Cellular immune therapy for chronic lymphocytic leukemia

NARCIS (Netherlands)

Kater, Arnon P.; van Oers, Marinus H. J.; Kipps, Thomas J.

2007-01-01

Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for

Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.

LENUS (Irish Health Repository)

Kenny-Walsh, E

2012-02-03

BACKGROUND AND METHODS: In February 1994, batches of anti-D immune globulin used in Ireland during 1977 and 1978 to prevent Rh isoimmunization were found to be contaminated with hepatitis C virus (HCV) from a single infected donor. In March 1994, a national screening program was initiated for all women who had received anti-D immune globulin between 1970 and 1994. Of the 62,667 women who had been screened when this study began, 704 (1.1 percent) had evidence of past or current HCV infection, and 390 of those 704 (55 percent) had positive tests for serum HCV RNA on reverse-transcription-polymerase-chain-reaction analysis. All 390 were offered a referral for clinical assessment and therapy. We evaluated 376 of these 390 women (96 percent); the other 14 were not seen at one of the designated treatment centers. RESULTS: The mean (+\\/-SD) age of the 376 women was 45+\\/-6 years at the time of screening. They had been infected with hepatitis C for about 17 years. A total of 304 women (81 percent) reported symptoms, most commonly fatigue (248 [66 percent]). Serum alanine aminotransferase concentrations were slightly elevated (40 to 99 U per liter) in 176 of 371 women (47 percent), and the concentrations were 100 U per liter or higher in 31 (8 percent). Liver biopsies showed inflammation in 356 of 363 women (98 percent); in most cases the inflammation was slight (41 percent) or moderate (52 percent). Although the biopsy samples from 186 of the 363 women (51 percent) showed evidence of fibrosis, only 7 women (2 percent) had probable or definite cirrhosis. Two of the seven reported excessive alcohol consumption. CONCLUSIONS: Most of the women with HCV infection 17 years after receiving HCV-contaminated anti-D immune globulin had evidence of slight or moderate hepatic inflammation on liver biopsy, about half had fibrosis, and 2 percent had probable or definite cirrhosis.

Relations between immune and mediator receptors of mouse lymphocytes

International Nuclear Information System (INIS)

Ado, A.D.; Alekseeva, T.A.; Kravchenko, S.A.

1985-01-01

This paper examines the action of the specific muscarinic antogonist tritium-quinuclidinyl benzilate (tritium-QNB) on immune rosette formation in mice. It is shown that since the specific muscarini antagonist tritium-QNB inhibits immune rosette formation, this process must be regarded as interconnected with muscarinic receptors of lymphocytes. Interaction of immune (antigen-binding) and mediator receptors, however, is an important factor maintaining immune homeostasis at a certain level

Asymmetric T lymphocyte division in the initiation of adaptive immune responses.

Science.gov (United States)

Chang, John T; Palanivel, Vikram R; Kinjyo, Ichiko; Schambach, Felix; Intlekofer, Andrew M; Banerjee, Arnob; Longworth, Sarah A; Vinup, Kristine E; Mrass, Paul; Oliaro, Jane; Killeen, Nigel; Orange, Jordan S; Russell, Sarah M; Weninger, Wolfgang; Reiner, Steven L

2007-03-23

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.

The cytotoxic T lymphocyte immune synapse at a glance.

Science.gov (United States)

Dieckmann, Nele M G; Frazer, Gordon L; Asano, Yukako; Stinchcombe, Jane C; Griffiths, Gillian M

2016-08-01

The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers. © 2016. Published by The Company of Biologists Ltd.

Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects.

Science.gov (United States)

Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens

2017-10-01

Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Simultaneous passive and active immunization against hepatitis B: noninterference of hepatitis B immune globulin with the anti-HBs response to reduced doses of heat-inactivated hepatitis B vaccine

NARCIS (Netherlands)

Lelie, P. N.; Reesink, H. W.; Grijm, R.; de Jong-van Manen, S. T.; Reerink-Brongers, E. E.

1986-01-01

The effect of simultaneous administration of hepatitis B immune globulin on the antibody response to a low dose of heat-inactivated hepatitis B vaccine was investigated in 175 health care workers. Subjects were divided into four groups: Groups I and II received 3 monthly injections of a reduced dose

Effect of Co-60 irradiation on hyperimmune antimeningococcus globulins-gamma

International Nuclear Information System (INIS)

Galguera, M.; Le Riverand, E.; Padron, S.

1990-01-01

Globulins-gamma from voluntary blood donors immunized with the Cuban BC antimeningococcus vaccine is now being used in our country for the treatment of the meningococcus disease. This study of the effect of Co-60 irradiation on antimeningococcus globulins-gamma was carried out to try to eliminate the inconvenience shown by the traditionally used sterilization procedures (losses in the filter and persistence of viral contamination). globulins-gamma was obtained by ethanol fractionation and was irradiated at a different dose in solution with different stabilizers and it was also lyophilized. Results of the chemical controls carried out lead to the conclusion that it is possible to use radiosterilization on this product in a lyophilized form. The preservation of bactericidal activity, even after the highest irradiation doses, confirms the above mentioned. 13 refs

Profile of total protein, albumin, globulin and albumin globulin ratio in bulls

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Ida Zahidah Irfan

2014-06-01

Full Text Available Determination of serum total protein concentration and main fractions (albumin and globulin can be used as an important diagnostic tool in clinical biochemistry. Several factors can affect the concentration of total protein, albumin, globulin and albumin globulin ratio (A/G. The aim of this study is to obtain serum protein profiles, albumin, globulin and A/G ratio based on breed, age and BCS (body condition score. Blood samples from 160 bulls were collected. Blood chemistry were analyzed by photometer principle using a commercial kit. There were significant (P<0.001 breed variation on total protein, albumin, globulin and albumin globulin ratio. Significant age differences were observed on total protein and albumin concentration (P<0.001, while globulin concentration and A/G ratio were also significant (P<0.05. Amongs groups of BCS, significant difference was verified only in the albumin concentration (P<0.05. The concentration of total proteins, albumins and globulins in the serum of the bulls are higher than standard values for cattle, while A/G ratio is lower.

Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

Science.gov (United States)

Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

2016-05-01

Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

A specific immune tolerance toward offspring cells is to exist after the mother lymphocyte infusion.

Science.gov (United States)

Xing, Haizhou; Liu, Shiqin; Chen, Xue; Fang, Fang; Wu, Xueqiang; Zhu, Ping

2017-04-01

To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10 7 of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected. CFSE+, CFSE-, CD3+, CD8+, CD4+, CD19+, NK1.1+, CD25+, and CD127+ lymphocytes in those samples were analyzed by flow cytometry. The distribution of donor T cells, B cells, NK cells, helper T cells, cytotoxic T cells, and recipient regulatory T cells in the tissues were then analyzed. Maternal lymphocytes were more likely to survive in offspring. At 120h after infusion, the percentages of maternal cells in the offspring were 0.52±0.11% in lymph nodes, 0.97±0.04% in peripheral blood, and 0.97±0.11% in the spleen. Few donor cells, if any, were detected in these tissues at 120h after aunt to child, father to child, and unrelated allogeneic infusions were performed. The subtype proportion of donor lymphocytes changed significantly in the recipient tissues. Recipient Treg cells increased in the mother to child group, but not in the aunt to child, father to child, and unrelated allogeneic groups, suggesting a decreased cellular immune response to allogeneic cells in the mother to child group. At 120h after the infusion, no donor cells were detected in the recipient livers and thymuses of all groups, implying that donor cells were barely able to colonize in the liver and thymus. Specific immune tolerance to maternal lymphocytes exists in offspring. An infusion of maternal donor lymphocytes may produce a relatively persistent effect of adoptive immunotherapy with reduced side-effects. Copyright © 2017 Elsevier GmbH. All rights

Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

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Pavlica Ljiljana

2003-01-01

Full Text Available INTRODUCTION Reiter's syndrome (RS is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlmaydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF and from peripheral blood (PB [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples and the results were compared with those found in 10 patients with rheumatoid arthritis (RA (10 PB samples, 5 SF samples. Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% Na

Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

Science.gov (United States)

Häyry, P.; Defendi, V.

1970-01-01

We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin

NARCIS (Netherlands)

Bos, J. D.; Zonneveld, I.; Das, P. K.; Krieg, S. R.; van der Loos, C. M.; Kapsenberg, M. L.

1987-01-01

The complexity of immune response-associated cells present in normal human skin was recently redefined as the skin immune system (SIS). In the present study, the exact immunophenotypes of lymphocyte subpopulations with their localizations in normal human skin were determined quantitatively. B cells

T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

Science.gov (United States)

Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

2017-03-01

Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

Requirement for Innate Immunity and CD90+ NK1.1− Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy

Science.gov (United States)

Moskalenko, Marina; Pan, Michael; Fu, Yichun; de Moll, Ellen H.; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Jayaraman, Padmini; Bernardo, Sebastian; Sikora, Andrew G.; Wolchok, Jedd; Bhardwaj, Nina; Merad, Miriam; Saenger, Yvonne

2015-01-01

We sought to define cellular immune mechanisms of synergy between tumor-antigen–targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1−/− mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, mice deficient in both classical natural killer (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain IL2γc−/−) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1+ cells does not impair antitumor effect. Depletion of CD90+NK1.1− lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the tumor. Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90+NK1.1− ILCs in chemo-immunotherapy. PMID:25600438

Synthesis and preliminary study of 99mTc-mercaptoacetyl-triglycine (99mTc-MAG3) for radiolabeling of immune globulins

International Nuclear Information System (INIS)

Reyes, L.; Navarrete, M.

2001-01-01

The synthesis of a complex molecule with its coordination center composed by a triamide monomercaptide tetradentate set of donor groups plus a phenyl-acetyl group as protector group of a sulphur atom is reported. This compound has been mixed with immune globulin G, labeled with 99m Tc and purified by high resolution liquid chromatography (HRLC). The biological behavior of this labeled compound was evaluated with mice of Balb-C origin, showing the biological properties of a protein. This molecule might be another option for radio-immuno-scintigraphic analysis when using proteins of antigenic nature. (author)

Pharmacokinetics and modeling of immune cell trafficking: quantifying differential influences of target tissues versus lymphocytes in SJL and lipopolysaccharide-treated mice

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Banks William A

2012-10-01

Full Text Available Abstract Background Immune cell trafficking into the CNS and other tissues plays important roles in health and disease. Rapid quantitative methods are not available that could be used to study many of the dynamic aspects of immune cell-tissue interactions. Methods We used pharmacokinetics and modeling to quantify and characterize the trafficking of radioactively labeled lymphocytes into brain and peripheral tissues. We used variance from two-way ANOVAs with 2 × 2 experimental designs to model the relative influences of lymphocytes and target tissues in trafficking. Results We found that in male CD-1 mice, about 1 in 5,000 intravenously injected lymphocytes entered each gram of brain. Uptake by brain was 2 to 3 times higher in naïve SJL females, but uptake by spleen and clearance from blood was lower, demonstrating a dichotomy in immune cell distribution. Treatment of CD-1 mice with lipopolysaccharide (LPS increased immune cell uptake into brain but decreased uptake by spleen and axillary nodes. Conclusions Differences in brain uptake and in uptake by spleen between SJL and CD-1 mice were primarily determined by lymphocytes, whereas differences in uptake with LPS were primarily determined by lymphocytes for the brain but by the tissues for the spleen and the axillary lymph node. These results show that immune cells normally enter the CNS and that tissues and immune cells interact in ways that can be quantified by pharmacokinetic models.

Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial

OpenAIRE

Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

2017-01-01

Background Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immunemediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II–IV acute graft-versus-host disease (GVHD). Methods We conducted a multicentre, randomised, open-label, p...

T Lymphocyte-Endothelial Interactions: Emerging Understanding of Trafficking and Antigen-Specific Immunity

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Christopher Vincent Carman

2015-11-01

Full Text Available Antigen-specific immunity requires regulated trafficking of T cells in and out of diverse tissues in order to orchestrate lymphocyte development, immune surveillance, responses and memory. The endothelium serves as a unique barrier, as well as a sentinel, between the blood and the tissues and as such it plays an essential locally tuned role in regulating T cell migration and information exchange. While it is well established that chemoattractants and adhesion molecules are major determinants of T cell trafficking, emerging studies have now enumerated a large number of molecular players as well as a range of discrete cellular remodeling activities (e.g. transmigratory cups and invadosome-like protrusions, IPLs that participate in directed migration and pathfinding by T cells. In addition to providing trafficking cues, intimate cell-cell interaction between lymphocytes and endothelial cells provide instruction to T cells that influence their activation and differentiation states. Perhaps the most intriguing and underappreciated of these ‘sentinel’ roles is the ability of the endothelium to act as a non-hematopoietic ‘semi-professional’ antigen-presenting cell. Close contacts between circulating T cells and antigen-presenting endothelium may play unique non-redundant roles in shaping adaptive immune responses within the periphery. A better understanding of the mechanisms directing T cell trafficking and the antigen-presenting role of the endothelium may not only increase our knowledge of the adaptive immune response but also empower the utility of emerging immunomodulatory therapeutics.

SHBG (Sex Hormone Binding Globulin)

Science.gov (United States)

... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

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CUPO Palmira

2001-01-01

Full Text Available An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG prevented the execution of the skin sensitivity test (SST and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP, a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71% received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2 and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP, with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out

Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

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Giuseppe Scapigliati

2018-05-01

Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

The immunophenotype of bone marrow lymphocytes in children with immune thrombocytopenic purpura.

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Alavi, Samin; Aryan, Zahra; Ghazizadeh, Farid; Arabi, Nahid; Nikougoftar, Mahin; Ebadi, Maryam

2014-09-01

Primary immune thrombocytopenic purpura (ITP), caused by immune system dysfunction, is recognized as the leading cause of thrombocytopenia in pediatric population. Nonetheless, inadequate studies have been performed on bone marrow immunophenotyping of children with ITP. In this study, we aimed to investigate the immunophenotype of bone marrow lymphocytes in these children. Between 2008 and 2012, 35 children with ITP and 26 age and sex matched healthy controls were recruited. All participants underwent bone marrow aspiration. Appropriate B-cell, T-cell, and myeloid lineage monoclonal antibodies were employed to determine the immunophenotype of these patients. CD10, CD19, and CD20, all indicative of premature B-cell markers, were significantly greater in children with ITP. CD22, mainly expressed on mature B cells was slightly, but not significantly reduced in the patients' group (P = .42). On the other hand, T cell markers including CD2, CD3, CD5, and CD7 were underexpressed. CD33, a specific marker for myeloid lineage, was underexpressed in the patients' group (5.6 ± 4.7 vs. 12.9 ± 7.3, P < .001). Noteworthy, the immunophenotype did not significantly differ between acute and persistent cases. Overall, a phenotype characterized by increased pre-B-cell markers along with decreased T cell immunophenotypic markers was observed in bone marrow lymphocytes of children with ITP in the present study. Further larger scale studies are recommended to confirm our findings, as precise mapping of the immunophenotype of lymphocytes in these patients would pave the road to improved diagnosis and treatment.

Killer B Lymphocytes and their Fas Ligand Positive Exosomes as Inducers of Immune Tolerance

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Steven Karl Lundy

2015-03-01

Full Text Available Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL, and their ability to kill T helper (TH lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed MHC Class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.

B and T lymphocyte attenuator restricts the protective immune response against experimental malaria.

Science.gov (United States)

Adler, Guido; Steeg, Christiane; Pfeffer, Klaus; Murphy, Theresa L; Murphy, Kenneth M; Langhorne, Jean; Jacobs, Thomas

2011-11-15

The immune response against the blood stage of malaria has to be tightly regulated to allow for vigorous antiplasmodial activity while restraining potentially lethal immunopathologic damage to the host like cerebral malaria. Coinhibitory cell surface receptors are important modulators of immune activation. B and T lymphocyte attenuator (BTLA) (CD272) is a coinhibitory receptor expressed by most leukocytes, with the highest expression levels on T and B cells, and is involved in the maintenance of peripheral tolerance by dampening the activation of lymphocytes. The function of BTLA is described in several models of inflammatory disorders and autoimmunity, but its function in infectious diseases is less well characterized. Also, little is known about the influence of BTLA on non-T cells. In this study, we analyzed the function of BTLA during blood-stage malaria infection with the nonlethal Plasmodium yoelii strain 17NL. We show that BTLA knockout mice exhibit strongly reduced parasitemia and clear the infection earlier compared with wild-type mice. This increased resistance was seen before the onset of adaptive immune mechanisms and even in the absence of T and B cells but was more pronounced at later time points when activation of T and B cells was observed. We demonstrate that BTLA regulates production of proinflammatory cytokines in a T cell-intrinsic way and B cell intrinsically regulates the production of P. yoelii 17NL-specific Abs. These results indicate that the coinhibitory receptor BTLA plays a critical role during experimental malaria and attenuates the innate as well as the subsequent adaptive immune response.

Admission levels of serum Gc-globulin

DEFF Research Database (Denmark)

Schiødt, F V; Bondesen, S; Petersen, I

1996-01-01

Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio...... in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L....

Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

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Caimi Luigi

2010-11-01

Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

Lymphocyte-Related Inflammation and Immune-Based Scores Predict Prognosis of Chordoma Patients After Radical Resection

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Wenhao Hu

2018-04-01

Full Text Available The inflammatory microenvironment plays a critical role in the development and progression of malignancies. In the present study, we aimed to evaluate the prognostic value of lymphocyte-related inflammation and immune-based prognostic scores in patients with chordoma after radical resection, including the neutrophil-lymphocyte ratio (NLR, platelet-lymphocyte ratio (PLR, monocyte-lymphocyte ratio (MLR, and systemic immune-inflammation index (SII. A total of 172 consecutive patients with chordoma who underwent radical resection were reviewed. R software was used to randomly select 86 chordoma patients as a training set and 86 chordoma patients as a validation set. Potential prognostic factors were also identified, including age, sex, tumor localization, KPS, Enneking stage, tumor size, and tumor metastasis. Overall survival (OS was calculated using the Kaplan–Meier method and multivariate Cox regression analyses. NLR, PLR, SII, Enneking stage, tumor differentiation and tumor metastasis were identified as significant factors from the univariate analysis in both the training and validation sets and were subjected to multivariate Cox proportional hazards analysis. The univariate analysis showed that NLR ≥1.65, PLR ≥121, and SII ≥370×109/L were significantly associated with poor OS. In the multivariate Cox proportional hazard analysis, SII, Enneking stage and tumor metastasis were significantly associated with OS. As noninvasive, low-cost, reproducible prognostic biomarkers, NLR, PLR and SII could help predict poor prognosis in patients with chordoma after radical resection. This finding may contribute to the development of more effective tailored therapy according to the characteristics of individual tumors.

Evolution and phylogeny of B lymphocytes

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Fabiola Claudio-Piedras

2016-05-01

Full Text Available B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

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Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael

2018-02-09

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

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Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

2015-07-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Preparation of anti-CEA and anti-goat γ-globulin sera for radioimmunologic assay of carcinoembryonic antigen

International Nuclear Information System (INIS)

Kusnierczyk-Glazman, H.; Breborowicz, J.

1977-01-01

Goats were immunized with purified carcinoembryonic antigen, and the suitability of the antisera for clinical assays of carcinoembryonic antigen was characterized. Reactivity of equine sera to goat γ-globulin as a precipitating factor in the radioimmunologic double antibody technique was also evaluated. (author)

Boron Affects Immune Function Through Modulation of Splenic T Lymphocyte Subsets, Cytokine Secretion, and Lymphocyte Proliferation and Apoptosis in Rats.

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Jin, Erhui; Li, Shenghe; Ren, Man; Hu, Qianqian; Gu, Youfang; Li, Kui

2017-08-01

This study demonstrated the mechanisms of boron effects in a rat model and provided a scientific basis for the rational of boron use. These findings were achieved by investigating the effects of boron (10, 20, 40, 80, 160, 320, and 640 mg/L in drinking water or 1.5, 3, 6, 12, 24, 48, and 96 mg/kg BW) on rat serum immunoglobulins (IgGs), splenic cytokines, lymphocyte subsets, as well as on lymphocyte proliferation and apoptosis. Addition of 20 (3) and 40 (6) mg/L (mg/kg BW) of boron to drinking water significantly increased rat serum IgG concentrations, splenic IFN-γ and IL-4 expression as well as the number of splenic CD3 + , CD4 + and proliferating cell nuclear antigen (PCNA) + cells. Supplementation of drinking water with 40 mg/L (6 mg/kg BW) boron also markedly increased splenic IL-2 expression and the CD4 + /CD8 + cell ratio and reduced splenic CD8 + cell number. Supplementation with 80 mg/L (12 mg/kg BW) boron significantly increased CD3 + and PCNA + cell numbers (P boron markedly reduced the serum IgG concentrations; splenic IL-2 and IL-10 expression; the number of CD3 + , CD4 + and PCNA + cells; and increased the number of splenic CD8 + and caspase-3 + cells and promoted caspase-3 expression in CD3 + cells. In conclusion, these findings suggest that the supplementation of rat drinking water with 20(3) and 40(6) mg/L (mg/kg BW) boron can markedly enhance humoral and cellular immune functions, while boron concentrations above 320 mg/L (48 mg/kg BW) can have an inhibitory effect or even toxicity on immune functions. These results exhibit a U-shaped response characteristic of low and high doses of boron supplementation on immune function and imply that proper boron supplementation in food for humans and animals could be used as an immunity regulator.

Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals

DEFF Research Database (Denmark)

Theander, T G; Bygbjerg, I C; Jepsen, S

1986-01-01

Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria-immune i......Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria...

Radiosensitivities of sensitized lymphocytes

International Nuclear Information System (INIS)

Taniguchi, Kazuto

1979-01-01

Immunization of mice with cell antigens such as allogeneic tumor cells or xenogeneic erythrocytes raises a variety of immune reactions mediated by T lymphocytes: i.e. delayed type hypersensitivity (DTH), cytotoxicity, and antibody production. The radiosensitivities of these reactions were examined in mice exposed to 600 R x-irradiation a few hours before or after immunization. 1) DTH to xenogeneic erythrocytes, as demonstrated by footpad reaction, was not suppressed by irradiation 3 h before or after immunization. DTH to allogeneic tumor cells, as demonstrated by a migration inhibition test, hardly developed in mice that had been irradiated before or after immunization. It may have belonged to distinct types of delayed reactions which were mediated by distinct subpopulations of T lymphocytes. 2) Cytotoxicity against allogeneic cells and xenogeneic erythrocytes showed almost the same radiosensitivity. It was scarcely detected in mice that had been irradiated before immunization. However, a low but definite degree of cytotoxicity was detected in mice that had been irradiated only a few hours after immunization. Solubilized allogeneic cells instead of native cells were used as immunizing antigens. It was also possible for precursor cells with cytotoxicity to acquire a radioresistant nature by immunization of solubilized antigens, but native cells were required as stimulation for radioresistant precursor cells to differentiated into nature cytotoxic effector cells. 3) Antibody production against xenogeneic erythrocytes or allogeneic cells was almost completely depleted in mice that had been irradiated before or after immunization. It is possible that antibody production essentially requires cell division and clonal expansion of B lymphocytes. (Bell, E.)

Immune Modulation in Normal Human Peripheral Blood Mononuclear Cells (PBMCs) (Lymphocytes) in Response to Benzofuran-2-Carboxylic Acid Derivative KMEG during Spaceflight

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Okoro, Elvis; Mann, Vivek; Ellis, Ivory; Mansoor, Elvedina; Olamigoke, Loretta; Marriott, Karla Sue; Denkins, Pamela; Williams, Willie; Sundaresan, Alamelu

2017-08-01

Microgravity and radiation exposure during space flight have been widely reported to induce the suppression of normal immune system function, and increase the risk of cancer development in humans. These findings pose a serious risk to manned space missions. Interestingly, recent studies have shown that benzofuran-2-carboxylic acid derivatives can inhibit the progression of some of these devastating effects on earth and in modeled microgravity. However, these studies had not assessed the impacts of benzofuran-2- carboxylic acid and its derivatives on global gene expression under spaceflight conditions. In this study, the ability of a specific benzofuran-2-carboxylic acid derivative (KMEG) to confer protection from radiation and restore normal immune function was investigated following exposure to space flight conditions on the ISS. Normal human peripheral blood mononuclear cells (lymphocytes) treated with 10 µ g/ml of KMEG together with untreated control samples were flown on Nanoracks hardware on Spacex-3 flight. The Samples were returned one month later and gene expression was analyzed. A 1g-ground control experiment was performed in parallel at the Kennedy spaceflight center. The first overall subtractive unrestricted analysis revealed 78 genes, which were differentially expressed in space flight KMEG, untreated lymphocytes as compared to the corresponding ground controls. However, in KMEG-treated space flight lymphocytes, there was an increased expression of a group of genes that mediate increased transcription, translation and innate immune system mediating functions of lymphocytes as compared to KMEG-untreated samples. Analysis of genes related to T cell proliferation in spaceflight KMEG-treated lymphocytes compared to 1g-ground KMEG- treated lymphocytes revealed six T cell proliferation and signaling genes to be significantly upregulated (p trafficking, promote early response, mediating C-myc related proliferation, promote antiapoptotic activity and protects

Cellular energy metabolism in T-lymphocytes.

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Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

2015-01-01

Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

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He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination

THE COLLOIDAL BEHAVIOR OF SERUM GLOBULIN

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Hitchcock, David I.

1922-01-01

1. The globulin prepared from ox serum by dilution and precipitation with carbon dioxide has been found, by electrometric titration experiments, to behave like an amphoteric electrolyte, reacting stoichiometrically with acids and bases. 2. The potential difference developed between a solution of globulin chloride, phosphate, or acetate and a solution of the corresponding acid, free from protein, separated from the globulin by a collodion membrane, was found to be influenced by hydrogen ion concentration and salt concentration in the way predicted by Donnan's theory of membrane equilibrium. In experiments with sodium globulinate and sodium hydroxide it was found that the potential difference could be similarly explained. 3. The osmotic pressure of such solutions could be qualitatively accounted for by the Donnan theory, but exhibited a discrepancy which is explicable by analogy with certain experiments of Loeb on gelatin. 4. The application of Loeb's theory of colloidal behavior, which had previously been found to hold in the case of gelatin, casein, egg albumin, and edestin, has thus been extended to another protein, serum globulin. PMID:19871977

Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control

NARCIS (Netherlands)

Ferreira, Manuel A. R.; Mangino, Massimo; Brumme, Chanson J.; Zhao, Zhen Zhen; Medland, Sarah E.; Wright, Margaret J.; Nyholt, Dale R.; Gordon, Scott; Campbell, Megan; McEvoy, Brian P.; Henders, Anjali; Evans, David M.; Lanchbury, Jerry S.; Pereyra, Florencia; Walker, Bruce D.; Haas, David W.; Soranzo, Nicole; Spector, Tim D.; de Bakker, Paul I. W.; Frazer, Ian H.; Montgomery, Grant W.; Martin, Nicholas G.; Agan, Brian; Agarwal, Shanu; Allen, Brady; Altidor, Sherly; Altschuler, Eric; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Andrady, Ushan; Angell, Teresa; Appelbaum, Jonathan; Arnold, Kathy; Arroyo, Julio; Arthur, Ernie; Barbaro, Daniel; Barrett, Tom; Barrie, William; Barthel, Vincent; Bartlett, Mary E.; Barton, Simon; Basden, Pat; Basgoz, Nesli; Bellos, Nicholas; Berger, Judith; Bernard, Annette; Bernard, Nicole; Blair, Donald; Schuitemaker, Hanneke

2010-01-01

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We

Opinion: Interactions of innate and adaptive lymphocytes

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Gasteiger, Georg; Rudensky, Alexander Y.

2015-01-01

Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

Immune Cell-Mediated Protection against Vaginal Candidiasis: Evidence for a Major Role of Vaginal CD4+ T Cells and Possible Participation of Other Local Lymphocyte Effectors

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Santoni, Giorgio; Boccanera, Maria; Adriani, Daniela; Lucciarini, Roberta; Amantini, Consuelo; Morrone, Stefania; Cassone, Antonio; De Bernardis, Flavia

2002-01-01

The protective roles of different lymphocyte subsets were investigated in a rat vaginal candidiasis model by adoptive transfer of vaginal lymphocytes (VL) or sorted, purified CD3+ T cells, CD4+ or CD8+ T cells, or CD3− CD5+ B cells from the vaginas of naïve or immune rats following three rounds of Candida albicans infection. The adoptive transfer of total VL from nonimmune animals did not alter the course of vaginal candidiasis of the recipient rats. In contrast, the animals receiving total VL or CD3+ T cells from immune rats showed a highly significant acceleration of fungus clearance compared with animals which received nonimmune VL. The animals with vaginal CD3− CD5+ B cells transferred from immune rats also had fewer Candida CFU than the controls, but fungal clearance was significantly retarded with respect to the animals administered immune T cells. Sorted, purified CD4+ and CD8+ vaginal T cells from immune rats were also adoptively transferred to naïve animals. Although both populations were seen to accelerate the clearance of the fungus from the vagina, CD4+ T cells were much more effective than CD8+ T cells. Overall, there was no difference between the antifungal effects of immune vaginal CD4+ T cells and those achievable with the transfer of whole, immune VL. Histological observations of the vaginal tissues of rats with adoptively transferred immune T cells demonstrated a remarkable accumulation of lymphocytes in the subepithelial lamina propria and also infiltrating the mucosal epithelium. These results strongly suggest that distinct vaginal lymphocyte subsets participate in the adaptive anti-Candida immunity at the vaginal level, with the vaginal CD4+ T cells probably playing a major role. PMID:12183521

Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

Directory of Open Access Journals (Sweden)

Dorward Heidi

2007-01-01

Full Text Available Abstract Background Hereditary Inclusion Body Myopathy (HIBM is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM, has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG, in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22% directly after IVIG loading to 25.6 kg (+35% at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44% directly after IVIG loading to 6.0 kg (+46% at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.

A New Enzyme-Linked Immunosorbent Assay for a Total Anti-T Lymphocyte Globulin Determination: Development, Analytical Validation, and Clinical Applications.

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Montagna, Michela; La Nasa, Giorgio; Bernardo, Maria E; Piras, Eugenia; Avanzini, Maria A; Regazzi, Mario; Locatelli, Franco

2017-06-01

Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological posttransplant complications, in particular rejection and graft-versus-host disease, after allogeneic hematopoietic stem cell transplantation (HSCT). We developed and validated a new enzyme-linked immunosorbent assay (ELISA) method to measure serum levels of total ATLG and evaluate the pharmacokinetics (PK) of the drug in children with β-Thalassemia, receiving allogeneic HSCT. Diluted serum samples were incubated with Goat-anti-Rabbit IgG antibody coated on a microtiter plate and then, with Goat-anti-Human IgG labeled with horseradish peroxidase. After incubation and washings, substrate solution was added and absorbance was read at 492 nm. ATLG concentrations in samples were determined by interpolation from a standard curve (range: 200-0.095 ng/mL), prepared by diluting a known amount of ATLG in phosphate-buffered saline (PBS). Low, medium, and high-quality control concentrations were 1.56, 6.25, and 25 ng/mL, respectively. This method was developed and validated within the acceptance criteria in compliance with the Guidelines for a biological method validation: the sensitivity of the method was 0.095 ng/mL. We analyzed serum samples from 14 children with β-Thalassemia who received ATLG (Grafalon) at a dose of 10 mg/kg administered as intravenous (IV) infusion on days -5, -4, and -3 before HSCT (day 0). Blood sampling for PK evaluation was performed on days -5, -4, and -3 before and after drug infusion; and then from day -2 to +56. The median total ATLG levels pre-IVand post-IV were 0 and 118 mcg/mL on day -5; 85.9 and 199.2 mcg/mL on day -4; 153 and 270.9 mcg/mL on day -3, respectively. The median PK values of CL was 0.0029 (range: 0.0028-0.0057) L·kg·d, Vd was 0.088 (range: 0.025-0.448) L/kg and t1/2 was 20.2 (range: 5.8-50.2) days. These data suggest that given the marked interindividual variability of total ATLG disposition, the development of

MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

Directory of Open Access Journals (Sweden)

S. V. Khaidukov

2009-01-01

Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

Astaxanthin, a Carotenoid, Stimulates Immune Responses by Enhancing IFN-γ and IL-2 Secretion in Primary Cultured Lymphocytes in Vitro and ex Vivo

Science.gov (United States)

Lin, Kuan-Hung; Lin, Kao-Chang; Lu, Wan-Jung; Thomas, Philip-Aloysius; Jayakumar, Thanasekaran; Sheu, Joen-Rong

2015-01-01

Astaxanthin, a potent antioxidant carotenoid, plays a major role in modulating the immune response. In this study, we examined the immunomodulatory effects of astaxanthin on cytokine production in primary cultured lymphocytes both in vitro and ex vivo. Direct administration of astaxanthin (70–300 nM) did not produce cytotoxicity in lipopolysaccharide (LPS, 100 µg/ mL)- or concanavalin A (Con A, 10 µg/ mL)-activated lymphocytes, whereas astaxanthin alone at 300 nM induced proliferation of splenic lymphocytes (p < 0.05) in vitro. Although astaxanthin, alone or with Con A, had no apparent effect on interferon (INF-γ) and interleukin (IL-2) production in primary cultured lymphocytes, it enhanced LPS-induced INF-γ production. In an ex vivo experiment, oral administration of astaxanthin (0.28, 1.4 and 7 mg/kg/day) for 14 days did not cause alterations in the body or spleen weights of mice and also was not toxic to lymphocyte cells derived from the mice. Moreover, treatment with astaxanthin significantly increased LPS-induced lymphocyte proliferation ex vivo but not Con A-stimulated lymphocyte proliferation ex vivo. Enzyme linked immunosorbent assay (ELISA) analysis revealed that administration of astaxanthin significantly enhanced INF-γ production in response to both LPS and Con A stimulation, whereas IL-2 production increased only in response to Con A stimulation. Also, astaxanthin treatment alone significantly increased IL-2 production in lymphocytes derived from mice, but did not significantly change production of INF-γ. These findings suggest that astaxanthin modulates lymphocytic immune responses in vitro, and that it partly exerts its ex vivo immunomodulatory effects by increasing INF-γ and IL-2 production without inducing cytotoxicity. PMID:26729100

Gc globulin as a diagnostic and prognostic marker in horses

DEFF Research Database (Denmark)

Pihl, Tina Holberg

can prevent development of shock and thereby increase survival chances. The in vivo toxicity of Gc-globulin infusion is currently being investigated in horses and other species. Gc-globulin has been demonstrated in horse plasma and its structure closely resembles that of human Gc-globulin. Gc......-globulin concentrations in horses under clinical conditions have never previously been investigated. The Ph.D. project focuses on Gc-globulin as a prognostic marker in horses with acute abdominal pain....

Clinical experience with thymoglobulin and antithymocyte globulin-Fresenius as induction therapy in renal transplant patients: a retrospective study.

Science.gov (United States)

Cicora, Federico; Mos, Fernando; Paz, Marta; Roberti, Javier

2013-10-01

We describe our experiences with, and compare the outcomes of, 2 groups of renal transplant patients treated with thymoglobulin or antithymocyte globulin-Fresenius as induction therapy at transplant to reduce the incidence of acute rejection and prevent delayed allograft function. Twenty-four recipients of deceased-donor or living-donor kidney transplants received thymoglobulin, and 23 patients received antithymocyte globulin-Fresenius. Patient and graft survival and efficacy and safety were assessed at 3 months. The demographic characteristics of both groups were comparable, but the predominant donor type was significantly different. Incidence of complications, delayed graft function, and creatinine concentrations were comparable in both groups. At 3 months after the transplant, patient survival rate was 92% in the thymoglobulin group and 96% in the antithymocyte globulin-Fresenius group (P > .05), and death-censored graft survival rate for both groups was not significantly different. Average hematocrit and lymphocyte, neutrophil, and platelet counts were comparable in both groups at 3 months' follow-up. Average white blood count at 1 month was significantly different between the groups: at 5.62 ± 2.45 × 103 cells/mm³ in the thymoglobulin group and 7.85 ± 4.10 × 103 cells/mm³ in the ATG-F group (P Fresenius were generally comparable.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

Science.gov (United States)

Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

2017-05-09

Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bone marrow-derived T lymphocytes responsible for allograft rejection

International Nuclear Information System (INIS)

Senjanovic, M.; Marusic, M.

1984-01-01

Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes

Radiation effects on lymphocytes

International Nuclear Information System (INIS)

Roser, B.

1976-01-01

This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

Lymphocyte mediators of delayed hypersensitivity; the early phase cells

Energy Technology Data Exchange (ETDEWEB)

Lefford, M J; McGregor, D D [Trudeau Inst., Saranac Lake, N.Y. (USA)

1978-04-01

Inbred rats were immunized with living Bacillus Calmette-Guerin (BCG) and lymphocytes which mediate tuberculin DTH and anti-tuberculosis immunity were found 10 days later in the draining lymph nodes, thoracic duct, blood, spleen, and acute peritoneal exudates. The lymphocytes that mediated DTH incorporated /sup 3/HT in vitro, were large in size, sensitive to vinblastine but relatively resistant to irradiation, and had a short effective lifespan in syngeneic recipients. These properties characterize the cells as short-lived, nonrecirculating immunoblasts. In some experimental situations it was possible to dissociate the expression of DTH and immunity following the transfer of sensitized lymphocytes.

Measles immune suppression: lessons from the macaque model.

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Rory D de Vries

Full Text Available Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

Immune and hormonal activity in adults suffering from depression

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S.O.V. Nunes

2002-05-01

Full Text Available An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5% were females and 11 (27.5% were males (2.6:1 ratio. The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and ß-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05. The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05. These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation.

T-cell-mediated immunity to lymphocytic choriomeningitis virus in beta2-integrin (CD18)- and ICAM-1 (CD54)-deficient mice

DEFF Research Database (Denmark)

Christensen, Jan Pravsgaard; Marker, O; Thomsen, Allan Randrup

1996-01-01

The T-cell response to lymphocytic choriomeningitis virus was studied in mice with deficient expression of beta2-integrins or ICAM-1. In such mice, the generation of virus-specific cytotoxic T lymphocytes was only slightly impaired and bystander activation was as extensive as that observed in wild-type...... mice. T-cell-mediated inflammation, assessed as primary footpad swelling and susceptibility to intracerebral infection, was slightly compromised only in beta2-integrin-deficient mice. However, adoptive immunization of mutant mice soon after local infection did reveal a reduced capacity to support...... the inflammatory reaction, indicating that under conditions of more limited immune activation both molecules do play a role in formation of the inflammatory exudate. Finally, virus control was found to be somewhat impaired in both mutant strains. In conclusion, our results indicate that although LFA-1-ICAM-1...

Extraction and characterization of chickpea (Cicer arietinum) albumin and globulin.

Science.gov (United States)

Liu, L H; Hung, T V; Bennett, L

2008-06-01

Albumin and globulin fractions of 1 Desi and 2 Kabuli varieties of chickpeas (Cicer arietinum) were extracted with water and salt solutions (K(2)SO(4) and NaCl). The extractable yields and particularly the albumin-globulin ratio varied greatly with the extraction medium and chickpea variety. Depending on the procedure employed, albumin could be extracted as a major fraction of chickpea proteins. Higher levels of essential amino acids and sulfur containing amino acids were found in albumins than in globulins of all chickpeas investigated. The common structural characteristics of both Kabuli and Desi chickpea albumins and globulins were clearly identified by densitometric profiles of their sodium dodecyl sulfate polyacrylamide gel patterns. Albumins contained subunits with higher molecular weights than those of globulins. The in vitro digestibility of the chickpea proteins by papain, pepsin, chymotrypsin, and trypsin indicated that globulins were more susceptible to proteolytic hydrolysis.

The molecular biology and biochemistry of rice endosperm α-globulin

International Nuclear Information System (INIS)

Shorrosh, B.S.

1989-01-01

The author's first objective was to isolate a cDNA clone that encodes the rice endosperm α-globulin. Purified antibodies against a rice storage protein, α-globulin, were used to screen a λgt11 cDNA expression library constructed from immature rice seed endosperm. The cDNA insert of clone 4A1 (identified by antibody screening) was used as a probe to identify long cDNA inserts in the library. The deduced amino acid sequence of clone A3-12 cDNA insert (identified by cDNA screening) contained the amino acid sequences of three cyanogen bromide peptides fragment of α-globulin. The calculated molecular weight and amino acid composition of the deduced amino acid sequence were similar to the α-globulin protein. Northern blot analysis indicated that mRNA of one size, approximately 1.0 kb, is expressed. Southern genomic blot analysis revealed one band with EcoRI or Hind III digestion. Cell-free translation and immunoprecipitation showed that the initial translation product is approximately 2,000 daltons larger than the mature protein. The amino acid sequence of α-globulin revealed limited regions of similarities with wheat storage proteins. The author concludes that the cDNA insert in clone A3-12 contained the entire coding region of α-globulin protein and that α-globulin is encoded by a single gene. My second objective was to inhibit the degradation of α-globulin in the salt extract of rice flour. The salt extract of rice flour contained an acid protease whose optimal pH was 3 for 3 H-casein hydrolysis. A polypeptide with molecular weight of 20,000 was immunologically reactive with α-globulin antibodies and is produced by limited proteolysis in the extract. Pepstatin inhibited the proteolysis of 3H-casein and slowed the proteolysis of α-globulin

Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress

International Nuclear Information System (INIS)

Walsh, Catherine J.; Butawan, Matthew; Yordy, Jennifer; Ball, Ray; Flewelling, Leanne; Wit, Martine de; Bonde, Robert K.

2015-01-01

Highlights: • Sublethal brevetoxin exposure affects manatee immune function. • Plasma brevetoxin levels correlate with oxidative stress in rescued manatees. • Brevetoxin exposure affects lymphocyte proliferation in rescued manatees. • Plasma brevetoxin concentrations ranged from 0 to 19 ng PbTx-3 eq/mL. - Abstract: The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida’s southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p < 0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the

Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Walsh, Catherine J., E-mail: cjwalsh@mote.org [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Butawan, Matthew, E-mail: mattbutawan@outlook.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Yordy, Jennifer, E-mail: jennifer.e.balmer@gmail.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Ball, Ray, E-mail: Ray.Ball@lowryparkzoo.com [Lowry Park Zoo, 1101 W Sligh Ave, Tampa, FL 33604 (United States); Flewelling, Leanne, E-mail: Leanne.Flewelling@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Wit, Martine de, E-mail: Martine.deWit@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Bonde, Robert K., E-mail: rbonde@usgs.gov [U.S. Geological Survey, Sirenia Project, 7920 NE 71st Street, Gainesville, FL 32653 (United States)

2015-04-15

Highlights: • Sublethal brevetoxin exposure affects manatee immune function. • Plasma brevetoxin levels correlate with oxidative stress in rescued manatees. • Brevetoxin exposure affects lymphocyte proliferation in rescued manatees. • Plasma brevetoxin concentrations ranged from 0 to 19 ng PbTx-3 eq/mL. - Abstract: The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida’s southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p < 0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the

Immune responses to metastases

International Nuclear Information System (INIS)

Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

1987-01-01

The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

Role of Circulating Lymphocytes in Patients with Sepsis

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Raul de Pablo

2014-01-01

Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

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Anna Kabanova

2016-04-01

Full Text Available Suppression of the cytotoxic T cell (CTL immune response has been proposed as one mechanism for immune evasion in cancer. In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs, but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL. Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8. We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may interfere with the formation of functional immune synapses by CTLs.

Meta-analysis on the Safety and Efficacy of the Reperfusion Use of a Single High Dose of Anti-T-Lymphocyte Globulin Fresenius in Kidney Transplantation.

Science.gov (United States)

Du, X; Wang, W; Sun, Z-J; Su, L L; Zhang, X-D

2016-01-01

The aim of this study was to evaluate the effects of a single high dose of the anti-T-lymphocyte globulin Fresenius (ATG-F), given before kidney transplantation, on the prevention of acute rejection response and infections and on the survival rate of the renal graft and patient. Databases including PubMed, Embase, and the Cochrane Library were searched to identify randomized controlled trials relevant to studying the presurgical use of a single high dose of ATG-F. Five RCTs that included 346 patients were selected. The meta-analysis suggested that the application of ATG-F reduced the postsurgical acute rejection reaction incidence compared to that of the control group (relative risk = 0.50, 95% confidence interval = 0.35-0.71, P = .0001). However, the application of ATG-F exhibited no significant effect on the incidence of urinary tract infection, cytomegalovirus infection, and delayed graft function. Furthermore, the one-year patient survival rate and kidney graft survival rate were not affected. The meta-analysis suggested that the reperfusion use of a single high dose (9 mg/kg) of ATG-F could effectively reduce the incidence of postsurgical acute rejection response without affecting the occurrence of infections, the survival rates of kidney grafts and patients, or the incidence of delayed graft function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Some biochemical studies on thyroid immunity

International Nuclear Information System (INIS)

Shoush, M.A.M.

1980-01-01

The present study was carried out to investigate the effect of induced immunological environment on: a - Carbohydrate metabolism as reflected by immunoreactive insulin and blood sugar levels. b - Biochemical parameters, namely total protein, albumin, globulin, alkaline phosphatase and transaminases, reflecting liver function. c - Radioimmunological tests reflecting thyroid function. The study comprised 36 male rabbits, boscate strain of six months age assigned randomly to : control, albumin immunized and thyroglobulin immunized groups

Endotoxemia-induced lymphocyte apoptosis is augmented by a hyperinsulinemic-euglycemic clamp

DEFF Research Database (Denmark)

Nielsen, Jeppe Sylvest; A, Larsson; Brix-Christensen, Vibeke

2005-01-01

BACKGROUND: Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors...... hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis...... sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number...

Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology

International Nuclear Information System (INIS)

Doherty, P.C.; Ceredig, R.; Allan, J.E.

1988-01-01

The Lyt2+ class I major histocompatibility complex (MHC)-restricted virus-immune T cells that induce murine lymphocytic choriomeningitis (LCM) are targeted onto radiation-resistant cells in the central nervous system of virus-infected mice. The use of appropriate bone marrow radiation chimeras as LCM virus-infected, (immunosuppressed recipients for immune T-cell transfer has established that, though bone marrow-derived cells can stimulate virus-specific cytotoxic T lymphocytes (CTL) in spleen, they do not reconstitute the barrier to T-cell recruitment from blood to cerebrospinal fluid. This is true for chimeras made up to 8 months previously, even though the inflammatory monocytes and macrophages in such chimeras are all of donor bone marrow origin. Radiation-resistant cells in the spleens of these chimeras are also still able to further stimulate virus-immune CTL. There is no requirement for H-2 compatibility between virus-immune T lymphocytes and secondarily recruited monocytes, or T cells of an inappropriate specificity. The key event in LCM immunopathology may thus be localization of T cells to the antigen-presenting endothelium in brain, leading to the secretion of mediators that promote the nonspecific recruitment of monocytes and other T cells

Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity

International Nuclear Information System (INIS)

Check, I.J.; Kidd, M.R.; Staton, G.W. Jr.

1986-01-01

BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Ten patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis

Genomic organization of the rat alpha 2u-globulin gene cluster.

Science.gov (United States)

McFadyen, D A; Addison, W; Locke, J

1999-05-01

The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

Effect of ionizing whole-body irradiation on the primary and secondary antibody reaction of cows to injection of human gamma globulin

International Nuclear Information System (INIS)

Koch, F.; Buchholz, I.; Mehlhorn, G.

1989-01-01

In 3 experiments 29 cows were exposed to whole-body irradiation, using 9 MeV X-rays of a linear accelerator, with doses of 1.50 and 2.00 Gy or 60 Co gamma rays with a dose of 2.75 Gy, as a midline dose. 2 weeks prior to irradiation the first immunization was applied using human gamma globulin. 4 or 5 weeks after irradiation a second immunization was carried out. The antibody titres were investigated. The irradiation failed to affect the antibody titres after the first immunization. After the second immunization the antibody titres of the irradiated animals remained diminished significantly (α = 0.05). This has been attributed to a damage of the memory cell pool. (author)

How safe is the use of chlorpyrifos: Revelations through its effect on 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 chlorpyrifos (CPF) insecticide after oral administration in layer chickens. A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose) for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF 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 CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

A flagellin-derived toll-like receptor 5 agonist stimulates cytotoxic lymphocyte-mediated tumor immunity.

Directory of Open Access Journals (Sweden)

Nicholas D Leigh

Full Text Available Toll-like receptor (TLR mediated recognition of pathogen associated molecular patterns allows the immune system to rapidly respond to a pathogenic insult. The "danger context" elicited by TLR agonists allows an initially non-immunogenic antigen to become immunogenic. This ability to alter environment is highly relevant in tumor immunity, since it is inherently difficult for the immune system to recognize host-derived tumors as immunogenic. However, immune cells may have encountered certain TLR ligands associated with tumor development, yet the endogenous stimulation is typically not sufficient to induce spontaneous tumor rejection. Of special interest are TLR5 agonists, because there are no endogenous ligands that bind TLR5. CBLB502 is a pharmacologically optimized TLR5 agonist derived from Salmonella enterica flagellin. We examined the effect of CBLB502 on tumor immunity using two syngeneic lymphoma models, both of which do not express TLR5, and thus do not directly respond to CBLB502. Upon challenge with the T-cell lymphoma RMAS, CBLB502 treatment after tumor inoculation protects C57BL/6 mice from death caused by tumor growth. This protective effect is both natural killer (NK cell- and perforin-dependent. In addition, CBLB502 stimulates clearance of the B-cell lymphoma A20 in BALB/c mice in a CD8(+ T cell-dependent fashion. Analysis on the cellular level via ImageStream flow cytometry reveals that CD11b(+ and CD11c(+ cells, but neither NK nor T cells, directly respond to CBLB502 as determined by NFκB nuclear translocation. Our findings demonstrate that CBLB502 stimulates a robust antitumor response by directly activating TLR5-expressing accessory immune cells, which in turn activate cytotoxic lymphocytes.

The determination of lymphocyte transformation in patients of various diseases

International Nuclear Information System (INIS)

Su Liaoyuan; Liu Ke Liang; Lin Xingcheng; Sun Guoqi; Xue Zhimou

1987-01-01

The synthesis of DNA, RNA and protein during the transformation of human lymphocytes induced by mitogen PHA and LPS was investigated by quantitation of 3 H-TdR, 14 C-UR and 14 C-valine incorporation method. 1666 tests were carried out in patients with various diseases and 424 tests in normal subjects. It was found that immunocompetence was closely related with the progress and prognosis in patients with leukemia. Impairment of the cell-mediated immunity in patients with squamous cell carcinoma and with encephlitis was observed. There was no difference in immunity between patients with adenocarcinoma and the normal subjects. The ionizing irradiation mainly exerts its effect on cell-mediated immunity. The cell-mediated immunity was found to be impaired while the humoral immune regulation was enhanced in tuberculosis and leprosy, indicating that these diseases were caused by impairment of cell-mediated immunity. Both humoral and cell-mediated immunity return to normal levels at convalescence. The uptake of 14 C-UR by lymphocytes in patients with hepatitis increased significantly. Lymphocytes reactivity was elevated in patients with vernal conjunctivities and normal in patients with uveitis. Low reactivity was observed in patients with keratitis. The immunity in various diseases was discussed

Antibody responses to vaccination and immune function in patients with haematological malignancies - studies in patients with chronic lymphocytic leukaemia autologous stem cell recipients

NARCIS (Netherlands)

Velden, A.M.T. van der

2007-01-01

This thesis concerns the antibody responses to vaccination and immune function of patients with several forms of haematological diseases. Antibody responses in patients with chronic lymphocytic leukaemia (CLL) and in autologous stem cell transplant recipients were studied. In the autologous stem

PROFIL PROTEIN TOTAL, ALBUMIN DAN GLOBULIN PADA AYAM BROILER YANG DIBERI KUNGIY, BAWANG PUTIH DAN ZINC (ZN

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Sus Derthi Widhyari

2011-12-01

Full Text Available The objective of this experiment was to study the effectiveness of turmeric, garlic and zinc supplementation on protein, albumin and globulin concentration of broiler. One hundred DOC were divided into five treatments, four replications, consist of five chicks in each replicate. The treatments were R0 (basal diet as a control, R1 (R0 + 1,5% turmeric powder +2,5 % garlic powder, R2 (R0 + 2,5% garlic powder + 120 ppm zinc, R3 (R0 +1,5% turmeric powder + 120ppm zinc and R4 (R0 +1,5 turmeric powder + 2,5% garlic powder + 120 ppm zinc. The diet contain 23,5% crude protein and 3215 kcal metabolizable energy. Blood samples were taken from axillary veins at the three and six weeks of age. The results showed that total protein and globulin concentration at 6 weeks slightly higher than 3 weeks old chicks but not significantly different (P>0.05. Albumin concentration were highest on R3 treatment. Total protein and globulin concentration was highest on the R2 treatment. In conclusion, the supplementation of garlic (2.5% and ZnO (120 ppm showed the best combination to improve immune response in broiler

Effect of Vibrio cholerae neuraminidase on the mitogen response of T lymphocytes. I. Enhancement of macrophage T-lymphocyte cooperation in concanavalin-A-induced lymphocyte activation.

Science.gov (United States)

Knop, J

1980-12-01

Vibrio cholerae neuraminidase (VCN) enhances the immune response of lymphocytes in various systems, such as antigen- and mitogen-induced blastogenesis, mixed lymphocyte culture (MLC) and tumor-cell response. We used macrophage-depleted and reconstituted murine lymph-node T-cells to investigate the effect of VCN on macrophage-T-lymphocyte co-operation in Con-A-induced lymphocyte activation. In unfractionated lymph-node cells VCN enhanced the Con-A-induced lymphocyte activation as measured by 3H-thymidine (3H-dThd) incorporation. Removing macrophages from the cells resulted in a significantly diminished response. In addition the enhancing effect of VCN was greatly reduced. Reconstitution of the lymphocyte cultures with macrophages in increasing numbers and from various sources rstored the lymphocyte response and the enhancing effect of VCN. VCN proved to be most efficient in cultures reconstituted with normal peritoneal macrophages. Some effect was also observed using bone-marrow-derived (BM) macrophages. However, higher numbers of normal PE macrophages in the presence of VCN inhibited lymphocyte activation, and inhibition by thioglycollate-broth-induced macrophages was considerably increased by VCN. These results suggest that VCN acts by increasing the efficiency of macrophage-T lymphocyte interaction.

T gamma/delta lymphocytes in renal transplant recipients

NARCIS (Netherlands)

Raasveld, M. H.; Bloemena, E.; Surachno, S.; ten Berge, R. J.

1992-01-01

T gamma/delta lymphocytes are able to perform allospecific cytotoxicity and natural killer cytotoxicity in vitro. However, very little is known about their function in vivo. To investigate the possible involvement of T gamma/delta lymphocytes in the immune response to renal allografts, fine-needle

Physicochemical, functional and angiotensin converting enzyme inhibitory properties of amaranth (Amaranthus hypochondriacus) 7S globulin.

Science.gov (United States)

Quiroga, Alejandra V; Aphalo, Paula; Ventureira, Jorge L; Martínez, E Nora; Añón, María C

2012-01-30

Amaranth 7S globulin is a minor globulin component and its impact on the properties of an amaranth protein ingredient depends on its proportion in the variety of amaranth being considered. Some physicochemical, functional and angiotesin I-converting enzyme (ACE) inhibitory properties of amaranth vicilin were studied in this work and compared with the 11S globulin. Fluorescence spectroscopy results indicated that 7S globulin tryptophans were more exposed to the solvent and, by calorimetry, the 7S globulin denaturation temperature (T(d) ) was found lower than the 11S globulin T(d) , suggesting a more flexible structure. The 7S globulin surface hydrophobicity was higher than that of the 11S globulin, which is in agreement with the better emulsifying properties of the 7S globulin. The solubility in neutral buffer of the 7S globulin (851 ± 25 g kg(-1) ) was also higher than that of the 11S globulin (195 ± 6 g kg(-1) ). Bioinformatic analyses showed the presence of ACE inhibitory peptides encrypted in 7S tryptic sequences and peptides released after in vitro gastrointestinal digestion showed a high ACE-inhibitory capacity (IC(50) = 0.17 g L(-1) ), similar to that of 11S globulin peptides. Compared with the 11S globulin, the 7S globulin presents similar ACE inhibitory activity and some functional advantages, better solubility and emulsifying activity, which suits some food requirements. The functional behavior has been related with the structural properties. Copyright © 2011 Society of Chemical Industry.

Autoimmune hepatitis in association with lymphocytic colitis.

LENUS (Irish Health Repository)

Cronin, Edmond M

2012-02-03

Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

Ectopic expression of X-linked lymphocyte-regulated protein pM1 renders tumor cells resistant to antitumor immunity.

Science.gov (United States)

Kang, Tae Heung; Noh, Kyung Hee; Kim, Jin Hee; Bae, Hyun Cheol; Lin, Ken Y; Monie, Archana; Pai, Sara I; Hung, Chien-Fu; Wu, T-C; Kim, Tae Woo

2010-04-15

Tumor immune escape is a major obstacle in cancer immunotherapy, but the mechanisms involved remain poorly understood. We have previously developed an immune evasion tumor model using an in vivo immune selection strategy and revealed Akt-mediated immune resistance to antitumor immunity induced by various cancer immunotherapeutic agents. In the current study, we used microarray gene analysis to identify an Akt-activating candidate molecule overexpressed in immune-resistant tumors compared with parental tumors. X-linked lymphocyte-regulated protein pM1 (XLR) gene was the most upregulated in immune-resistant tumors compared with parental tumor cells. Furthermore, the retroviral transduction of XLR in parental tumor cells led to activation of Akt, resulting in upregulation of antiapoptotic proteins and the induction of immune resistance phenotype in parental tumor cells. In addition, we found that transduction of parental tumor cells with other homologous genes from the mouse XLR family, such as synaptonemal complex protein 3 (SCP3) and XLR-related, meiosis-regulated protein (XMR) and its human counterpart of SCP3 (hSCP3), also led to activation of Akt, resulting in the upregulation of antiapoptotic proteins and induction of immune resistance phenotype. Importantly, characterization of a panel of human cervical cancers revealed relatively higher expression levels of hSCP3 in human cervical cancer tissue compared with normal cervical tissue. Thus, our data indicate that ectopic expression of XLR and its homologues in tumor cells represents a potentially important mechanism for tumor immune evasion and serves as a promising molecular target for cancer immunotherapy. (c) 2010 AACR.

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

International Nuclear Information System (INIS)

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J.; Bridges, Lance C.

2014-01-01

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH) 2 D 3 , a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

Energy Technology Data Exchange (ETDEWEB)

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

2014-11-28

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

The behavior of pig lymphocyte populations in vivo

International Nuclear Information System (INIS)

Binns, R.M.; Licence, S.T.; Pabst, R.

1986-01-01

Lymphocyte migration provides the means of rapidly recognizing and responding to antigen and widely disseminating the resulting immune response. The porcine lymphoid system differs from that of man in structural inversion of lymph nodes and route of lymphocyte recirculation and the existence of two Peyer's patch types, one of which differs from the conventional pattern in structure, cell content and lack of lymphocyte traffic and in its regression in old age. Recirculating T and B lymphocytes enter and leave spleen and lymph nodes by the blood but Null cells do not; lymphocytes also migrate through nonlymphoid tissues. The lung is one such important site, with a small migration in and out of alveolar space and a large traffic associated with the blood vessel wall, predominantly involving T cells. Blood lymphocytes hardly traffic into the peritoneal cavity, yet major traffic of particulate material or cells is possible in this important site of abdominal defense, so often used for immunization, and follows a distinct, well defined route. Cells migrate out of subcutaneous tissue via the draining node. Lymphocytes are produced and emigrate into blood from labelled thymus. They differ in size and surface phenotype from both thymocytes and peripheral T cells. Lymphocytes also migrate from blood into most tissues. In most nonlymphoid tissues, entry relates to blood flow but in many lymphoid tissues it is an active process which differs in tempo and extent, eg, between different nodes and between the two Peyer's patch types

The potential impact of low dose ionizing γ-radiation on immune response activity up-regulated by Ikaros in IM-9 B lymphocytes

International Nuclear Information System (INIS)

Kim Sung Jn; Jang, Seon A; Yang, Kwang Hee; Kim, Ji Young; Kim, Cha Soon; Nam, Seon Young; Jeong, Mee Seon; Jin, Young Woo

2011-01-01

The biological effects of low dose ionizing radiation (LDIR) remain insufficiently understood. We examined for the scientific evidence to show the biological effects of LDIR using radiation-sensitive immune cells. We found that Ikaros protein was responded to low dose-dependent effects of gamma radiation in IM-9 B lymphocytes. Ikaros encodes zinc finger transcription factors that is important regulators of a hematopoietic stem cells (HSCs) progression to the B lymphoid lineage development, differentiation and proliferation. In this study, we observed that cell proliferation was enhanced from 10% to 20% by LDIR (0.05 Gy) in IM-9 B lymphocytes. The Ikaros protein was phosphorylated in its serine/threonine (S/T) region and decreased its DNA binding activity in the cells exposed to LDIR. We found that Ikaros phosphorylation was up-regulated by CK2/AKT pathway and the residues of ser-304 and ser-306 in Ikaros was phosphorylated by LDIR. We also observed that Ikaros protein was localized from the nucleus to the cytoplasm after LDIR and bound with Autotaxin (ENPP2, ATX) protein, stimulating proliferation, migration and survival of immune cells. In addition, we found that the lysoPLD activity of ATX was dependent on Ikaros-ATX binding activity. These results indicate that the Ikaros is an important regulator of immune activation. Therefore, we suggest that low dose ionizing radiation can be considered as a beneficial effects, stimulating the activation of immune cells.

Investigation of the cytotoxicity, antioxidative and immune-modulatory effects of Ligusticum porteri (Osha) root extract on human peripheral blood lymphocytes.

Science.gov (United States)

Nguyen, Khanh; Sparks, Jean; Omoruyi, Felix O

2016-11-01

Ligusticum porteri is a traditional Native American herb. The roots of L. porteri are traditionally used in the treatment of many diseases, however, its cytotoxicity, antioxidative and immune-modulatory effects need to be investigated. In this study, we evaluated the effects of the root extract at different doses on human peripheral blood lymphocytes (PBLs). The lymphocytes were incubated with different concentrations of the root extracts (0, 50, 100, 200, and 400 μg/mL) and harvested every 6 h for 2 d (Peffect of the herb against oxidative damage was determined by inducing oxidative stress with the administration of 50 μmol/L of hydrogen peroxide (H 2 O 2 ). Treatments with L. porteri at 200 and 400 μg/mL increased the viability of PBLs. The deleterious effect of H 2 O 2 was ameliorated by 400 μg/mL L. porteri treatment. Addition of 400 μg/mL L. porteri reduced lipid peroxidation in stressed PBLs by 94% (P0.05). The findings suggest that L. porteri might be a potential immune-modulating agent involving protective effects against oxidative damage.

Isolation, characterization and radioimmunoassay of corticosteroid-binding globulin (CBG) in human serum - clinical significance and comparison to thyroxine-binding globulin (TBG)

International Nuclear Information System (INIS)

Bernutz, C.; Haensle, W.O.; Horn, K.; Pickardt, C.R.; Scriba, P.C.; Fink, E.; Kolb, H.; Tschesche, H.

1979-01-01

Isolation of the corticosteroid-binding globulin CBG was achieved by 5 chromatographical steps on cortisol Sepharose, QAE-Sephadex A-50, Con A-Sepharose and hydroxylapatite. The purity of the isolated CBG was demonstrated in polyacrylamide gel electrophoresis, SDS electrophoresis, immunodiffusion and ultracentrifugation. Microheterogeneity was shown in isoeletric focusing by 5 bands in the pH range of 3.7-4.2, which could be reduced to one major band after neuraminidase treatment. The equimolar binding of cortisol to CBG was demonstrated by binding studies. The association constant for cortisol was 2.8 x 10 8 M -1 , for progesterone 1.7 x 10 6 M -1 . From analytical ultracentrifugation, the molecular weight was calculated on 50 700; the sedimentation coefficient was 3.6 S, the partial specific volume 0.690 ml/g, the Stokes radius 38 A and the frictional coefficient ratio 1.5. A specific radioimmunoassay for CBG was established using the purified CBG for immunization, radioiodination and for calibration standards. The normal range of CBG levels in human serum was 2.4-4.4 mg/100 ml (mean +- 2SD). Studies were performed to compare the levels of CBG and thyroxine-binding globulin (TBG). No sex differences but a significant biphasic age dependence were observed for both proteins. In pregnancy and under oestrogen treatment of women and men, CBG was demonstrated to be the more distinct indicator of oestrogenic activity as compared with TBG, whereas the sensitivity of TBG was more pronounced to supposedly antioestrogenic substances like Danazol, and in severe disease. No coincidence of genetic CBG and TBG deficiencies have been found so far. (author)

Low-level radiation effects on immune cells

International Nuclear Information System (INIS)

Makinodan, T.

1995-01-01

The purpose of this study was to characterize the effects of chronic low-dose ionizing radiation (LDR) on murine immune cells. Previously, it had been reported that LDR enhances the proliferative activity of T cells in vitro and delays the growth of transplantable immunogenic tumors in vivo. This suggests that LDR eliminates immune suppressor cells, which downregulates immune response and/or adoptively upregulates the responsiveness of immune effector cells. It had also been reported that human lymphocytes become refractive to high dose radiation-induced chromosomal aberrations by pretreating mitotically active lymphocytes in vitro with very low doses of ionizing radiation, and the adaptive effect can be abrogated by cycloheximide. This suggests that protein synthesis is required for lymphocytes to respond adoptively to LDR

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

Science.gov (United States)

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

Discordance of epstein-barr virus (ebv) specific humoral and cellular immunity in patients with malignant lymphomas : Elevated antibody titers and lowered invitro lymphocyte-reactivity

NARCIS (Netherlands)

ten Napel, C. H. H.; The, T. Hauw; van Egten-Bijker, J; de Gast, G. C.; Halie, M. R.; Langenhuysen, M. M. A. C.

1978-01-01

The relationship between specific viral cellular and humoral immunity to the Epstein–Barr Virus (EBV) was investigated in thirty-one untreated patients with malignant lymphoma (ML) and sex- and age-matched controls. In vitro reactivity of peripheral blood lymphocytes to heatinactivated purified EBV,

Bovine immune response to inoculation with Neospora caninum surface antigen SRS2 lipopeptides mimics immune response to infection with live parasites.

Science.gov (United States)

Baszler, Timothy V; Shkap, Varda; Mwangi, Waithaka; Davies, Christopher J; Mathison, Bruce A; Mazuz, Monica; Resnikov, Dror; Fish, Lea; Leibovitch, Benjamin; Staska, Lauren M; Savitsky, Igor

2008-04-01

Infection of cattle with Neospora caninum protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4(+) T-lymphocyte activation and gamma interferon (IFN-gamma) secretion. In the present study, N. caninum SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4(+) cell proliferation and IFN-gamma T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-gamma secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-gamma-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that N. caninum NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-gamma secretion. The findings support the investigation of NcSRS2 immunogens for protection against N. caninum-induced fetal infection and abortion in cattle.

Immunological reactivity of patients with malignant tumor of the head and neck, 4

International Nuclear Information System (INIS)

Sakaguchi, Kosaku; Okuda, Minoru; Tomiyama, Shunichi

1981-01-01

Before and after two different methods of treatment (operation and radiation), humoral and cellular immunities were examined in patients with head and neck cancer. Variation of immunological reactivity exhibited different patterns between the two groups, even when malignant tumors disappeared. In the operation group, humoral immunities were elevated in terms of the serum levels of α 2 -globulin, complement (CH 50 ), IgA, IgG and Carcinoembrionic Antigen (CEA). Cellular immunities, however, showed no change. In the irradiation group, humoral immunities were not changed, but cellular immunities were significantly depressed showing decreases in the number of peripheral lymphocytes and in the degree of PHA-induced lymphocyte transformation. The above-mentioned patterns of immunological changes were observed in patients without cancer as well. The elevated humoral immunity in the operation group recovered to the pre-treatment level within a few months, whereas the suppressed cellular immunity in the irradiation group was presumed to persist for a longer time. (author)

Indicators of allogenic interactions of lymphocytes in spouses as additional diagnostic and prognostic criteria of immune forms of reproductive failures

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Belenkova O.V.

2013-12-01

Full Text Available Research objective: to search new laboratory approaches to the diagnostics of immune forms of reproductive failures. Materials and methods. Retrospective research a case — control of 54 married couples with idiopathic reproductive failures (in the anamnesis — 3 and more spontaneously interrupted pregnancy in the 4-8th weeks and 47 married couples having two and more children has been conducted. Results. It has been revealed that at the immune form of reproductive failures increase of cells of level A- mononuclear cells, expression of HLDR takes place that promotes tolerance cancellation to allogenic germs and to immune interruption of pregnancy. At reproductive failures female au-toserum positively influences activation of T-lymphocyte (CD3 +/HLADR + that may lead to the death of half- allogenic germ. Conclusion. Level of expression of CD3 and HLADR on CD45 + of mixed allogenic mononuclear cells of spouses may serve as a diagnostic significant criterion for revealing immune reasons of reproductive failures.

Normal lymphocyte immunophenotype in an elderly population

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Sâmia Macedo Queiroz Mota Castellão Tavares

2014-06-01

Full Text Available OBJECTIVE: The aim of this work was to evaluate the lymphocyte immunophenotype in an elderly population.METHODS: This study enrolled 35 over 60-year-old volunteers and a control group composed of 35 young adults. The study included elderly without diseases that might affect the functioning of the immune system. These individuals were consulted by doctors and after a physical examination, laboratory tests were performed using a Beckman Coulter (r flow cytometer. The GraphPad Prism computer program was employed for statistical analysis with the level of significance being set for p-values <0.05.RESULTS: There is a statistically significant reduction in the number of lymphocytes (CD8 +, CD2 + and CD3 + cells in the elderly compared to young adults. These low rates are explained by changes attributed to aging and may be partly responsible for the reduction in the cellular immune response, lower proliferative activity and the low cytotoxicity of lymphocytes.CONCLUSION: These parameters showed greater impairment of adaptive immunity in the elderly population and can therefore explain the greater fragility of the aged body to developing diseases.

SIFAT FUNGSIONAL PRODUK INTERAKSI FRAKSI GLOBULIN 7S KOMAK (Dolichos lablab DAN GUM XANTAN [Functional Properties of the Interaction Product Between Globulin of 7S Fraction of Lablab Bean (Dolichos lablab with Xantan Gum

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Sukamto1*

2009-12-01

Full Text Available Lablab bean (Dolichos lablab seeds is a potential source of protein globulin.The bean’s protein content is 20.86 %, and the amount of globulin was more than 60% from the total protein, having major fractions of 7S and 11S. The objectives of this research were to explore the 7S globulin fractions, to study interaction between 7S globulin fractions with xanthan gum, and to observe the functional properties of the product of the interaction. The research was conducted in 2 steps. The first step was to fractionate the 7S fractions from globulin. The second steps was to interact 7S globulin fraction with xanthan gum. The yield of these interaction were examined for its physicochemical and functional properties. The results showed that the 7S globulin fractions could be interacted by xanthan gum at pH 7. The interacted product of globulin 7S fraction 10 % with xanthan gum 0,75 % had good functional properties than globulin 7S fraction, such as oil holding capacity, foaming capacity, and emulsion activity. Water holding capacity could not be detected because the yield became soluble. However,the foaming and emulsifying stability were still lower than those of soybean protein isolates. The research concluded that xanthan gum could be used to improve the physicochemical and functional properties of globulin 7S fraction.

Intestinal T lymphocytes of different rat strains in immunotoxicity

NARCIS (Netherlands)

Bruder, M.C.; Spanhaak, S.; Bruijntjes, J.P.; Michielsen, C.P.P.C.; Vos, J.G.; Kuper, C.F.

1999-01-01

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytcs, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes

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.

How safe is the use of chlorpyrifos: Revelations through its effect on layer birds

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P. P. Singh

2016-07-01

Full Text Available Aim: The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF insecticide after oral administration in layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. Results: There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF 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 CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

Immune-directed therapy for type 1 diabetes at the clinical level: the Immune Tolerance Network (ITN) experience.

Science.gov (United States)

Ehlers, Mario R; Nepom, Gerald T

2012-01-01

Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. Results have been mixed in terms of clinical efficacy, but the studies have provided valuable mechanistic insight that are enhancing our understanding of the disease and guiding the design of future trials. Trials of non-Fc-binding anti-CD3 mAbs have revealed that modulation of this target leads to partial responses, and ITN's AbATE trial led to identification of a robust responder group that could be distinguished from non-responders by baseline metabolic and immunologic features. A pilot study of the combination of IL-2 and rapamycin gave the first demonstration that frequency and function of regulatory T cells (Tregs) can be enhanced in T1D subjects, although the therapy triggered the activation of effectors with transient β-cell dysfunction. Similarly, therapy with anti-thymocyte globulin led to substantial lymphocyte depletion, but also to the activation of the acute-phase response with no clinical benefit during preliminary analyses. These and other results provide mechanistic tools that can be used as biomarkers for safety and efficacy in future trials. Furthermore, our results, together with those of other organizations, notably TrialNet, delineate the roles of the major components of the immune response in T1D. This information is setting the stage for future combination therapy trials. The development of disease-relevant biomarkers will also enable the implementation of innovative trial designs, notably adaptive trials, which will increase efficiencies in terms of study duration and sample size, and which will expedite the conduct of trials in which there are uncertainties about dose response and effect size.

Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

Science.gov (United States)

Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

2017-05-01

Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

Effect of low doses of ionizing radiation on the thymus-dependent humoral immune response and the polyclonal activation of B-lymphocytes

International Nuclear Information System (INIS)

Sharetskij, A.N.; Surinov, B.P.; Abramova, M.R.

2000-01-01

The results of studies on the effect of the low-dose (10 cGy with the dose rate of 1cGy/min) γ-radiation on the indices of the mice system and local immune response are presented. The sheep erythrocytes were used as a thymus-dependent antigen. It is shown that the total irradiation with the above dose rate induced the increase in the primary thymus-dependent humoral immune response on the sheep erythrocytes and polyclonal activation of the B-lymphocytes. The sharp oppression of the antibody formation was observed in the immune response dynamics after the phase of the radiation-induced elevation. The injection of hydroquinone right after the irradiation resulted in elimination of the radiation stimulation of the polyclonal response of the B-cells. The essential decrease in the immunoantilogarithmic radiation effect took place in the animals treated with thymogen. The possible negative consequences of the low-dose ionizing radiation impact on the body immune system are discussed [ru

FEATURES OF METABOLIC INDEXES OF BLOOD LYMPHOCYTES IN THE PATIENTS WITH EPIDURAL FIBROSIS FOLLOWING LUMBAR MICRODISCECTOMY

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N. V. Isaeva

2008-01-01

Full Text Available Abstract. A complex immunologic examination of fifty patients with clinically significant postoperative fibrosis has been performed. Immunogram indexes were determined, and activities of basic oxidation-reduction enzymes were investigated in blood lymphocytes. What concerned immune status of the patients under study, some peculiar features have been revealed, with respect to cellular and humoral compartments, i.e., relative increase in CD3+ population, a shift to CD4+ cells in the ratio of lymphocyte subpopulations, higher indexes of immune regulation and phagocytosis, increased IgG level, and lower content of IgA, as compared to appropriate controls. Metabolic parameters of lymphocytes reflect their functional activation, being expressed as an enhanced ability for intracellular synthetic processes, elevated functional activity of lymphocytes, and increased immune response. The general pattern of changes in immune status and metabolic indexes of lymphocytes allow us to assume participation of autoimmune component in progression of epidural fibrosis. The data obtained may be used in combined diagnostics and correction of this disorder. (Med. Immunol., vol. 10, N 6, pp 589-592.

Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes

NARCIS (Netherlands)

Nijhara, Ruchika; van Hennik, Paula B.; Gignac, Michelle L.; Kruhlak, Michael J.; Hordijk, Peter L.; Delon, Jerome; Shaw, Stephen

2004-01-01

Lymphocytes circulate in the blood and upon chemokine activation rapidly bind, where needed, to microvasculature to mediate immune surveillance. Resorption of microvilli is an early morphological alteration induced by chemokines that facilitates lymphocyte emigration. However, the antecedent

Electrophoretic Profile of Albumin, α1, α2, β and γ Globulin in Sera of Opioid Dependants and Non-dependants

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koros Div-salaar

2008-02-01

Full Text Available Div-salaar K1, Saravani R2, Shamsi-e-meimandi M3, Taei M4, Sheikholeslami A5 1. MSc. Staff member of Neurology Sciences Research Center, Kerman University of Medical Sciences 2. Instructor, Department of Biochemistry, Faculty of Medicine, Zahedan University of Medical Sciences 3. Instructor, Department of Physiology and Pharmacology, Faculty of Medicine, Neurology Sciences Research Center, Karman University of Medical Sciences 4. Researcher, Neurology Sciences Research Center, Karman University of Medical Sciences 5. B.Sc in Environmental Hygiene, Kerman University of Medical Sciences Abstract Background: The prevalence rate of opioids consumption is high in Iran. The latest research approach related to substance abuse considers the role of plasma proteins in novel treatments of addiction. Since long-term consumption of opioids has some effects on liver function and plasma transfer systems, the present study was designed to determine the electrophoretic profile of plasma proteins in opiates-addict subjects. Materials and methods: In this cross-control study, the sample groups consisted of 42 opium consumers and 35 heroine dependents as case group and 35 non-addict volunteers as control group. The control group was matched with addicts for age and sex. Opioid consumption was confirmed by laboratory diagnostic tests on urine samples such as immunochromatography (RSA, rapidosis and complementary tests including liquid-solid column chromatography and thin layer chromatography (TLC. After blood collection and serum preparation, serum electrophoresis was performed. Data were presented as mean±SEM and analyzed by SPSS ver.11.5. The comparison of groups was done by using parametric tests and p<0.01 was considered as statistically significant. Results: There was no significant difference in the amounts of albumin, alpha-1-globulin, alpha-2-globulin and beta-globulin between groups. Gamma-globulin concentration was not significantly different between

Cell-mediated immunity to herpes simplex in humans: lymphocyte cytotoxicity measured by 51Cr release from infected cells

International Nuclear Information System (INIS)

Russell, A.S.; Percy, J.S.; Kovithavongs, T.

1975-01-01

We assessed cell-mediated immunity to herpes simplex virus type 1 antigen in patients suffering from recurrent cold sores and in a series of healthy controls. Paradoxically, all those subject to recurrent herpetic infections had, without exception, evidence of cell-mediated immunity to herpes antigens. This was demonstrated by lymphocyte transformation and specific 51 Cr release from infected human amnion cells after incubation with peripheral blood mononuclear cells. Where performed, skin tests with herpes antigen were also positive. In addition, serum from these patients specifically sensitized herpes virus-infected cells to killing by nonimmune, control mononuclear cells. These tests were negative in the control patients except in a few cases, and it is suggested that these latter may be the asymptomatic herpes virus carriers previously recognized or that they may have experienced a genital infection. (U.S.)

The conservative physiology of the immune system

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N.M. Vaz

2003-01-01

Full Text Available Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies. Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

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Tobias Roider

2016-12-01

Full Text Available Antithymocyte globulin (ATG is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon® on human monocyte-derived dendritic cells (DC. ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

The role of nucleotides in augmentation of lymphocyte locomotion: Adaptional countermeasure development in microgravity analog environments

Science.gov (United States)

Sundaresan, Alamelu; Kulkarni, Anil D.; Yamauchi, Keiko; Pellis, Neal R.

2006-09-01

Space travel and long-term space residence such as envisaged in the exploration era implicates burdens on the immune system. An optimal immune response is required to countered and with-stand exposure to pathogens. Countermeasure development is an important avenue in space research especially for long-term space exploration. Microgravity exposure causes detrimental effects in lymphocyte functions which may impair immune response. Impaired lymphocyte function can be remedied by bypassing cell membrane events. This is done by using compounds such as Phorbol Myristate Acetate (PMA). Since activation in mouse splenocytes was augmented using nucleotides, it was essential to observe their effects on human lymphocyte locomotion. A nucleotide/nucleoside (NT/NT) mixture from Otsuka Pharmaceuticals (Naruto, Japan) was used at recommended doses. In lymphocytes cultured in modeled microgravity, the NT/NT mixture used orchestrated locomotion recovery by more than 87%, similar to the response documented with PMA in lymphocytes. Both 12µM and 120µM doses worked similarly. These are preliminary results leading to the possible use of the NT/NT mixture to mitigate immune suppression in micro-gravity. More studies in this direction are required to delineate the role of NT/NT on the immune response in microgravity.

Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis.

Science.gov (United States)

Tong, Tong; Zhao, Wei; Wu, Ying-Qi; Chang, Yan; Wang, Qing-Tong; Zhang, Ling-Ling; Wei, Wei

2010-05-01

To investigate the effect of the oral administration of chicken type II collagen (CCII) on T cells from mesenteric lymph node (MLN) lymphocytes in rats with collagen-induced arthritis (CIA). CIA was induced in male Sprague-Dawley rats immunized with CCII in Freund's complete adjuvant. CCII (10, 20, and 40 microg kg(-1) day(-1), i.g. x 7 days) was administered orally to rats from day 14 to 21 after immunization. Arthritis was evaluated by hind paw swelling and polyarthritis index, and MLNs and synovium were harvested for histological examination. Activity of interleukin-2 (IL-2) in MLN lymphocyte supernatant was measured by ConA-induced splenocyte proliferation in C57BL/6J mice, and IL-4, IL-17, and transforming growth factor beta (TGF-beta) levels in MLN lymphocytes were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD4(+)CD25(+) Treg cells and Th17 cells was determined by double-color labeling for flow cytometry analysis. The administration of CCII (10, 20, 40 microg/kg, i.g. x 7 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The activity of IL-2 and IL-17 produced by MLN lymphocytes from CIA rats was significantly inhibited by the administration of CCII (10, 20, and 40 microg kg(-1) day(-1)). The levels of IL-4 and TGF-beta were increased in CCII (10, 20, and 40 microg kg(-1) day(-1)) groups. The flow cytometry analysis showed that CCII (10, 20, and 40 microg kg(-1) day(-1)) significantly increased the proportion of Treg and decreased the proportion of Th17. These results indicate that oral administration of CCII had therapeutic effects on CIA rats, which was related to decreased production of pro-inflammatory mediators (IL-2, IL-17) and increased production of anti-inflammatory mediators (IL-4, TGF-beta). This suggests that CCII plays an important role in regulating the immune balance of Th1/Th2 and Th17/Treg in rats with CIA.

Evolution of vertebrate adaptive immunity: immune cells and tissues, and AID/APOBEC cytidine deaminases.

Science.gov (United States)

Hirano, Masayuki

2015-08-01

All surviving jawed vertebrate representatives achieve diversity in immunoglobulin-based B and T cell receptors for antigen recognition through recombinatorial rearrangement of V(D)J segments. However, the extant jawless vertebrates, lampreys and hagfish, instead generate three types of variable lymphocyte receptors (VLRs) through a template-mediated combinatorial assembly of different leucine-rich repeat (LRR) sequences. The clonally diverse VLRB receptors are expressed by B-like lymphocytes, while the VLRA and VLRC receptors are expressed by lymphocyte lineages that resemble αβ and γδ T lymphocytes, respectively. These findings suggest that three basic types of lymphocytes, one B-like and two T-like, are an essential feature of vertebrate adaptive immunity. Around 500 million years ago, a common ancestor of jawed and jawless vertebrates evolved a genetic program for the development of prototypic lymphoid cells as a foundation for an adaptive immune system. This acquisition preceded the convergent evolution of alternative types of clonally diverse receptors for antigens in all vertebrates, as reviewed in this article. © 2015 WILEY Periodicals, Inc.

A simple and rapid Hepatitis A Virus (HAV titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

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Kaplan Gerardo G

2008-12-01

Full Text Available Abstract Background Hepatitis A virus (HAV, the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the

Targeted in vitro and in vivo gene transfer into T Lymphocytes: potential of direct inhibition of allo-immune activation

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Mehra Mandeep R

2006-11-01

Full Text Available Abstract Background Successful inhibition of alloimmune activation in organ transplantation remains one of the key events in achieving a long-term graft survival. Since T lymphocytes are largely responsible for alloimmune activation, targeted gene transfer of gene of cyclin kinase inhibitor p21 into T cells might inhibit their aberrant proliferation. A number of strategies using either adenoviral or lentiviral vectors linked to mono or bispecific antibodies directed against T cell surface markers/cytokines did not yield the desired results. Therefore, this study was designed to test if a CD3promoter-p21 chimeric construct would in vitro and in vivo transfer p21 gene to T lymphocytes and result in inhibition of proliferation. CD3 promoter-p21 chimeric constructs were prepared with p21 in the sense and antisense orientation. For in vitro studies EL4-IL-2 thyoma cells were used and for in vivo studies CD3p21 sense and antisense plasmid DNA was injected intramuscularly in mice. Lymphocyte proliferation was quantified by 3H-thymidine uptake assay; IL-2 mRNA expression was studied by RT-PCR and using Real Time PCR assay, we monitored the CD3, p21, TNF-α and IFN-γ mRNA expression. Results Transfection of CD3p21 sense and antisense in mouse thyoma cell line (EL4-IL-2 resulted in modulation of mitogen-induced proliferation. The intramuscular injection of CD3p21 sense and antisense plasmid DNA into mice also modulated lymphocyte proliferation and mRNA expression of pro-inflammatory cytokines. Conclusion These results demonstrate a novel strategy of in vitro and in vivo transfer of p21 gene to T cells using CD3-promoter to achieve targeted inhibition of lymphocyte proliferation and immune activation.

Immunophenotypic enumeration of CD4 T-lymphocyte values in ...

African Journals Online (AJOL)

McRoy

lymphocytes play a central role in regulation of immune response.[2] These ..... influence of sex hormones on lymphocyte subpopulations. ... Friedland GH. Early treatment for HIV-The Time. Has Come. N Engl J Med 1990;322:1000-1002. 7. Gebo KA, Gallant JE, Keruly JC, Moore RD. Absolute CD4 vs. CD4 percentage for ...

Measurement of exercise-induced oxidative stress in lymphocytes.

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Turner, James E; Bosch, Jos A; Aldred, Sarah

2011-10-01

Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia

NARCIS (Netherlands)

Kekre, Natasha; Zhang, Ying; Zhang, Mei Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem M.; Joachim Deeg, H.; Kapoor, Neena; Lee, Jong Wook; Nakamura, Ryotaro; Pulsipher, Michael A.; Eapen, Mary; Antin, Joseph H

2017-01-01

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin

Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

International Nuclear Information System (INIS)

Urso, P.; Gengozian, N.

1977-01-01

The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

T lymphocytes and normal tissue responses to radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; McBride, William H.

2012-01-01

There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

Science.gov (United States)

Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

2016-02-04

Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.

Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes

DEFF Research Database (Denmark)

Kloverpris, Henrik; Karlsson, Ingrid; Bonde, Jesper

2009-01-01

OBJECTIVE:: To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. DESIGN:: We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent...... epitopes were modified as anchor-optimized peptides to improve immunogenicity and delivered on autologous monocyte-derived dendritic cells (MDDCs). METHODS:: Twelve treatment-naïve HLA-A*0201 HIV-1-infected Danish individuals received 1 x 10 MDDCs subcutaneously (s.c.) (weeks 0, 2, 4 and 8), pulsed......-cell counts was observed. CONCLUSION:: These data show that it is possible to generate new T-cell responses in treatment-naive HIV-1-infected individuals despite high viral loads, and thereby redirect immunity to target new multiple and rationally selected subdominant CTL epitopes. Further optimization could...

Radioresistance of immunized animals in internal irradiation

International Nuclear Information System (INIS)

Kal'nitskij, S.A.; Ponomareva, T.V.; Shubik, V.M.

1981-01-01

The influence of an immunization with bacterial vaccines and antimeasles-gamma-globulin on the radioresistance of raceless white mice was studied. In the vaccinated animals a higher survival rate and duration of life, a better general condition and a better curve of weight and stronger physical stamina were stated compared to the merely irradiated mice. The higher radioresistance is ascribed to the stimulation of cellular and humoral factors of the unspecific protection against infection, to the repair of the lymphoid tissue of the immunized animals and to the decrease in autosensibilization. (author)

Innate immunity

African Journals Online (AJOL)

Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

B-lymphocyte differentiation in lethally irradiated and reconstituted mice. II. Recovery of humoral immune responsiveness

International Nuclear Information System (INIS)

Rozing, J.; Brons, N.H.C.; Benner, R.

1977-01-01

The recovery of humoral immune responsiveness was studied in lethally irradiated, fetal liver-reconstituted mice. By means of both membrane fluorescence and antibody formation to sheep red blood cells (SRBC) as a functional assay, the rate of recovery of the compartments of B and T lymphocytes was determined in various lymphoid organs. The recovery of the immunoglobulin-positive (B) cell compartment after irradiation and reconstitution started in the spleen. This organ was also found to be the first in which the recovery of the B-cell population was completed. The interval between the recovery of the B-cell population in the spleen and that in the other organs tested was found to increase when the irradiated mice were reconstituted with spleen colony cells instead of fetal liver cells. This proved to be caused by the number and nature of the reconstituting hemopoietic stem cells. The immunoglobulin-positive (B) cells were found to appear before SRBC-reactive B cells could be demonstrated in spleen, lymph nodes, and Peyer's patches. The appearance of T lymphocytes in the various lymphoid organs required even more time. By means of cell transfer experiments, a sequential appearance of the precursors of anti-SRBC IgM-, IgG-, and IgA-plaque-forming cells could be demonstrated in spleen, bone marrow, lymph nodes, and Peyer's patches

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

Science.gov (United States)

Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

2017-07-01

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

The role of lymphocytes in radiotherapy-induced adverse late effects in the lung

Directory of Open Access Journals (Sweden)

Florian Wirsdörfer

2016-12-01

Full Text Available Radiation-induced pneumonitis and fibrosis are dose-limiting side effects of thoracic irradiation. Thoracic irradiation triggers acute and chronic environmental lung changes that are shaped by the damage response of resident cells, by the resulting reaction of the immune system, and by repair processes. Although considerable progress has been made during the last decade in defining involved effector cells and soluble mediators, the network of pathophysiological events and the cellular cross-talk linking acute tissue damage to chronic inflammation and fibrosis still require further definition. Infiltration of cells from the innate and adaptive immune systems is a common response of normal tissues to ionizing radiation. Herein lymphocytes represent a versatile and wide-ranged group of cells of the adaptive immune system that can react under specific conditions in various ways and participate in modulating the lung environment by adopting pro-inflammatory, anti-inflammatory or even pro- or anti-fibrotic phenotypes. The present review provides an overview on published data about the role of lymphocytes in radiation-induced lung disease and related damage-associated pulmonary diseases with a focus on T-lymphocytes and B-lymphocytes. We also discuss the suspected dual role of specific lymphocyte subsets during the pneumonitic phase and fibrotic phase that is shaped by the environmental conditions and the interaction and the intercellular cross-talk between cells from the innate and adaptive immune systems and (damaged resident epithelial cells and stromal cells (e.g. endothelial cells, mesenchymal stem cells (MSC, fibroblasts. Finally, we highlight potential therapeutic targets suited to counteract pathological lymphocyte responses to prevent or treat radiation-induced lung disease.

Immune Responses following Stereotactic Body Radiotherapy for Stage I Primary Lung Cancer

Directory of Open Access Journals (Sweden)

Yoshiyasu Maehata

2013-01-01

Full Text Available Purpose. Immune responses following stereotactic body radiotherapy (SBRT for stage I non-small cell lung cancer (NSCLC were examined from the point of view of lymphocyte subset counts and natural killer cell activity (NKA. Patients and Methods. Peripheral blood samples were collected from 62 patients at 4 time points between pretreatment and 4 weeks post-treatment for analysis of the change of total lymphocyte counts (TLC and lymphocyte subset counts of CD3+, CD4+, CD8+, CD19+, CD56+, and NKA. In addition, the changes of lymphocyte subset counts were compared between patients with or without relapse. Further, the correlations between SBRT-related parameters and immune response were analyzed for the purpose of revealing the mechanisms of the immune response. Results. All lymphocyte subset counts and NKA at post-treatment and 1 week post-treatment were significantly lower than pre-treatment (P<0.01. No significant differences in the changes of lymphocyte subset counts were observed among patients with or without relapse. The volume of the vertebral body receiving radiation doses of 3 Gy or more (VV3 significantly correlated with the changes of nearly all lymphocyte subset counts. Conclusions. SBRT for stage I NSCLC induced significant immune suppression, and the decrease of lymphocyte subset counts may be associated with exposure of the vertebral bone marrow.

Immune networks: multitasking capabilities near saturation

International Nuclear Information System (INIS)

Agliari, E; Annibale, A; Barra, A; Coolen, A C C; Tantari, D

2013-01-01

Pattern-diluted associative networks were recently introduced as models for the immune system, with nodes representing T-lymphocytes and stored patterns representing signalling protocols between T- and B-lymphocytes. It was shown earlier that in the regime of extreme pattern dilution, a system with N T T-lymphocytes can manage a number N B =O(N T δ ) of B-lymphocytes simultaneously, with δ B = αN T , with a high degree of pattern dilution, in agreement with immunological findings. We use graph theory and statistical mechanical analysis based on replica methods to show that in the finite-connectivity regime, where each T-lymphocyte interacts with a finite number of B-lymphocytes as N T → ∞, the T-lymphocytes can coordinate effective immune responses to an extensive number of distinct antigen invasions in parallel. As α increases, the system eventually undergoes a second order transition to a phase with clonal cross-talk interference, where the system’s performance degrades gracefully. Mathematically, the model is equivalent to a spin system on a finitely connected graph with many short loops, so one would expect the available analytical methods, which all assume locally tree-like graphs, to fail. Yet it turns out to be solvable. Our results are supported by numerical simulations. (paper)

NEW ASPECTS OF ANTI-INFECTION IMMUNITY

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E. P. Kisseleva

2011-01-01

Full Text Available Abstract. Four types of adaptive immune response which are regulated by different T-cell populations, namely Th1, Th2, Th17 and T regs have been described. At the first time classification is based on the difference in transcription factors but not due to diversity of cytokines produced. Each population of T-lymphocytes possesses a set of unique transcription factors and directions of cell signaling. Each type of immune responses plays a key role in the protection against certain types of pathogens. The Th1-response is important against intracellular bacteria and fungi, the Th17 — against extracellular, the Th2 — against yeasts and protozoa. T-regulatory cells control all types of immune responses. Diversity of immune response mechanisms occurs due to involvement of different effector cells. The Th1-type of response is connected with macrophage activation, Th2-cells cooperate with B-lymphocytes as well as attract eosinophils and mast cells. Th17 lymphocytes stimulate neutrophils and epithelial cells. T-cell differentiation is directed by the cytokines produced by innate immune cells. Phagocytes recognize molecular patterns at the surface of pathogens via pattern-recognition receptors (PRR, become activated and synthesize cytokines. Pathogen plays important role in this process while instructing dendritic cells. Pathogen dials a special code from a number of phagocyte surface receptors, which is named as «combinatory» recognition. Phagocytes possess several different types of activation and synthesize different cytokines that direct T-lymphocytes to a certain type of differentiation.

Spleen lymphocyte function modulated by a cocoa-enriched diet.

Science.gov (United States)

Ramiro-Puig, E; Pérez-Cano, F J; Ramírez-Santana, C; Castellote, C; Izquierdo-Pulido, M; Permanyer, J; Franch, A; Castell, M

2007-09-01

Previous studies have shown the down-regulating in vitro effect of cocoa flavonoids on lymphocyte and macrophage activation. In the present paper, we report the capacity of a long-term rich cocoa diet to modulate macrophage cytokine secretion and lymphocyte function in young rats. Weaned rats received natural cocoa (4% or 10% food intake), containing 32 mg flavonoids/g, for 3 weeks. Spleen immune function was then evaluated through the analysis of lymphocyte composition, their proliferative response and their ability to secrete cytokines and Ig. In addition, the status of activated peritoneal macrophages was established through tumour necrosis factor (TNF)-alpha secretion. The richest cocoa diet (10%) caused a reduction of TNF-alpha secretion by peritoneal macrophages showing anti-inflammatory activity. Similarly, although a 10% cocoa diet increased lymphocyte proliferation rate, it down-regulated T helper 2 (Th2)-related cytokines and decreased Ig secretion. These changes were accompanied by an increase in spleen B cell proportion and a decrease in Th cell percentage. In summary, these results demonstrate the functional activity of a cocoa-high dosage in down-regulating the immune response that might be beneficial in hypersensitivity and autoimmunity.

Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

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Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

2017-12-20

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib.

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Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E M; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E; Farooqui, Mohammed Z; Notkins, Abner L; Wiestner, Adrian; Aue, Georg

2015-11-05

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330.

Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

Science.gov (United States)

Boga, Can; Yeral, Mahmut; Gereklioglu, Ciğdem; Asma, Suheyl; Maytalman, Erkan; Aytan, Pelin; Kozanoglu, Ilknur; Sariturk, Cagla; Ozdogu, Hakan

2018-02-20

Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). Dose difference of

Immune response to UV-induced tumors: mediation of progressor tumor rejection by natural killer cells

International Nuclear Information System (INIS)

Streeter, P.R.; Fortner, G.W.

1986-01-01

Skin tumors induced in mice by chronic ultraviolet (UV) irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic animals. In the present study, the authors compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either regressor or progressor UV-tumors. The results of this comparison implicated tumor-specific cytolytic T (Tc) lymphocytes in rejection of regressor UV-tumors, and revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific Tc cells even as the tumors rejected. Following in vitro resensitization of spleen cells from either regressor or progressor tumor immune animals, the authors found NK-like lymphocytes with anti-tumor activity. As the authors had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, the authors examined lymphocytes from the local tumor environment during the course of progressor tumor rejection for this activity. This analysis revealed NK lymphocytes exhibiting significant levels of cytolytic activity against UV-tumors. These results implicate NK cells as potential effector cells in the rejection of progressor UV-tumors by immune animals, and suggests that these cells may be regulated by T lymphocytes

The effect of yeast β-glucan on the amount of albumin, globulin, urea and total protein of broiler chickens

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ali kargarirezapour

2013-08-01

Full Text Available Glucans derived from yeast cell wall are promising alternatives to antibiotics, as they have been shown to improve growth performance and stimulate the immune system of immature broilers. In this study we evaluated the effect of different levels of yeast beta-glucan (YBG on some blood parametrs of broiler chickens. In a factorial experiment based on completely randomized design (the first factor: YBG levels: 0, 0.04 and 0.08% of basal diet and sex as a second factor 144 day old chicks (72 male and 72 female were selected and allocated to different treatments (three replicates of each treatment. The overall experimental period was 34 days. At the end of study, two birds from each pen were randomly selected as a sample. The level of albumin, globulin, urea and total protein was measured on blood samples. Statistical analysis of the results showed that the YBG had no significant effect on albumin, globulin, urea and total protein level. But the amount of plasma albumin and total protein in female chicks was significantly higher than male chicks (p

Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology

DEFF Research Database (Denmark)

Bartholdy, C; Nansen, A; Christensen, Jeanette Erbo

1999-01-01

-mediated immune response was found to be unaltered in iNOS-deficient mice compared with wild-type C57BL/6 mice, and LCMV- induced general immunosuppression was equally pronounced in both strains. In vivo analysis revealed identical kinetics of virus clearance, as well as unaltered clinical severity of systemic......By using mice with a targetted disruption in the gene encoding inducible nitric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) in lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protective immunity and immunopathology. The afferent phase of the T cell...... LCMV infection in both strains. Concerning the outcome of intracerebral infection, no significant differences were found between iNOS-deficient and wild-type mice in the number or composition of mononuclear cells found in the cerebrospinal fluid on day 6 post-infection. Likewise, NO did not influence...

Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?

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Busse, Stefan; Busse, Mandy; Schiltz, Kolja; Bielau, Hendrik; Gos, Tomasz; Brisch, Ralf; Mawrin, Christian; Schmitt, Andrea; Jordan, Wolfgang; Müller, Ulf J; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

2012-11-01

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain's mononuclear phagocyte system (microglial cells) is activated during acute psychosis. Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P=0.047, right: P=0.038; CD20: left: P=0.020, right: P=0.010) and controls (CD3: left: P=0.057, right: P=0.069; CD20: left: P=0.008, right: P=0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P=0.030, right: P=0.012). A similar trend emerged when this group was compared to controls (left: P=0.090, right: P=0.090). BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity. Copyright © 2012 Elsevier Inc. All rights reserved.

Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.

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Tokoyoda, Koji; Zehentmeier, Sandra; Hegazy, Ahmed N; Albrecht, Inka; Grün, Joachim R; Löhning, Max; Radbruch, Andreas

2009-05-01

CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.

Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression by Ganoderma Lucidum Polysaccharides

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Li-Xin Sun

2014-01-01

Full Text Available Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.

Repair of UV-induced DNA damage in aplastic anaemia: Changes after treatment with antilymphocyte globulin (ALG)

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Kovacs, E.; Nissen, C.; Speck, B.; Signer, E.

1988-01-01

The extent of DNA-repair induced by UV-C irradiation was measured in peripheral unstimulated lymphocytes of 24 patients with aplastic anaemia at different stages of disease and compared with the results obtained in 92 controls. As parameter of the DNA-repair synthesis, the incorporation of (/sup 3/H)thymidine in the presence of 2 mmol/l hydroxyurea (HU) was taken. Of 19 patients tested after treatment with antilymphocyte globulin (ALG), 5 were in complete autologous haemopoietic remission, defined as > 1000 granulocytes/mm/sup 3/, > 100 000 platelets/mm/sup 3/ and a nontransfused haemoglobin value > 10 g%. 14 patients were in partial remission, defined as improvement of haemopoietic function, not meeting the criteria for complete remission. 4/5 patients in complete remission had normal DNA-repair synthesis, compared to 4/14 patients in partial remission. In 92 controls, a normal level was found in 70 cases. In 4/5 patients examined at diagnosis and at various intervals after ALG-treatment, DNA-repair synthesis was low at diagnosis. It increased after therapy and paralleled improvement of haemopoietic function to some extent. It is suggested that in aplastic anaemia there are different populations of lymphocytes with differing DNA-repair capacity; ALG treatment seems to favour expansion of the normal population, which is associated with improvement of haemopoietic function.

Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Barsegian, Vahe; Moeckel, Daniel [Helios Kliniken, Institute of Nuclear Medicine, Schwerin (Germany); Mueller, Stefan P.; Bockisch, Andreas [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Horn, Peter A.; Lindemann, Monika [University Hospital Essen, Institute for Transfusion Medicine, Essen (Germany)

2017-02-15

Therapy with the alpha-emitter radium-223 chloride ({sup 223}Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if {sup 223}Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving {sup 223}Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after {sup 223}Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

Adaptive immunity in autoimmune hepatitis.

Science.gov (United States)

Longhi, Maria Serena; Ma, Yun; Mieli-Vergani, Giorgina; Vergani, Diego

2010-01-01

The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of alphabeta-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (T(H)0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, T(H)0 lymphocytes can differentiate into T(H)1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into T(H)2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25(high) regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses. Copyright 2010 S. Karger AG, Basel.

The effects of low dose radiation (LDR) on lymphocytes

International Nuclear Information System (INIS)

Su Liaoyuan; Du Zeji; Tian Hailin; Zhao Yujie; Zou Huawei; Zhou Jianhua; Kong Xiangrong; Zhang Jianhua; Shen Wei

2001-01-01

LDR could stimulate lymphocyte transformation for adults, children and infants. The effect of LDR on lymphocytes in malnourished children was lower, but higher on lymphocytes in cord blood. The effect of LDR on CD 4 + cells in adult persons was higher than that on CD + cells. NK cells were radioresistant. The stimulative effect of LDR on NK activity in tumor patients was lower than that in normal individuals. For the mice with tumors, LDR could increase the ratio of L 3 T 4 cells in blood, spleen and the number of cytotoxic T cells in the tumors. Extracellular fluid of the lymphocytes operated by LDR could also stimulate the lymphocyte transformation. The preliminary LDR could decrease the injuries to macromolecules, membrane antigens and chromosomes in lymphocytes which were induced by high dose radiation. The LDR- induced protein might be found from mouse spleen cells, and this protein could increase immune function in human and animals

In vitro stimulation of rabbit T lymphocytes by cells expressing herpes simplex antigens.

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Kapoor, A K; Ling, N R; Nash, A A; Bachan, A; Wildy, P

1982-04-01

Lymphocyte stimulation responses to herpes antigens were studied using virus-infected X-irradiated cells. Rabbits were immunized with herpes simplex virus type 1 (strain HFEM) grown in RK 13 cells. For in vitro stimulation assay BHK21 cells were X-irradiated (15 000 rad) and infected with a high m.o.i. of a temperature-sensitive (ts) mutant (N102) of HFEM strain at the non-permissive temperature (38.5 degrees C) of virus. Virus antigens were expressed on the infected cells and there was no leakage of infectious virus into the medium at 38.5 degrees C. T lymphocytes from rabbits immunized with herpes simplex virus were specifically activated by herpesvirus-infected X-irradiated cells; lymph node cells from rabbits immunized with RK13 cells and from non-immune rabbits showed no proliferative response.

Auto-immune Haematological Complications Occurring during the ...

African Journals Online (AJOL)

1974-10-19

Oct 19, 1974 ... Immunohaematological disorders may complicate the clini- cal course of patients with chronic lymphocytic leukaemia, lymphocytic lymphoma and Hodgkin's disease.'" Auto- immune haemolytic anaemia is the most common of these complications, occurring in approximately 10 - 25'% of patients with ...

Diversity, Function and Transcriptional Regulation of Gut Innate Lymphocytes

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Lucille eRankin

2013-03-01

Full Text Available The innate immune system plays a critical early role in host defense against viruses, bacteria and tumour cells. Until recently, natural killer (NK cells and lymphoid tissue inducer (LTi cells were the primary members of the innate lymphocyte family: NK cells form the front-line interface between the external environment and the adaptive immune system, while LTi cells are essential for secondary lymphoid tissue formation. More recently, it has become apparent that the composition of this family is much more diverse than previously appreciated and newly recognized populations play distinct and essential functions in tissue protection. Despite the importance of these cells, the developmental relationships between different innate lymphocyte populations (ILCs remain unclear. Here we review recent advances in our understanding of the development of different innate immune cell subsets, the transcriptional programs that might be involved in driving fate decisions during development, and their relationship to NK cells.

Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercaria- I. analysis of antibody and T-lymphocyte responses in mouse strains developing differing levels of immunity

International Nuclear Information System (INIS)

James, S.L.; Labine, M.; Sher, A.

1981-01-01

The kinetics of cellular and humoral responses directed against schistosomula were examined in mice of three inbred strains which demonstrate differences in the degree of resistance induced by immunization with irradiated cercariae. T-Cell reactivity was observed during the first 4 weeks after vaccination but declined to control levels thereafter. Anti-schistosomulum antibody was first detected 2 weeks after vaccination, peaked by 6 weeks, and persisted as late as 15 weeks. In sera obtained at 6 weeks, antibody activity was detected in affinity chromatography-purified fractions containing IgM, IgA, IgG 1 , IgG 2 /sub a/, and IgG 3 immunoglobulins. In general, the cellular and humoral responses observed in C57Bl/6J mice, which consistently developed a high level of immunity after vaccination, were not significantly different from those observed in C3H/HeJ or CBA/J mice, which achieved only low to moderate levels of immunity. Thus, although antibody production appears to correlate more closely than T lymphocyte responsiveness with the typical long-term resistance pattern observed in this model, the absence of striking differences in parasite-specific antibody levels between mice of these different strains suggests that additional mechanisms may be involved in the development of immunity after vaccination

Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

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Barragry, J M; Makin, H L; Trafford, D J; Scott, D F

1978-01-01

Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG. PMID:569688

T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1

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Malika Trad

2015-01-01

Full Text Available T lymphocytes activated by dendritic cells (DC which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.

Bare lymphocyte syndrome: imaging findings in an adult

International Nuclear Information System (INIS)

Bernaerts, A.; Vandevenne, J.E.; De Schepper, A.M.; Lambert, J.; De Clerck, L.S.

2001-01-01

Bare lymphocyte syndrome (BLS) is a rare primary immune disorder characterized by defective expression of human leukocyte antigen (HLA) on lymphocytes, often resulting in extensive and recurrent multi-organ infections. We describe a previously undiagnosed case of an adult woman who presented with radiological findings of severe bronchiectases, near-total granulomatous destruction of facial bones, and osteomyelitis. Diagnosis of BLS should be considered when evaluating children with unexplained bronchiectases or adults with long history of chronic multi-organ infections. (orig.)

Study of the influence of homologous serum globulin preparations on the intestinal automicroflora in irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Pinegin, B.V.; Klemparskaya, N.N.; Mal' tsev, V.N.; Korshunov, G.A.; Shal' nova, G.A.; Kuz' mina, T.D.

1984-09-01

In spite of considerable experience of practical use of serum globulin preparations, their effect on automicroflora wasn't studied. The favorable effect of therapeutic injection of homologous serum globulin preparations on automicroflora of small and large intestine of mices was established for the model of acute radiation sickness caused by /sup 60/Co irradiation with 700 R dose. The effect of injecting two types of globulin preparations was studied: ones prepared of blood of intact and hemostimulated mices (to increase the content of normal antitissue antibodies in the serum). Besides the general globulin fraction isolated by ammonium sulfate precipitation a study was made on the effect of purified IgG and IgM preparations. Threefold subcutaneous or intraperitoneal globulin in ection of 1 ..mu..g dose in a mice prevented after 2, 24, 48 h after irradiation the development of bacteriosis, typical for radiation injury - decreased accumulation of putrefactive bacteria and reduced the suppression of lactobacilli content. Globulin preparations and fractions of hemostimulated mice serum, enriched by normal antitissue antibodies are the most effective ones.

Sensitization with 7S Globulins from Peanut, Hazelnut, Soy or Pea Induces IgE with Different Biological Activities Which Are Modified by Soy Tolerance

DEFF Research Database (Denmark)

Kroghsbo, Stine; Bøgh, Katrine Lindholm; Rigby, Neil M.

2011-01-01

, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their ‘normal’ matrix. Methods: Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3......Background: It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure...... times with 100 μg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. Results: The 4 related 7S globulins induced a response with an almost identical...

Vaccines and immunization

African Journals Online (AJOL)

Prof Ezechukwu

vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...

Effects of medicinal herbs "Plantago asiatica", "Houttuynia cordata" and "Mentha haplocalyx" on non-specific immune responses of cobia (Rachycentron canadum).

Science.gov (United States)

Wu, Yu-Sheng; Chen, Yin-Yu; Ueng, Pien-Sheng; Nan, Fan-Hua

2016-11-01

This study investigated the effects of orally administered Plantago asiatica, Houttuynia cordata, and Mentha haplocalyx on the growth and nonspecific immune responses of cobia (Rachycentron canadum). The nonspecific immune parameters assessed were weight gain, feed conversion ratio, superoxide anion (O 2 - ) production, superoxide dismutase (SOD) activity, phagocytic rate, phagocytic index, lysozyme activity, serum albumin and globulin, and albumin:globulin (A/G) ratio. The growth experiment indicated that 6-week dietary treatments did not significantly affect on the growth of cobia. Nonspecific immune responses showed that O 2 - production, SOD and lysozyme activity, and phagocytosis were significantly increased after the oral administration of P. asiatica and H. cordata, and the serum albumin:globulin ratio (A/G) gradually decreased. In this study, treatment of the Mentha haplocalyx on the cobia didn't present with the inducing of the phagocytosis ability compared with the treatment of P. asiatica and H. cordata. We suggest that oral administration of the 10 g/kg or 20 g/kg of the P. asiatica and H. cordata is exactly inducing the phagocytosis, ROS production, lysozyme activity and SOD production in the cobia. Copyright © 2016 Elsevier Ltd. All rights reserved.

The twilight of immunity: emerging concepts in aging of the immune system.

Science.gov (United States)

Nikolich-Žugich, Janko

2018-01-01

Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

Science.gov (United States)

Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

2015-09-01

In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

Genetics Home Reference: corticosteroid-binding globulin deficiency

Science.gov (United States)

... There may also be other genetic or environmental factors that influence whether an affected individual is more likely to develop pain or fatigue. Learn more about the gene associated with corticosteroid-binding globulin deficiency SERPINA6 Related Information What is a gene? What is a ...

Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

International Nuclear Information System (INIS)

Barsegian, Vahe; Moeckel, Daniel; Mueller, Stefan P.; Bockisch, Andreas; Horn, Peter A.; Lindemann, Monika

2017-01-01

Therapy with the alpha-emitter radium-223 chloride ("2"2"3Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if "2"2"3Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving "2"2"3Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after "2"2"3Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

Lymphocyte proliferation in Peyer's patches of Giardia muris-infected mice.

OpenAIRE

Hill, D R

1990-01-01

Gastrointestinal immune events in giardiasis are important in controlling infection. In this study, Peyer's patch lymphocytes from mice infected with Giardia muris developed specific, proliferative responses to G. muris antigen. This proliferation correlated with clearance of infection. Further understanding of the gut immune response will be helpful in developing immunoprophylactic strategies in the control of giardiasis.

Proteomic analysis of albumin and globulin fractions of pea (Pisum sativum L.) seeds.

Science.gov (United States)

Dziuba, Jerzy; Szerszunowicz, Iwona; Nałęcz, Dorota; Dziuba, Marta

2014-01-01

Proteomic analysis is emerging as a highly useful tool in food research, including studies of food allergies. Two-dimensional gel electrophoresis involving isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis is the most effective method of separating hundreds or even thousands of proteins. In this study, albumin and globulin tractions of pea seeds cv. Ramrod were subjected to proteomic analysis. Selected potentially alergenic proteins were identified based on their molecular weights and isoelectric points. Pea seeds (Pisum sativum L.) cv. Ramrod harvested over a period of two years (Plant Breeding Station in Piaski-Szelejewo) were used in the experiment. The isolated albumins, globulins and legumin and vicilin fractions of globulins were separated by two-dimensional gel electrophoresis. Proteomic images were analysed in the ImageMaster 2D Platinum program with the use of algorithms from the Melanie application. The relative content, isoelectric points and molecular weights were computed for all identified proteins. Electrophoregrams were analysed by matching spot positions from three independent replications. The proteomes of albumins, globulins and legumin and vicilin fractions of globulins produced up to several hundred spots (proteins). Spots most characteristic of a given fraction were identified by computer analysis and spot matching. The albumin proteome accumulated spots of relatively high intensity over a broad range of pi values of ~4.2-8.1 in 3 molecular weight (MW) ranges: I - high molecular-weight albumins with MW of ~50-110 kDa, II - average molecular-weight albumins with MW of ~20-35 kDa, and III - low molecular-weight albumins with MW of ~13-17 kDa. 2D gel electrophoregrams revealed the presence of 81 characteristic spots, including 24 characteristic of legumin and 14 - of vicilin. Two-dimensional gel electrophoresis proved to be a useful tool for identifying pea proteins. Patterns of spots with similar isoelectric

Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients

Directory of Open Access Journals (Sweden)

Lardon Filip

2010-04-01

Full Text Available Abstract Background There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial. Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential. Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI, were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis. Results Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables. Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients' overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes. When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained. Only early stage and young age

Recovery of the immune system after exercise.

Science.gov (United States)

Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J

2017-05-01

The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8 + T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes. Copyright © 2017 the American Physiological Society.

PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

Directory of Open Access Journals (Sweden)

M. V. Osikov

2016-01-01

Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

Canine lymphocyte activating factor (LAF)

International Nuclear Information System (INIS)

Shifrine, M.; Whaley, C.B.; Wilson, F.D.; Taylor, N.J.

1979-01-01

The immune response of an animal is the sum of the result of the interaction of various cells mainly through soluble mediators. It is not enough to look at specific cell populations, it is also necessary to study the interactions between purified cell population. The effect of one subpopulation on another is via soluble mediators. We have been studying one (of several) such mediators in its relation to radiation effects on the immune response. Lymphocyte activating factor (LAF) is defined functionally as a potentiator of the response of thymocytes to phytohemagglutinin (PHA) or concanavalin (con-A). It can also elicit response of unstimulated subpopulations separated from the thymus. It is a product of adherent populations, presumably macrophages. It has been shown to be produced by human, rabbit, and mouse cells, but has not been reported in the dog. It also was shown to be present in higher concentrations in irradiated mice than in comparable unirradiated mice. We have shown that LAF is produced by plastic-adherent populations derived from peripheral blood. Currently we are working to determine the lymphocyte subpopulations with which LAF interacts

In Utero Exposure to Histological Chorioamnionitis Primes the Exometabolomic Profiles of Preterm CD4+ T Lymphocytes.

Science.gov (United States)

Matta, Poojitha; Sherrod, Stacy D; Marasco, Christina C; Moore, Daniel J; McLean, John A; Weitkamp, Joern-Hendrik

2017-11-01

Histological chorioamnionitis (HCA) is an intrauterine inflammatory condition that increases the risk for preterm birth, death, and disability because of persistent systemic and localized inflammation. The immunological mechanisms sustaining this response in the preterm newborn remain unclear. We sought to determine the consequences of HCA exposure on the fetal CD4 + T lymphocyte exometabolome. We cultured naive CD4 + T lymphocytes from HCA-positive and -negative preterm infants matched for gestational age, sex, race, prenatal steroid exposure, and delivery mode. We collected conditioned media samples before and after a 6-h in vitro activation of naive CD4 + T lymphocytes with soluble staphylococcal enterotoxin B and anti-CD28. We analyzed samples by ultraperformance liquid chromatography ion mobility-mass spectrometry. We determined the impact of HCA on the CD4 + T lymphocyte exometabolome and identified potential biomarker metabolites by multivariate statistical analyses. We discovered that: 1) CD4 + T lymphocytes exposed to HCA exhibit divergent exometabolomic profiles in both naive and activated states; 2) ∼30% of detected metabolites differentially expressed in response to activation were unique to HCA-positive CD4 + T lymphocytes; 3) metabolic pathways associated with glutathione detoxification and tryptophan degradation were altered in HCA-positive CD4 + T lymphocytes; and 4) flow cytometry and cytokine analyses suggested a bias toward a T H 1-biased immune response in HCA-positive samples. HCA exposure primes the neonatal adaptive immune processes by inducing changes to the exometabolomic profile of fetal CD4 + T lymphocytes. These exometabolomic changes may link HCA exposure to T H 1 polarization of the neonatal adaptive immune response. Copyright © 2017 by The American Association of Immunologists, Inc.

Investigating the effect of ionizing radiations on humoral immune system in industrial radiographers

International Nuclear Information System (INIS)

Zakeri, Fariedeh.

1993-01-01

A general review of radiobiology, immunology system,mechanism of biological effect of radiation and their biological damaging on cells and organs and specifically radiation effects on humoral immune system are given. The purpose is investigating the side effects of occupational exposures caused by ionizing radiation, and reviewing the decreasing probability of humoral immune responses in industrial radiographers. Generally, it measures the following humoral factors of industrial radiographers by value of different exposures: 1-Measuring immunoglobulins serum which consist of IgM, IgG, IgA, IgE. 2-Electrophoresis of serum proteins to investigate gamma globulins changes and also the changes occur in serum globulins after exposure. 3-Investigating the titration of isohem glutins serum (or natural immunoglobulins) that is mostly from IgM. 4-Measuring the above experiments on health control personnel who have not exposed to occupational or biological radiation effects. 5-Comparing the results of the two groups by statistical analysis. 6-Trying to relate the exposure to the information obtained from the above experiments. 7-Finally, to obtain this response whether mutation as low dose of radiation as investigated in this project is a threatening factor to the health and immunity of industrial radiographers

Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study.

Science.gov (United States)

Mirjolet, C; Charon-Barra, C; Ladoire, S; Arbez-Gindre, F; Bertaut, A; Ghiringhelli, F; Leroux, A; Peiffert, D; Borg, C; Bosset, J F; Créhange, G

2018-01-01

Introduction : Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods : We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results : In univariate analysis, several factors significantly correlated (pguide physicians in adjuvant treatment decision-making.

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Directory of Open Access Journals (Sweden)

Joel Saltz

2018-04-01

Full Text Available Summary: Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment. : Tumor-infiltrating lymphocytes (TILs were identified from standard pathology cancer images by a deep-learning-derived “computational stain” developed by Saltz et al. They processed 5,202 digital images from 13 cancer types. Resulting TIL maps were correlated with TCGA molecular data, relating TIL content to survival, tumor subtypes, and immune profiles. Keywords: digital pathology, immuno-oncology, machine learning, lymphocytes, tumor microenvironment, deep learning, tumor-infiltrating lymphocytes, artificial intelligence, bioinformatics, computer vision

Role of interferon in lymphocyte recruitment into the skin

International Nuclear Information System (INIS)

Issekutz, T.B.; Stoltz, J.M.; Webster, D.M.

1986-01-01

Large numbers of lymphocytes are recruited from the blood into sites of cutaneous DTH reactions. Our goal was to investigate the factors controlling this recruitment. 111 In-labeled peritoneal exudate lymphocytes were injected iv and the accumulation of these cells in skin sites injected with a variety of stimuli, was used to measure lymphocyte recruitment in rats. Large numbers of lymphocytes migrated into vaccinia- and KLH-injected sites in sensitized animals, but only into the viral and not the KLH lesions in non-immune animals. Lymphocytes also migrated efficiently into sites injected with the alpha-interferon (IFN) inducers, uv-inactivated vaccinia virus and poly I:C, as well as into sites injected with IFN. In each case there was a dose-response relationship. Analysis of the kinetics of lymphocyte recruitment demonstrated that the peak rate of migration occurred most rapidly after the injection of IFN, later after poly I:C, and was slowest to be reached after vaccinia virus. Rabbit anti-IFN blocked the recruitment of lymphocytes by uv-inactivated vaccinia and by IFN. Histologically, all of these sites demonstrated a dense mononuclear cell infiltrate in the dermis. It is suggested that IFN may be an important mediator in the recruitment of lymphocytes into inflammatory reactions

Initial experience with laparoscopic splenectomy for immune ...

African Journals Online (AJOL)

Immune thrombocytopenic purpura (ITP) is an immune- mediated disease characterised by thrombocytopenia, the degree of which determines the increased risk of bleeding.[1] It can be primary (idiopathic) or secondary. Secondary ITP can occur with systemic lupus erythematosus, chronic lymphocytic leukaemia,.

Sex Hormone–Binding Globulin and Risk of Type 2 Diabetes in Women and Men

Science.gov (United States)

Ding, Eric L.; Song, Yiqing; Manson, JoAnn E.; Hunter, David J.; Lee, Cathy C.; Rifai, Nader; Buring, Julie E.; Gaziano, J. Michael; Liu, Simin

2009-01-01

BACKGROUND Circulating sex hormone–binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. METHODS We performed a nested case–control study of postmenopausal women in the Women’s Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone–binding globulin were measured; two polymorphisms of the gene encoding sex hormone–binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians’ Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). RESULTS Among women, higher plasma levels of sex hormone–binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone–binding globulin levels (P = 0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P = 0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone–binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per

Failure of attenuated canine distemper virus (Rockborn strain) to suppress lymphocyte blastogenesis in dogs.

Science.gov (United States)

Schultz, R D

1976-01-01

The attenuated Rockborn strain of canine distemper virus is commonly used in commercial vaccines. Since immunosuppression is a common feature of virulent (Snyder Hill) distemper virus infection of the dog, an evaluation of the cellular immune functions of dogs given inoculums of the less virulent Rockborn strain was done using lymphocyte blastogenesis responses to various mitogens. Unlike the viruslent Snyder Hill strain, the attenuated distemper virus did not alter lymphocyte blastogenesis responses to phytohemaglutinin (PHA) and pokeweed mitogen (PWM) which are considered in vitro correlates of T and B cell immunity.

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents - Retention of naive T lymphocytes in HIV-infected adolescents

NARCIS (Netherlands)

Douglas, SD; Rudy, B; Muenz, L; Starr, SE; Campbell, DE; Wilson, C; Holland, C; Crowley-Nowick, P; Vermund, SH

Background: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. Objective: To assess lymphocyte subsets in HIV-infected and high-risk

Immune system investigations for radiation workers

International Nuclear Information System (INIS)

Obreja, Doina; Tulbure, Rodica; Marinescu, Irina

2001-01-01

During the last decade a great deal of attention has been paid to the research in the field of the immune system. Some important steps forward have been achieved in understanding the mechanisms of action and control of the immunologic responses. At the same time the concern for the possible health effects of exposure to ionizing radiation has considerably increased. On the purpose of the evaluation of the modifications induced by the ionizing radiation for radiation workers, we have applied the method of lymphocytic subpopulations, a method that evinces the proportions for the various subtypes of lymphocytes having different roles within the immune system. A number of 62 persons, employees of the Institute of Physics and Nuclear Engineering at Bucharest - Magurele were involved in this study. All radiation workers from 2 departments characterized by a high exposure to ionizing radiation were included, as follows: Group no. 1, consisting of 20 persons working at RWTS (Radioactive Waste Treating Station), thus presenting both external and internal irradiation; Group no. 2, consisting of 18 persons working at RPC (Radioactive Isotopes Preparing Center), a place where besides the radioactive contamination, the chemical risk was also present. The control group (consisting of 24 persons) was formed of employees from the same institute, with the difference that they were not radiation workers. For the statistical processing of the results the programs EPI INFO 6 and CIA were used. Significantly, when analyzing globally the lymphocytic modifications for TT and/or B lymphocytes (either increments or decrements when compared to the normal values), a noticeable statistical difference among the groups in terms of the frequency of the immune system modifications (Hi square test p=0.001) occurs. The results are in accordance to those in special literature mentioning age as a factor having a role in the appearance of the immune modifications. The obtained results indicate a

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches.

Science.gov (United States)

Behzad, Masumeh Maleki; Asnafi, Ali Amin; Jaseb, Kaveh; Jalali Far, Mohammad Ali; Saki, Najmaldin

2017-12-01

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Human Gc Globulin (Vitamin D Binding Protein)

DEFF Research Database (Denmark)

Pihl, Tina Holberg; Jørgensen, Charlotte Svaerke; Santoni-Rugiu, Eric

2010-01-01

Gc globulin is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with Gc globulin could therefore...

Is the sex hormone binding globulin related to preeclampsia independent of insulin resistance

International Nuclear Information System (INIS)

Rahmanian, M.; Salari, Z.; Mirmohammadkhani, M.; Ghorbani, R.

2014-01-01

Objective: To evaluate the association between Sex Hormone Binding Globulin and preeclampsia in Iranian women considering the probable confounding effect of insulin resistance. Methods: The case-control study was conducted at the Semnan University of Medical Sciences, Iran, and comprised pregnant women who received prenatal care at Amiralmomenin Hospital in 2011. Cases represented patients admitted because of preeclampsia, while controls were randomly selected eligible pregnant women without hypertension and/or proteinuria. Fasting blood sugar and insulin were assessed for all participants as well as their blood concentration of Sex Hormone Binding Globulin. The Homeostasis Model Assessment of Insulin Resistance Score was used. The correlation between dependant and independent variables was reported by crude and adjusted odds ratio applying logistic regression models. SPSS 16.0 was used for statistical analysis. Results: Of the 100 pregnant women in the study, 45(45%) were cases. Insulin resistance was found to be significantly more frequent in the cases compared to the controls (adjusted odds ratio=2.78; 95% Confidence Interval: 1.11, 6.90; p<0.01). There was a significant reverse correlation between level of Sex Hormone Binding Globulin in blood and being a case of preeclampsia (adjusted odds ratio=0.99; 95% Confidence Interval: 0.98, 1.00; p=0.04). Conclusion: Independent of insulin resistance, every 1nmol/l increase in Sex Hormone Binding Globulin, decreases the odds of preeclampsia by 1%, notifying Sex Hormone Binding Globulin as an important biomarker about its etiology and prediction. (author)

Stress, cortisol, and B lymphocytes: a novel approach to understanding academic stress and immune function.

Science.gov (United States)

McGregor, Bonnie A; Murphy, Karly M; Albano, Denise L; Ceballos, Rachel M

2016-01-01

Animal and human in vitro models suggest that stress-related B lymphocyte decrements are due to high levels of glucocorticoids which cause apoptosis of pre-B-cells as they emerge from the bone marrow. The present study sought to explore the relationships among distress, salivary cortisol, and human B lymphocytes in vivo. Distress (perceived stress, negative affect, depressive symptoms), lymphocyte phenotype, and salivary cortisol were assessed among first-year graduate students (n = 22) and a community control sample (n = 30) at the start of classes in the fall and the week immediately before spring preliminary exams. Compared to controls, students reported greater distress on all measures at each time point except baseline perceived stress. Hierarchical linear regression with necessary control variables was used to assess the effect of student status on the three measures of distress, the four measures of lymphocyte phenotype, and cortisol AUC and CAR over time (T1-T2). Student status was associated with a significant decrease in CD19 + B lymphocytes and flattened cortisol awakening response (CAR). Change in CAR was associated with the decrease in CD19 + B lymphocytes. Results indicated that there are significant associations among student status, flattening of CAR, and decrements in CD19 + lymphocytes.

Interaction of T- and B-lymphocytes in the immune respouse of lethally irradiated dogs thymus and part of bone marrow being shielded

International Nuclear Information System (INIS)

Petrov, R.V.; Khaitov, R.M.; Sbitneva, M.F.; Fedorovskij, L.L.; Nazhmitdinov, A.M.; Ataullakhanov, R.I.; Gvozdeva, N.I.

1978-01-01

It has been first shown in experiments with sublethally irradiated dogs that it is possible to simulate and study the role of the co-operative interaction of T- and B-lymphocytes in the immune response. A model has been developed for determining dynamically the number of antibody-forming cells in the spleen of dogs in the course of the chronic experiment. The proposed model may be used for assessing the role of the substances that affect the interaction of T- and B-cells in the irradiated dog organism

Biochemical studies of immune RNA using a cell-mediated cytotoxicity assay

Energy Technology Data Exchange (ETDEWEB)

Griffin, G.D.; Sellin, H.G.; Novelli, G.D.

1980-01-01

Immune RNA (iRNA), a subcellular macromolecular species usually prepared by phenol extraction of lymphoid tissue, can confer some manifestation(s) of cellular immunity on naive lymphocytes. Experiments were done to develop an assay system to detect activation of lymphocytes by iRNA to become cytotoxic toward tumor cells, and to study certain properties of iRNA using this system. Guinea pigs were immunized with human mammary carcinoma cells and the iRNA, prepared from spleens of animals shown by prior assay to have blood lymphocytes highly cytotoxic against the tumor cells, was assayed by ability of iRNA-activated lymphocytes to lyse /sup 51/Cr-labelled tumor cells. The ability of iRNA to activate lymphocytes to tumor cytotoxicity could only be differentiated from a cytotoxic activation by RNA preparations from unimmunized animals at very low doses of RNA. The most active iRNA preparations were from cytoplasmic subcellular fractions, extracted by a cold phenol procedure, while iRNA isolated by hot phenol methods was no more active than control RNA prepared by the same techniques. Attempts to demonstrate poly(A) sequences in iRNA were inconclusive.

Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice

International Nuclear Information System (INIS)

Jerrells, T.R.; Palmer, B.A.; Osterman, J.V.

1983-01-01

Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice

A Novel Antagonist of the Immune Checkpoint Protein Adenosine A2a Receptor Restores Tumor-Infiltrating Lymphocyte Activity in the Context of the Tumor Microenvironment

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Melanie Mediavilla-Varela

2017-07-01

Full Text Available BACKGROUND: Therapeutic strategies targeting immune checkpoint proteins have led to significant responses in patients with various tumor types. The success of these studies has led to the development of various antibodies/inhibitors for the different checkpoint proteins involved in immune evasion of the tumor. Adenosine present in high concentrations in the tumor microenvironment activates the immune checkpoint adenosine A2a receptor (A2aR, leading to the suppression of antitumor responses. Inhibition of this checkpoint has the potential to enhance antitumor T-cell responsiveness. METHODS: We developed a novel A2aR antagonist (PBF-509 and tested its antitumor response in vitro, in a mouse model, and in non-small cell lung cancer patient samples. RESULTS: Our studies showed that PBF-509 is highly specific to the A2aR as well as inhibitory of A2aR function in an in vitro model. In a mouse model, we found that lung metastasis was decreased after treatment with PBF-509 compared with its control. Furthermore, freshly resected tumor-infiltrating lymphocytes from lung cancer patients showed increased A2aR expression in CD4+ cells and variable expression in CD8+ cells. Ex vivo studies showed an increased responsiveness of human tumor-infiltrating lymphocytes when PBF-509 was combined with anti-PD-1 or anti-PD-L1. CONCLUSIONS: Our studies demonstrate that inhibition of the A2aR using the novel inhibitor PBF-509 could lead to novel immunotherapeutic strategies in non-small cell lung cancer.

The Immune Landscape of Cancer

OpenAIRE

Thorsson, Vésteinn; Gibbs, David L.; Brown, Scott D.; Wolf, Denise; Bortone, Dante S.; Ou Yang, Tai Hsien; Porta-Pardo, Eduard; Gao, Galen F.; Plaisier, Christopher L.; Eddy, James A.; Ziv, Elad; Culhane, Aedin C.; Paull, Evan O.; Sivakumar, I. K.Ashok; Gentles, Andrew J.

2018-01-01

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell prolifer...

Safety pharmacology, toxicology and pharmacokinetic assesment of human Gc globulin (vitamin d binding protein)

DEFF Research Database (Denmark)

Pihl, Tina Holberg; Jørgensen, Charlotte Sværke; Santoni Rugiu, Eric

2010-01-01

  Gc globulin is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with Gc globulin could therefore...

Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

Science.gov (United States)

He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

2007-10-01

The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

Science.gov (United States)

Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

2017-01-01

Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

[The liver and the immune system].

Science.gov (United States)

Jakab, Lajos

2015-07-26

The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row "endothelium", stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes

Comparison of bovine lymphocyte antigen DRB3.2 allele ...

African Journals Online (AJOL)

STORAGESEVER

2008-08-04

Aug 4, 2008 ... The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell ... alleles were more resistant to clinical mastitis. ... DRB3.2 allele pattern in two Iranian Holstein cow .... observed and the number of immune parameters with.

CONFORMATION CHANGES OF HUMAN SERUM γ–GLOBULIN IN THE PRESENCE OF ZINC IONS

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S. B. Cheknev

2005-01-01

Full Text Available Abstract. Conformational changes of human serum γ–globulin during interaction with the zinc ions were studied in a solution. It has been shown that the presence of zinc in over its physiological concentrations led to increase in optical density across the whole spectrum of γ–globulin ultraviolet absorption. On the contrary, hypochromia in the spectrum was registered after interaction of the protein with zinc used in subphisiological concentrations. Possible role of divalent metal cations in changes in conformation of the blood serum γ–globulins, and thereby in regulation of their effector functions was discussed. (Med. Immunol., 2005, vol.7, № 4, pp. 375–380

Influence factors of human T lymphocyte co-stimulatory effect in vitro

International Nuclear Information System (INIS)

Zhou Jianhua; Su Liaoyuan; Tong Jian; Xue Lian

2000-01-01

Objective: Effects of CD3 McAb, CD28 McAb, PHA and low-dose γ-ray irradiation on T lymphocytes were investigated to explore factors of influencing T cell signals transduction. Method: Using CD3 McAb and CD28 McAb mimicking as the first and the second signals, and using PHA and low dose γ-rays irradiation as stimulatory factors in T cell activation, the influences of these factors and the two signals on human lymphocyte proliferation response were studied with 3 H-thymidine incorporation. Results: Lymphocyte proliferation response occurred when the two signals were treated co-stimulation or within certain intervals (within 40h). PHA and 10 cGy γ-rays irradiation can also activate lymphocytes to proliferate. However, each of the two signals alone did not activate lymphocytes to proliferate. Conclusion: CD3 McAb, CD28 McAb, PHA and low-dose γ-rays irradiation could stimulate T lymphocyte proliferation, which is an important aspect in cellular immune regulation

Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis

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Sacdalan DB

2018-02-01

Full Text Available Danielle Benedict Sacdalan,1 Josephine Anne Lucero,2 Dennis Lee Sacdalan1 1Section of Medical Oncology, Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines; 2Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines Introduction: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients.Methods: We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor.Results/discussion: A high NLR resulted in worse overall survival (OS (HR, 1.92; 95% CI, 1.29–2.87; p=0.001 and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38–2.01; p<0.00001 across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer. Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.83; 95% CI, 0.97–3

Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

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Haifeng C. Xu

2017-11-01

Full Text Available NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV. However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity.

[Impact of thymic function in age-related immune deterioration].

Science.gov (United States)

Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

2013-01-01

Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

Effect of rosemary (Rosmarinus officinalis extract on weight, hematology and cell-mediated immune response of newborn goat kids

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Borhan Shokrollahi

2015-06-01

Full Text Available This study aimed at evaluating the effects of different levels of rosemary (Rosmarinus officinalis extract on growth rate, hematology and cell-mediated immune response in Markhoz newborn goat kids. Twenty four goat kids (aged 7±3 days were randomly allotted to four groups with six replicates. The groups included: control, T1, T2 and T3 groups which received supplemented-milk with 0, 100, 200 and 400mg aqueous rosemary extract per kg of live body weight per day for 42 days. Body weights of kids were measured weekly until the end of the experiment. On day 42, 10 ml blood samples were collected from each kid through the jugular vein. Cell-mediated immune response was assessed through the double skin thickness after intradermal injection of phyto-hematoglutinin (PHA at day 21 and 42. No significant differences were seen in initial body weight, average daily gain (ADG and total gain. However, significant differences in globulin (P<0.05, and white blood cells (WBC (P<0.001 were observed. There were no significant differences in haemoglobin (Hb, packed cell volume (PCV, red blood cells (RBC, lymphocytes and neutrophils between the treatments. Skin thickness in response to intra dermal injection of PHA significantly increased in the treated groups as compared to the control group at day 42 (P<0.01 with the T3 group showing the highest response to PHA injection. In conclusion, the results indicated that aqueous rosemary extract supplemented-milk had a positive effect on immunity and skin thickness of newborn goat kids.

Analysis and comparison of immune reactivity in guinea-pigs immunized with equivalent numbers of normal or radiation-attenuated cercariae of Schistosoma mansoni

International Nuclear Information System (INIS)

Rogers, M.V.; McLaren, D.J.

1987-01-01

Guinea-pigs immunized with equivalent numbers of normal or radiation-attenuated cercariae of Schistosoma mansoni develop close to complete resistance to reinfection at weeks 12 and 4.5 respectively. We here analyse and compare the immune responses induced by the two populations of cercariae. Both radiation-attenuated and normal parasites of S. mansoni elicited an extensive germinal centre response in guinea-pigs by week 4.5 post-immunization. The anti-parasite antibody titre and cytotoxic activity of serum from 4.5-week-vaccinated, or 4.5-week-infected guinea-pigs were approximately equal, but sera from 12-week-infected individuals had high titres of anti-parasite antibody, which promoted significant larvicidal activity in vitro. In all cases, larvicidal activity was mediated by the IgG 2 fraction of the immune serum. Lymphocyte transformation tests conducted on splenic lymphocytes from 4.5-week vaccinated guinea-pigs revealed maximal stimulation against cercarial, 2-week and 3-week worm antigens, whereas spleen cells from 4.5-week-infected guinea-pigs were maximally stimulated by cercarial and 6-week worm antigens. The splenic lymphocyte responses of 12-week infected animals were dramatic against antigens prepared from all life-stages of the parasite. (author)

Blastogenic response of bovine lymphocytes to Brucella abortus lipopolysaccharide.

OpenAIRE

Baldwin, C L; Winter, A J

1985-01-01

Brucella abortus lipopolysaccharide was tested in a blastogenesis assay with unfractionated and nylon wool-separated peripheral blood lymphocytes of Brucella-naive cattle and cattle immunized with B. abortus. Our results indicated that in cattle the lipopolysaccharide of B. abortus is not a B-cell mitogen. In immunized animals it stimulated predominantly nylon wool-adherent cells. The lipopolysaccharide of Escherichia coli O128:B12, in contrast, induced a substantially greater proliferative r...

The fourth dimension in immunological space: how the struggle for nutrients selects high-affinity lymphocytes.

Science.gov (United States)

Wensveen, Felix M; van Gisbergen, Klaas P J M; Eldering, Eric

2012-09-01

Lymphocyte activation via the antigen receptor is associated with radical shifts in metabolism and changes in requirements for nutrients and cytokines. Concomitantly, drastic changes occur in the expression of pro-and anti-apoptotic proteins that alter the sensitivity of lymphocytes to limiting concentrations of key survival factors. Antigen affinity is a primary determinant for the capacity of activated lymphocytes to access these vital resources. The shift in metabolic needs and the variable access to key survival factors is used by the immune system to eliminate activated low-affinity cells and to generate an optimal high-affinity response. In this review, we focus on the control of apoptosis regulators in activated lymphocytes by nutrients, cytokines, and costimulation. We propose that the struggle among individual clones that leads to the formation of high-affinity effector cell populations is in effect an 'invisible' fourth signal required for effective immune responses. © 2012 John Wiley & Sons A/S.

Immunostimulation by cytomegalovirus (CMV): helper T cell-dependent activation of immunoglobulin production in vitro by lymphocytes from CMV-immune donors

International Nuclear Information System (INIS)

Yachie, A.; Tosato, G.; Straus, S.E.; Blaese, R.M.

1985-01-01

Cytomegalovirus (CMV) is the cause of a number of different diseases ranging from self-limited benign infections in healthy adults to life threatening illnesses among immunocompromised hosts and newborns. Suppression of cell-mediated immunity is often found in cases of acute CMV infection, and in addition, the virus may also be a potent stimulant of lymphoid cells in vivo. The authors studied cellular proliferation and immunoglobulin (Ig) production induced by CMV to determine its effect on human lymphocytes in vitro. The CMV that was added to cultures of lymphocytes from CMV-seronegative donors failed to induce either significant cellular proliferation or Ig production. By contrast, CMV-stimulated cultures from CMV-seropositive donors induced both prominent cellular proliferation and Ig production. B cell differentiation into Ig-secreting cells required the presence of T cells, and this T cell help was sensitive to irradiation with 2000 rad and to treatment with cyclosporin A. When T cells were depleted of OKT4+ cells with monoclonal antibody and complement, the co-cultured B cells failed to produce Ig, whereas the depletion of OKT8+ cells had no effect on the Ig-secreting cell response. Inactivation of CMV before culture did not result in a reduction of either cellular proliferation or Ig production. Thus, infection of target cells is not required for in vitro lymphocyte activation by CMV. These results demonstrate that CMV is a potent activator of B cells inducing Ig production in vitro, and that this process requires the presence of virus-specific memory T cells

Effect of low dose x-irradiation on alloantigen sensitized and unsensitized lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Dohi, Kiyohiko; Yahata, Hiroshi; Fukuda, Yasuhiko; Asahara, Toshimasa; Ono, Eiji; Ezaki, Haruo

1984-12-01

The effect of local graft irradiation on immune response in allograft in which acute rejection occurs was studied using an in vitro model. Unidirectional mixed lymphocyte culture (MLC) was used as the in vitro model of acute rejection. 150 and 300 rad x-irradiation suppressed mixed lymphocyte reaction (MLR) but did not cell-mediated-lympholysis (CML) of unsensitized lymphocytes. X-irradiated alloantigen sensitized cells (ASC) generated in 6-day MLC suppressed MLR and CML of unsensitized lymphocytes. Suppressive effects of x-irradiated ASC were of the same degree by x-irradiation doses of 150-500 rad. Suppressive effect of x-irradiation was maintained for only a short period after x-irradiation. Potential function of suppressor precursor cells among unsensitized lymphocytes was abolished by x-irradiation of 300 rad. (author).

Konsentrasi Protein Total, Albumin, dan Globulin Anak Kambing Peranakan Etawah Setelah Pemberian Berbagai Sediaan Kolostrum* (TOTAL PROTEIN, ALBUMIN, AND GLOBULIN CONCENTRATIONS ON ETTAWAH CROSSBREED NEONATES FOLLOWING THE ADMINISTRATION OF VARIOUS FORM O

Directory of Open Access Journals (Sweden)

Anita Esfandiari

2014-10-01

Full Text Available This experiment was conducted to study the profile of total protein, albumin, and globulin concentrationson Ettawah crossbreed neonates after consuming various colostrums. Twenty four healthy neonatal kidswere used in this study. The neonates were divided into four groups. Each group received fresh maternal(goat colostrum, frozen-thawed bovine colostrum, bovine spray dried colostrum, and bovine powdercommercial colostrum, respectively. Colostrums were given at 10% of body weight directly after birth andfollowed by the same amount every 12 hours, for three days. The blood was taken from jugular vein at 0, 12,24, 48, 72, and 168 hours after birth to determine total protein, albumin, and globulin concentrations.Results of this study indicated that the serum total protein and globulin concentration increased andreached the peak at 24 hours after birth. Compared to the concentration at birth, the increase of totalprotein concentration were 62.77%, 59.26%, 48.05%, and 66.67% in fresh maternal (goat, frozen-thawedbovine, bovine spray dried, and commercial bovine colostrum, respectively. Serum globulin concentrationincreased 4.9, 4.4, 4.8, and 14.6 times in fresh matermnal goat, frozen-thawed bovine, spray dried, andcommercial bovine colostrums respectively, compared to the concentration at birth. In conclusion, theconsumption of various colostrums i.e. fresh maternal goat colostrums, bovine colostrums (frozen-thawed,spray dried and commercial colostrums would increase the concentration of blood total protein and globulin,which both reached the highest concentration at 24 h after birth.

Co-Culturing of Multipotent Mesenchymal Stromal Cells with Autological and Allogenic Lymphocytes.

Science.gov (United States)

Kapranov, N M; Davydova, Yu O; Gal'tseva, I V; Petinati, N A; Bakshinskaitė, M V; Drize, N I; Kuz'mina, L A; Parovichnikova, E N; Savchenko, V G

2018-03-01

We studied the effect of autologous and allogeneic lymphocytes on multipotent mesenchymal stromal cells in co-culture. It is shown that changes in multipotent mesenchymal stromal cells and in lymphocytes did not depend on the source of lymphocytes. Contact with lymphocytes triggers expression of HLA-DR molecules on multipotent mesenchymal stromal cells and these cells lose their immune privilege. In multipotent mesenchymal stromal cells, the relative level of expression of factors involved in immunomodulation (IDO1, PTGES, and IL-6) and expression of adhesion molecule ICAM1 increased, while expression of genes involved in the differentiation of multipotent mesenchymal stromal cells remained unchanged. Priming of multipotent mesenchymal stromal cells with IFN did not affect these changes. In turn, lymphocytes underwent activation, expression of HLA-DR increased, subpopulation composition of lymphocytes changed towards the increase in the content of naïve T cells. These findings are important for cell therapy.

Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

International Nuclear Information System (INIS)

Hau, D.M.

1984-01-01

The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats

Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Hau, D.M.

The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats.

Hapten-specific lymphocyte transformation in humans sensitized with NDMA or DNCB.

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SoebergB; Andersen, V

1976-01-01

The primary immune response to a contact sensitizing dose of para-N-dimethylnitrosaniline (NDMA) and dinitrochlorobenzene (DNCB) was obtained in humans and measured in vitro by increased thymidine incorporation into sensitized lymphocytes. No cross-reaction was found between these two haptens, and it is thus possible on two separate occasions to quantify and follow the primary cellular immune response in man. PMID:963911

CHARACTERISTICS OF SIGNALING PATHWAYS MEDIATING A CYTOTOXIC EFFECT OF DENDRITIC CELLS UPON ACTIVATED Т LYMPHOCYTES AND NK CELLS

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T. V. Tyrinova

2012-01-01

Full Text Available Abstract. Cytotoxic/pro-apoptogenic effects of IFNα-induced dendritic cells (IFN-DCs directed against Т-lymphocytes and NK cells were investigated in healthy donors. Using an allogenic MLC system, it was revealed that IFN-DCs induce apoptosis of both activated CD4+ and CD8+ T-lymphocytes, and NK cells. Apoptosis of CD4+ and CD8+ T-lymphocytes induced by their interaction with IFN-DCs was mediated by various signaling pathways. In particular, activated CD4+Т-lymphocytes were most sensitive to TRAIL- и Fas/ FasL-transduction pathways, whereas activated CD8+ T-lymphocytes were induced to apoptosis via TNFα-mediated pathway. PD-1/B7-H1-signaling pathway also played a distinct role in cytotoxic activity of IFNDCs towards both types of T lymphocytes and activated NK cells. The pro-apoptogenic/cytotoxic activity of IFN-DC against activated lymphocytes may be regarded as a mechanism of a feedback regulation aimed at restriction of immune response and maintenance of immune homeostasis. Moreover, upregulation of proapoptogenic molecules on DCs under pathological conditions may lead to suppression of antigen-specific response, thus contributing to the disease progression.

Immune Interventions to Eliminate the HIV Reservoir.

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Hsu, Denise C; Ananworanich, Jintanat

2017-10-26

Inducing HIV remission is a monumental challenge. A potential strategy is the "kick and kill" approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV. Specific strategies include increasing the magnitude and breadth of T cell responses through therapeutic vaccinations, reversing the effects of T cell exhaustion using immune checkpoint inhibition, employing bispecific T cell targeting immunomodulatory proteins or dual-affinity re-targeting molecules to direct cytotoxic T lymphocytes to virus-expressing cells and broadly neutralizing antibody infusions. Methods to steer immune responses to tissue sites where latently infected cells are located need to be further explored. Ultimately, strategies to induce HIV remission must be tolerable, safe, and scalable in order to make a global impact.

Detection of a novel specificity (CTLA-4) in ATG/TMG globulins and sera from ATG-treated leukemic patients.

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Pistillo, Maria Pia; Tazzari, Pier Luigi; Bonifazi, Francesca; Bandini, Giuseppe; Kato, Tomohiro; Matsui, Toshihiro; Nishioka, Kusuki; Conte, Roberto; Ferrara, Giovanni Battista

2002-04-27

T-cell costimulation has been shown to provide positive signals for T-cell activation and generation of effector activity. In this study, we analyzed the presence of antibodies (Abs) against the T-lymphocyte costimulatory molecules CD28, CTLA-4, CD80, and CD86 in anti-T-lymphocyte (ATG) and antithymocyte (TMG) globulin preparations to address their mechanism of action. We focused our attention on the role of CTLA-4-specific Abs in the immunosuppressive effect of ATG/TMG, because anti-CTLA-4 agonistic Abs may suppress T-cell proliferation and nonagonistic Abs may lead to T-cell depletion through an Ab-dependent cell cytotoxicity mechanism. ATG/TMG and patients' sera were tested for binding to recombinant human costimulatory molecules by ELISA techniques. CTLA-4 specificity was also analyzed by cytoplasmic immunofluorescence staining of a CTLA-4 transfectant by competitive inhibition immunofluorescence and by cell proliferation assay in allogeneic mixed lymphocyte reaction (MLR). Either ATG or TMG predominantly contained anti-CTLA-4 Abs, with higher reactivity in ATG followed by anti-CD86 and -CD28 Abs, whereas anti-CD80 Abs were found only in ATG. Anti-CTLA-4 Abs present in ATG/TMG recognized the native form of CTLA-4 molecule, and their removal reduced the effect of ATG in an allogeneic MLR. Kinetic studies indicated that such Abs were present in the sera of 12 ATG-treated leukemic patients up to 21 days after ATG administration. These data suggest that the novel anti-CTLA-4 Abs found in ATG may greatly contribute to its immunosuppressive effect, thus accounting for the absence of rejection and exceptionally low incidence of graft-versus-host disease in the group of patients analyzed.

Ultrastructural studies of human and rabbit alpha-M-globulins.

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Bloth, B; Chesebro, B; Svehag, S E

1968-04-01

Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

Immunometabolism of lymphocytes and its changes in experimental diabetes mellitus

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A. M. Kamyshny

2016-12-01

Full Text Available Lymphocytes are sensitive to changes in metabolism. Metabolic changes, which develop in conditions of diabetes mellitus, especially hyperglycemia, can directly influence the immunometabolism of lymphocytes. The T cells express a series of glucose transporters, the main of which is the Glut 1. The prodiabetogenic Th1 and Th17-cells that cause insulitis are characterized by high level of expression of Glut 1 and tendency to glycolysis. The suppressor Treg, on the contrary, has the low expression of Glut 1 and the high rate of oxidative metabolism. Purpose of the study: to analyze the contemporary literature and own data, obtained concerning the immunometabolism of lymphocyte and its changes in conditions of diabetes. To determine the role of 6 key metabolic ways that play a crucial role in the differentiation and survival of immune cells: 1 glycolysis; 2 tricarboxylic acid (TCA cycle; 3 pentose-phosphate cycle; 4 fatty acid oxidation; 5 fatty acid synthesis and 6 metabolism of amino acids, each of which have different activity level in specific types of immune cells. Conclusions: different types of immune cells prefer different ways of metabolism. The effector Th1-, Th2-, Th17-cells and М1-macrophages use primarily glycolysis, pentose-phosphate cycle and synthesis of fatty acids, while T-regulatory, CD8+ memory cells and M2-macrophages use the TCA cycle and oxidation of fatty acids. Changes in the metabolism of different amino acids can influence the generation of effector and Treg lymphocytes. The high activity of mTOR can enhance the progression of diabetes by activating the effector proinflammatory subpopulations of lymphocytes, and vice versa, the low activity promotes the differentiation of Treg, blocking the insulitis. In our work we investigated the level of expression of mRNA of genes Glut 1, mTOR and AMPK1α in PLN of rats with experimental streptozotocin-induced diabetes and after metformin introduction and found that the hyperglycemia

Chemokines, lymphocytes, and HIV

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Farber J.M.

1998-01-01

Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

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Law, Philip J; Berndt, Sonja I; Speedy, Helen E; Camp, Nicola J; Sava, Georgina P; Skibola, Christine F; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R; Clot, Guillem; Teras, Lauren R; Quintela, Inés; Birmann, Brenda M; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R; Hall, Andrew G; Purdue, Mark P; Mainou-Fowler, Tryfonia; Vajdic, Claire M; Jackson, Graham H; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G; Lawrence, Charles; Call, Timothy G; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K; Conde, Lucia; Bracci, Paige M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C H; Southey, Melissa C; Milne, Roger L; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M; Harris, Robert J; Miligi, Lucia; Pettitt, Andrew R; North, Kari E; Allsup, David J; Fraumeni, Joseph F; Bailey, James R; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J S; Catovsky, Daniel; Campo, Elias; Cerhan, James R; Allan, James M; Rothman, Nathanial; Houlston, Richard; Slager, Susan

2017-02-06

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10 -13 ), 1q42.13 (rs41271473, P=1.06 × 10 -10 ), 4q24 (rs71597109, P=1.37 × 10 -10 ), 4q35.1 (rs57214277, P=3.69 × 10 -8 ), 6p21.31 (rs3800461, P=1.97 × 10 -8 ), 11q23.2 (rs61904987, P=2.64 × 10 -11 ), 18q21.1 (rs1036935, P=3.27 × 10 -8 ), 19p13.3 (rs7254272, P=4.67 × 10 -8 ) and 22q13.33 (rs140522, P=2.70 × 10 -9 ). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection.

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Ferraz, Marcela L; Gazzinelli, Ricardo T; Alves, Rosana O; Urbina, Julio A; Romanha, Alvaro J

2009-01-01

We investigated the influence of CD4(+) T lymphocytes, CD8(+) T lymphocytes, and B lymphocytes on the efficacy of posaconazole (POS) and the reference drug benznidazole (BZ) during treatment of acute Trypanosoma cruzi infection in a murine model. Wild-type mice infected with T. cruzi and treated with POS or BZ presented no parasitemia, 100% survival, and 86 to 89% cure rates, defined as the percentages of animals with negative hemocultures at the end of the observation period. CD4(+)-T-lymphocyte-knockout (KO) mice infected with T. cruzi and treated with BZ or POS controlled parasitemia during treatment, although circulating parasites reappeared after drug pressure cessation, leading to only a 6% survival rate and no cure. CD8(+)-T-lymphocyte-KO mice infected with T. cruzi and treated with POS or BZ had intermediate results, displaying discrete parasitemia after the treatment was ended, 81 and 86% survival, and cure rates of 31 and 66%, respectively. B-lymphocyte-KO mice infected with T. cruzi and treated with BZ relapsed with parasitemia 1 week after the end of treatment and had a 67% survival rate and only a 22% cure rate. In contrast, the activity of POS was much less affected in these animals, with permanent suppression of parasitemia, 100% survival, and a 71% cure rate. Our results demonstrate that abrogation of different lymphocytes' activities has distinct effects on the efficacy of POS and BZ in this experimental model, probably reflecting different parasite stages preferentially targeted by the two drugs and distinct cooperation patterns with the host immune system.

B-cell-rich T-cell lymphoma associated with Epstein-Barr virus-reactivation and T-cell suppression following antithymocyte globulin therapy in a patient with severe aplastic anemia

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Nobuyoshi Hanaoka

2015-09-01

Full Text Available B-cell lymphoproliferative disorder (B-LPD is generally characterized by the proliferation of Epstein-Barr virus (EBV-infected B lymphocytes. We here report the development of EBV-negative B-LPD associated with EBV-reactivation following antithymocyte globulin (ATG therapy in a patient with aplastic anemia. The molecular autopsy study showed the sparse EBV-infected clonal T cells could be critically involved in the pathogenesis of EBV-negative oligoclonal B-LPD through cytokine amplification and escape from T-cell surveillances attributable to ATG-based immunosuppressive therapy, leading to an extremely rare B-cell-rich T-cell lymphoma. This report helps in elucidating the complex pathophysiology of intractable B-LPD refractory to rituximab.

NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

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Lucian Hritcu

2007-08-01

Full Text Available Dopamine is one of the principal neurotransmitters in the central nervous system (CNC, and its neuronal pathways are involved in several key functions such as behavior (Hefco et al., 2003a,b, control of movement, endocrine regulation, immune response (Fiserova et al., 2002; Levite et al., 2001, Hritcu et al., 2006a,b,c, and cardiovascular function. Dopamine has at least five G-protein, coupled receptor subtypes, D1-D5, each arising from a different gene (Sibley et al., 1993. Traditionally, these receptors have been classified into D1-like (the D1 and D5 and D2-like (D2, D3 and D4 receptors subtypes, primarily according to their ability to stimulate or inhibit adenylate cyclase, respectively, and to their pharmacological characteristics (Seeman et al., 1993. Receptors for dopamine (particularly of D2 subclass are the primary therapeutic target in a number of neuropathological disorders including schizophrenia, Parkinson’s disease and Huntington’s chorea (Seeman et al., 1987. Neither dopamine by itself, nor dopaminergic agonists by themselves, has been shown to activate T cell function. Nevertheless, lymphocytes are most probably exposed to dopamine since the primary and secondary lymphoid organs of various mammals are markedly innervated, and contain nerve fibers which stain for tyrosine hydroxylase (Weihe et al., 1991, the enzyme responsible for dopamine synthesis. Moreover, cathecolamines and their metabolites are present in single lymphocytes and in extracts of T and B cell clones, and pharmacological inhibition of tyrosine hydroxylase reduces catecholamine levels, suggesting catecholamine synthesis by lymphocytes (Bergquist et al., 1994. The existence of putative dopamine receptors of D2, D3, D4 and D5 subtypes on immune cells has been proposed of several authors, primarily on the basis of dopaminergic ligand binding assays and specific mRNA expression as monitored by reverse transcription-PCR. Several experiments evoked the idea of a

Evaluation of early recognition of viral infections in man. [using specific gravity of lymphocytes

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Kelton, A. A.; Lawton, M. B.

1975-01-01

The potential of Lymphocyte Specific Gravity Distribution (LSGD) as a non-specific procedure for early diagnosis of viral disease in astronauts is considered. Results of experiments and a literature search show that several virus diseases result in distinctive changes in the specific gravity distribution of peripheral blood lymphocytes as a result of disease process and associated immune response. A tentative model is proposed which relates the shape of LSGD to the identity of subpopulations of peripheral lymphocytes in a preclinical viral disease situation.

PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

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Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

2017-11-01

Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

Liquid scintillation vial for radiometric assay of lymphocyte carbohydrate metabolism in response to mitogens

International Nuclear Information System (INIS)

Tran, N.; Wagner, H.N. Jr.

1978-01-01

We have demonstrated that mitogens--i.e., PHA and Con.A--stimulate lymphocyte carbohydrate metabolism using a liquid-scintillation vial with conventional liquid-scintillation detectors. The results showed that this enclosed system can be useful for development of rapid in vitro tests of lymphocytes immune responsiveness, as well as for radiometric detection of bacterial growth in various gaseous atmospheres

Iron, folacin, vitamin B12 and zinc status and immune response in the elderly

International Nuclear Information System (INIS)

Henry-Christian, J.R.; Johnson, A.A.; Walters, C.S.; Greene, E.J.; Lindsey, A.A.

1986-01-01

The relationships of iron, folacin, vitamin B 12 and zinc status to cell-mediated immune response were investigated among 125 healthy, elderly persons (60-87 years of age). Plasma ferritin, plasma and red cell folate, and plasma vitamin B 12 levels were assayed immuno-radiometrically. Plasma and hair zinc levels were determined by atomic absorption spectroscopy. Immune response was determined by transformation of peripheral blood lymphocytes after stimulation with phytohemagglutinin (PHA) and concanavalin A (con A), and in mixed lymphocyte reaction. Deficiencies of iron, folacin vitamin B 12 and zinc were each associated (independently) with significantly lower lymphocyte responses to PHA and con A, and mixed lymphocyte reaction (P 12 or zinc. Further, they suggest that deficiencies of these nutrients may play a role in the depression of cell-mediated immunity with age, which in turn may lead to increased susceptibility to infectious diseases and cancer in the elderly

Vitamin effects on the immune system: vitamins A and D take centre stage.

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Mora, J Rodrigo; Iwata, Makoto; von Andrian, Ulrich H

2008-09-01

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.

Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

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Cuq, B; Blois, S L; Mathews, K A

2017-06-01

To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

Cell-mediated immunity during syphilis. A review

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Pavia, Charles S.; Folds, James D.; Baseman, Joel B.

1978-01-01

Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types. PMID:350348

Late effects of radiation on immune system; a review

International Nuclear Information System (INIS)

Sado, T.

1979-01-01

Lymphocytes are divided into 2 major classes: T and B lymphocytes (or cells). T cells are responsible for cell-mediated immune response, and B cells for humoral immune response or antibody formation. The possible immunological complications that might develop as the late manifestation of radiation effects include: lymphoid neoplasms, immune complex diseases, auto-aggressive immune reactions, and other degenerative diseases of immunological nature. The development of lymphoid neoplasma following the exposure to radiation was extensively studied with mice. Radiation-induced immunological compications would not contribute significantly to the life-shortening of exposed individuals. The extensive health survey of adult A-bomb survivors revealed little evidence of immunological complications such as rheumatoid arthritis, kidney diseases, paraproteinemia, etc. The young healthy adults who had received thymic irradiation during infancy for the treatment of enlarged thymus manifested higher incidence of illness with abnormal immunological features. Immune complex diseases, particularly the inter-capillary glomerulosclerosis of kidneys, develop as a result of earlier exposure to high dose of radiation. (Yamashita, S.)

Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

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Robert J. Torphy

2017-12-01

Full Text Available Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3, B and T lymphocyte attenuator (BTLA, programmed death-1 homolog (PD-1H, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1, and the poliovirus receptor (PVR-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.

Immune Checkpoint Molecules on Tumor-Infiltrating Lymphocytes and Their Association with Tertiary Lymphoid Structures in Human Breast Cancer

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Cinzia Solinas

2017-10-01

Full Text Available There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC, particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes. Flow cytometric analysis of fresh tissue homogenates from untreated primary tumors show that PD-1 is principally expressed on CD4+ or CD8+ T cells and CTLA-4 is expressed on CD4+ T cells. The global proportion of PD-L1+, PD-L2+, LAG3+, and TIM3+ tumor-infiltrating lymphocytes (TIL was low and detectable in only a small number of tumors. Immunohistochemically staining fixed tissues from the same tumors was employed to score TIL and tertiary lymphoid structures (TLS. PD-L1+, PD-L2+, LAG3+, and TIM3+ cells were detected in some TLS in a pattern that resembles secondary lymphoid organs. This observation suggests that TLS are important sites of immune activation and regulation, particularly in tumors with extensive baseline immune infiltration. Significantly improved overall survival was correlated with PD-1 expression in the HER2-enriched and PD-L1 or CTLA-4 expression in basal-like BC. PD-1 and CTLA-4 proteins were most frequently detected on TIL, which supports the correlations observed between their gene expression and improved long-term outcome in basal-like and HER2-enriched BC. PD-L1 expression by tumor or immune cells is uncommon in BC. Overall, the data presented here distinguish PD-1 as a marker of T cell activity in both the T and B cell areas of BC associated TLS. We found that immune checkpoint molecule expression parallels the extent of TIL and TLS, although there is a noteworthy amount of heterogeneity

The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

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María Guadalupe Reyes García

2013-01-01

Full Text Available T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95% are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

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Maria Isabel Carvalho

2014-01-01

Full Text Available Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

Lack of Globulin Synthesis during Seed Development Alters Accumulation of Seed Storage Proteins in Rice

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Hye-Jung Lee

2015-06-01

Full Text Available The major seed storage proteins (SSPs in rice seeds have been classified into three types, glutelins, prolamins, and globulin, and the proportion of each SSP varies. It has been shown in rice mutants that when either glutelins or prolamins are defective, the expression of another type of SSP is promoted to counterbalance the deficit. However, we observed reduced abundances of glutelins and prolamins in dry seeds of a globulin-deficient rice mutant (Glb-RNAi, which was generated with RNA interference (RNAi-induced suppression of globulin expression. The expression of the prolamin and glutelin subfamily genes was reduced in the immature seeds of Glb-RNAi lines compared with those in wild type. A proteomic analysis of Glb-RNAi seeds showed that the reductions in glutelin and prolamin were conserved at the protein level. The decreased pattern in glutelin was also significant in the presence of a reductant, suggesting that the polymerization of the glutelin proteins via intramolecular disulfide bonds could be interrupted in Glb-RNAi seeds. We also observed aberrant and loosely packed structures in the storage organelles of Glb-RNAi seeds, which may be attributable to the reductions in SSPs. In this study, we evaluated the role of rice globulin in seed development, showing that a deficiency in globulin could comprehensively reduce the expression of other SSPs.

Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia.

Science.gov (United States)

Cubillos-Zapata, Carolina; Avendaño-Ortiz, Jose; Córdoba, Raúl; Hernández-Jiménez, Enrique; Toledano, Victor; Pérez de Diego, Rebeca; López-Collazo, Eduardo

2016-01-01

Ibrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimulus in CD14 + cells, improving levels of phospho-Erk1/2 and antigen presentation. Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression. Our data suggest the impact of BTK inhibition along with immunomodulation on the innate immune response and a switch to the specific adaptive immune response, which might help to decrease infectious complications. The potential effect of ibrutinib on CLL patient outcomes is worthy of further study, because infections could be reduced with the use of ibrutinib.

Age- and dose-related alteration of in vitro mixed lymphocyte culture response of blood lymphocytes from A-bomb survivors

International Nuclear Information System (INIS)

Akiyama, Mitoshi; Zhou, Ou-Liang; Kusunoki, Yoichiro; Kyoizumi, Seishi; Kohno, Nobuoki; Akiba, Suminori; Delongchamp, R.R.

1988-07-01

The responsiveness of peripheral blood lymphocytes to allogenic antigens in mixed lymphocyte culture (MLC) was measured in 139 atomic bomb survivors. The study revealed a significant decrease in MLC with increasing dose of previous radiation exposure. This decline was remarkable in the survivors who were older than 15 at the time of the bomb (ATB). The results suggest a possible relationship between the recovery of T-cell-related function and the thymic function which processes mature T-cells for the immune system. Thus it may be that, in the advanced age ATB group, the thymus function has started to involute allowing less recovery of T-cell function compared to young survivors who have adequate processing T-cell activity. (author)

FOXP3-specific immunity

DEFF Research Database (Denmark)

Andersen, Mads Hald

2013-01-01

Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

AMP-activated protein kinase regulates lymphocyte responses to metabolic stress but is largely dispensable for immune cell development and function.

Science.gov (United States)

Mayer, Alice; Denanglaire, Sébastien; Viollet, Benoit; Leo, Oberdan; Andris, Fabienne

2008-04-01

AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, represents an energy sensor able to adapt cellular metabolism in response to nutritional environmental variations. TCR stimulation activates AMPK, a regulatory event that is known to stimulate ATP-producing processes, possibly in anticipation of the increased energetic needs associated with cell division and expression of effector function. Taking advantage of the selective expression of the AMPKalpha1 catalytic subunit in lymphoid cells, we have analyzed the in vitro and in vivo capacity of lymphocytes lacking AMPK activity (AMPKalpha1-KO cells) to respond to metabolic stress and to initiate and sustain an immune response. AMPKalpha1-KO cells displayed increasing sensitivity to energetic stress in vitro, and were found unable to maintain adequate ATP levels in response to ATP synthase inhibition. These cells were, however, able to respond to antigen stimulation in vitro, as shown by optimal proliferation and cytokine production. Similarly, AMPKalpha1-KO mice were fully immunocompetent in vivo and displayed normal cell proliferation, humoral, cytotoxic and delayed-type hypersensitivity (DTH) responses following antigen injection. In conclusion, AMPK represents an important enzyme allowing lymphocytes to resist a mild energy crisis in vitro, but is largely dispensable for activation and expression of effector function in response to antigen stimulation.

Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes.

Science.gov (United States)

Pilli, T; Toti, P; Occhini, R; Castagna, M G; Cantara, S; Caselli, M; Cardinale, S; Barbagli, L; Pacini, F

2017-12-11

An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial. The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI). We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response. Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation. Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

Protective effect of citrullus vulgaris on irradiated lymphocyte membrane ultrastructure

International Nuclear Information System (INIS)

Khairul Osman; Norashikin, M.S.; Hing Hiang Lian; Siti Fatimah Ibrahim; Seetha Khartini Abdul Wahab; Jamaludin Mohamed; Proom Promwichit

2004-01-01

Radiotherapy causes various complications including low immunity. Past research that the low immunity is due to the low amount of lymphocytes and consumption vulgaris will alleviate this problem. Based on this a study was conducted to identify vulgaris was able to produce radioprotection on the lymphocyte membrane. A total of 30 adult male Sprague-Dawley rats were used and divided into three equals groups of positive control and treatment. For seven days, positive control and negative control were force fed with normal saline of 40 ml/kg animal weight while the treatment group received 40g/kg animal weight fresh juice of citrullus vulgaris daily. After a week positive control an group were irradiated with 0.9 Gy gamma ray. Viable lymphocyte were determined using propidium iodine and acridine orange stain. Results clearly shows that positive con and treatment group were significantly different at 34 ± 3% , 80 ± 2% an 71 ± 2% respectively. SEM results shows that pores were present on the membrane of the pos while the negative control had none. Similar results were also found on the treatment group. Based on the result it had shown that citrullus vulgaris had radioprotection properties and lymphocytes were destroyed by the formation of pores on their membrane. It is very likely that the radioprotection properties could be due to the presence of antioxidants particularly vitamin A, C and lycopene. In conclusion, citrullus vulgaris could be used as a safe radioprotection agent. (Author)

Levels of immune cells in transcendental meditation practitioners

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Jose R Infante

2014-01-01

Conclusions: The technique of meditation studied seems to have a significant effect on immune cells, manifesting in the different circulating levels of lymphocyte subsets analyzed. The significant effect of TM on the neuroendocrine axis and its relationship with the immune system may partly explain our results.

Lymphocytic subsets and low-dose exposure

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.; Eybl, E.

1993-03-01

The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

Unexpected suppression of anti-Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin.

Science.gov (United States)

Branch, Donald R; Scofield, Terry L; Moulds, John J; Swanson, Jane L

2011-04-01

Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D- mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis. Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation. A group A, D-(cde), K+, Fy(a-b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy(a) titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D-(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy(a) eluted from his cells and the titer in the cord serum was 4. This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1-mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms. © 2010 American Association of Blood Banks.

Immune selection of tumor cells in TCR β-chain transgenic mice.

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Silaeva, Yulia Yu; Grinenko, Tatyana S; Vagida, Murad S; Kalinina, Anastasia A; Khromykh, Ludmila M; Kazansky, Dmitry B

2014-10-01

The concept of immunological surveillance implies that immunogenic variants of tumor cells arising in the organism can be recognized by the immune system. Tumor progression is provided by somatic evolution of tumor cells under the pressure of the immune system. The loss of MHC Class I molecules on the surface of tumor cells is one of the most known outcomes of immune selection. This study developed a model of immune selection based on the immune response of TCR 1d1 single β-chain transgenic B10.D2(R101) (K(d)I(d)D(b)) mice to allogeneic EL4 (H-2(b)) thymoma cells. In wild-type B10.D2(R101) mice, immunization with EL4 cells induced a vigorous CTL response targeted to the H-2K(b) molecule and results in full rejection of the tumor cells. In contrast, transgenic mice developed a compromised proliferative response in mixed-lymphocyte response assays and were unable to reject transplanted allogeneic EL4 cells. During the immune response to EL4 cells, CD8(+) T-lymphocytes with endogenous β-chains accumulated predominantly in the spleen of transgenic mice and only a small part of the T-lymphocytes expressing transgenic β-chains became CD8(+)CD44(+)CD62L(-) effectors. Then, instead of a full elimination of tumor cells as in wild-type mice, a reproducible prolonged equilibrium phase and subsequent escape was observed in transgenic mice that resulted in death of 90% of the mice in 40-60 days after grafting. Prolonged exposure of tumor cells to the pressure of the immune system in transgenic mice in vivo resulted in a stable loss of H-2K(b) molecules on the EL4 cell surface. Genetic manipulation of the T-lymphocyte repertoire was sufficient to reproduce the classic pattern of interactions between tumor cells and the immune system, usually observed in reliable syngeneic models of anti-tumor immunity. This newly-developed model could be used in further studies of immunoregulatory circuits common for transplantational and anti-tumor immune responses.

The proteomic analysis of barley albumins and globulins

Czech Academy of Sciences Publication Activity Database

Laštovičková, Markéta; Bobálová, Janette

2008-01-01

Roč. 102, č. 15 (2008), s709-s711 ISSN 1803-2389. [Meeting on Chemistry and Life /4./. Brno, 09.09.2008-11.09.2008] R&D Projects: GA MŠk 1M0570 Institutional research plan: CEZ:AV0Z40310501 Keywords : barley * albumins * globulins Subject RIV: CB - Analytical Chemistry, Separation

Natural killer cells enhance the immune surveillance of cancer

African Journals Online (AJOL)

Faisal Nouroz

2015-09-11

Sep 11, 2015 ... and lymphocytes, while AIR is comprised of T and B lymphocytes. All the cells of the .... through blood and physical barriers and both immunities cor- respond with each other .... Cancer stem cells (CSCs) retain the growth of tumor and resist .... kidney, liver, heart and lung transplant recipients 1970 to 2008.

Anaplasma phagocytophilum-Related Defects in CD8, NKT, and NK Lymphocyte Cytotoxicity

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Diana G. Scorpio

2018-04-01

Full Text Available Human granulocytic anaplasmosis, caused by the tick-transmitted Anaplasma phagocytophilum, is not controlled by innate immunity, and induces a proinflammatory disease state with innate immune cell activation. In A. phagocytophilum murine infection models, hepatic injury occurs with production of IFNγ thought to be derived from NK, NKT cells, and CD8 T lymphocytes. Specific A. phagocytophilum ligands that drive inflammation and disease are not known, but suggest a clinical and pathophysiologic basis strikingly like macrophage activation syndrome (MAS and hemophagocytic syndrome (HPS. We studied in vivo responses of NK, NKT, and CD8 T lymphocytes from infected animals for correlates of lymphocyte-mediated cytotoxicity and examined in vitro interactions with A. phagocytophilum-loaded antigen-presenting cells (APCs. Murine splenocytes were examined and found deficient in cytotoxicity as determined by CD107a expression in vitro for specific CTL effector subsets as determined by flow cytometry. Moreover, A. phagocytophilum-loaded APCs did not lead to IFNγ production among CTLs in vitro. These findings support the concept of impaired cytotoxicity with A. phagocytophilum presentation by APCs that express MHC class I and that interact with innate and adaptive immune cells with or after infection. The findings strengthen the concept of an enhanced proinflammatory phenotype, such as MAS and HPS disease states as the basis of disease and severity with A. phagocytophilum infection, and perhaps by other obligate intracellular bacteria.

Heterogeneity in the seed globulin and albumin fractions from ...

African Journals Online (AJOL)

Successful fractionation of albumin, globulin and vicilin fractions from dry seeds of African yam bean (Sphenostylis stenocarpa) was achieved using established procedures for preparation of legume seed proteins. The resulting polypeptides were separated by native polyacrylamide gel electrophoresis under both reducing ...

Serum total protein, albumin and globulin levels in Trypanosoma ...

African Journals Online (AJOL)

The effect of orally administered Scoparia dulcis on Trypanosoma brucei-induced changes in serum total protein, albumin and globulin were investigated in rabbits over a period of twenty eight days. Results obtained show that infection resulted in hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. However ...

The essential role of chemokines in the selective regulation of lymphocyte homing.

Science.gov (United States)

Bono, María Rosa; Elgueta, Raúl; Sauma, Daniela; Pino, Karina; Osorio, Fabiola; Michea, Paula; Fierro, Alberto; Rosemblatt, Mario

2007-01-01

Knowledge of lymphocyte migration has become a major issue in our understanding of acquired immunity. The selective migration of naïve, effector, memory and regulatory T-cells is a multiple step process regulated by a specific arrangement of cytokines, chemokines and adhesion receptors that guide these cells to specific locations. Recent research has outlined two major pathways of lymphocyte trafficking under homeostatic and inflammatory conditions, one concerning tropism to cutaneous tissue and a second one related to mucosal-associated sites. In this article we will outline our present understanding of the role of cytokines and chemokines as regulators of lymphocyte migration through tissues.

Effect of regular circus physical exercises on lymphocytes in overweight children.

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Cesar Miguel Momesso dos Santos

Full Text Available Obesity associated with a sedentary lifestyle can lead to changes in the immune system balance resulting in the development of inflammatory diseases. The aim of this study was to compare lymphocyte activation mechanisms between overweight children practicing regular circus physical exercises with non-exercised children. The study comprised 60 pubescent children randomly divided into 4 groups: Overweight Children (OWC (10.67 ± 0.22 years old, Overweight Exercised Children (OWE (10.00 ± 0.41 years old, Eutrophic Children (EC (11.00 ± 0.29 years old and Eutrophic Exercised Children (EE (10.60 ± 0.29 years old. OWE and EE groups practiced circus activities twice a week, for 4.3 ± 0.5 and 4.4 ± 0.5 months, respectively. Percentage of T regulatory cells (Treg and the expression of CD95 and CD25 in CD4+ lymphocytes were evaluated by flow cytometry. Lymphocyte proliferation capacity was measured by [14C]-thymidine incorporation and mRNA expression of IL-35, TGF-beta, IL-2 and IL-10 by real-time PCR. Lymphocyte proliferation was higher in OWC and OWE groups compared with the EC (3509 ± 887; 2694 ± 560, and 1768 ± 208 cpm, respectively and EE (2313 ± 111 cpm groups. CD95 expression on lymphocytes was augmented in the EC (953.9 ± 101.2 and EE groups (736.7 ± 194.6 compared with the OWC (522.1 ± 125.2 and OWE groups (551.6 ± 144.5. CTLA-4 expression was also lower in the OWC and OWE groups compared with the EC and EE groups. Percentage of Treg, IL-35, and IL-10 mRNA expression were lower in the OWC and OWE groups compared with the EC and EE groups. In conclusion, overweight children present altered immune system balance characterized by elevated lymphocyte proliferation due to a decrease in T regulatory cell percentage. These effects were partially reverted by moderate physical exercise, as demonstrated by decreased lymphocyte proliferation.

T-lymphocyte subsets in West African children: impact of age, sex, and season

DEFF Research Database (Denmark)

Lisse, I M; Aaby, P; Whittle, H

1997-01-01

method to determine T-lymphocyte subsets. RESULTS: We found differences by age, sex, and season, whereas there were no significant differences by birth order, twinning, or ethnic group. The CD4+ percentage declined from birth to age 2 years, at which time it started to increase to higher levels at age 4......OBJECTIVE: There has been no reference material for T-lymphocyte subsets for normal children in developing countries. We therefore used T-lymphocyte subset determinations among children in three different studies in Guinea-Bissau to construct age-related reference material and to examine possible...... determinants of T-lymphocyte subset levels. METHODS: A total of 803 healthy West African children younger than 6 years were included in the three community studies of T-lymphocyte subsets among twins and singletons, after measles infection and after measles immunization. We used the immunoalkaline phosphatase...

Peripheral lymphocyte subset variation predicts prostate cancer carbon ion radiotherapy outcomes

Science.gov (United States)

Shi, Ze-Liang; Li, Bing-Xin; Wu, Xian-Wei; Li, Ping; Zhang, Qing; Wei, Xun-Bin; Fu, Shen

2016-01-01

The immune system plays a complementary role in the cytotoxic activity of radiotherapy. Here, we examined changes in immune cell subsets after heavy ion therapy for prostate cancer. The lymphocyte counts were compared with acute radiotherapy-related toxicity, defined according to the Common Terminology Criteria for Adverse Events, and short-term local efficacy, defined based on prostate-specific antigen concentrations. Confirmed prostate cancer patients who had not received previous radiotherapy were administered carbon ion radiotherapy (CIR) in daily fractions of 2.74 GyE with a total dose of 63-66 GyE. Lymphocyte subset counts were investigated before, during and after radiotherapy, and at a 1 month follow-up. Most notable among our findings, the CD4/CD8 ratio and CD19+ cell counts were consistently higher in patients with a complete response (CR) or partial response (PR) to CIR than in those classified in the stable disease (SD) group (P<0.05 for both). But CD3+ and CD8+ cell counts were lower in the CR and PR groups than in the SD group. These results indicate that variations in peripheral lymphocyte subpopulations are predictive of outcome after CIR for prostate cancer. PMID:27029063

Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

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Song C

2016-08-01

Full Text Available Chanyoung Song,* Young-Woock Noh,* Yong Taik Lim SKKU Advanced Institute of Nanotechnology (SAINT, School of Chemical Engineering, Sungkyunkwan University, Suwon, South Korea *These authors contributed equally to this work Abstract: Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI-coated polymer nanoparticles (NPs as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide (PLGA NPs containing ovalbumin (OVA by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA NPs for antigen delivery and cross-presentation on dendritic cells (DCs were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA NPs. Therefore, the PEI-coated PLGA (OVA NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. Keywords: antigen delivery, dendritic cells, polymer NPs, vaccine, cross-presentation

The Effect of Cardiac Surgery on Peripheral Blood Lymphocyte Populations

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Karolína Jankovičová

2008-01-01

Full Text Available Background: Cardiac surgery using cardiopulmonary bypass (CPB is associated with some adverse postoperative complications caused by an altered immune response. An alternative approach to cardiac surgery, operating without the use of CPB (i.e. off-pump surgery, seems to display less adverse impacts on the immune response. Patients and Methods: Peripheral blood lymphocytes in 40 patients undergoing cardiac surgery either with CPB (“on-pump” or without CPB (“off-pump” were followed using flow cytometry. The samples of peripheral blood were taken at five intervals: preoperatively, after termination of the surgery, on the first, on the third and on the seventh postoperative day, respectively. Results: The most substantial changes appeared on the first postoperative day in both subgroups of patients. While the percentage of both total T cells and CD4+ T cells were decreased, the percentage of HLA-DR+ activated lymphocytes was increased. These changes were more profound in the “on-pump” subgroup compared to the “off-pump” subgroup. Conclusion: Our results may suggest that the “off-pump” surgical approach reveals less adverse impact on adaptive immune responses.

HUMORAL AND CELLULAR IMMUNITY PARAMETERS IN CHILDREN BEFORE AND AFTER ADENOTONSILLECTOMY

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M. H. Baradaranfar

2007-08-01

Full Text Available Adenoids and tonsils are active lymphoid organs and play an important role ‎against invading antigens of upper aerodigestive tract in children. ‎The present study analyzes the changes in cellular and humoral immunity of children six ‎months after adenotonsillectomy. The study population consisted of 30 children whit chronic adenotonsillar hypertrophy and 30 age-matched healthy children. ‎In all children serum level of IgM and IgG, percentage of T lymphocytes (CD3, T ‎helper cells (CD4, T cytotoxic ‎cells (CD8 and B lymphocytes (CD20 were measured before surgery. These parameters were ‎remeasured in patients 6 months after adenotonsillectomy. ‎Before the operation, a reduction in percentage of T lymphocytes (CD3,TCD4,TC8 ‎and B CD20 was seen compared to control group. This reduction was only significant in T ‎lymphocytes (CD3.The serum IgM and IgG levels were not different in two groups. Six months after ‎operation, the percentage of lymphocytes T CD3, T CD8 and BCD20 was increased and ‎reached the control group. The IgM level was also significantly decreased in patients after ‎operation. ‎Our results indicate that cellular and humoral immunity decreases in children ‎with chronic adenotonsiller hypertrophy preoperatively and increases to healthy children ‎level, six months postoperatively. It means that chronic adenotosillar hypertrophy affect ‎some parameters of cellular and humoral immunity and adenotonsillectomy by removing ‎chronic stimulations and reverses these changes without any negative effect on immune ‎function of patients.

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

Science.gov (United States)

Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A

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Marlene Pereira Garanito

2014-09-01

Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States.

Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death

DEFF Research Database (Denmark)

Andersen, Michael Asger; Vojdeman, Fie Juhl; Andersen, Mette Klarskov

2016-01-01

Hypogammaglobulinemia is the most common immune deficiency in chronic lymphocytic leukemia (CLL). However, the prognostic significance in terms of morbidity and mortality remains controversial. We here evaluate the significance of hypogammaglobulinemia in terms of infections, treatment-free survi......Hypogammaglobulinemia is the most common immune deficiency in chronic lymphocytic leukemia (CLL). However, the prognostic significance in terms of morbidity and mortality remains controversial. We here evaluate the significance of hypogammaglobulinemia in terms of infections, treatment......-free survival (TFS), and overall survival (OS). A total of 159 consecutive, newly diagnosed patients were included for analysis. Twenty-five patients (16%) had a moderate or severe infection within one year of diagnosis, but no associations were found between low immunoglobulin (Ig) levels and infections...

Serum protein changes in immune and nonimmune pigeons infected with various strains of Trichomonas gallinae

Science.gov (United States)

Kocan, R.M.; Herman, C.M.

1970-01-01

Serum protein changes were studied in immune and nonimmune pigeons infected with three different strains of Trichomonas gallinae. Strain I (nonvirulent) produced no change in the relative concentration of serum components. Strains II (oral canker) and III (Jones' Barn) produced decreases in albumin and alpha globulins, and increases in beta and gamma globulins between the 7th and 20th days post infection. Birds infected with strain II began to return to normal by the 20th day, while all those infected with strain III were dead between 10 and 14 days post infection. Two serum protein patterns resulted from infection of immune birds with the Jones' Barn strain. One showed no change in relative protein concentrations and no tissue invasion by the parasite while the other was similar to that seen in nonimmune birds infected with a strain producing oral canker. These also showed evidence of tissue invasion by the parasite. It was concluded that tissue invasion was necessary to evoke a quantitative change in serum protein concentrations.

Increased innate and adaptive immune responses in induced sputum of young smokers

Directory of Open Access Journals (Sweden)

Agnese Kislina

2015-01-01

Conclusions: This study demonstrates that young smokers have early inflammatory changes in their airways that not only initiate nonspecific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T regulatory lymphocytes. The lymphocyte response is probably adaptive.

[EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

Science.gov (United States)

Zabrodskii, P F; Maslyakov, V V; Gromov, M S

2016-01-01

It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

Immune Evasion by Epstein-Barr Virus.

Science.gov (United States)

Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, Emmanuel J H J

2015-01-01

Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.

Evaluation of humoral and cell-mediated inducible immunity to Haemophilus ducreyi in an animal model of chancroid.

Science.gov (United States)

Desjardins, M; Filion, L G; Robertson, S; Kobylinski, L; Cameron, D W

1996-01-01

To study the mechanisms of inducible immunity to Haemophilus ducreyi infection in the temperature-dependent rabbit model of chancroid, we conducted passive immunization experiments and characterized the inflammatory infiltrate of chancroidal lesions. Polyclonal immunoglobulin G was purified from immune sera raised against H. ducreyi 35000 whole-cell lysate or a pilus preparation and from naive control rabbits. Rabbits were passively immunized with 24 or 48 mg of purified polyclonal immunoglobulin G intravenously, followed 24 h after infusion by homologous titered infectious challenge. Despite titratable antibody, no significant difference in infection or disease was observed. We then evaluated the immunohistology of lesions produced by homologous-strain challenge in sham-immunized rabbits and those protectively vaccinated by pilus preparation immunization. Immunohistochemical stains for CD5 and CD4 T-lymphocyte markers were performed on lesion sections 4, 10, 15, and 21 days from infection. Lesions of pilus preparation vaccinees compared with those of controls had earlier infiltration with significantly more T lymphocytes (CD5+) and with a greater proportion of CD4+ T lymphocytes at day 4 (33% +/- 55% versus 9.7% +/- 2%; P = 0.002), corroborating earlier sterilization (5.0 +/- 2 versus 13.7 +/- 0.71 days; P < 0.001) and lesion resolution. Intraepithelial challenge of pilus-vaccinated rabbits with 100 micrograms of the pilus preparation alone produced indurated lesions within 48 h with lymphoid and plasmacytoid infiltration, edema, and extravasation of erythrocytes. We conclude that passive immunization may not confer a vaccine effect in this model and that active vaccination with a pilus preparation induces a delayed-type hypersensitivity skin test response and confers protection through cell-mediated immunity seen as an amplified lymphocytic infiltrate and accelerated maturation of the T-lymphocyte response. PMID:8613391

CD4+ LYMPHOCYTES IMPROVE VENOUS BLOOD FLOW IN EXPERIMENTAL ARTERIOVENOUS FISTULAE

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Duque, Juan C.; Martinez, Laisel; Mesa, Annia; Wei, Yuntao; Tabbara, Marwan; Salman, Loay H.; Vazquez-Padron, Roberto I.

2015-01-01

Background The role of immune cells in arteriovenous fistulae (AVF) maturation is poorly understood and has received, until quite recently, little attention. This study examines the role of T lymphocytes in AVF vascular remodeling. Methods Experimental fistulae were created in athymic rnu nude rats lacking mature T lymphocytes and euthymic control animals by anastomosing the left superior epigastric vein to the nearby femoral artery. Blood flow rates, wall morphology and histological changes were assessed in AVF 21 days after creation. The effect of CD4+ lymphocytes on AVF maturation in athymic animals was analyzed by adoptive transfer of cells after fistula creation. Results The absence of T lymphocytes compromised blood flow in experimental fistulae. Histopathological inspection of AVF from athymic rats revealed that T cell immunodeficiency negatively affected venous vascular remodeling, as evidenced by a reduced lumen, a thick muscular layer and a low number of inflammatory cells compared to control animals. Adoptive transfer of CD4+ lymphocytes from euthymic rats into athymic animals before and after fistula creation improved blood flow and reduced intima-media thickness. Conclusion These results point at the protective role of CD4+ lymphocytes in the remodeling of the AVF vascular wall. PMID:25999254

Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia.

Science.gov (United States)

Janikashvili, Nona; LaCasse, Collin J; Larmonier, Claire; Trad, Malika; Herrell, Amanda; Bustamante, Sara; Bonnotte, Bernard; Har-Noy, Michael; Larmonier, Nicolas; Katsanis, Emmanuel

2011-02-03

Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4(+)CD25(+)FoxP3(+) regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3(+) Tregs from naive CD4(+)CD25(-)FoxP3(-) T cells by an interferon-γ-dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.

Hormesis of Low Doses of Ionizing Radiation Exposure on Immune System

International Nuclear Information System (INIS)

Ragab, M.H.; Abbas, M.O.; El-Asady, R.S.; Amer, H.A.; El-Khouly, W.A.; Shabon, M.H.

2015-01-01

The effect of low doses of ionizing radiation on the immune system has been a controversial subject. To evaluate the effect of low-doses γ-irradiation exposure on immune system. An animal model, using Rattus Rattus rats was used. The rats were divided into groups exposed to either continuous or fractionated 100, 200, 300, 400 and 500 mSv of radiation and compared to control rats that did not receive radiation. All groups were exposed to a total white blood count (Wcs), lymphocyte count and serum IgG level measurement, as indicators of the function of the cell-mediated (T lymphocytes) and the humoral (B lymphocytes) immune system. The results of the current study revealed that the counts of total leukocytes (WBCs) and lymphocytes, as well as the serum level of IgG were increased significantly in rats receiving low dose radiation, indicating enhancement of immune system. The data suggests that low-dose gamma-radiation improved hematological parameters and significantly enhances immune response indices of the exposed rats. These findings are similar to the radiation adaptive responses in which a small dose of pre irradiation would induce certain radiation resistance and enhances the cell response after exposure to further irradiation doses The applied low doses used in the present study may appear effective inducing the radio adaptive response. Farooqi and Kesavan (1993) and Bravard et al. (1999) reported that the adaptive response to ionizing radiation refers to the phenomenon by which cells irradiated with low (cGy) or sublethal doses (conditioning doses) become less susceptible to genotoxic effects of a subsequent high dose (challenge dose, several Gy).

Suppression of immune-mediated liver injury after vaccination with attenuated pathogenic cells.

Science.gov (United States)

Mei, Yunhua; Wang, Ying; Xu, Lingyun

2007-05-15

Cell vaccination via immunization with attenuated pathogenic cells is an effective preventive method that has been successfully applied in several animal models of inflammatory or autoimmune diseases. Concanavalin A (Con A)-induced hepatitis (CIH) is a commonly used experimental model to study immune-mediated liver injury. Multiple cell types including T lymphocytes, macrophages and neutrophils have been found to be involved in the pathogenesis of CIH. In this study, we used attenuated spleen lymphocytes or peripheral blood lymphocytes as vaccines to investigate whether they could induce protective immune responses to prevent mice from developing CIH. We found that mice receiving such vaccination before CIH induction developed much milder diseases, exhibited a lower level of alanine aminotransferase (ALT) released into their plasma and had less inflammatory lesions in their livers. Such CIH-suppression is dose- and frequency-dependent. The suppressive effect was associated with inhibition of several major inflammatory mediators, pro-inflammatory cytokines and chemokines.

Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes.

Science.gov (United States)

Pongsavee, Malinee

2009-10-30

Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

Lymphocyte subsets and response to PHA among atomic bomb survivors

International Nuclear Information System (INIS)

Nakao, Susumu; Noguchi, Kyouichi; Eida, Kazuyuki; Tashiro, Kazunori; Hayashida, Ken

1986-01-01

In an effort to elucidate the effect of radiation exposure on immune competence in man, the number of lymphocytes, lymphocyte subsets, and the percentage of phytohemagglutinin (PHA)-induced transformation of lymphocytes were determined in 66 cancer patients, 25 of whom were exposed to atomic radiation at ≤ 2,000 m from ground zero and 41 others were not exposed. The number of lymphocytes was decreased with increasing age at exposure. The percentage of OKT3-positive cells tended to be lower in exposed patients who were in their twenties at the time of exposure than the non-exposed patients. Among patients in their teens and twenties at the time of exposure, there was a tendency toward decreased percentage of OKT4-positive cells (T4) and increased percentage of OKT8-positive cells (T8). The T4/T8 ratio was reduced. Patients who were in their first decade of life at the time of exposure tended to have decreased OKIa 1-positive cells, and increased Leulla-positive cells. Patients exposed in their twenties and thirties had slightly decreased percentage of PHA-induced transformation of lymphocytes. (Namekawa, K.)

Lymphocyte Proliferation Response in Patients with Acute and Chronic Brucellosis

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Khadijeh Khosravi

2016-05-01

Full Text Available Abstract Background: Brucella is an intracellular bacterium that causes chronic infection in humans and domestic animals. The underlying mechanisms that cause prolonged illness are complex and not fully understood. Immune responses may have an important role in the chronicity of infection. Here, we evaluated the lymphocyte proliferation responses in patients with chronic and acute brucellosis. Materials and Methods: This descriptive - analytical study was performed on 22 patients with acute brucellosis, 21 patients with chronic brucellosis and 21 healthy people with the similar age, sex and genetic background as control group. Peripheral lymphocytes were isolated using Ficoll and the cellular proliferation was quantified in presence of antigen and phytohemaglutinin-A by MTT method. Results: The brucella antigen-specific stimulation index in patients with chronic brucellosis was significantly lower than the acute brucellosis patients (p=0.001. Also, stimulating the lymphocytes with phytohemaglutinin-A has shown that proliferative response in patients with chronic brucellosis was lower than the other groups (p=0.04. Conclusion: The results indicated that chronic brucellosis inhibits lymphocyte proliferation. This inhibition of lymphocyte proliferation may be due to the induction of anergy.

The effect of ionizing radiation on immune system

International Nuclear Information System (INIS)

Gyuleva, I.

1999-01-01

Delayed radiation effects of irradiation at relatively high doses - 0.52- 2 Gy in result of severe accidents are discussed. The immune response of lymphocyte populations manifested in formation of different kind of mutant cells at Hiroshima-A-bombing and Chernobyl accident are presented. It is of great interest the hypothesis presented launched by RERF (Japanese Foundation for Radiation Effect Research, Hiroshima) for radiation induced predominant of T H2 -lymphocytes in comparison to T H1 as delayed immune response at the Hiroshima-A-bomb survivors. The aspect of immune status is quite different at low doses irradiation (0.02 - 0.2 Gy). There is some stimulation in immune response known as hormesis effect. It is suggested that T-cell activation has key role in immune system stimulation at doses under 0.2 Gy. There is also activation of DNA-reparation mechanisms. Suppression of the hypothalamus-hypophysis-suprarenal axis brings to enhancing of immune potential. Chinese people living in a region with three-times higher background radiation, X-ray examined patients as well as occupationally exposed personnel have been investigated. Radioprotective effect of some cytokines and their influence on the individual radiosensitivity are also discussed.The investigations have to be continued because of some inconsistent results

Zinc and immunity: An essential interrelation.

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Maares, Maria; Haase, Hajo

2016-12-01

The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of bestatin on the host immunity in patients treated for urogenital cancer

International Nuclear Information System (INIS)

Ozono, S.; Iwai, A.; Babaya, K.; Hiramatsu, T.; Yoshida, K.; Yamada, K.; Hirao, Y.; Aoyama, H.; Ohara, S.; Okajima, E.

1990-01-01

To examine effects of bestatin on the host immunity of patients with urogenital cancer, 54 patients were randomized into 2 groups: bestatin treated and controls. In each group, the patients were divided into 2 subgroups: one which received basic treatment expected to greatly affect host immunity ('invasive treatment') while the other one received other types of basic treatment ('non-invasive treatment'). Peripheral lymphocyte, OKT 4/8 ratio and purified protein derivative (PPD) skin reaction were used as immunological markers. There were significant differences in the 'invasive' treatment group between bestatin treated patients and controls concerning lymphocyte counts and PPD skin reactions and in the 'non-invasive' group concerning lymphocyte counts and OKT 4/8 ratios. These results suggest that bestatin may potentiate host immunity in patients with urogenital cancer. Further studies on larger materials are, however, needed before more definite conclusions can be drawn. (orig.)

Immune and hemorheological changes in Chronic Fatigue Syndrome

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Ashton Kevin J

2010-01-01

Full Text Available Abstract Background Chronic Fatigue Syndrome (CFS is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. Methods Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ and CD56brightCD16- and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed. Results CFS patients (n = 10 had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56brightCD16- NK phenotypes in comparison to healthy controls (n = 10. However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56dimCD16+ NK cells were similar between the two groups. Conclusion These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients.

Peripheral Blood Lymphocyte Depletion After Hepatic Arterial {sup 90}Yttrium Microsphere Therapy for Hepatocellular Carcinoma

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Carr, Brian I., E-mail: brianicarr@hotmail.com [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy); Metes, Diana M. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy)

2012-03-01

Purpose: The short- and long-term effects of {sup 90}Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a {sup 90}Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in addition to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-{sup 90}Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial {sup 90}Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.

Changes in total and differential white cell counts, total lymphocyte ...

African Journals Online (AJOL)

Background: Published reports on the possible changes in the various immune cell populations, especially the total lymphocyte and CD4 cell counts, during the menstrual cycle in Nigerian female subjects are relatively scarce. Aim: To determine possible changes in the total and differential white blood cell [WBC] counts, ...

Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response

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Mariona Camps-Bossacoma

2017-06-01

Full Text Available Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells. Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies.

The percentage of iNKT cells among other immune cells at various clinical stages of laryngeal cancer

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Janusz Klatka

2016-04-01

Full Text Available Introduction: Invariant natural killer T (iNKT cells constitute a small population of immune cells that share functional and phenotypic characteristics of T lymphocytes and NK cells. Due to their involvement in specific and non-specific immune responses, iNKT cells may represent an important component of antitumor and anti-infectious immunity. Material and methods: Using flow cytometry, we analyzed the percentages of iNKT cells as well as T and B lymphocytes in peripheral blood of 50 laryngeal cancer patients at various clinical stages in comparison to healthy controls (n=15. Moreover, we determined the expression of CD25, CD69 and CD95 antigens on T lymphocytes.Results: The percentage of CD4+/CD3+ T lymphocytes in the controls was higher than in laryngeal cancer patients, both with early and late stages of the disease. The percentage of CD8+/CD3+ T lymphocytes in healthy controls was lower than in patients with early and late clinical stages of laryngeal cancer. Patients with advanced laryngeal cancer showed a lower percentage of iNKT cells and higher frequencies of T regulatory cells (Tregs than the controls. Advanced clinical stages of laryngeal cancer are associated with impaired activation of lymphocytes.Conclusions: Our study confirmed that laryngeal cancer cells exert a strong suppressor effect on the immune system of the host. This is reflected by a decrease in the percentage of iNKT cells that are capable of cancer cell elimination, and a concomitant increase in the percentage of Tregs. However, further studies are needed in order to explain the underlying mechanisms of immunosuppression and understand interactions between immune and cancer cells.

Autoradiographic study of gamma-irradiated mouse spleen during primary immune response

International Nuclear Information System (INIS)

Gitsov, L.G.; Kyncheva, L.S.; Burneva, V.G.; Martinova, J.Sh.; Viklichka, S.

1978-01-01

Study on the kinetics of the cells in the mouse spleen during the primary immune response against thymusdependent antigen after sublethal irradiation was carried out. For this purpose the animals were immunized with sheep erythrocytes one day after their irradiation with 700 r gamma rays. On the 5th day after the immunization, tritium labelled thymidine was injected three times at two hourly intervals. Mice were killed two hours after the third injection for preparation of routine histological samples and autoradiographs. Immunized, but not irradiated mice were utilized as controls. Extensive zones of lymphocyte destruction were observed in the spleen of the irradiated mice - accumulation of picnotic lymphocyte nuclei, surrounded by reticulo-histocyte elements. The number of the labelled cells and the intensity of labelled are lower than that of the germinal centres in control animal. There is no marked cell destruction in the periarteriolar zone nor labelled cells, whereas in the controls there is a considerable number of labelled blast cells. In the red pulp of the irradiated animals islands of erythroblasts were found, whereas in the controls - parallely to the erythroblast islands, there are islands of proliferating lymphocytes and plasmocytes. The decrease of lymphocyte number in irradiated mice is connected with their destruction and with the altered lymphocytopoiesis in the red pulp. It is assumed that the observed preservation of the periarteriolar lymphatic sheaths in an expression of a higher radioresistance of the T-cells as compared to the B-cells in the white pulp. This study contributes for elucidation of the irradiation immunosuppressive effect. It points out also that the post-irradiation lymphopaenia is due not only to the cell death but also to the exclusion of part of the T-lymphocytes from the circulation and their selective deposition in the thymus-dependent zones of the peripheral lymphoid organs. (A.B.)

The Immune Landscape of Cancer

NARCIS (Netherlands)

Thorsson, Vésteinn; Gibbs, David L.; Brown, Scott D.; Wolf, Denise; Bortone, Dante S.; Ou Yang, Tai Hsien; Porta-Pardo, Eduard; Gao, Galen F.; Plaisier, Christopher L.; Eddy, James A.; Ziv, Elad; Culhane, Aedin C.; Paull, Evan O.; Sivakumar, I. K.Ashok; Gentles, Andrew J.; Malhotra, Raunaq; Farshidfar, Farshad; Colaprico, Antonio; Parker, Joel S.; Mose, Lisle E.; Vo, Nam Sy; Liu, Jianfang; Liu, Yuexin; Rader, Janet; Dhankani, Varsha; Reynolds, Sheila M.; Bowlby, Reanne; Califano, Andrea; Cherniack, Andrew D.; Anastassiou, Dimitris; Bedognetti, Davide; Rao, Arvind; Chen, Ken; Krasnitz, Alexander; Hu, Hai; Malta, Tathiane M.; Noushmehr, Houtan; Pedamallu, Chandra Sekhar; Bullman, Susan; Ojesina, Akinyemi I.; Lamb, Andrew; Zhou, Wanding; Shen, Hui; Choueiri, Toni K.; Weinstein, John N.; Guinney, Justin; Saltz, Joel; Holt, Robert; Rabkin, Charles E.; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, onathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Lazar, Alexander J.; Serody, Jonathan S.; Demicco, Elizabeth G.; Disis, Mary L.; Vincent, Benjamin G.; Shmulevich, llya

2018-01-01

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β

IMMUNITY AND INFECTION IN WOMEN WITH HYPERPLASTIC STATES OF IMMUNE SYSTEM

Directory of Open Access Journals (Sweden)

A. A. Lukach

2008-01-01

Full Text Available Abstract. One hundred and ninety-nine patients with hyperplastic processes of reproductive system were examined, and 131 (66.16% of them were found to be infected with Chlamydia or Ureaplasma. The mean age of female patients was 42,7±1,35 years. Different infectious agents (e.g. Chlamydia trachomatis, Ureaplasma urealiticum, Mycoplasma hominis were identified in cervical canal of uterine cervix and surgical specimens (biopsy samples of excised myoma, adenomyosis or endometrial hyperplasia. The infected patients were found to have decreased monocytes and neutrophils in blood counts, lower phagocytic activity of monocytes and neutrophils, and decreased bactericidal activity of leukocytes. Other findings included lower CD20+, CD8+ and rFAS CD 95 lymphocytes. Assessment of cytokine-synthesizing activity of CD3+ lymphocytes showed a decrease in both spontaneous and stimulated response (р < 0,001. A weakest spontaneous and stimulated response was found in CD3+/IL-4+ lymphocytes. Analysis of results obtained shows systemic immune disorders and impaired cytokine-synthesizing activity of CD3+ lymphocytes correlating with infection factors in the women with hyperplastic processes of reproductive system. (Med. Immunol., 2008, vol. 10, N 2-3, pp 223-228.

Sympathetic neural modulation of the immune system

International Nuclear Information System (INIS)

Madden, K.S.

1989-01-01

One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125 iododeoxyuridine ( 125 IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125 IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51 Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

Skin Immunization Obviates Alcohol-Related Immune Dysfunction

Directory of Open Access Journals (Sweden)

Rhonda M. Brand

2015-11-01

Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

Immune Modulation by Vitamin D and Its Relevance to Food Allergy

Directory of Open Access Journals (Sweden)

Noor H. A. Suaini

2015-07-01

Full Text Available Apart from its classical function in bone and calcium metabolism, vitamin D is also involved in immune regulation and has been linked to various cancers, immune disorders and allergic diseases. Within the innate and adaptive immune systems, the vitamin D receptor and enzymes in monocytes, dendritic cells, epithelial cells, T lymphocytes and B lymphocytes mediate the immune modulatory actions of vitamin D. Vitamin D insufficiency/deficiency early in life has been identified as one of the risk factors for food allergy. Several studies have observed an association between increasing latitude and food allergy prevalence, plausibly linked to lower ultraviolet radiation (UVR exposure and vitamin D synthesis in the skin. Along with mounting epidemiological evidence of a link between vitamin D status and food allergy, mice and human studies have shed light on the modulatory properties of vitamin D on the innate and adaptive immune systems. This review will summarize the literature on the metabolism and immune modulatory properties of vitamin D, with particular reference to food allergy.

Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

Centers for Disease Control (CDC) Podcasts

Three organ transplant recipients died from infection with lymphocytic choriomeningitis virus (LCMV), which was traced back to a hamster owned by the daughter of the organ donor. Dr. Brian Amman, a mammalogist with the Special Pathogens Branch at CDC, discusses the dangers LCMV may pose to people with immune disorders, as well as to pregnant women.

The Bidirectional Relationship between Sleep and Immunity against Infections

Directory of Open Access Journals (Sweden)

Elizabeth G. Ibarra-Coronado

2015-01-01

Full Text Available Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.

Sex hormone binding globulin phenotypes

DEFF Research Database (Denmark)

Cornelisse, M M; Bennett, Patrick; Christiansen, M

1994-01-01

Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib

OpenAIRE

Okamoto, Koh; Proia, Laurie A.; Demarais, Patricia L.

2016-01-01

Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. It acts by inhibitin...

Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

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Caroline Boda

Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

Blood metal levels and metal-influenced immune functions of harbour seals in captivity

International Nuclear Information System (INIS)

Kakuschke, Antje; Valentine-Thon, Elizabeth; Griesel, Simone; Rosenberger, Tanja; Mundry, Roger; Siebert, Ursula; Prange, Andreas

2008-01-01

Immunological blood parameters and the effects of environmental pollutants on the immune system are important to assess the health status of seals. Animals living permanently in seal centres are useful for development and validation of diagnostic tools for free-ranging animals. In this study, parameters of cellular immunity as well as metal concentrations in blood and metal influence on cell proliferation of seven seals from a seal centre were investigated repeatedly using multi-element analysis and a lymphocyte proliferation assay. The metal concentrations, except for tin and chromium, were in general comparable to those of free-ranging animals of the North Sea. The unstimulated and mitogen-stimulated lymphocyte proliferation showed strong intra- and inter-individual variability, which reflected variability in activation of the immune status. Furthermore, both immunosuppressive and stimulative influences of metals on lymphocytes were found. Summarising, the methods used in this investigation provided useful information on these animals, and their application to free-ranging animals can be recommended

Blood metal levels and metal-influenced immune functions of harbour seals in captivity

Energy Technology Data Exchange (ETDEWEB)

Kakuschke, Antje [GKSS Research Centre, Institute for Coastal Research, Max-Planck-Strasse 1, 21502 Geesthacht (Germany)], E-mail: antje.kakuschke@gkss.de; Valentine-Thon, Elizabeth [Department of Immunology, Laboratory Center Bremen, Friedrich-Karl-Strasse 22, 28205 Bremen (Germany); Griesel, Simone [GKSS Research Centre, Institute for Coastal Research, Max-Planck-Strasse 1, 21502 Geesthacht (Germany); Rosenberger, Tanja [Seal Centre Friedrichskoog e.V., 25718 Friedrichskoog (Germany); Mundry, Roger [Research and Technology Centre Westcoast (FTZ), University of Kiel, Hafentoern 1, 25761 Buesum (Germany); Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig (Germany); Siebert, Ursula [Research and Technology Centre Westcoast (FTZ), University of Kiel, Hafentoern 1, 25761 Buesum (Germany); Prange, Andreas [GKSS Research Centre, Institute for Coastal Research, Max-Planck-Strasse 1, 21502 Geesthacht (Germany)

2008-04-15

Immunological blood parameters and the effects of environmental pollutants on the immune system are important to assess the health status of seals. Animals living permanently in seal centres are useful for development and validation of diagnostic tools for free-ranging animals. In this study, parameters of cellular immunity as well as metal concentrations in blood and metal influence on cell proliferation of seven seals from a seal centre were investigated repeatedly using multi-element analysis and a lymphocyte proliferation assay. The metal concentrations, except for tin and chromium, were in general comparable to those of free-ranging animals of the North Sea. The unstimulated and mitogen-stimulated lymphocyte proliferation showed strong intra- and inter-individual variability, which reflected variability in activation of the immune status. Furthermore, both immunosuppressive and stimulative influences of metals on lymphocytes were found. Summarising, the methods used in this investigation provided useful information on these animals, and their application to free-ranging animals can be recommended.

The Effects Radiation on Cellular Components of the Immune

International Nuclear Information System (INIS)

Zubaidah-Alatas

2001-01-01

The immune system describes the body's ability to defend itself against various foreign intruders named as antigens by calling on an immune mechanism. Antigens penetration into body activate the body's immune system that may be humoral response, cellular response, or both. The immune response is primarily mediated by two cell types, lymphocyte and macrophage. This paper will discuss the cellular component of immune system and the radiation effects on various cells involved in system. Moreover, the effects of radiation on humoral and cellular responses and the relation among immunity, cancer and radiotherapy are also described. (author)

Discovery of skin lymphocytes was a game changer in experimental dermatology

NARCIS (Netherlands)

Matos, Tiago R.; de Rie, Menno A.

2017-01-01

A substantial part of ongoing research in experimental dermatology focuses on skin T cellsfor that reason, we find important to highlight the pioneering work of Jan D. Bos et al. from 1987 (The skin immune system (SIS): Distribution and immunophenotype of lymphocyte subpopulations in normal skin)

Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

DEFF Research Database (Denmark)

Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

2013-01-01

T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indic......T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions...... is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

Alteration of Lymphocyte Phenotype and Function in Sickle Cell Anemia: Implications for Vaccine Responses

Science.gov (United States)

Balandya, Emmanuel; Reynolds, Teri; Obaro, Stephen; Makani, Julie

2016-01-01

Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper : CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27+IgMhighIgDlow memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research. PMID:27237467

Behavioral Fever Drives Epigenetic Modulation of the Immune Response in Fish.

Science.gov (United States)

Boltana, Sebastian; Aguilar, Andrea; Sanhueza, Nataly; Donoso, Andrea; Mercado, Luis; Imarai, Monica; Mackenzie, Simon

2018-01-01

Ectotherms choose the best thermal conditions to mount a successful immune response, a phenomenon known as behavioral fever. The cumulative evidence suggests that behavioral fever impacts positively upon lymphocyte proliferation, inflammatory cytokine expression, and other immune functions. In this study, we have explored how thermal choice during infection impacts upon underpinning molecular processes and how temperature increase is coupled to the immune response. Our results show that behavioral fever results in a widespread, plastic imprint on gene regulation, and lymphocyte proliferation. We further explored the possible contribution of histone modification and identified global associations between temperature and histone changes that suggest epigenetic remodeling as a result of behavioral fever. Together, these results highlight the critical importance of thermal choice in mobile ectotherms, particularly in response to an infection, and demonstrate the key role of epigenetic modification to orchestrate the thermocoupling of the immune response during behavioral fever.

Immunodepressive effect of Friend virus. 4. Effects on spleen B lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Dracott, B N; Wedderburn, N [Royal Coll. of Surgeons of England, London; Doenhoff, M J

1978-04-01

Splenic immune responses having varying dependence on accessory cell cooperation have been studied after infection of mice with Friend virus. Infection had no effect on cell proliferation or antibody production in cultures stimulated with E.coli lipopolysaccharide. The response in vivo to type III pneumococcal polysaccharide was depressed only moderately. The response to sheep red blood cells was depressed severely both in vivo and in vitro. Depression in vitro was greatly reduced by co-stimulation with E.coli lipopolysaccharide. Depletion of potential suppressor lymphocyte populations by irradiation or adult thymectomy did not ameliorate depression of responses to sheep red blood cells or pneumococcal polysaccharide. Responses after adult thymectomy plus irradiation were not affected by the virus. Although it is known that macrophage and helper T-lymphocyte cooperation are not themselves impaired by infection, these results suggest that there is a direct relationship between severity of immune depression and dependence on cooperation. Implications for the action of the virus are discussed.

Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

OpenAIRE

Benjamin Arthurs, MD; Kathy Wunderle, MD; Maylee Hsu, MD; Suil Kim, MD, PhD

2017-01-01

We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia.

Science.gov (United States)

Arthurs, Benjamin; Wunderle, Kathy; Hsu, Maylee; Kim, Suil

2017-01-01

We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus . Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

Immune function in arctic mammals

DEFF Research Database (Denmark)

Desforges, Jean-Pierre; Jasperse, Lindsay; Jensen, Trine Hammer

2018-01-01

Natural killer (NK) cells are a vital part of the rapid and non-specific immune defense against invading pathogens and tumor cells. This study evaluated NK cell-like activity by flow cytometry for the first time in three ecologically and culturally important Arctic mammal species: polar bear (Ursus...... the effector:target cell ratio increased. Comparing NK activity between fresh and cryopreserved mouse lymphocytes revealed little to no difference in function, highlighting the applicability of cryopreserving cells in field studies. The evaluation of this important innate immune function in Arctic mammals can...... contribute to future population health assessments, especially as pollution-induced suppression of immune function may increase infectious disease susceptibility....

Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

Science.gov (United States)

Antonini, James M; Zeidler-Erdely, Patti C; Young, Shih-Houng; Roberts, Jenny R; Erdely, Aaron

2012-01-01

Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a

Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node.

Science.gov (United States)

Zhang, Yang; Roth, Theodore L; Gray, Elizabeth E; Chen, Hsin; Rodda, Lauren B; Liang, Yin; Ventura, Patrick; Villeda, Saul; Crocker, Paul R; Cyster, Jason G

2016-08-03

Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular sinus (SCS) and associated macrophages for pathogen entry. The factors promoting this surveillance behavior have not been defined. Here, we report that IL7R(hi)Ccr6(+) lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal challenge. We show that these innate-like lymphocytes are mostly LN resident. Ccr6 is required for their accumulation near the SCS and for efficient IL17 induction. Migration into the SCS intrinsically requires S1pr1, whereas movement from the sinus into the parenchyma involves the integrin LFA1 and its ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within the sinus, preventing their loss in lymph flow. These findings establish a role for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens, and they define requirements for cell movement between parenchyma and SCS in what we speculate is a program of immune surveillance that helps achieve LN barrier immunity.

Activation of immune functions via induction of glutathione of lymphocytes by low-dose, whole-body irradiation with gamma-rays

International Nuclear Information System (INIS)

Shuji Kojima; Hisatake Hayase; Mareyuki Takahashi

2007-01-01

Complete text of publication follows. We have recently found that low doses of radiation, unlike higher doses, do not always cause a decrease of cellular glutathione, but they can increase it, leading to an elevation of Con A-induced proliferation of splenocytes. In this study, we first examined whether the increase of glutathione level induced by low-dose gamma-ray irradiation is involved in the appearance of enhanced natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC), leading to delayed tumor growth in Ehrlich solid tumor (EST)-bearing mice. NK activity in ICR mouse splenocytes was significantly increased from 4 h to 6 h after a single whole-body gamma-ray irradiation at 0.5 Gy, and thereafter decreased almost to the zero-time level by 24 h post-irradiation. ADCC was also increased significantly in a similar way. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced both NK activity and ADCC in a dose-dependent manner. The inhibitory effect of the radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after the inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance (Th1/Th2) was examined in order to elucidate the mechanism underlying the anti-tumor immunity. Recent studies indicate that Th1/Th2 balance plays an important role in the immune responses involved in anti-tumor immunity. The activity of NK is hallmarks of cell-mediated immunity, and play key roles in anti-tumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after the radiation, concomitantly with an increase in that of helper T cell population, favoring Th1 polarization. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after the radiation, though the level of

Evidence for significant influence of host immunity on changes in differential blood count during malaria.

Science.gov (United States)

Berens-Riha, Nicole; Kroidl, Inge; Schunk, Mirjam; Alberer, Martin; Beissner, Marcus; Pritsch, Michael; Kroidl, Arne; Fröschl, Günter; Hanus, Ingrid; Bretzel, Gisela; von Sonnenburg, Frank; Nothdurft, Hans Dieter; Löscher, Thomas; Herbinger, Karl-Heinz

2014-04-23

Malaria has been shown to change blood counts. Recently, a few studies have investigated the alteration of the peripheral blood monocyte-to-lymphocyte count ratio (MLCR) and the neutrophil-to-lymphocyte count ratio (NLCR) during infection with Plasmodium falciparum. Based on these findings this study investigates the predictive values of blood count alterations during malaria across different sub-populations. Cases and controls admitted to the Department of Infectious Diseases and Tropical Medicine from January 2000 through December 2010 were included in this comparative analysis. Blood count values and other variables at admission controlled for age, gender and immune status were statistically investigated. The study population comprised 210 malaria patients, infected with P. falciparum (68%), Plasmodium vivax (21%), Plasmodium ovale (7%) and Plasmodium malariae (4%), and 210 controls. A positive correlation of parasite density with NLCR and neutrophil counts, and a negative correlation of parasite density with thrombocyte, leucocyte and lymphocyte counts were found. An interaction with semi-immunity was observed; ratios were significantly different in semi-immune compared to non-immune patients (P value of the ratios was fair but limited. However, these changes were less pronounced in patients with semi-immunity. The ratios might constitute easily applicable surrogate biomarkers for immunity.

Innate immunity in the pathogenesis of psoriasis.

LENUS (Irish Health Repository)

Sweeney, Cheryl M

2011-12-01

Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

Immune Response to Electromagnetic Fields through Cybernetic Modeling

International Nuclear Information System (INIS)

Godina-Nava, J. J.; Segura, M. A. Rodriguez; Cadena, S. Reyes; Sierra, L. C. Gaitan

2008-01-01

We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen

Immune Response to Electromagnetic Fields through Cybernetic Modeling

Science.gov (United States)

Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

2008-08-01

We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

Frequencies of circulating B- and T-lymphocytes as indicators for stroke outcomes

Directory of Open Access Journals (Sweden)

Wang Y

2017-10-01

Full Text Available Yanling Wang,1 Jihong Liu,1 Xuemei Wang,1 Zongjian Liu,2 Fengwu Li,1 Fenghua Chen,3 Xiaokun Geng,1 Zhili Ji,2 Huishan Du,1 Xiaoming Hu1,3 1Department of Neurology, China-America Institute of Neuroscience, 2Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Background: Stroke has high mortality and morbidity. Biomarkers are required for to predict stroke outcomes, which could help clinicians to provide rationale approaches for patient management. The dynamic changes in circulating immune cells have been reported in stroke patients and animal models of stroke.Aim: The aim of this study was to explore biomarkers to predict stroke outcomes by investigating the relationship between the frequencies of circulating immune cells and stroke outcomes.Methods: In all, 50 acute ischemic stroke (AIS patients were enrolled. Their blood samples were collected upon hospital admission and on day 1 and day 7 after stroke, and the leukocyte subsets were analyzed by flow cytometry. The dynamic changes in some types of immune cells in the AIS course and their correlation with clinical parameters were analyzed. Blood samples from 123 age- and gender-matched healthy subjects were used as controls.Results: The proportions of T-lymphocytes and NK cells in stroke patients were significantly lower than in healthy controls. The frequencies of B- and T-lymphocytes were negatively correlated with stroke severity at onset, including neurological deficits as assessed by National Institutes of Health Stroke Scale (NIHSS, and infarct volume as measured by the diffusion-weighted images (DWIs of magnetic resonance (MR. Logistic regression analysis showed that modified Rankin scale (mRs scores, a score system for the long-term neurological dysfunctions, were negatively correlated

Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

2012-08-01

Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

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Pongsavee Malinee

2009-10-01

Full Text Available Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI. The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

International Nuclear Information System (INIS)

Han, T.; Dadey, B.

1978-01-01

Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

Heterologous Prime-Boost Immunizations with a Virosomal and an Alphavirus Replicon Vaccine

NARCIS (Netherlands)

Walczak, Mateusz; de Mare, Arjan; Riezebos-Brilman, Annelies; Regts, Joke; Hoogeboom, Baukje-Nynke; Visser, Jeroen T.; Fiedler, Marc; Jansen-Duerr, Pidder; van der Zee, Ate G. J.; Nijman, Hans W.; Wilschut, Jan; Daemen, Toos

2011-01-01

Heterologous prime-boost immunization strategies in general establish higher frequencies of antigen-specific T lymphocytes than homologous prime-boost protocols or single immunizations. We developed virosomes and recombinant Semliki Forest virus (rSFV) as antigen delivery systems, each capable of

The Immune System Out of Shape? : Shaping of adaptive immunity by persistent viral infections in young children

NARCIS (Netherlands)

D. van den Heuvel (Diana)

2015-01-01

markdownabstractDuring pregnancy, a fetus is protected from a large part of the pathogens of the environment. As a result, a newborn’s immune system is immature and unexperienced, and mainly composed of innate leukocytes and naive lymphocytes. Immunological memory, and concomitant functional

Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

DEFF Research Database (Denmark)

Khamri, Wafa; Abeles, Robin D; Hou, Tie Zheng

2017-01-01

, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood...... mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF......BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86...

Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin.

OpenAIRE

Moayyedi, P; O'Mahony, S; Jackson, P; Lynch, D A; Dixon, M F; Axon, A T

1997-01-01

There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous...

Effects of dietary supplementation with phytonutrients on vaccine-stimulated immunity against infection with Eimeria tenella.

Science.gov (United States)

Lee, Sung Hyen; Lillehoj, Hyun S; Jang, Seung I; Lee, Kyung Woo; Bravo, David; Lillehoj, Erik P

2011-09-27

Two phytonutrient mixtures, VAC (carvacrol, cinnamaldehyde, and Capsicum oleoresin), and MC (Capsicum oleoresin and turmeric oleoresin), were evaluated for their effects on chicken immune responses following immunization with an Eimeria profilin protein. Chickens were fed with a non-supplemented diet, or with VAC- or MC-supplemented diets, immunized with profilin, and orally challenged with virulent oocysts of Eimeria tenella. Immunity against infection was evaluated by body weight, fecal oocyst shedding, profilin antibody levels, lymphocyte recall responses, cytokine expression, and lymphocyte subpopulations. Following immunization and infection, chickens fed the VAC- or MC-supplemented diets showed increased body weights, greater profilin antibody levels, and/or greater lymphocyte proliferation compared with non-supplemented controls. Prior to Eimeria infection, immunized chickens on the MC-supplemented diet showed reduced IFN-γ and IL-6 levels, but increased expression of TNFSF15, compared with non-supplemented controls. Post-infection levels of IFN-γ and IL-6 were increased, while IL-17F transcripts were decreased, with MC-supplementation. For VAC-supplemented diets, decreased IL-17F and TNFSF15 levels were observed only in infected chickens. Finally, immunized chickens fed the MC-supplemented diet exhibited increased MHC class II(+), CD4(+), CD8(+), TCR1+, or TCR2(+) T cells compared with nonsupplemented controls. Animals on the VAC-containing diet only displayed an increase in K1(+) macrophages. In conclusion, dietary supplementation with VAC or MC alters immune parameters following recombinant protein vaccination against avian coccidiosis. Published by Elsevier B.V.

How T lymphocytes see antigen

Science.gov (United States)

Chakraborty, Arup K.

2009-03-01

Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (``on'' or ``off''), and how this molecular machinery coupled with frustration (a la spin glasses) plays a key role in designing the special properties of the T cell repertoire during development in the thymus.

Multispectral imaging for highly accurate analysis of tumour-infiltrating lymphocytes in primary melanoma

NARCIS (Netherlands)

Vasaturo, A.; Di Blasio, S.; Verweij, D.; Blokx, W.A.M.; Krieken, J.H.J.M. van; Vries, I.J.M. de; Figdor, C.G.

2017-01-01

AIMS: The quality and quantity of the infiltration of immune cells into tumour tissues have substantial impacts on patients' clinical outcomes, and are associated with response to immunotherapy. Therefore, the precise analysis of tumour-infiltrating lymphocytes (TILs) is becoming an important

Impairment of lymphocyte adhesion to cultured fibroblasts and endothelial cells by γ-irradiation

International Nuclear Information System (INIS)

Piela-Smith, T.H.; Aneiro, L.; Nuveen, E.; Korn, J.H.; Aune, T.

1992-01-01

A critical component of immune responsiveness is the localization of effector cells at sites of inflammatory lesions. Adhesive molecules that may play a role in this process have been described on the surfaces of both lymphocytes and connective tissue cells. Adhesive interactions of T lymphocytes with fibroblasts or endothelial cells can be inhibited by preincubation of the fibroblasts or endothelial cells with antibody to intercellular adhesion molecule 1 (CD54) or by preincubation of the T cells with antibody to lymphocyte function-associated Ag 1 (CD11a/CD18), molecules shown to be important in several other cell-cell adhesion interactions. Here the authors show that γ-irradiation of human T lymphocytes impaired their ability to adhere to both fibroblasts and endothelial cells. This impairment was not associated with a loss of cell viability or of cell surface lymphocyte function-associated Ag 1 expression. γ-Irradiation of T cells is known to result in the activation of ADP-ribosyltransferase, an enzyme involved in DNA strand-break repair, causing subsequent depletion of cellular nicotinamide adenine dinucleotide (NAD) pools by increasing NAD consumption for poly(ADP-ribose) formation. Preincubation of T cells with either nicotinamide or 3-aminobenzamide, both known inhibitors of ADP-ribosyltransferase, completely reversed the suppressive effects of γ-irradiation on T cell adhesion. The maintenance of adhesion was accompanied by inhibition of irradiation-induced depletion of cellular NAD. These experiments suggest that the impairment of cellular immune function after irradiation in vivo may be caused, in part, by defective T cell emigration and localization at inflammatory sites. 44 refs., 5 figs., 3 tabs

Combination approaches with immune checkpoint blockade in cancer therapy

Directory of Open Access Journals (Sweden)

Maarten Swart

2016-11-01

Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

Membrane receptors for very low density lipoprotein (VLDL) inhibitor of lymphocyte proliferation

International Nuclear Information System (INIS)

Yi, P.I.; Beck, G.; Zucker, S.

1981-01-01

Physiologic concentrations of human plasma very low density lipoproteins inhibit the DNA synthesis of lymphocytes stimulated by allogeneic cells or lectins. In this report reachers have compared the effects of isolated lipoproteins [very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)] and lipoprotein-depleted plasma (LDP) on DNA synthesis by phytohemagglutinin-stimulated human lymphocytes. The relative potency for the inhibition of lymphocyte proliferation was VLDL greater than LDL greater than HDL greater than LDP. Fifty percent inhibition of DNA synthesis was observed at a VLDL protein concentration of 1.5--2.0 microgram/ml. Researchers have further demonstrated the presence of specific receptors for VLDL on human lymphocytes. Native VLDL was more effective than LDL in competing for 125I-VLDL binding sites. Subsequent to binding to lymphocytes, 125I-VLDL was internalized and degraded to acid-soluble products. Based on a Scatchard analysis of VLDL binding at 4 degrees C, the number of VLDL receptors per lymphocyte was estimated at 28,000 +/- 1300. Based on an estimated mean binding affinity for the VLDL receptor complex at half saturation of approximately 8.8 X 10(7) liter/mole, it is estimated that 91% of lymphocyte VLDL receptors are occupied at physiologic VLDL concentrations in blood. Although the immune regulatory role of plasma lipoproteins is uncertain, researchers suggest tha VLDL and LDL-In may maintain circulating blood lymphocytes in a nonproliferative state via their respective cell receptor mechanisms

Suspected primary immune deficiency in a Donge de Bordeaux dog : short communication

Directory of Open Access Journals (Sweden)

R.G. Lobetti

2002-07-01

Full Text Available A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic responsive gastrointestinal and respiratory disease. Further evaluation showed bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers. As the dog came from a narrow genetic base, with related dogs showing similar clinical signs, possible B-cell congenital immune deficiency was suspected.

A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells

Directory of Open Access Journals (Sweden)

Brandon K. Hadland

2017-06-01

Full Text Available Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs. However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes.

Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

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Benjamin Arthurs, MD

2017-01-01

Full Text Available We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

T- and NK-cell populations with regulatory phenotype and markers of apoptosis in circulating lymphocytes of patients with CIN3 or microcarcinoma of the cervix: evidence for potential mechanisms of immune suppression.

Science.gov (United States)

Kurmyshkina, Olga V; Kovchur, Pavel I; Schegoleva, Ludmila V; Volkova, Tatyana O

2017-01-01

Processes and mechanisms responsible for systemic immune suppression in early-stage cervical cancer remain substantially underinvestigated. In this work, we focused on studying the frequencies of circulating regulatory T (CD4 and CD8 Tregs) and NK (NKregs) cells in parallel with assessment of apoptotic markers expression in T cells from patients with preinvasive and microinvasive cervical cancer, with the aim to determine whether up-regulation of apoptosis-associated markers in Т lymphocytes accompanies cervical cancer development and correlates with the change in percentages of regulatory cell populations at systemic level during the initial stages of invasive cervical cancer progression. Fourty two women with histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3, including carcinoma in situ) or cervical cancer (stage IA) and 30 healthy women (control) were enrolled in the study. Peripheral blood samples were taken immediately before surgery or any treatment and immediately subjected to multicolor flow cytometry. Analysis of a combination of CD4/CD8, CD25, CD127, and FoxP3 markers revealed a statistically significant increase in the frequencies of Tregs within both the CD4 and CD8 subsets of circulating lymphocytes in patients with CIN3 and stage IA cancer. In contrast, lower numbers of NKregs (defined as CD16 dim/neg CD56 bright subpopulation) and increased CD56 dim /CD56 bright NK ratio were found in patients compared to controls, with the percentage of CD16 bright CD56 dim cells (major subtype of circulating NKs) showing no difference. Patients also exhibited an increased expression of CD95 in total peripheral blood T lymphocytes, along with increased level of Annexin V binding to CD95-positive cells, suggesting higher susceptibility of T cells to apoptosis and potential involvement of CD95-dependent pathway in early-stage cervical cancer. Differential analysis of CD4 and CD8 T cells revealed different trends in the change of CD95

Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss)

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Hoeger, Birgit [Environmental Toxicology, University of Konstanz, P.O. Box X918, D-78457 Constance (Germany); Heuvel, Michael R. van den [Forest Research, Private Bag 3020, Sala St., Rotorua (New Zealand); Hitzfeld, Bettina C. [Swiss Agency for the Environment, Forests and Landscape (SAEFL), Substances, Soil, Biotechnology Division, Section Substances, 3003 Bern (Switzerland); Dietrich, Daniel R. [Environmental Toxicology, University of Konstanz, P.O. Box X918, D-78457 Constance (Germany)]. E-mail: daniel.dietrich@uni-konstanz.de

2004-12-20

In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune

Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss)

International Nuclear Information System (INIS)

Hoeger, Birgit; Heuvel, Michael R. van den; Hitzfeld, Bettina C.; Dietrich, Daniel R.

2004-01-01

In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune

AUTOIMMUNE CYTOPENIAS IN CHRONIC LYMPHOCYTIC LEUKEMIA, FACTS AND MYTHS

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Pavankumar Tandra

2013-11-01

Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

THE CHANGES IN SEMEN LYMPHOCYTE SUBPOPULATION’S RATIO IN MEN INFERTILITY

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A. V. Semenov

2007-01-01

Full Text Available Abstract. The aim of present study was to investigate the ratios of semen lymphocyte subpopulations in males with infertility. Twenty-six men (20 to 45 years old suffering from different genital diseases (chronic prostatitis, idiopathic varicocoele, testicular atrophy were enrolled into the study. Six healthy age-matched normozoospermic male volunteers with normal fertility comprised a control group. Lymphocyte phenotyping was performed by flow cytometric technique. The patients with pathospermia showed increased numbers of CD25+ lymphocytes (p < 0.05, and unchanged levels of CD95+ cells, thus leading to increased CD25+/CD95+ ratio. In the patients with normozoospermia, the value of this index was 0.94±0.18. Increase of this parameter to > 1.2, as well as its reduction to < 0.7 was associated with sterility. We suggest that suppressed apoptosis of activated lymphocytes in semen may be potentially dangerous to spermatogenesis, since both immune response and associated inflammatory reactions can cause nonspecific lesions of surrounding tissues, and induction of pathospermia.

Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast: friends or foes?

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Agahozo, Marie Colombe; Hammerl, Dora; Debets, Reno; Kok, Marleen; van Deurzen, Carolien H M

2018-02-20

In the past three decades, the detection rate of ductal carcinoma in situ of the breast has dramatically increased due to breast screening programs. As a consequence, about 20% of all breast cancer cases are detected in this early in situ stage. Some ductal carcinoma in situ cases will progress to invasive breast cancer, while other cases are likely to have an indolent biological behavior. The presence of tumor-infiltrating lymphocytes is seen as a promising prognostic and predictive marker in invasive breast cancer, mainly in HER2-positive and triple-negative subtypes. Here, we summarize the current understanding regarding immune infiltrates in invasive breast cancer and highlight recent observations regarding the presence and potential clinical significance of such immune infiltrates in patients with ductal carcinoma in situ. The presence of tumor-infiltrating lymphocytes, their numbers, composition, and potential relationship with genomic status will be discussed. Finally, we propose that a combination of genetic and immune markers may better stratify ductal carcinoma in situ subtypes with respect to tumor evolution.

Immune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma.

Science.gov (United States)

Schadendorf, Dirk; Nghiem, Paul; Bhatia, Shailender; Hauschild, Axel; Saiag, Philippe; Mahnke, Lisa; Hariharan, Subramanian; Kaufman, Howard L

2017-01-01

Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance. Unlike chemotherapy, treatment with anti-PD-L1 (avelumab) or anti-PD-1 (pembrolizumab) antibodies leads to durable responses in MCC, in both virus-positive and virus-negative tumors. As many tumors are established through the evasion of infiltrating immune-cell clearance, the lessons learned in MCC may be broadly relevant to many cancers.

Characterization of an adaptive immune response in microsatellite-instable colorectal cancer

Science.gov (United States)

Boissière-Michot, Florence; Lazennec, Gwendal; Frugier, Hélène; Jarlier, Marta; Roca, Lise; Duffour, Jacqueline; Du Paty, Emilie; Laune, Daniel; Blanchard, France; Le Pessot, Florence; Sabourin, Jean-Christophe; Bibeau, Frédéric

2014-01-01

Sporadic or hereditary colorectal cancer (CRC) with microsatellite instability (MSI) is frequently characterized by inflammatory lymphocytic infiltration and tends to be associated with a better outcome than microsatellite stable (MSS) CRC, probably reflecting a more effective immune response. We investigated inflammatory mechanisms in 48 MSI CRCs and 62 MSS CRCs by analyzing: (1) the expression of 48 cytokines using Bio-Plex multiplex cytokine assays, and (2) the in situ immune response by immunohistochemical analysis with antibodies against CD3 (T lymphocytes), CD8 (cytotoxic T lymphocytes), CD45RO (memory T lymphocytes), T-bet (Th1 CD4 cells), and FoxP3 (regulatory T cells). MSI CRC exhibited significantly higher expression of CCL5 (RANTES), CXCL8 (IL-8), CXCL9 (MIG), IL-1β, CXCL10 (IP-10), IL-16, CXCL1 (GROα), and IL-1ra, and lower expression of MIF, compared with MSS CRC. Immunohistochemistry combined with image analysis indicated that the density of CD3+, CD8+, CD45RO+, and T-bet+ T lymphocytes was higher in MSI CRC than in MSS CRC, whereas the number of regulatory T cells (FoxP3+) was not statistically different between the groups. These results indicate that MSI CRC is associated with a specific cytokine expression profile that includes CCL5, CXCL10, and CXCL9, which are involved in the T helper type 1 (Th1) response and in the recruitment of memory CD45RO+ T cells. Our findings highlight the major role of adaptive immunity in MSI CRC and provide a possible explanation for the more favorable prognosis of this CRC subtype. PMID:25101223

Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

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Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

2016-10-01

The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: relationship to S-100B levels and blood-brain barrier function.

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Gressner, Olav A; Schifflers, Marie-Claire; Kim, Philipp; Heuts, Leo; Lahme, Birgit; Gressner, Axel M

2009-02-01

Preliminary studies report on significantly higher levels of the major cytoskeleton protein actin in CSF of patients with neurodegenerative conditions and that the dynamics of these levels obviously correlates with disease progression and clinical disability. One of the primary functions of actinfree Gc-Globulin is to bind and neutralize extracellular monomeric actin, released into the circulation by necrotic or ruptured cells, and thus ameliorating the clinical outcome in situations of severe organ damage. This is the first study to investigate actinfree Gc-Globulin and S100-B levels (as reliable marker of neurodegeneration) in paired CSF and serum samples of patients with multietiological CNS diseases. 42% of all patients with CNS disease displayed serum concentrations of actinfree Gc-Globulin above the established reference range. CSF concentrations of actinfree Gc-Globulin and S100-B were positively correlated with the severity of blood-brain barrier (BBB) dysfunction. Furthermore, patients with severe BBB dysfunction presented a higher percentage of intrathecal synthesis of actinfree Gc-Globulin compared to patients with mild to moderate dysfunction and to patients with normal BBB function. Representative longitudinal data from selected patients demonstrated an inverse behaviour of actinfree Gc-Globulin and S100-B CSF concentrations, suggesting a consumption of the actin scavenger capacity of Gc-Globulin in times of increased neuronal damage. This presumption was supported by the fact that those conditions associated with a severe neuronal damage, in particular CNS trauma, and highest S100-B concentrations simultaneously displayed lowest actinfree Gc-Globulin levels, and thus residual actin binding capacity of Gc-Globulin. In summary, our data propose a function of actinfree Gc-Globulin also in the clearance of actin filaments from CSF of patients with neuronal damage. However, active recruitment of hepatic derived actinfree Gc-Globulin to the site of CNS

Effects of alcohol consumption on the allergen-specific immune response in mice

DEFF Research Database (Denmark)

Linneberg, Allan; Roursgaard, Martin; Hersoug, Lars-Georg

2008-01-01

There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization....

Effect of Smoking on Peripheral Blood Lymphocyte Subsets of Patients With Chronic Renal Failure.

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Düvenci Birben, Özlem; Akçay, Şule; Sezer, Siren; Şirvan, Şale; Haberal, Mehmet

2016-11-01

Smoking is known to suppress the immune system. It is also known that chronic renal failure affects the immune system. However, the number of studies investigating the effects of chronic renal failure and smoking together is limited. In our study, we examined whether smoking affects the diminished response of the immune system in patients with chronic renal failure. We compared peripheral blood lymphocyte subsets in smoking and nonsmoking patients with chronic renal failure. We also used the Fagerström Test for Nicotine Dependence to evaluate its correlation with the lymphocyte subset count in patients who are current smokers. Our study included 126 patients with chronic renal failure. According to their smoking habits, patients were divided into 2 groups: smokers and nonsmokers. The average age of patients who were smokers was 53.2 ± 1.5 years, with average age of nonsmokers being 59.2 ± 2.2 years. The average duration of smoking in smokers was 30.7 ± 2.7 packyears. We found that the percentage of cluster of differentiation 16-56 cells (natural killer cells) and lymphocyte percentage were significantly lower among smokers in our study (P chronic renal failure, similar to that shown in healthy smokers. According to our findings, patients with chronic renal failure, where infection is the primary reason for mortality and morbidity, must be questioned for smoking and referred to smoking cessation clinics. Because of its immunosuppressive effects, smoking behaviors must be solved preoperatively in transplant candidates.

T lymphocyte migration: an action movie starring the actin and associated actors

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Loïc eDupré

2015-11-01

Full Text Available The actin cytoskeleton is composed of a dynamic filament meshwork that builds the architecture of the cell to sustain its fundamental properties. This physical structure is characterized by a continuous remodeling, which allows cells to accomplish complex motility steps such as directed migration, crossing of biological barriers and interaction with other cells. T lymphocytes excel in these motility steps to ensure their immune surveillance duties. In particular, actin cytoskeleton remodeling is key to facilitate the journey of T lymphocytes through distinct tissue environments and to tune their stop and go behavior during the scanning of antigen-presenting cells. The molecular mechanisms controlling actin cytoskeleton remodeling during T lymphocyte motility have been only partially unraveled, since the function of many actin regulators has not yet been assessed in these cells. Our review aims to integrate the current knowledge into a comprehensive picture of how the actin cytoskeleton drives T lymphocyte migration. We will present the molecular actors that control actin cytoskeleton remodeling, as well as their role in the different T lymphocyte motile steps. We will also highlight which challenges remain to be addressed experimentally and which approaches appear promising to tackle them.

T Lymphocyte Migration: An Action Movie Starring the Actin and Associated Actors.

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Dupré, Loïc; Houmadi, Raïssa; Tang, Catherine; Rey-Barroso, Javier

2015-01-01

The actin cytoskeleton is composed of a dynamic filament meshwork that builds the architecture of the cell to sustain its fundamental properties. This physical structure is characterized by a continuous remodeling, which allows cells to accomplish complex motility steps such as directed migration, crossing of biological barriers, and interaction with other cells. T lymphocytes excel in these motility steps to ensure their immune surveillance duties. In particular, actin cytoskeleton remodeling is a key to facilitate the journey of T lymphocytes through distinct tissue environments and to tune their stop and go behavior during the scanning of antigen-presenting cells. The molecular mechanisms controlling actin cytoskeleton remodeling during T lymphocyte motility have been only partially unraveled, since the function of many actin regulators has not yet been assessed in these cells. Our review aims to integrate the current knowledge into a comprehensive picture of how the actin cytoskeleton drives T lymphocyte migration. We will present the molecular actors that control actin cytoskeleton remodeling, as well as their role in the different T lymphocyte motile steps. We will also highlight which challenges remain to be addressed experimentally and which approaches appear promising to tackle them.

Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

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Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

1989-06-01

Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

Growth performance, immune status and organ morphometry in ...

African Journals Online (AJOL)

MyUserName

2017-04-28

Apr 28, 2017 ... morphology of lymphoid organs and gut mucosa in broilers. ... mucosae, the dendritic cells present these fragments to T and B lymphocytes in the ...... Probiotics in valorization of innate immunity across various animal models.

6. THE ROLE OF SELENIUM IN HUMAN IMMUNITY

African Journals Online (AJOL)

Esem

lymphocyte (CD3+) immune response was enhanced in persons that ... Selenium and Disease Conditions ... In China, Keshan and Kashin-Beck diseases are human. 21,22,23 ... and cytotoxic cell activities that act against the HIV virus.

In vitro measles virus infection of human lymphocyte subsets demonstrates high susceptibility and permissiveness of both naive and memory B cells

NARCIS (Netherlands)

B.M. Laksono (Brigitta); C. Grosserichter-Wagener (Christina); R.D. de Vries (Rory); Langeveld, S.A.G. (Simone A.G.); M.D. Brem (Maarten); J.J.M. van Dongen (Jacques); Katsikis, P.D. (Peter D.); M.P.G. Koopmans D.V.M. (Marion); M.C. van Zelm (Menno); R.L. de Swart (Rik)

2018-01-01

textabstractMeasles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and

Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

Science.gov (United States)

Shi, Yufang

Space radiation, composed of high-energy charged nuclei (HZE particles) and protons, has been previously shown to severely impact immune homeostasis in mice. To determine the molecular mechanisms that mediate acute lymphocyte depletion following exposure to HZE particle radiation mice were exposed to particle radiation beams at Brookhaven National Laboratory. We found that mice given whole body 5 6Fe particle irradiation (1GeV /n) had dose-dependent losses in total lymphocyte numbers in the spleen and thymus (using 200, 100 and 50 cGy), with thymocytes being more sensitive than splenocytes. All phenotypic subsets were reduced in number. In general, T cells and B cells were equally sensitive, while CD8+ T cells were more senstive than CD4+ T cells. In the thymus, immature CD4+CD8+ double-positive thymocytes were exquisitely sensitive to radiation-induced losses, single-positive CD4 or CD8 cells were less sensitive, and the least mature double negative cells were resistant. Irradiation of mice deficient in genes encoding essential apoptosis-inducing proteins revealed that the mechanism of lymphocyte depletion is independent of Fas ligand and TRAIL (TNF-ralated apoptosis-inducing ligand), in contrast to γ-radiation-induced lymphocyte losses which require the Fas-FasL pathway. Using inhibitors in vitro, lymphocyte apoptosis induced by HZE particle radiation was found to be caspase dependent, and not involve nitric oxide or oxygen free radicals.

Cell mediated immunity in patients with osteosarcoma

International Nuclear Information System (INIS)

Lloyd, E.L.; Henning, C.B.

1975-01-01

Because of the difficulty of obtaining suitable material, earlier studies on cell mediated immunity in the radium patients failed to include positive controls. Recently we were fortunate in obtaining samples of lymphocytes from two suitable patients who had had amputations for spontaneous osteosarcoma six months previously. Lymphocytes from both of these patients showed cytotoxicity to cultured cells derived from a human osteogenic sarcoma but not to normal fibroblasts. These results help to validate our test for early detection of osteosarcoma in the radium patients using measurements of cytotoxicity

Kidney and innate immunity.

Science.gov (United States)

Wang, Ying-Hui; Zhang, Yu-Gen

2017-03-01

Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

REGULATORY T-CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA

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Giovanni D'arena

2012-08-01

Full Text Available Regulatory T-cells (Tregs constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL. Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosis, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in either cancer and autoimmune disorders.

T lymphocyte subsets in prostate cancer subjects in south eastern ...

African Journals Online (AJOL)

Humoral and cellular mechanisms play roles in immune response to foreign antigens. The present study was designed to determine the T lymphocyte subsets (CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) in the prostate cancer subjects and control subjects. CD4 + T cells (`l/count) and CD8 + T cells (`l/count) were ...

Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia.

Science.gov (United States)

Pleyer, Christopher; Wiestner, Adrian; Sun, Clare

2018-05-15

Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib. While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents. This review discusses the impact of ibrutinib and idelalisib on the immune system, including infectious and auto-immune complications as well as their specific effects on the B-cell, T-cell, and myeloid compartment.

Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

Science.gov (United States)

Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-09-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

[Comparison of two types of antithymocyte globulin in the treatment of children with aplastic anemia].

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Xie, X T; He, W; Shi, W; Zhou, X X; Qiao, X H

2016-04-01

This study was designed to compare the effects of the anti-human T lymphocyte globulin (Fresenius, ATG-F)and rabbit anti-human thymocyte immunoglobulin (Genzyme, R-ATG)in the treatment of childhood aplastic anemia (AA) and their effects. A total of 59 children with aplastic anemia were analyzed in the present study, including 34 cases of severe aplastic anemia (SAA), 12 cases of very severe aplastic anemia (VSAA) and 13 cases of transfusion-dependent non-severe aplastic anemia (NSAA). While receiving immunosuppressive therapy (IST), 30 and 29 patients, with long-term oral supplement with cyclosporin A (CSA), androgen and Chinese traditional medicines, were treated with ATG-F and R-ATG, respectively. When it was necessary, some supportive cares such as component transfusion and infection control were also employed. Absolute counts of peripheral blood lymphocyte (ALC) at various time points were dynamically detected after ATG therapy. According to the International Aplastic Anemia Treatment and Effect standards. There were no statistically significant differences in the overall response rate (67%(20/30)vs. 69%(20/29), χ(2)=0.036, P=0.676) and the survival rate (87%(26/30)vs. 83%(24/29), χ(2)=0.173, P=0.676) between the ATG-F and R-ATG groups. There were significant and long-term ALC decrease after ATG therapy, the rate of ALC decrease in ATG-F and R-ATG group, the ALC only recovered to 47.8% (ATG-F group) and 47.4% (R-ATG group) of the pre-treatment level respectively. ATG-F 5 mg/(kg·d) and R-ATG 3.75 mg/(kg·d)could achieve similar effects in the treatment of childhood AA, through similar significant clearance of T cells. Therefore, all of these suggest that ATG-F and R-ATG might serve as the drugs of front-line choice for IST in childhood AA patients who do not have an available human leukocyte antigen identical related donor.

INFLUENCE OF MODIFIED BIOFLAVONOIDS UPON EFFECTOR LYMPHOCYTES IN MURINE MODEL OF CONTACT SENSITIVITY

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D. Z. Albegova

2015-01-01

Full Text Available Contact sensitivity reaction (CSR to 2,4-dinitrofluorobenzene (DNFB in mice is a model of in vivo immune response, being an experimental analogue to contact dermatitis in humans. CSR sensitization phase begins after primary contact with antigen, lasting for 10-15 days in humans, and 5-7 days, in mice. Repeated skin exposure to the sensitizing substance leads to its recognition and triggering immune inflammatory mechanisms involving DNFB-specific effector T lymphocytes. The CSR reaches its maximum 18-48 hours after re-exposure to a hapten. There is only scarce information in the literature about effects of flavonoids on CSR, including both stimulatory and inhibitory effects. Flavonoids possessed, predominantly, suppressive effects against the CSR development. In our laboratory, a model of contact sensitivity was reproduced in CBA mice by means of cutaneous sensitization by 2,4-dinitrofluorobenzene. The aim of the study was to identify the mechanisms of immunomodulatory action of quercetin dihydrate and modified bioflavonoids, using the method of adoptive transfer contact sensitivity by splenocytes and T-lymphocytes. As shown in our studies, a 30-min pre-treatment of splenocytes and T-lymphocytes from sensitized mice with modified bioflavonoids before the cell transfer caused complete prevention of contact sensitivity reaction in syngeneic recipient mice. Meanwhile, this effect was not associated with cell death induction due to apoptosis or cytotoxicity. Quercetin dihydrate caused only partially suppression the activity of adaptively formed T-lymphocytes, the contact sensitivity effectors. It was shown that the modified bioflavonoid more stronger suppress adoptive transfer of contact sensitivity in comparison with quercetin dehydrate, without inducing apoptosis of effector cells. Thus, the modified bioflavonoid is a promising compound for further studies in a model of contact sensitivity, due to its higher ability to suppress transfer of CSR with

PHENOTYPIC PROFILE OF B-LYMPHOCYTES IN WOMEN WITH CHRONIC ENDOMETRITIS AND ADNEXITIS

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A. A. Savchenko

2016-01-01

Full Text Available The aim of this study was to investigate phenotypic profile of B lymphocytes in peripheral blood of the patients with chronic endometritis and adnexitis. The study involved 89 women in their reproductive age (18 to 45 years with chronic endometritis (48 cases and adnexitis (41 cases. Ninety-eight healthy agematched women participated as a control group. Phenotypic B-cell subpopulations were analyzed by flow cytometry performed with direct immunofluorescent staining of peripheral cells from whole blood using the following antibody panel: CD5-FITC/CD23-PE/CD19-ECD/CD45-PC5/CD27-PC7. A significantly reduced B-lymphocyte content was revealed in peripheral blood of women with chronic endometritis and adnexitis. The reduced cell numbers occurred due to reduced B2 (main fraction of B-lymphocytes and as B1 cells (minor fraction which determines insufficient reactivity of specific humoral immune response, including immune reactions at the mucous membranes. However, percentage of B2-lymphocytes was decreased only in endometriosis, whereas patients with adnexitis showed decrease in both relative and absolute counts of this B cell subpopulation. A decreased content of naive B-cells in the peripheral blood is another feature of the B cell phenotypic profile in chronic endometritis and adnexitis. Moreover, the drop of the naive B-cell levels in patients with adnexitis proved to be more pronounced than in persons with endometritis. Expression of CD23- antigen (a low-affinity receptor for IgE has been investigated as a functional marker of B cells. All the studied peripheral B cell subpopulations expressing CD23 were decreased in the patients with chronic endometritis. The numbers of different B cell fractions expressing CD23 antigen were also reduced in the women with chronic adnexitis as compared to the levels detected in patients with chronic endometritis. Alterations of the B-cell immunity were more pronounced in chronic adnexitis, due to more extensive

Specific proliferative response of human lymphocytes to purified soluble antigens from Plasmodium falciparum in vitro cultures and to antigens from malaria patients' sera

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Bygbjerg, I C; Jepsen, S; Theander, T G

1985-01-01

Antigens of Plasmodium falciparum, in supernatants of in vitro cultures of the parasite were affinity purified on columns prepared with the IgG fraction of the serum of an immune individual. The purified antigens induced proliferation of lymphocytes from persons who had recently had malaria....... The responses were strongest with lymphocytes from individuals infected with falciparum and ovale malaria; vivax malaria infections induced a lower level of response and lymphocytes of unsensitized individuals were little affected. Lymphocytes from unsensitized individuals did not respond to the affinity...

Mucosal immunity and B cells in teleosts: effect of vaccination and stress.

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David eParra

2015-07-01

Full Text Available Fish are subjected to several insults from the environment, which may endanger animal survival. Mucosal surfaces are the first line of defense against those threats and they act as a physical barrier to protect the animal but also function as immunologically active tissues. Thus, four mucosal-associated lymphoid tissues have been described in fish, which lead the immune responses in gut, skin, gills and nose. Humoral and cellular immunity, as well as its regulation and the factors that influence the response in these mucosal lymphoid tissues is still not well known in most of fish species. Mucosal B-lymphocytes and immunoglobulins (Igs are one of the key players in the immune response after vaccination. Recent findings about IgT in trout have delimited the compartmentalization of immune response in systemic and mucosal. The existence of IgT as a specialized mucosa Ig gives us the opportunity of measuring mucosal specific responses after vaccination, a fact that was not possible until recently in most of the fish species. Vaccination process is influenced by several factors, being stress one of the main stimuli determining the success of the vaccine. Thus, one of the major goals in a vaccination process is to avoid possible situations of stress, which might interfere with fish immune performance. However, the interaction between immune and neuroendocrine systems at mucosal tissues is still unknown. In this review we will summarized the latest findings about B-lymphocytes and immunoglobulins in mucosal immunity and the effect of stress and vaccines on B cell response at mucosal sites. It is important to point out that a small number of studies have been published regarding mucosal stress and very few about the influence of stress over mucosal B-lymphocytes.

THE EFFECTS OF COPPER AND ZINC IONS DURING THEIR BINDING WITH HUMAN SERUM γ-GLOBULIN

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S. B. Cheknev

2006-01-01

Full Text Available Abstract. Conformational changes of human serum γ-globulin were studied during and after its binding with copper and zinc ions, using molecular ultrafiltration and differential spectrophotometry. The contents of nonbound metals in the filtrate were evaluated, resp., with sodium diethyl thyocarbamate and o-phenanthroline. It has been shown that copper and zinc exhibited common biological properties during their interactions with protein, but the binding differed sufficiently under similar experimental conditions. E.g., it was confirmed that copper was more active at the external sites of γ-globulin molecule, whereas zinc demonstrated tropicity for the areas of protein intraglobular compartments. The metal-binding sites have been described that differ in their parameters of interactions with cations and their spatial location within globular domains. Approaches are suggested for dynamic analysis of saturation for these differently located sites by the metal ions. We discuss the issues of altered conformational state of the γ-globulin molecule during the binding of cations, as well as potential usage of these data in clinical immunology.

Functional disorders of T-cell immunity at persons engaged in the Chernobyl emergency operations in a 10 years after the accident

International Nuclear Information System (INIS)

Potapnev, M.P.; Kuz'menok, O.I.; Potapova, S.M.; Smol'nikova, V.V.; Myslitskj, V.F.; Rzheutskij, V.A.; Vaslevskaya, T.A.; Vasyukhina, L.V.

1998-01-01

Functional disorders of T-cell immunity in persons engaged in Chernobyl emergency operations - 10 years after the accident. The results evaluating T-cell immunity of 148 liquidators of Chernobyl accident are presented. It was estimated that 10 years after the accident immuno phenotyping of peripheral blood lymphocytes did not reveal marked disturbance in lymphocyte subpopulation content in exposed group as compared with healthy control. Determination of cell proliferation in vitro indicated the decrease in DNA synthesis of T-lymphocytes stimulated with optimal and particularly suboptimal concentrations of polyclonal T-cell activators. Based on individual deviation of the results of T-lymphocyte proliferation the groups with high and low level of response were sorted out for future examination

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocytes: A Review of the Literature.

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Pala, Ozlem; Diaz, Alain; Blomberg, Bonnie B; Frasca, Daniela

2018-05-22

responses to vaccination. B lymphocytes play a significant role in the pathogenesis of rheumatoid arthritis, and B cell-depletion therapy has a major effect on the course of the disease. The advances in treatment of rheumatoid arthritis include the development of targeted therapies. Anti-TNF-α therapies are widely used despite potentially serious adverse events. The data on the effects of anti-TNF-α therapies on B lymphocytes are limited and conflicting. There is a need for larger studies to better understand the effects of newly discovered therapies on the different cells of the immune system. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Ex vivo cytosolic delivery of functional macromolecules to immune cells.

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Armon Sharei

Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

Protection against rat vaginal candidiasis by adoptive transfer of vaginal B lymphocytes.

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De Bernardis, Flavia; Santoni, Giorgio; Boccanera, Maria; Lucciarini, Roberta; Arancia, Silvia; Sandini, Silvia; Amantini, Consuelo; Cassone, Antonio

2010-06-01

Vulvovaginal candidiasis is a mucosal infection affecting many women, but the immune mechanisms operating against Candida albicans at the mucosal level remain unknown. A rat model was employed to further characterize the contribution of B and T cells to anti-Candida vaginal protection. Particularly, the protective role of vaginal B cells was studied by means of adoptive transfer of vaginal CD3(-) CD5(+) IgM(+) cells from Candida-immunized rats to naïve animals. This passive transfer of B cells resulted into a number of vaginal C. albicans CFU approximately 50% lower than their controls. Sorted CD3(-) CD5(+) IgM(+) vaginal B lymphocytes from Candida-infected rats proliferated in response to stimulation with an immunodominant mannoprotein (MP) antigen of the fungus. Importantly, anti-MP antibodies and antibody-secreting B cells were detected in the supernatant and cell cultures, respectively, of vaginal B lymphocytes from infected rats incubated in vitro with vaginal T cells and stimulated with MP. No such specific antibodies were found when using vaginal B cells from uninfected rats. Furthermore, inflammatory and anti-inflammatory cytokines, such as interleukin-2 (IL-2), IL-6 and IL-10, were found in the supernatant of vaginal B cells from infected rats. These data are evidence of a partial anti-Candida protective role of CD3(-) CD5(+) IgM(+) vaginal B lymphocytes in our experimental model.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

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Miró, Lluïsa; Garcia-Just, Alba; Amat, Concepció; Polo, Javier; Moretó, Miquel; Pérez-Bosque, Anna

2017-12-11

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

Evidence for a common mucosal immune system in the pig.

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Wilson, Heather L; Obradovic, Milan R

2015-07-01

The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Protein chemical characterization of Gc globulin (vitamin D-binding protein) isoforms; Gc-1f, Gc-1s and Gc-2

DEFF Research Database (Denmark)

Christiansen, Maja; Jørgensen, Charlotte S; Laursen, Inga

2007-01-01

-survival of patients with fulminant hepatic failure and trauma. Here, we characterize the dominant isoforms of plasma-derived Gc globulin from Cohn fraction IV paste with respect to amino acid sequence and posttranslational modifications. Gc globulin was purified in large scale and the isoforms separated by ion...

Associations of Circulating Lymphocyte Subpopulations with Type 2 Diabetes: Cross-Sectional Results from the Multi-Ethnic Study of Atherosclerosis (MESA.

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Nels C Olson

Full Text Available Distinct lymphocyte subpopulations have been implicated in the regulation of glucose homeostasis and obesity-associated inflammation in mouse models of insulin resistance. Information on the relationships of lymphocyte subpopulations with type 2 diabetes remain limited in human population-based cohort studies.Circulating levels of innate (γδ T, natural killer (NK and adaptive immune (CD4+ naive, CD4+ memory, Th1, and Th2 lymphocyte subpopulations were measured by flow cytometry in the peripheral blood of 929 free-living participants of the Multi-Ethnic Study of Atherosclerosis (MESA. Cross-sectional relationships of lymphocyte subpopulations with type 2 diabetes (n = 154 and fasting glucose and insulin concentrations were evaluated by generalized linear models.Each standard deviation (SD higher CD4+ memory cells was associated with a 21% higher odds of type 2 diabetes (95% CI: 1-47% and each SD higher naive cells was associated with a 22% lower odds (95% CI: 4-36% (adjusted for age, gender, race/ethnicity, and BMI. Among participants not using diabetes medication, higher memory and lower naive CD4+ cells were associated with higher fasting glucose concentrations (p<0.05, adjusted for age, sex, and race/ethnicity. There were no associations of γδ T, NK, Th1, or Th2 cells with type 2 diabetes, glucose, or insulin.A higher degree of chronic adaptive immune activation, reflected by higher memory and lower naive CD4+ cells, was positively associated with type 2 diabetes. These results are consistent with a role of chronic immune activation and exhaustion augmenting chronic inflammatory diseases, and support the importance of prospective studies evaluating adaptive immune activation and type 2 diabetes.

Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

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Petrás, G; Kiss, S; Juraszek, J; Merétey, K

1978-01-01

The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

The emergence of neurotransmitters as immune modulators.

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Franco, Rafael; Pacheco, Rodrigo; Lluis, Carmen; Ahern, Gerard P; O'Connell, Peta J

2007-09-01

Initially, the idea that neurotransmitters could serve as immunomodulators emerged with the discovery that their release and diffusion from nervous tissue could lead to signaling through lymphocyte cell-surface receptors and the modulation of immune function. It is now evident that neurotransmitters can also be released from leukocytes and act as autocrine or paracrine modulators. Here, we review the data indicating that leukocytes synthesize and release 'neurotransmitters' and we also discuss the diverse effects that these compounds exert in a variety of immune cells. The role of neurotransmitters in immune-related diseases is also reviewed succinctly. Current and future developments in understanding the cross-talk between the immune and nervous systems will probably identify new avenues for treating immune-mediated diseases using agonists or antagonists of neurotransmitter receptors.

Preliminary studies of the effects of psychological stress on circulating lymphocytes analyzed by synchrotron radiation based-Fourier transform infrared microspectroscopy

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Vargas-Caraveo, Alejandra; Castillo-Michel, Hiram; Mejia-Carmona, Gloria Erika; Pérez-Ishiwara, David Guillermo; Cotte, Marine; Martínez-Martínez, Alejandro

2014-07-01

Psychological stress is a condition that not only generates behavioral disorders but also disrupts homeostasis and immune activity that can exacerbate or lead to inflammatory diseases. The aim of this work was to study biochemical changes in circulating immune cells from rats under psychological stress by using vibrational spectroscopy. A stress model was used, where exposure to a stressor was repeated for 5 days. Subsequently, circulating lymphocytes were examined for their biomolecular vibrational fingerprints with synchrotron radiation based-Fourier transform infrared microspectroscopy. The results showed an increased absorption at the ester lipid region (1720-1755 cm-1) in lymphocytes from stressed rats, suggesting lipid peroxidation. Statistical significant changes in wavenumber peak position and absorbance in the nucleic acid region were also observed (915-950 cm-1 Z-DNA, 1090-1150 cm-1 symmetric stretching of Psbnd Osbnd C, 1200-1260 cm-1 asymmetric PO2 and 1570-1510 cm-1 methylated nucleotides) which suggest a reduction of transcriptional activity in lymphocytes from stressed rat. These results unravel part of the mechanisms by which psychological stress may affect the immune system leading to systemic consequences.

A three-dimensional approach to in vitro culture of immune-related cells

DEFF Research Database (Denmark)

Hartmann, Sofie Bruun

setups for improved activation/differentiation of immune cells. Conclusively, this work highlights the importance of acknowledging the effect from external factors when analyzing data generated from in vitro cultures. This being even more important when working with immune cells since these cells adopt......T lymphocytes are key players during the initiation of an adaptive immune response. The activation of these cells in vivo requires migration within the lymph nodes until they encounter antigen presenting cells (APCs) that can activate them to secrete IFN-γ which mediates downstream effector...... functions. The in vitro reactivation of antigen-experienced T lymphocytes and detection of IFN-γ from cell cultures can be used in a diagnostic assay to test for disease or vaccine efficacy. Practical procedures of the IFN-γ release assay (IGRA) was investigated using bovine cells and whole blood cultures...

Changes in nonspecific immune parameters during radiation therapy

International Nuclear Information System (INIS)

Fukasawa, Hiroyuki; Okamoto, Mie; Narushima, Masaaki; Nakamura, Kiyoshi

1986-01-01

The effects of radiation on cellular immunity were examined in 7 patients with squamous cell carcinoma of the uterine cervix. Peripheral lymphocyte count decreased by 67 % in patients of stage I or II, and by 74 % in a patient of stage III or a relapsing patient. At the time of completion of irradiation with 48.6 Gy, the counts of T lymphocytes, B lymphocytes, T4+ lymphocytes, and T8+ lymphocytes decreased by 67 %, 93 %, 74 %, and 68 %, respectively. There was no consistent tendency for the OKT4+/OKT8+, peripheral natural killer cell (NK) activity, and serum levels of IgG. Serum levels of immunosuppresive acidic protein (IAP) increased in one patient of stage I, and decreased in two patients of stage I and two of stage II. In a patient of stage III, it decreased with radiation. In a relapsing patient, a decrease in serum IAP was not associated with radiation. There was a slight negative correlation between serum IAP levels and NK activity and PPD skin reactin, while there was a slight positive correlation between PHA skin reaction and T lymphocyte count and NK activity. (Namekawa, K.)

The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

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Dyah Ayu Hewajuli

2015-09-01

Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

Studies on a possible using of penicillin and specific globulin for treatment of Siberia ulcer infection in irradiated animals

International Nuclear Information System (INIS)

Strel'nikov, V.A.; Mal'tsev, V.N.

1975-01-01

The efficiency of anti-anthracic globulin and penicillin for treating infectious anthrax was compared in experiments on 160 guinea pigs and 400 white mice irradiated with sub-lethal doses of cobalt-60 gamma rays. It was found that penicillin retained its effectiveness in the irradiated animals whereas anti-anthracic globulin lost much of its therapeutic efficiency. (auth.)

A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells.

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Hadland, Brandon K; Varnum-Finney, Barbara; Mandal, Pankaj K; Rossi, Derrick J; Poulos, Michael G; Butler, Jason M; Rafii, Shahin; Yoder, Mervin C; Yoshimoto, Momoko; Bernstein, Irwin D

2017-06-06

Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A mechanism for trauma induced muscle wasting and immune dysfunction

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Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

Effect of Scoparia dulcis on noise stress induced adaptive immunity and cytokine response in immunized Wistar rats.

Science.gov (United States)

Sundareswaran, Loganathan; Srinivasan, Sakthivel; Wankhar, Wankupar; Sheeladevi, Rathinasamy

Noise acts as a stressor and is reported to have impact on individual health depending on nature, type, intensity and perception. Modern medicine has no effective drugs or cure to prevent its consequences. Being an environmental stressor noise cannot be avoided; instead minimizing its exposure or consuming anti-stressor and adaptogens from plants can be considered. The present study was carried out to evaluate the anti-stressor, adaptogen and immunostimulatory activity of Scoparia dulcis against noise-induced stress in Wistar rat models. Noise stress in rats was created by broadband white noise generator, 100 dB A/4 h daily/15 days and S. dulcis (200 mg/kg b.w.) was administered orally. 8 groups of rats were used consisting of 6 animals each; 4 groups for unimmunized and 4 groups for immunized. For immunization, sheep red blood cells (5 × 10 9  cells/ml) were injected intraperitoneally. Sub-acute noise exposed rats showed a significant increase in corticosterone and IL-4 levels in both immunized and unimmunized rats whereas lymphocytes, antibody titration, soluble immune complex, IL-4 showed a marked increase with a significant decrease in IL-2, TNF-α, IFN-γ cytokines only in unimmunized rats. Immunized noise exposed rats presented increased leukocyte migration index and decreased foot pad thickness, IL-2, TNF-α, IFN-γ with no changes in the lymphocytes. S. dulcis (SD) has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung's Disease.

Directory of Open Access Journals (Sweden)

Ankush Gosain

Full Text Available Hirschsprung's disease (HSCR is characterized by aganglionosis from failure of neural crest cell (NCC migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC, with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/- resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P 21-24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer's Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer's Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted

Involvement of T- and B-lymphocytes in the immune response to the protein exotoxin and the lipopolysaccharide antigens of Vibrio cholerae

International Nuclear Information System (INIS)

Kateley, J.R.; Patel, C.B.; Friedman, H.

1975-01-01

The immune response at the level of individual immunocytes to the somatic lipopolysaccharide antigen derived from whole Vibrio cholerae and to the purified protein exotoxin from this organism were studied in terms of the role of T- and B-lymphocytes. By adoptive cell transfer studies with irradiated recipient mice, it was shown that normal spleen cells from normal syngeneic mice could readily transfer the capability of responding to both types of cholera antigens. However, when the spleen cells were depleted of T-cells with anti-theta serum and complement, antibody responsiveness to the LPS antigen, but not the exotoxin, could be achieved in recipients. Furthermore, by appropriate transfer of either bone marrow, thymus, or thymus-marrow cell mixtures to irradiated mice, it was shown that the response to the cholera somatic antigen was relatively independent of thymus cells, whereas the response to exotoxin required ''helper'' T-cells

Apoptosis in fatal Ebola infection. Does the virus toll the bell for immune system?

Science.gov (United States)

Baize, S; Leroy, E M; Mavoungou, E; Fisher-Hoch, S P

2000-02-01

In fatal Ebola virus hemorrhagic fever massive intravascular apoptosis develops rapidly following infection and progressing relentlessly until death. While data suggest that T lymphocytes are mainly deleted by apoptosis in PBMC of human fatal cases, experimental Ebola infection in animal models have shown some evidence of destruction of lymphocytes in spleen and lymph nodes probably involving both T and B cells. Nevertheless, we are able to conclude from the accumulated evidence that early interactions between Ebola virus and the immune system, probably via macrophages, main targets for viral replication, lead to massive destruction of immune cells in fatal cases.

Impact of carbon nanotubes and graphene on immune cells

Science.gov (United States)

2014-01-01

It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine. PMID:24885781

Impact of carbon nanotubes and graphene on immune cells.

Science.gov (United States)

Orecchioni, Marco; Bedognetti, Davide; Sgarrella, Francesco; Marincola, Francesco M; Bianco, Alberto; Delogu, Lucia Gemma

2014-05-21

It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.

Autocine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin

National Research Council Canada - National Science Library

Rosner, William

2004-01-01

We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and this SHBG functions to alter the effects of estrogens within the breast cancer cell...

Radioimmunotoxicological effect of enriched uranium on central and peripheral immune cells and the protective action of IL-1 and IL-2

International Nuclear Information System (INIS)

Zhu Shoupeng; Lai Guanhua; Wang Liuyi

1993-01-01

With accumulation of enriched uranium 235 U-UO 2 F 2 in organism, it was found that enriched uranium had injurious effect on the immune function of central and peripheral immune cells. After intravenous injection of enriched uranium the spontaneous 3 H-TdR incorporation in thymocytes and bone marrow cells decreased. Though the sensitivity of immune cells to 235 U-UO 2 F 2 was different, the thymocytes were destroyed more markedly. Also the proliferation ability of T and B lymphocytes were both inhibited by enriched uranium 235 U. As compared with them, spleen B lymphocytes were inhibited more markedly than T lymphocytes. At the same time spleen lymphocytes IL-1 production and IL 2 consumption were diminished. It should be noted that the inhibition of spleen B lymphocytes proliferation by enriched uranium 235 U-UO 2 F 2 was partially restored by exogenous IL-1 or IL-2. The recovery rate of protective action at the very most was 67.1 +- 11.2% with exogenous IL-1 and 50.2 +- 8.0% with IL-2. Moreover, both exogenous IL-1 and IL-2 had synergetic effect, and the recovery rate was elevated to 83.1 +-12.3%

Radiotherapy and immune checkpoint blockades: a snapshot in 2016

Energy Technology Data Exchange (ETDEWEB)

Koo, Tae Yool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2016-12-15

Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

Centers for Disease Control (CDC) Podcasts

2007-05-16

Three organ transplant recipients died from infection with lymphocytic choriomeningitis virus (LCMV), which was traced back to a hamster owned by the daughter of the organ donor. Dr. Brian Amman, a mammalogist with the Special Pathogens Branch at CDC, discusses the dangers LCMV may pose to people with immune disorders, as well as to pregnant women.  Created: 5/16/2007 by CDC, Office of the Director.   Date Released: 5/16/2007.

The effects of phototherapy on the numbers of circulating natural killer cells and T lymphocytes in psoriasis.

LENUS (Irish Health Repository)

Tobin, A M

2009-04-01

The innate immune system is believed to be important in the pathogenesis of psoriasis and natural killer (NK) have been found in increased numbers in psoriatic plaques. Alterations in the numbers of NK cells in peripheral blood have been reported. We investigated the effect of phototherapy on levels of peripheral NK cells and lymphocytes in patients with psoriasis. In nine patients whom we followed before, during and after narrowband ultraviolet B (UVB) treatment there were no differences in the numbers of circulating lymphocytes, lymphocyte subsets or cells expressing NK markers and controls. Treatment with narrowband UVB did, however, significantly lower circulating CD4 counts which gradually recovered posttreatment.

Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation.

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Rodriguez-Lara, Vianey; Muñiz-Rivera Cambas, Angelica; González Villalva, Adriana; Fortoul, Teresa I

2016-07-01

Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V2O5) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis.

Bestatin treatment enhances the recovery of radiation induced impairments of the immunological reactivity of the blood lymphocyte population in bladder cancer patients

International Nuclear Information System (INIS)

Blomgren, H.; Edsmyr, F.; Stedingk, L.V. von; Wasserman, J.

1986-01-01

Bestatin, an immunostimulating substance of microbial origin, was examined for its capacity to augment immune responses of blood lymphocytes in bladder cancer patients having received a full course of local irradiation (64 Gy). Following irradiation the patients became lymphopenic and the lymphocytes exhibited impaired mitogenic responses to phytohemagglutinin (PHA) and purified protein derivative of tuberculin (PPD) and reduced poke weed mitogen induced secretion of immunoglobulins in vitro. Patients who were randomized to receive daily oral Bestatin treatment exhibited enhanced recoveries of PHA- and PPD- responses and enhanced recovery of the IgM secreting capacity compared to irradiated patients who did not receive Bestatin. Repopulation of the blood lymphocyte population, however, was not enhanced by Bestatin treatment. It is concluded that Bestatin treatment may enhance the recovery of radiation induced functional defects of the immune system in cancer patients

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...

Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin

National Research Council Canada - National Science Library

Rosner, Wiliam

2003-01-01

We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and that this SHBG functions to alter the effects of estrogens within the breast cancer cell...

Increased sex hormone-binding globulin levels in children and adolescents with thyrotoxicosis

DEFF Research Database (Denmark)

Nielsen, J; Jensen, Rikke Bodin Beck; Juul, Anders

2013-01-01

Thyrotoxicosis is a rare condition in pediatric patients, and optimal treatment can be difficult to achieve in some children. To our knowledge, no studies have evaluated sex hormone-binding globulin (SHBG) levels in hyperthyroid children and adolescents in relation to age- and gender...

The measurement of cell mediated immunity by radioimmunoassay in desensitizing treatment with acupoints for allergic asthma

International Nuclear Information System (INIS)

Zhou Ronglin; Luan Meiling; Wang Mingsuo; Liu Keliang

1994-05-01

Three mitogens consisted of PHA, PWM, LPS were used to activate lymphocytes. Lymphocyte transformation with radioisotope incorporation of 3 H-TdR was done in 20 patients with allergic asthma and 14 healthy persons as control groups. Cell mediated immune in these cases of desensitizing treatment with acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, activated by PHA, PWM, LPS, of the allergic asthma patients were P>0.05, P 3 H-TdR in lymphocytes after desensitizing treatment with acupoints compared with that before the treatment tended to be normal. Lymphocyte transformation difference of 3 H-TdR incorporation rates between this group and A or B control groups was significant (P<0.01). This study provides scientific clinical experimental evidences for researching cell mediated immune in attack and curative effects of allergic asthma

Evaluation of local immune response to Fasciola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigen

Directory of Open Access Journals (Sweden)

Ricardo E Mendes

2010-08-01

Full Text Available Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14 was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN. The goats used consisted of group 1 (unimmunized and uninfected, group 2 [infected control - immunized with Quillaia A (Quil A] and group 3 (immunized with rSm14 in Quil A and infected, each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6% (p < 0.001 and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05. This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.

Irritable bowel syndrome immune hypothesis: the role of lymphocytes and mast cells Hipótesis inmune del síndrome del intestino irritable: Primera parte: papel de los linfocitos y mastocitos

Directory of Open Access Journals (Sweden)

M. Ortiz Lucas

2010-11-01

Full Text Available Objective: To review the available evidence on the role of T-lymphocytes and mast cells in the etiopathogenesis of Irritable Bowel Syndrome. Methods: Bibliographic retrieval on PubMed including the terms "Irritable Bowel Syndrome, "Immune System", "T-Lymphocytes" and "Mast Cells". Results: Twenty-five case-control studies and one randomized controlled trial were retrieved. Noteworthy in the blood is the increase in activated T cells destined to migrate to the bowel in these patients. A high frequency of T-lymphocytes is described in the intestinal mucosa, although the study findings are, at times, contradictory. An evident increase in mast cells (and in their activity between the terminal ileum and descending colon is also observed. Conclusions: The heterogeneity of diagnostic criteria and experimentation methods could account for some of the differences in the results found in the selected research. There are indications that give reason to believe these patients have "low-grade intestinal inflammation", and the increase in T-lymphocytes and mast cells has been associated with disorders found in IBS such as the communication between the intestine and the nervous system, the increase in intestinal permeability and changes in the microbiota.Objetivo: Revisar la evidencia disponible sobre el papel de los linfocitos T y mastocitos en la etiopatogenia del Síndrome del Intestino Irritable. de las vías biliares. Métodos: Recuperación bibliográfica en PubMed incluyendo los términos "Irritable Bowel Syndrome, "Immune System", "T-Lymphocytes" y "Mast Cells". Resultados: Se recuperaron 25 estudios casos-control y un ensayo clínico aleatorizado. A nivel sanguíneo destaca el aumento de células T activadas destinadas a migrar al intestino en estos pacientes. En la mucosa intestinal se describe un patrón elevado de linfocitos T, aunque los resultados de los estudios son en ocasiones contradictorios, y un aumento claro de mastocitos (y de su

B Lymphocytes: Development, Tolerance, and Their Role in Autoimmunity—Focus on Systemic Lupus Erythematosus

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Gabriel J. Tobón

2013-01-01

Full Text Available B lymphocytes are the effectors of humoral immunity, providing defense against pathogens through different functions including antibody production. B cells constitute approximately 15% of peripheral blood leukocytes and arise from hemopoietic stem cells in the bone marrow. It is here that their antigen receptors (surface immunoglobulin are assembled. In the context of autoimmune diseases defined by B and/or T cell autoreactive that upon activation lead to chronic tissue inflammation and often irreversible structural and functional damage, B lymphocytes play an essential role by not only producing autoantibodies but also functioning as antigen-presenting cells (APC and as a source of cytokines. In this paper, we describe B lymphocyte functions in autoimmunity and autoimmune diseases with a special focus on their abnormalities in systemic lupus erythematosus.

Generation of specific antitumor cytotoxic T-lymphocytes in the monoculture

International Nuclear Information System (INIS)

Lupatov, A.Yu.; Brondz, B.D.

1992-01-01

A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1-fold as well as 2-fold immunization. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2 + , Lyt2 + , L3T4 - phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. The release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors

The top ten clues to understand the origin of chronic lymphocytic leukemia (CLL).

Science.gov (United States)

García-Muñoz, Ricardo; Feliu, Jesús; Llorente, Luis

2015-01-01

The fundamental task of the immune system is to protect the individual from infectious organisms without serious injury to self. The essence of acquired immunity is molecular self/non self discrimination. Chronic lymphocytic leukemia is characterized by a global failure of immune system that begins with the failure of immunological tolerance mechanisms (autoimmunity) and finish with the incapacity to response to non-self antigens (immunodeficiency). Immunological tolerance mechanisms are involved in chronic lymphocytic leukemia (CLL) development. During B cell development some self-reactive B cells acquire a special BCR that recognize their own BCR. This self-autoantibody-self BCR interaction promotes survival, differentiation and proliferation of self-reactive B cells. Continuous self-autoantibody-self BCR interaction cross-linking induces an increased rate of surface BCR elimination, CD5+ expression, receptor editing and anergy. Unfortunately, some times this mechanisms increase genomic instability and promote additional genetic damage that immortalize self-reactive B cells and convert them into CLL like clones with the capability of clonal evolution and transformed CLL B cells. This review summarizes the immunological effects of continuous self-autoantibody-self BCR interaction cross-linking in the surface of self-reactive B cells and their role in CLL development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

Science.gov (United States)

Zak, Daniel E; Andersen-Nissen, Erica; Peterson, Eric R; Sato, Alicia; Hamilton, M Kristina; Borgerding, Joleen; Krishnamurty, Akshay T; Chang, Joanne T; Adams, Devin J; Hensley, Tiffany R; Salter, Alexander I; Morgan, Cecilia A; Duerr, Ann C; De Rosa, Stephen C; Aderem, Alan; McElrath, M Juliana

2012-12-11

To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

Effects of smoking on activation markers, Fas expression and apoptosis of peripheral blood lymphocytes

NARCIS (Netherlands)

Bijl, Marc; Limburg, Piet; Kallenberg, Cees; Horst, G.

Background Smoking influences numbers and function of peripheral blood lymphocytes (PBL) by a process that is badly understood. We conducted this study to evaluate whether the immune impairment of smoking might be related to changes in the expression or functionality of Fas, a cell surface molecule

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice

Directory of Open Access Journals (Sweden)

Lluïsa Miró

2017-12-01

Full Text Available Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP, which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT in rodents challenged by S. aureus enterotoxin B (SEB, and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8 at different ages (compared to mice resistant to accelerated senescence; SAMR1. Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer’s patches (all, p < 0.05, as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05. With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05. However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

Science.gov (United States)

Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

2016-01-01

This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

Study of the immune response to thyroglobulin through a model of experimental autoimmune thyroiditis

International Nuclear Information System (INIS)

Santos Castro, M. dos.

1981-01-01

The cellular and humoral immune response to thyroglobulin of different species was studied in guinea pigs. The experiments described suggested that the immune system can be activated against self-determinants. Human and pork thyroglobulin were able to induce the experimental thyroiditis as well as some immune responses, such as in vitro proliferative response, delayed hypersensitivity and antibodies. Although guinea pig thyroglobulin was unable to induce specific T-lymphocyte proliferation in vitro, delayed hypersensitivity response and antibodies, it was very efficient in inducing the autoimmune thyroiditis. On the contrary, bovine thyroglobulin did not induce experimental autoimmune thyroiditis despite producing good responses as determined by similar in vitro proliferative response, delayed hypersensitivity and on the humoral level. These results suggest that the assays utilised were not able to evaluate the relevant immune response to genesis of the thyroiditis. The determinant selection mechanisms operating in these immune responses are probably selecting determinants not responsible for self-recognition in vivo. It was suggested that the macrophage could be the cell responsible for the presentation of these determinants to the lymphocyte in an immunogenic form. (Author) [pt

The immune enhancement of propolis adjuvant on inactivated porcine parvovirus vaccine in guinea pig.

Science.gov (United States)

Ma, Xia; Guo, Zhenhuan; Shen, Zhiqiang; Wang, Jinliang; Hu, Yuanliang; Wang, Deyun

2011-01-01

Two experiments were carried out. In immune response test, the immune enhancement of propolis, oilemulsion and aluminium salt were compared in guinea pig vaccinated with inactivated porcine parvovirus (PPV) vaccine. The result showed that three adjuvants could enhance antibody titer, T lymphocyte proliferation, IL-2 and IL-4 secretion of splenic lymphocyte. The action of propolis was similar to that of oilemulsion and superior to that of aluminium salt, especially in early period of vaccination propolis could accelerate antibody production. In immune protection test, the effects of three adjuvants on PPV infection were compared in guinea pig vaccinated with PPV vaccine then challenged with PPV. The result showed that propolis and oilemulsion could enhance the antibody titer, IL-2 and IL-4 content in serum and decrease the PPV content in blood and viscera. In the effect of improving cellular immune response, the propolis was the best. These results indicated that propolis possessed better immune enhancement and would be exploited into a effective adjuvant of inactivated vaccine. Copyright © 2011 Elsevier Inc. All rights reserved.

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

Science.gov (United States)

Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

2018-06-08

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Lymphocytic infiltration of bladder after local cellular immunotherapy.

Science.gov (United States)

Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

2000-01-01

This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

Cell-extrinsic defective lymphocyte development in Lmna(-/- mice.

Directory of Open Access Journals (Sweden)

J Scott Hale

2010-04-01

Full Text Available Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development.Lmna(-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+ and CD8(+ T cells. Transplantation of Lmna(-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development.Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.

PPARγ Agonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

Directory of Open Access Journals (Sweden)

Laurindo Ferreira da Rocha Junior

2013-01-01

Full Text Available Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPARγ are members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPARγ is activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPARγ has also been associated with B cells. The present review addresses these issues by placing PPARγ agonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.

Cell-mediated immune responses in the head-associated lymphoid tissues induced to a live attenuated avian coronavirus vaccine.

Science.gov (United States)

Gurjar, Rucha S; Gulley, Stephen L; van Ginkel, Frederik W

2013-12-01

Humoral immunity is important for controlling viral diseases of poultry, but recent studies have indicated that cytotoxic T cells also play an important role in the immune response to infectious bronchitis virus (IBV). To better understand the cell mediated immune responses to IBV in the mucosal and systemic immune compartments chickens were ocularly vaccinated with IBV. This induced a lymphocyte expansion in head-associated lymphoid tissues (HALT) and to a lesser extent in the spleen, followed by a rapid decline, probably due to homing of lymphocytes out of these organs and contraction of the lymphocyte population. This interpretation was supported by observations that changes in mononuclear cells were mirrored by that in CD3(+)CD44(+) T cell abundance, which presumably represent T effector cells. Increased interferon gamma (IFN-γ) expression was observed in the mucosal immune compartment, i.e., HALT, after primary vaccination, but shifted to the systemic immune compartment after boosting. In contrast, the expression of cytotoxicity-associated genes, i.e., granzyme A (GZMA) and perforin mRNA, remained associated with the HALT after boosting. Thus, an Ark-type IBV ocular vaccine induces a central memory IFN-γ response in the spleen while the cytotoxic effector memory response, as measured by GZMA and perforin mRNA expression, remains associated with CALT after boosting. Copyright © 2013. Published by Elsevier Ltd.

Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths

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Herr Caroline EW

2010-08-01

Full Text Available Abstract Background Toxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month. Methods Cord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3+ cells and their subsets, CD4+ and CD8+, B lymphocytes (CD19+ and natural killer (NK cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH and particulate matter 2.5 were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM2.5 and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births. Results The adjusted models show significant associations between PAHs or PM2.5 during early gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in CD19+ and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3+ and CD4+ fractions and increases in CD19+ and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation. Conclusions PAHs and PM2.5 in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.

Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus

OpenAIRE

Cromwell, Mandy A.; Veazey, Ronald S.; Altman, John D.; Mansfield, Keith G.; Glickman, Rhona; Allen, Todd M.; Watkins, David I.; Lackner, Andrew A.; Johnson, R. Paul

2000-01-01

Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-...

[Immunologic indexes, enzyme status of lymphocytes and functional activity of blood neutrophils in children with infectious mononucleosis caused by Epstein-Barr virus].

Science.gov (United States)

Kurtasova, L M; Tolstikova, A E; Savchenko, A A

2013-01-01

Explore the immunological parameters, levels of activity of NAD(P)-dependent dehydrogenases lymphocytes, interferon status parameters, phagocytic activity and chemiluminescence response of neutrophils in the blood of children in the acute phase of infectious mononucleosis caused by the Epstein-Barr virus. 65 children at the age of 4-6 years old with infectious mononucleosis caused by EBV in acute phase were observed. Such indexes as cell-mediated, humoral and interferon immunity, NAD(P)-depended dehydrogenases activity in blood lymphocyte, phagocytes activity, levels of spontaneous and induced chemiluminescence ofperipheral blood neutrophils were studied. Children with EVB-infection have immunophenotype spectrum changes and changes of enzymes status of blood lymphocytes against the increasing in leucocytes and the useful increasing in lymphocytes. The useful increasing in IgA, IgM, IgG contenting in serum blood were found. The decreasing of spontaneous production of IFN alpha and the decreasing of induced production of IFNalpha, IFNgamma were determined. The breach of phagocytes activity and chemiluminescent response of blood neutrophils were found. The children in the acute phase of infectious mononucleosis caused by the Epstein-Barr virus, there are changes in the immune status, changes the activity of NAD(P)-dependent dehydrogenases in blood lymphocytes, marked changes in functional and metabolic state of peripheral blood neutrophils.

Perturbation of cellular immune functions in cigarette smokers and protection by palm oil vitamin E supplementation

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Jubri Zakiah

2013-01-01

Full Text Available Abstract Background Cigarette smoke contains free radicals and an have adverse effect to the immune system. Supplementation of palm oil vitamin E (palmvitee, is known has antioxidant properties is thought to be beneficial for system immune protection against free radicals activity. The objective of the study was to determine the effect of palmvitee supplementation on immune response in smokers. Methods This study involved a group of smokers and nonsmokers who received 200 mg/day palmvitee and placebo for the control group. Blood samples were taken at 0, 12 and 24 weeks of supplementation. Plasma tocopherol and tocotrienol were determined by HPLC, lymphocyte proliferation by lymphocyte transformation test (LTT and enumeration of lymphocytes T and B cells by flow cytometry. Statistical analysis was performed by Mann–Whitney U-test for non-parametric data distribution and correlation among the variables was examined by Spearman. Results Plasma tocopherol and tocotrienol were increased in vitamin E supplemented group as compared to placebo group. Urine cotinine levels and serum α1-antitrypsin were significantly higher in smokers compared to nonsmokers. Lymphocyte proliferation induced by PHA showed an increasing trend with palmvitee supplementation in both smokers and nonsmokers. Natural killer cells were decreased; CD4+ cells and B cells were increased in smokers compared to nonsmokers but were unaffected with vitamin E supplementation except in the percentage of B cells which were increased in nonsmokers supplemented palmvitee compared to placebo. CD4+/CD8+ ratio was increased in smokers compared to nonsmokers. The high TWBC count observed in smokers correlated with the increased CD4+ and B cells. Conclusions Smoking caused alterations in certain immune parameters and palmvitee supplementation tended to cause an increase in lymphocytes transformation test but had no effect on CD3+, CD4+, CD8+, NK cells and B cells except B cells percentage

Immune-checkpoint inhibitors in the era of precision medicine: What radiologists should know

Energy Technology Data Exchange (ETDEWEB)

Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Hodi, Frank Stephan Jr; Nishno, Mizuki [Dept. of Radiology, Brigham and Women' s Hospital and Dana Farber Cancer Institute, Boston (United States)

2017-01-15

Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events. This article will review the molecular mechanism, clinical applications, imaging of immune-related response patterns and adverse events associated with immune-checkpoint inhibitors.

Immune-checkpoint inhibitors in the era of precision medicine: What radiologists should know

International Nuclear Information System (INIS)

Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Hodi, Frank Stephan Jr; Nishno, Mizuki

2017-01-01

Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events. This article will review the molecular mechanism, clinical applications, imaging of immune-related response patterns and adverse events associated with immune-checkpoint inhibitors

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

Science.gov (United States)

Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

2016-03-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

N-(4-F-18-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes

NARCIS (Netherlands)

Di Gialleonardo, Valentina; Signore, Alberto; Glaudemans, Andor W. J. M.; Dierckx, Rudi A. J. O.; De Vries, Erik F. J.

Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the

The effects of radioiodine therapy on peripheral blood lymphocyte subpopulations in patients with Graves' disease. Preliminary report

International Nuclear Information System (INIS)

Turowska, M.D.; Rogowski, F.; Turowski, D.; Wysocka, J.

2002-01-01

Treatment of Graves' disease patients with radioactive iodide ( 131 I) is becoming the standard therapy in an increasing group of cases but can induce alterations in immune response, like increasing levels of thyroid autoantibodies, and, in part, exacerbation of ophthalmopathy. The aim of this study was to assess the changes in peripheral blood (PB) lymphocyte subpopulations after 131 I treatment of patients with Graves' disease. The study was carried out in a group of 30 patients with Graves' disease (23 f; 7 m) 49.5±10.0 years of age, 26 with different subjective ocular signs like gritty sensation, increased lacrimation, orbital pain, and exophthalmos. PB lymphocyte subsets were analysed by cytofluorometry, serum concentration of TSH and fT4 were evaluated before and 6 weeks after radioiodine treatment. After 131 I treatment a significant increase in CD3+, CD4+, CD3+HLA-DR+ and a decrease in CD19+ percentages of lymphocyte subsets were found in comparison with the initial evaluation. No significant changes in percentage of CD8+ and NK (CD3-CD16+ CD56+) cells were observed during this study. A significant increase in TSH and a slight decrease in fT4 concentration concentration took place in the 6th week after 131 I application. The patients without subjective improvement of ocular signs during the therapy initially had a percentage of CD3+, CD8+ lymphocytes which was significantly lower compared with those with regression of ocular signs observed after 131 I treatment. The changes in PB lymphocyte subsets caused by 131 I treatment of Graves' disease confirm the involvement of acquired cellular immunity after radiation damage of the thyroid gland. The decreased initial percentage of CD8+ and CD3+ lymphocytes could help make a prediction of ocular symptoms persisting after radioiodine treatment in some patients with ophthalmopathy. (author)

Cortisol-binding globulin and meat quality in five European lines of pigs

NARCIS (Netherlands)

Geverink, N.A.; Foury, A.; Plastow, G.S.; Gil, L.; Gispert, M.; Hortós, M.; Font I Furnols, M.; Gort, G.; Moisan, M.P.; Mormède, P.

2006-01-01

The gene (Cbg) encoding cortisol-binding globulin (CBG) has been proposed as a candidate gene to explain genetic variation in cortisol secretion and carcass composition in pigs. The objective of this study was to evaluate the association between CBG and pork quality in 5 European breeding lines,

In vitro interactions of lymphocytes and cultured cells from beagles with plutonium-induced bone tumors

International Nuclear Information System (INIS)

Frazier, M.E.; Lund, J.E.; Busch, R.H.

1976-01-01

Cell cultures have been prepared from lung and bone tumors arising in beagle dogs following exposure to inhaled plutonium. Evaluation of the cultured cells by commonly applied criteria (i.e., cell morphology, lack of contact inhibitory mechanisms, cloning efficiency, growth in soft agar, and tumor production in vivo) indicated that tumor cells were being grown in culture. Blood leukocytes and peripheral lymphocytes from beagle dogs were tested for cytotoxic effects against several cell cultures. Lymphocytes from normal dogs or dogs with unrelated tumors would not kill the bone tumor cells unless monocytes (macrophage) were present, in which case the leukocyte preparation was capable of mounting de novo cytotoxic immune reactions after 3 to 5 days in culture. In contrast, the dogs with plutonium-induced bone tumors had circulating lymphocytes that appeared to have undergone presensitization to bone-tumor-distinctive antigens in vivo. Consequently these lymphocytes interacted with cultured cells promptly after encounter in vitro

Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae).

Science.gov (United States)

Nehete, Pramod N; Nehete, Bharti P; Chitta, Sriram; Williams, Lawrence E; Abee, Christian R

2017-02-01

Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

Thymus: The site for Development of Cellular Immunity

Indian Academy of Sciences (India)

The immune system protects our bodies against infectionsand cancers. This review introduce readers to the thymus. – a primary lymphoid organ – which is the site of developmentand maturation of functional T lymphocytes. Progenitorstem cells arise from the bone marrow and undergo sequentialdevelopment in the thymus ...

Antibody Production From Immunized Rabbits By Brucella Abortus

International Nuclear Information System (INIS)

Sadi, Suharni

2002-01-01

In this research Brucella abortus was used as antigen which was made by killing the bacteria in boiling water for 1 hour and then add 0.5% phenol. The suspension of bacteria of 6x10 8 cells/mm 3 was used as antigen. Rabbits of about 3 months old were injected with 0.50 mI of the antigen by intradermal route with an interval of two weeks. The animals were divided in three groups i.e. A (control group), B (immunization group) and C (immunization and irradiation group). In C group, the animals were first immunized by the antigen and then 2 days later were irradiated by a low dose of 0.50 Gy of gamma rays. Each group consisted of 3 animals. Parameters were observed by weighing the animals, counting leucocyte and lymphocyte cells, and anaIysing the antisera. The research were done two times, included immunization I x, boostered 4 x and analysed 5x. The results obtained were as follows: A (control group) yielded 2.34 g/dl of non specific antibody, B (immunization group) yielded 3.22 g/dI of specific antibody, C (immunization and irradiation group) yielded 3.50 g/dl of spesific antibody. The leucocyte cells of A, B , and C group were 8.240, 7.887, and 8.120 cells/mm 3, respectively. The lymphocyte cells of A, B, and C group were 69%, respectively. The weigh of A, B, and C group were 1.44; 1.53; and l.41 kg, respectively. The purpose of this research was prepared to produce the diagnostic reagen (RIA Kit) for a rapid detection of animals disease especially brucellosis. It seemed that C group (the combination of immunization and irradiation treatments) yielded the highest value of antibody production compared to another group

Effects of vitamin nutrition on the immune response of hatchery-reared salmonids. Annual report, 1984

International Nuclear Information System (INIS)

Leith, D.; Holmes, J.; Kaattari, S.; Yui, M.; Jones, T.

1985-09-01

Results demonstrate that immunological assays. Lymphocytes from both of the major lymphoid organs (spleen and anterior kidney) produce significant in vitro antibody responses to the antigen, trinitrophenyl-lipopolysaccharide. These cells also demonstrate significant mitogenic stimulation (proliferation) in response to bacterial lipopolysaccharide, phytohemagglutinin, and to a novel mitogen, Vibrio anguillarum extract. As an assessment of cell-mediated immunity, we have found that lymphocytes are capable of responding in a mixed lymphocyte reaction as demonstrated by increased incorporation of tritiated thymidine. Results also indicate that phagocytosis can be quantified by the uptake of radioiodinated Renibacterium salmoninarum and that production of migration inhibition factor (MIF)-like activity can be induced in immunized animals. Polyclonal activation of chinook lymphocytes was elicited by both Vibrio anguillarum extract and E. coli lipopolysaccharide. Groups of spring chinook salmon were fed a formula diet containing five dietary levels of pyridoxine (15, 30, 60, 120, and 1500 mg/kg diet). Data collected on growth and feed efficiency in the first eighteen weeks show no significant difference between these formulations. 46 refs., 20 figs., 7 tabs

A simple ligand-binding assay for thyroxine-binding globulin on reusable Sephadex columns

International Nuclear Information System (INIS)

Bastomsky, C.H.; Kalloo, H.; Frenkel-Leith, D.B.; McGill Univ., Montreal, Quebec

1977-01-01

A method for the assay of thyroxine-binding globulin on reusable Sephadex G-25 columns is described. It depends upon elution by diluted iodothyronine-free serum of protein-bound [ 125 I]thyroxine from the columns under conditions where binding to thyroxine-binding prealbumin and albumin are abolished. It is simple, rapid and precise, and permits determinations inlarge numbers of samples. Values (mg/l; mean +- S.D.) were: normals 31.6+-5.4, hyperthyroid 28.3+-4.8, hypothyroid 40.6+-7.5, oral contraceptives 40.1+-6.8, pregnant 50.3+-5.4, cirrhotics 20.7+-4.3. Concentrations were reduced in serum heated at 56degC, while the uptake of [ 125 I]triiodothyronine was increased. There was a significant negative correlation between thyroxine-binding globulin concentration and triiodothyronine uptake in the heated serum samples and in euthyroid subjects

The role of the immune system in Alzheimer disease: Etiology and treatment.

Science.gov (United States)

Jevtic, Stefan; Sengar, Ameet S; Salter, Michael W; McLaurin, JoAnne

2017-11-01

The immune system is now considered a major factor in Alzheimer Disease (AD). This review seeks to demonstrate how various aspects of the immune system, both in the brain and peripherally, interact to contribute to AD. We highlight classical nervous system immune components, such as complement and microglia, as well as novel aspects of the peripheral immune system that can influence disease, such as monocytes and lymphocytes. By detailing the roles of various immune cells in AD, we summarize an emerging perspective for disease etiology and future therapeutic targets. Copyright © 2017. Published by Elsevier B.V.

Role of immune system in type 1 diabetes mellitus pathogenesis.

Science.gov (United States)

Szablewski, Leszek

2014-09-01

The immune system is the body's natural defense system against invading pathogens. It protects the body from infection and works to communicate an individual's well-being through a complex network of interconnected cells and cytokines. This system is an associated host defense. An uncontrolled immune system has the potential to trigger negative complications in the host. Type 1 diabetes results from the destruction of pancreatic β-cells by a β-cell-specific autoimmune process. Examples of β-cell autoantigens are insulin, glutamic acid decarboxylase, tyrosine phosphatase, and insulinoma antigen. There are many autoimmune diseases, but type 1 diabetes mellitus is one of the well-characterized autoimmune diseases. The mechanisms involved in the β-cell destruction are still not clear; it is generally believed that β-cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes are involved in the β-cell-specific autoimmune process. It is necessary to determine what exact factors are causing the immune system to become unregulated in such a manner as to promote an autoimmune response. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes

Directory of Open Access Journals (Sweden)

Pushpa Ruwali

2018-01-01

Full Text Available Aim: Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD in chicken lymphocytes. Materials and Methods: Fresh aerial parts of A. indica Willd. (family: Asteraceae specimens were collected (altitude 1560 m, gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME. Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 107 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS and concanavalin A (Con A, respectively. Results: Maximum concentration of AME exhibiting 100% cell viability (MNCD was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 μg/ml dose of AME, resulted in significant (p<0.05 upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS and a significant (p<0.05 increase of 12.018% T cells proliferation in the presence of the mitogen (Con A, as compared to the control. Conclusion: The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes.

Science.gov (United States)

Ruwali, Pushpa; Ambwani, Tanuj Kumar; Gautam, Pankaj

2018-01-01

Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells) proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD) in chicken lymphocytes. Fresh aerial parts of A. indica Willd. (family: Asteraceae) specimens were collected (altitude 1560 m), gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME). Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 10 7 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS) and concanavalin A (Con A), respectively. Maximum concentration of AME exhibiting 100% cell viability (MNCD) was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 µg/ml dose of AME, resulted in significant (p<0.05) upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS) and a significant (p<0.05) increase of 12.018% T cells proliferation in the presence of the mitogen (Con A), as compared to the control. The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

Mathematical modeling reveals kinetics of lymphocyte recirculation in the whole organism.

Directory of Open Access Journals (Sweden)

Vitaly V Ganusov

2014-05-01

Full Text Available The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours. Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs or the gut (mesenteric LNs or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.

In vitro cell-mediated immunity assay using 125I-iododeoxyuridine

International Nuclear Information System (INIS)

Morris, J.E.; Graham, T.M.

1979-01-01

We investigated an in vitro cell-mediated immunity assay using incorporation of 125 I-iododeoxyuridine as an indicator of lymphocyte responsiveness to mitogen stimulation. The system permits the use of whole-blood cultures in rats and dogs

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

Science.gov (United States)

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

Molecular mechanism and function of CD40/CD40L engagement in the immune system.

Science.gov (United States)

Elgueta, Raul; Benson, Micah J; de Vries, Victor C; Wasiuk, Anna; Guo, Yanxia; Noelle, Randolph J

2009-05-01

During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.