5minutes and vitrification solution for 1 and 3 minutes, and (III oocytes were vitrified by cryotopfollowing exposure to equilibration for 5 minutes and vitrification for 1 minute, respectively.Results: Maturation and developmental rates of the COCs were higher than CDOs in the nonvitrifiedgroup (p<0.05. The survival and maturation rates were low in all oocytes exposed tovitrification solution for 5 minutes (p <0.05. In vitrified CDOs and COCs using straws, the survivalrates ranged from 56.9% to 85.4% and 44.0% to 84.5%, and the maturation rates from 35.3% to56.8% and 25.8% to 56.2%, respectively; which were lower than non-vitrified samples (p <0.05.Cryotop vitrified oocytes showed higher survival, maturation and fertilization rates when comparedto straw in both CDOs and COCs (p <0.05.Conclusion: The presence of cumulus cells improves developmental competence of GV oocytesin control groups but it did not affect the vitrified group. Vitrification of mouse GV oocytes usingcryotop was more effective than straws, however both vitrification techniques did not improve thecleavage rate.

  9. 10 workshops on Immunology of preeclampsia.

    Science.gov (United States)

    Gerard, Chaouat

    2017-09-01

    For the 10th issue of the « island workshops », now the Reunion Workshops, organised by Pierre Yves Robillard since the first one in Tahiti challenging the "vascular disease only" theory of pre eclampsia and introducing the primipaternity concept, we examined the reasons for considering an Immunological approach to the disease. This (brief) overview thus examines several important topics in an Immunological framework. I have chosen to present here the evolution of the main themes rather than a purely chronological vision. Copyright © 2017. Published by Elsevier B.V.

  10. Immunologic Abnormalities, Treatments, and Recurrent Pregnancy Loss

    DEFF Research Database (Denmark)

    Wang, Nathalie F; Kolte, Astrid M; Larsen, Elisabeth C

    2016-01-01

    Recurrent pregnancy loss, depending on the definition, affects 1% to 3% of women aiming to have a child. Little is known about the direct causes of recurrent pregnancy loss, and the condition is considered to have a multifactorial and complex pathogenesis. The aim of this review was to summarize ...... the evaluation and the management of the condition with specific emphasis on immunologic biomarkers identified as risk factors as well as current immunologic treatment options. The review also highlights and discusses areas in need of further research....

  11. On immunological polymorphism of autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Karachentsev, Yu.Yi.

    1999-01-01

    The study involved 46 persons. In the majority of patients the exposure dose was 0.155±0.01 Gy. Clinical, ultrasound, immunological, statistical and non-parametric methods were used. Considerable immunological polymorphism of autoimmune thyroiditis in the liquidators has been established; 1) with disturbances in the cellular immunity and low antithyroid antibody index, 2) without disturbances in the cellular immunity with positive indices of antithyroid antibodies, 3) with disturbances in cellular immunity and high indices of TH and MA antibodies

  12. POST-EXPOSURE IMMUNOLOGICAL PREVENTION AGAINST VARICELLA

    Directory of Open Access Journals (Sweden)

    V.K. Tatochenko

    2010-01-01

    Full Text Available The article focuses on immunological prevention of varicella, particularly efficacy and advisability of vaccinating contact individuals in a pocket (post-exposure vaccination: its role in reducing the epidemiological process and economic burden of the infection, in achieving control over outbreak disease incidence. It features data obtained by foreign researchers and own research results. It demonstrates that vaccination of children and adults immediately after contact with the individual suffering from varicella allows significant reduction in disease incidence. Key words: varicella, vaccination, post-exposure immunological prevention, children. (Pediatric Pharmacology. – 2010; 7(4:30-33

  13. GnRH receptor activation competes at a low level with growth signaling in stably transfected human breast cell lines

    International Nuclear Information System (INIS)

    Morgan, Kevin; Meyer, Colette; Miller, Nicola; Sims, Andrew H; Cagnan, Ilgin; Faratian, Dana; Harrison, David J; Millar, Robert P; Langdon, Simon P

    2011-01-01

    Gonadotrophin releasing hormone (GnRH) analogs lower estrogen levels in pre-menopausal breast cancer patients. GnRH receptor (GnRH-R) activation also directly inhibits the growth of certain cells. The applicability of GnRH anti-proliferation to breast cancer was therefore analyzed. GnRH-R expression in 298 primary breast cancer samples was measured by quantitative immunofluorescence. Levels of functional GnRH-R in breast-derived cell lines were assessed using 125 I-ligand binding and stimulation of 3 H-inositol phosphate production. Elevated levels of GnRH-R were stably expressed in cells by transfection. Effects of receptor activation on in vitro cell growth were investigated in comparison with IGF-I and EGF receptor inhibition, and correlated with intracellular signaling using western blotting. GnRH-R immunoscoring was highest in hormone receptor (triple) negative and grade 3 breast tumors. However prior to transfection, functional endogenous GnRH-R were undetectable in four commonly studied breast cancer cell lines (MCF-7, ZR-75-1, T47D and MDA-MB-231). After transfection with GnRH-R, high levels of cell surface GnRH-R were detected in SVCT and MDA-MB-231 clones while low-moderate levels of GnRH-R occurred in MCF-7 clones and ZR-75-1 clones. MCF-7 sub-clones with high levels of GnRH-R were isolated following hygromycin phosphotransferase transfection. High level cell surface GnRH-R enabled induction of high levels of 3 H-inositol phosphate and modest growth-inhibition in SVCT cells. In contrast, growth of MCF-7, ZR-75-1 or MDA-MB-231 clones was unaffected by GnRH-R activation. Cell growth was inhibited by IGF-I or EGF receptor inhibitors. IGF-I receptor inhibitor lowered levels of p-ERK1/2 in MCF-7 clones. Washout of IGF-I receptor inhibitor resulted in transient hyper-elevation of p-ERK1/2, but co-addition of GnRH-R agonist did not alter the dynamics of ERK1/2 re-phosphorylation. Breast cancers exhibit a range of GnRH-R immunostaining, with higher levels of

  14. Immunology of IgG4-related disease

    Science.gov (United States)

    Della-Torre, E; Lanzillotta, M; Doglioni, C

    2015-01-01

    Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4+ plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed. PMID:25865251

  15. INFLUENCE OF IMMUNOLOGICAL DISORDERS ON AN OUTCOME FOR THE FIRST TIME DIAGNOSED INFILTRATIVE TUBERCULOSIS IN SOCIALLY SAFE PATIENTS

    Directory of Open Access Journals (Sweden)

    A. V. Mordyk

    2014-01-01

    Full Text Available The assessment of immunological indicators in 76 first time diagnosed infiltrative tuberculosis of lungs in socially safe patients prior to treatment and in 2 months of chemotherapy was carried out. It is revealed that immunological disorders are connected with efficiency of tuberculosis treatment . It can be criterion of quality of provided chemotherapy. The activation of cell immunity, stimulation of phagocytosis activity of neutrophils would contribute for effective treatment of tuberculosis.

  16. T cells from fully H-2 allogeneic (A replaced by B) radiation bone marrow chimeras are functionally competent and host restricted but are alloreactive against hybrid Ia determinants expressed on (A x B)F1 cells

    International Nuclear Information System (INIS)

    Kruisbeek, A.M.; Hathcock, K.S.; Hodes, R.J.; Singer, A.

    1982-01-01

    In this communication it is demonstrated that T cells from fully allogeneic A replaced by B radiation bone marrow chimeras are alloreactive against the hybrid Ia molecules expressed on the surface of heterozygous A X B cells. These results suggested that previous failures to generate cytotoxic T lymphocyte (CTL) responses from fully allogeneic chimeras by sensitizing the chimeric T cells to antigen in an (A X B)F1-priming environment might have been confounded by an ongoing alloreaction against determinants created by hybrid Ia molecules expressed on F1 cells. Consequently, the ability to generate CTL responses from fully allogeneic chimeras was re-examined by sensitizing the chimeric T cells to antigen presented by homozygous rather that F1 stimulator cells. It was found that T cells of donor bone marrow origin that mediate cytotoxic responses to trinitrophenyl-modified self determinants do differentiate into functional competence in an H-2-incompatible host environment and are restricted to the host H-2 haplotype

  17. Outcomes of allergy/immunology follow-up after an emergency department evaluation for anaphylaxis.

    Science.gov (United States)

    Campbell, Ronna L; Park, Miguel A; Kueber, Michael A; Lee, Sangil; Hagan, John B

    2015-01-01

    Anaphylaxis guidelines currently recommend referring patients with anaphylaxis seen in the emergency department (ED) to an allergist for follow up. The objective of our study was to evaluate outcomes of allergy/immunology follow-up after an ED visit for anaphylaxis. A retrospective health records review was conducted from April 2008 to August 2012. Charts were reviewed independently by 2 allergists to determine outcomes. Descriptive statistics with corresponding 95% CIs were calculated. Among 573 patients seen in the ED who met anaphylaxis diagnostic criteria, 217 (38%) had a documented allergy/immunology follow-up. After allergy/immunology evaluation, 16 patients (7% [95% CI, 5%-12%]) had anaphylaxis ruled out. Among those with an unknown ED trigger (n = 74), 24 (32% [95% CI, 23%-44%]) had a trigger identified; and, among those who had a specific suspected ED trigger (n = 143), 9 (6% [95% CI, 3%-12%]) had a trigger identified in a category other than the one suspected in the ED, and 28 (20% [95% CI, 14%-27%]) had an unknown trigger. Thus, there were a total of 77 patients (35% [95% CI, 29%-42%]) who had an alteration in the diagnosis of anaphylaxis or trigger after allergy/immunology evaluation. Four patients (2% [95% CI, 0.7%-4.6%]) were diagnosed with a mast cell activation disorder, and 13 patients (6% [95% CI, 4%-10%]) underwent immunotherapy or desensitization. Overall, 35% of the patients with suspected anaphylaxis in the ED had an alteration in the diagnosis or suspected trigger after allergy/immunology evaluation. These results underscore the importance of allergy/immunology follow-up after an ED visit for anaphylaxis. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Immunological Risk of Injectable Drug Delivery Systems

    NARCIS (Netherlands)

    Jiskoot, W.; van Schie, R.M.F.; Carstens, M.G.; Schellekens, H.

    2009-01-01

    Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These

  19. Immunology of Paratuberculosis Infection and Disease

    Science.gov (United States)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...

  20. What's so special about chicken immunology?

    Science.gov (United States)

    What’s so special about chickens? Firstly, chickens are not only an invaluable model for studying immunology, they also provide the world’s main source of meat and will be a key protein source needed to feed the growing human population into the future. Poultry meat production is highly efficient ...

  1. Prevalence of biochemical and immunological abnormalities in ...

    African Journals Online (AJOL)

    Tile prevalence of biochemical and immunological abnormalities was studied in a group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52 blacks). The most common biochemical abnormalities detected were a reduction in the serum creatinine value (43,4%), raised globulins (39,7%), raised serum ...

  2. Simple Calculation Programs for Biology Immunological Methods

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Simple Calculation Programs for Biology Immunological Methods. Computation of Ab/Ag Concentration from EISA data. Graphical Method; Raghava et al., 1992, J. Immuno. Methods 153: 263. Determination of affinity of Monoclonal Antibody. Using non-competitive ...

  3. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably

  4. Egyptian Journal of Pediatric Allergy and Immunology (The): Site Map

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The): Site Map. Journal Home > About the Journal > Egyptian Journal of Pediatric Allergy and Immunology (The): Site Map. Log in or Register to get access to full text downloads.

  5. 21 CFR 866.5230 - Colostrum immunological test system.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230... colostrum. Colostrum is a substance excreted by the mammary glands during pregnancy and until production of...

  6. Investigation of Macrophage Differentiation and Cytokine Production in an Undergraduate Immunology Laboratory

    Science.gov (United States)

    Berkes, Charlotte; Chan, Leo Li-Ying

    2015-01-01

    We have developed a semester-long laboratory project for an undergraduate immunology course in which students study multiple aspects of macrophage biology including differentiation from progenitors in the bone marrow, activation upon stimulation with microbial ligands, expression of cell surface markers, and modulation of cytokine production. In…

  7. Hematology/immunology (M110 series). [human hemodynamic response to weightlessness simulation

    Science.gov (United States)

    1973-01-01

    The hematology/immunology experiments in the Skylab mission study various aspects of the red blood cell, including its metabolism and life span, and blood volume changes under zero gravity conditions to determine the precise mechanism of the transient changes which have been seen on the relatively brief missions of the past.

  8. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

    DEFF Research Database (Denmark)

    Muenchhoff, Maximilian; Adland, Emily; Karimanzira, Owen

    2016-01-01

    nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved...

  9. Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant

    NARCIS (Netherlands)

    Overwijk, Willem W.; de Visser, Karin E.; Tirion, Felicia H.; de Jong, Laurina A.; Pols, Thijs W. H.; van der Velden, Yme U.; van den Boorn, Jasper G.; Keller, Anna M.; Buurman, Wim A.; Theoret, Marc R.; Blom, Bianca; Restifo, Nicholas P.; Kruisbeek, Ada M.; Kastelein, Robert A.; Haanen, John B. A. G.

    2006-01-01

    The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory

  10. Immunological Factors in the Pathogenesis and Treatment of Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Kijlstra, A.; Heij, La E.C.; Hendrikse, F.

    2005-01-01

    Recent findings indicate that immunological factors are involved not only in the pathogenesis of age-related macular degeneration (AMD), but also in its treatment. Earlier data showing the presence of inflammatory cells in affected areas of AMD retinas support this statement. Although a possible

  11. The immunologic considerations in human head transplantation.

    Science.gov (United States)

    Hardy, Mark A; Furr, Allen; Barret, Juan P; Barker, John H

    2017-05-01

    The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) [1]. The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Immunology in the liver--from homeostasis to disease.

    Science.gov (United States)

    Heymann, Felix; Tacke, Frank

    2016-02-01

    The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance. Tolerance is also relevant for chronic persistence of hepatotropic viruses or allograft acceptance after liver transplantation. The liver can rapidly activate immunity in response to infections or tissue damage. Depending on the underlying liver disease, such as viral hepatitis, cholestasis or NASH, different triggers mediate immune-cell activation. Conserved mechanisms such as molecular danger patterns (alarmins), Toll-like receptor signalling or inflammasome activation initiate inflammatory responses in the liver. The inflammatory activation of hepatic stellate and Kupffer cells results in the chemokine-mediated infiltration of neutrophils, monocytes, natural killer (NK) and natural killer T (NKT) cells. The ultimate outcome of the intrahepatic immune response (for example, fibrosis or resolution) depends on the functional diversity of macrophages and dendritic cells, but also on the balance between pro-inflammatory and anti-inflammatory T-cell populations. As reviewed here, tremendous progress has helped to understand the fine-tuning of immune responses in the liver from homeostasis to disease, indicating promising targets for future therapies in acute and chronic liver diseases.

  13. [Inflammasome and its role in immunological and inflammatory response at early stage of burns].

    Science.gov (United States)

    Zhang, Fang; Li, Jiahui; Xia, Zhaofan

    2014-06-01

    Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

  14. Immunological changes following a combined effect of chromic small dose γ-irradiation and toxic agents

    International Nuclear Information System (INIS)

    Shubik, V.M.; Zykova, I.A.

    1981-01-01

    Immunologic changes under conditions of durable effect of low dose γ-radiation on people in the case of combining radiation with the effect of low concentrations of toxic substances, are studied. Under the above effect, the appearance of deviations from the side of immunologic status is possible. Taking into account the important role of the immunity system in homeostasis preservation and the formation of a series of pathological states it is advisable to use figures, and characteristics inherent in the state of the cell immunity to autoallergic processes to estimate a combined effect of radiation and toxic substances on the organism of people [ru

  15. Immunological effects in acute radiation sickness reconvalescents - results of thirteen years of follow-up

    International Nuclear Information System (INIS)

    Chumak, A.A.; Bazyka, D.A.; Belyaeva, N.V.; Azarskova, M.B.; Minchenko, Zh.N.; Pleskach, O.Ya.; Mishchenko, L.P.

    2000-01-01

    For immunological follow-up of people who had suffered from acute radiation sickness in 1986 connected with the Chernobyl NPP accident different immunological reactions were used. Both in the period of early recovery and remote reconvalescence period people had changes in expression of lymphocytes surface antigens, suggesting that even in the cases of satisfactory compensations functional reserves of immune system was narrow. Correlations with absorbed doses and somatic mutations in the locus of T-cell receptor were found. Results of the study suggested that individual characteristics of postirradiation recovery depended both on absorbed doses and genetically determined responses on the radiation hazard

  16. Hierarchy of stroma-derived factors in supporting growth of stroma-dependent hemopoietic cells: membrane-bound SCF is sufficient to confer stroma competence to epithelial cells.

    Science.gov (United States)

    Friel, Jutta; Itoh, Katsuhiko; Bergholz, Ulla; Jücker, Manfred; Stocking, Carol; Harrison, Paul; Ostertag, Wolfram

    2002-03-01

    Hemopoiesis takes place in a microenvironment where hemopoietic cells are closely associated with stroma by various interactions. Stroma coregulates the proliferation and differentiation of hemopoietic cells. Stroma-hemopoietic-cell contact can be supported by locally produced membrane associated growth factors. The stroma derived growth factor, stem cell factor (SCF) is important in hemopoiesis. We examined the different biological interactions of membrane bound and soluble SCF with human hemopoietic cells expressing the SCF receptor, c-kit. To analyze the function of the SCF isoforms in inducing the proliferation of hemopoietic TF1 or Cord blood (CB) CD34+ cells we used stroma cell lines that differ in their presentation of no SCF, membrane SCF, or soluble SCF. We established a new coculture system using an epithelial cell line that excludes potential interfering effects with other known stroma encoded hemopoietic growth factors. We show that soluble SCF, in absence of membrane-bound SCF, inhibits long term clonal growth of primary or established CD34+ hemopoietic cells, whereas membrane-inserted SCF "dominantly" induces long term proliferation of these cells. We demonstrate a hierarchy of these SCF isoforms in the interaction of stroma with hemopoietic TF1 cells. Membrane-bound SCF is "dominant" over soluble SCF, whereas soluble SCF acts epistatically in interacting with hemopoietic cells compared with other stroma derived factors present in SCF deficient stroma. A hierarchy of stroma cell lines can be arranged according to their presentation of membrane SCF or soluble SCF. In our model system, membrane-bound SCF expression is sufficient to confer stroma properties to an epithelial cell line but soluble SCF does not.

  17. Graduate Students' Interest in Immunology as a Discipline

    Science.gov (United States)

    Kwarteng, Alexander; Frimpong, Michael; Sylverken, Augustina Angelina; Arthur, Yarhands D.; Ahuno, Samuel T.; Owusu-Dabo, Ellis

    2017-01-01

    Interest and motivation significantly influence achievement; however, interest in immunology remains to be determined. Using a structured questionnaire, the current study assessed for the first time interest in immunology among biomedical graduate students in Ghana after a one-week introduction to immunology course. Our results revealed that…

  18. 21 CFR 866.5640 - Infectious mononucleosis immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious mononucleosis immunological test system is a device that consists of the reagents used to measure by...

  19. Egyptian Journal of Pediatric Allergy and Immunology (The ...

    African Journals Online (AJOL)

    Focus and Scope. This journal is the official journal of the Egyptian Society of Pediatric Allergy and Immunology. It is he first Egyptian Journal specialized in the field of allergy and immunology in the pediatric age group. It is a forum for the presentation and promotion of new researches in the field of allergy and immunology, ...

  20. 42 CFR 493.1208 - Condition: General immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

  1. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

  2. Egyptian Journal of Pediatric Allergy and Immunology (The)

    African Journals Online (AJOL)

    This journal is the official journal of the Egyptian Society of Pediatric Allergy and Immunology. It is he first Egyptian Journal specialized in the field of allergy and immunology in the pediatric age group. It is a forum for the presentation and promotion of new researches in the field of allergy and immunology, for maintaining ...

  3. The competing roles of i-ZnO in Cu(ln,Ga)Se¬2 solar cells

    NARCIS (Netherlands)

    Williams, B.L.; Zardetto, V.; Kniknie, B.J.; Verheijen, M.A.; Kessels, W.M.M.; Creatore, M.

    2016-01-01

    The electrical role of the highly resistive and transparent (HRT) i-ZnO layer in Cu(In, Ga)Se2(CIGS) solar cells is investigated. By tuning the resistivity of atomic layer deposited (ALD) i-ZnO through the use of post-growth O2-plasma treatments, it is shown that low i-ZnO carrier densities (i.e.

  4. The competing roles of i-ZnO in Cu(In,Ga)Se2 solar cells

    NARCIS (Netherlands)

    Williams, B.L.; Zardetto, V.; Kniknie, B.; Verheijen, M.A.; Kessels, W.M.M.; Creatore, M.

    2016-01-01

    The electrical role of the highly resistive and transparent (HRT) i-ZnO layer in Cu(In, Ga)Se2(CIGS) solar cells is investigated. By tuning the resistivity of atomic layer deposited (ALD) i-ZnO through the use of post-growth O2-plasma treatments, it is shown that low i-ZnO carrier densities (i.e.

  5. Deposition of tropoelastin into the extracellular matrix requires a competent elastic fiber scaffold but not live cells.

    Science.gov (United States)

    Kozel, Beth A; Ciliberto, Christopher H; Mecham, Robert P

    2004-04-01

    The initial steps of elastic fiber assembly were investigated using an in vitro assembly model in which purified recombinant tropoelastin (rbTE) was added to cultures of live or dead cells. The ability of tropoelastin to associate with preexisting elastic fibers or microfibrils in the extracellular matrix was then assessed by immunofluorescence microscopy using species-specific tropoelastin antibodies. Results show that rbTE can associate with elastic fiber components in the absence of live cells through a process that does not depend on crosslink formation. Time course studies show a transformation of the deposited protein from an initial globular appearance early in culture to a more fibrous structure as the matrix matures. Deposition required the C-terminal region of tropoelastin and correlated with the presence of preexisting elastic fibers or microfibrils. Association of exogenously added tropoelastin to the cellular extracellular matrix was inhibited by the addition of heparan sulfate but not chondroitin sulfate sugars. Together, these results suggest that the matrix elaborated by the cell is sufficient for the initial deposition of tropoelastin in the extracellular space and that elastin assembly may be influenced by the composition of sulfated proteoglycans in the matrix.

  6. Controlling the Immunological Crosstalk during Conception and Pregnancy

    DEFF Research Database (Denmark)

    Lynge Nilsson, Line; Djurisic, Snezana; Hviid, Thomas Vauvert F

    2014-01-01

    of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G plays an important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels...... in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact, its expression pattern is primarily limited to extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. Due to low polymorphism, almost......, and is present in seminal fluid from men. In addition, HLA-G expression has been found in the pre-implanted embryo. Therefore, we propose that a combined contribution from the mother, the father, and the embryo/fetus is likely to be important. Furthermore, this review presents important aspects of HLA...

  7. Comparative immunology of allergic responses.

    Science.gov (United States)

    Gershwin, Laurel J

    2015-01-01

    Allergic responses occur in humans, rodents, non-human primates, avian species, and all of the domestic animals. These responses are mediated by immunoglobulin E (IgE) antibodies that bind to mast cells and cause release/synthesis of potent mediators. Clinical syndromes include naturally occurring asthma in humans and cats; atopic dermatitis in humans, dogs, horses, and several other species; food allergies; and anaphylactic shock. Experimental induction of asthma in mice, rats, monkeys, sheep, and cats has helped to reveal mechanisms of pathogenesis of asthma in humans. All of these species share the ability to develop a rapid and often fatal response to systemic administration of an allergen--anaphylactic shock. Genetic predisposition to development of allergic disease (atopy) has been demonstrated in humans, dogs, and horses. Application of mouse models of IgE-mediated allergic asthma has provided evidence for a role of air pollutants (ozone, diesel exhaust, environmental tobacco smoke) in enhanced sensitization to allergens.

  8. Tula hantavirus isolate with the full-length ORF for nonstructural protein NSs survives for more consequent passages in interferon-competent cells than the isolate having truncated NSs ORF.

    Science.gov (United States)

    Jääskeläinen, Kirsi M; Plyusnina, Angelina; Lundkvist, Ake; Vaheri, Antti; Plyusnin, Alexander

    2008-01-11

    The competitiveness of two Tula hantavirus (TULV) isolates, TULV/Lodz and TULV/Moravia, was evaluated in interferon (IFN) -competent and IFN-deficient cells. The two isolates differ in the length of the open reading frame (ORF) encoding the nonstructural protein NSs, which has previously been shown to inhibit IFN response in infected cells. In IFN-deficient Vero E6 cells both TULV isolates survived equally well. In contrast, in IFN-competent MRC5 cells TULV/Lodz isolate, that possesses the NSs ORF for the full-length protein of 90 aa, survived for more consequent passages than TULV/Moravia isolate, which contains the ORF for truncated NSs protein (66-67 aa). Our data show that expression of a full-length NSs protein is beneficial for the virus survival and competitiveness in IFN-competent cells and not essential in IFN-deficient cells. These results suggest that the N-terminal aa residues are important for the full activity of the NSs protein.

  9. Sex Reporting in Preclinical Microbiological and Immunological Research.

    Science.gov (United States)

    Potluri, Tanvi; Engle, Kyrra; Fink, Ashley L; Vom Steeg, Landon G; Klein, Sabra L

    2017-11-14

    Both sex (i.e., biological construct of male and female) and gender (i.e., social construct of masculine and feminine) impact the pathogenesis of diseases, including those caused by microbial infections. Following the 2015 NIH policy for consideration of sex as a biological variable in preclinical research, in 2018, authors of papers published in primary-research American Society for Microbiology (ASM) journals will be asked to report the sex of the research subjects and animals and of materials derived directly from them. To address the need for sex reporting in ASM journals, we systematically reviewed 2,928 primary-research articles published in six primary-research ASM journals ( Antimicrobial Agents and Chemotherapy , Clinical and Vaccine Immunology , Infection and Immunity , Journal of Bacteriology , Journal of Virology , and mBio ) in 2016. Approximately 37% of animal studies and 9% of primary cell culture papers published in 2016 would have been affected by the new sex-reporting policy. For animal studies (i.e., studies with any nonhuman vertebrate hosts), most published papers either did not report the sex of the animals or used only female animals, and a minority used only males or both sexes. For published studies using primary cells from diverse animal species (i.e., humans and nonhuman vertebrates), almost all studies failed to report the sex of donors from which the cells were isolated. We believe that reporting the sex of animals and even of the donors of derived cells could improve the rigor and reproducibility of research conducted in microbiology and immunology and published in ASM journals. Copyright © 2017 Potluri et al.

  10. Pediatric allergy and immunology in Italy.

    Science.gov (United States)

    Tozzi, Alberto E; Armenio, Lucio; Bernardini, Roberto; Boner, Attilio; Calvani, Mauro; Cardinale, Fabio; Cavagni, Giovanni; Dondi, Arianna; Duse, Marzia; Fiocchi, Alessandro; Marseglia, Gian L; del Giudice, Michele Miraglia; Muraro, Antonella; Pajno, Giovanni B; Paravati, Francesco; Peroni, Diego; Tripodi, Salvatore; Ugazio, Alberto G; Indinnimeo, Luciana

    2011-05-01

    In Italy, according to the International Study on Asthma and Allergies in Childhood study, the prevalence of current asthma, allergic rhinoconjunctivitis, and atopic eczema in 2006 was 7.9%, 6.5%, and 10.1% among children aged 6-7 and 8.4%, 15.5%, and 7.75% among children aged 13-14 yr. University education in this field is provided by the Postgraduate Schools of Pediatrics and those of Allergology and Clinical Immunology, as well as several annual Master courses. The Italian Society of Pediatric Allergology and Immunology (SIAIP) was founded in 1996 and counts about 1000 members. SIAIP promotes evidence-based management of allergic children and disseminates information to patients and their families through a quite innovative website and the National Journal 'Rivista Italiana di Allergologia Pediatrica'. In the last decade, four major regional, inter-regional, and national web-based networks have been created to link pediatric allergy centers and to share their clinical protocols and epidemiologic data. In addition, National Registers of Primary Immune-deficiencies and on Pediatric HIV link all clinical excellence centers. Research projects in the field of pediatric allergy and immunology are founded by the Italian Ministry of Education, University and Research (MIUR) and by the National Research Council (CNR), but the overall investments in this research area are quite low. Only a handful Italian excellence centers participate in European Projects on Pediatric Allergy and Immunology within the 7th Framework Program. The European Academy of Allergy and Clinical Immunology currently hosts two Italians in its Executive Committee (EC) and one in the EC of the Pediatric Section; moreover, major European Academy of Allergy and Clinical Immunology meetings and courses in the area of pediatrics (e.g., PAAM, Venice, 2009) have been held in Italy in the last 3 yr. Italian hallmarks in the management of allergic diseases in childhood are a quite alive and spread interest in

  11. Summary of the primer on tumor immunology and the biological therapy of cancer

    Directory of Open Access Journals (Sweden)

    Margolin Kim

    2009-01-01

    Full Text Available Abstract The International Society for Biological Therapy of Cancer (iSBTc is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1 cytokines in cancer immunology; (2 anti-angiogenic therapy; (3 end stage: immune killing of tumors; (4 blocking T cell checkpoints; (5 approach to identification and therapeutic exploitation of tumor antigens; (6 T regulatory cells; (7 adoptive T cell therapy; (8 immune monitoring of cancer immunotherapy; and (9 immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.

  12. Unique topics and issues in rheumatology and clinical immunology.

    Science.gov (United States)

    Selmi, Carlo

    2014-08-01

    Clinicians are facing unexpected issues in everyday practice, and these may become counterintuitive or challenging. Illustrative examples are provided by the hypersensitivity to universally used immunosuppressants such as corticosteroids or antibiotics such as beta-lactam. Secondly, additional issues are represented by the discovery of new pathogenetic mechanisms involved in rheumatoid and psoriatic arthritis or other chronic inflammatory diseases, genomic susceptibility to enigmatic diseases such as giant cell arteritis, or the shared role of specific mediators such as semaphorins. Third, the therapeutic armamentarium has dramatically changed over the past decade following the introduction of biotechnological drugs, and new mechanisms are being proposed to reduce adverse events or increase the drug effectiveness, particularly on cardiovascular comorbidities. Finally, rare diseases continue to represent difficult cases, as for Cogan's syndrome, with limited literature available for clinical recommendations. For these reason, the present issue of Clinical Reviews in Allergy and Immunology is timely and dedicated to these and other unique topics in clinical immunology and allergy. The aim of this issue is thus to help clinicians involved in internal medicine as well as allergists and clinical immunologists while discussing new pathways that will prove important in the near future.

  13. Immunology Guides Skeletal Muscle Regeneration

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    F. Andrea Sass

    2018-03-01

    Full Text Available Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

  14. Multiple sclerosis: current immunological aspects

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    Carlos Cuevas-García

    2017-02-01

    Full Text Available Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed on its origin: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments’ main purpose is to modulate aspects related to the adaptive immune response (B and T cells. The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

  15. The Immunological Basis of Hypertension

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    Pons, Héctor; Quiroz, Yasmir; Johnson, Richard J.

    2014-01-01

    A large number of investigations have demonstrated the participation of the immune system in the pathogenesis of hypertension. Studies focusing on macrophages and Toll-like receptors have documented involvement of the innate immunity. The requirements of antigen presentation and co-stimulation, the critical importance of T cell–driven inflammation, and the demonstration, in specific conditions, of agonistic antibodies directed to angiotensin II type 1 receptors and adrenergic receptors support the role of acquired immunity. Experimental findings support the concept that the balance between T cell–induced inflammation and T cell suppressor responses is critical for the regulation of blood pressure levels. Expression of neoantigens in response to inflammation, as well as surfacing of intracellular immunogenic proteins, such as heat shock proteins, could be responsible for autoimmune reactivity in the kidney, arteries, and central nervous system. Persisting, low-grade inflammation in these target organs may lead to impaired pressure natriuresis, an increase in sympathetic activity, and vascular endothelial dysfunction that may be the cause of chronic elevation of blood pressure in essential hypertension. PMID:25150828

  16. Potential immunological benefits of Echinacea

    International Nuclear Information System (INIS)

    Abbas, M.M.; Mahmoud, A.H.; Sharoud, M.N.M.

    2009-01-01

    Nowadays, herbal remedy is becoming as the spotlight which capture the public attention. Echinacea is marketed as a dietary supplement to promote the immune system and it is currently one of the best-selling herbs according to the Nutrition Business Journal, and is touted as a favourite botanical remedy among herbal and alternative medicine experts. The goal of this study is to evaluate the effect of oral application of a commercially available Echinacea preparation on the immune system in Egyptian male and female volunteers. For this purpose, 25 healthy male and female adults, 23-45 years, will receive Echinacea preparation. The total daily dose 125 mg for consecutive 10 days. Blood was withdrawn to assess some immune markers just before beginning the study and after completing the course of medication. The herb extract induced a significant increase in IgG level and the percentage of immune cell populations, including CD4 and CD8 in both male and female volunteers. Also, there is a significant increase in CD4/CD8 ratio. In addition, there is a significant increase in the total leucocyte. In regard to the differential leucocyte, the Echinacea preparation significantly increased the lymphocytes in peripheral blood. For other leucocyte subpopulations (neutrophil, monocyte, eosinophil and basophil), no significant difference was observed after Echinacea treatment. The erythrocytic counts, the haemoglobin concentration and the haematocrit were in significantly increased in male but insignificantly in female. No remarkable change was noted in the platelets count after the treatment of Echinacea. These findings demonstrated that the plant Echinacea have immune-enhancing properties in male and female Egyptian volunteers

  17. In vitro evaluation of immunological properties of extracellular polysaccharides produced by Lactobacillus delbrueckii strains.

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    Kishimoto, Mana; Nomoto, Ryohei; Osawa, Ro

    2015-01-01

    We investigated the variation in immunological properties of the extracellular polysaccharides (EPSs) produced by different Lactobacillus delbrueckii strains as well as that of their monosaccharide composition. The monosaccharide composition of each EPS produced by L. delbrueckii strains, as determined by thin layer chromatography (TLC), showed an appreciable variation in a strain-dependent manner, which could be broadly assigned to 4 TLC groups. Meanwhile, the immunological properties of the EPSs produced by 10 L. delbrueckii strains were evaluated in a semi-intestinal model using a Transwell co-culture system, which employed human intestinal epithelial Caco-2 cells on the apical side and murine macrophage RAW264.7 cells on the basolateral side. Each EPS was added to the apical side to allow direct contact with Caco-2 cells and incubated for 6 hr. After incubation, the amounts of TNF-α and several cytokines that had been released by either RAW264.7 or Caco-2 cells were then quantified by cytotoxic activity on L929 cells or the RT-PCR method. It was found that the EPS-stimulated RAW264.7 cells express different profiles of cytokine production via Caco-2 cells but that the profile difference could not be related to the above TLC grouping. The evidence suggests that the EPSs of L. delbrueckii strains are diverse not only in their biochemical structure but also in their immunological properties.

  18. The immunological mechanisms that control pneumococcal carriage.

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    Simon P Jochems

    2017-12-01

    Full Text Available Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.

  19. What Can Vampires Teach Us about Immunology?

    Science.gov (United States)

    Schneider, David S

    2016-04-01

    Speculative fiction examines the leading edge of science and can be used to introduce ideas into the classroom. For example, most students are already familiar with the fictional infectious diseases responsible for vampire and zombie outbreaks. The disease dynamics of these imaginary ailments follow the same rules we see for real diseases and can be used to remind students that they already understand the basic rules of disease ecology and immunology. By engaging writers of this sort of fiction in an effort to solve problems in immunology we may be able to perform a directed evolution experiment where we follow the evolution of plots rather than genetic traits. Copyright © 2016. Published by Elsevier Ltd.

  20. Immunological effects of ayahuasca in humans.

    Science.gov (United States)

    dos Santos, Rafael Guimarães

    2014-01-01

    Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.