Rozprawy doktorskie: „Immunotoxicity”

1

Karrow, Niel. "Chemical mixture immunotoxicity to rainbow trout". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0005/NQ44769.pdf.

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2

Bartlett, Alison. "QSAR study of immunotoxicity in antibiotics". Thesis, Liverpool John Moores University, 1995. http://researchonline.ljmu.ac.uk/5135/.

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Since their inception the B-Iactam antibiotics have become one of the most important classes of phannaceutical agents, both therapeutically and economically, in modern day usage for the treatment of a wide spectrum of bacterial infections. However, due to the versatility of bacteria many previously treatable species are developing resistance to the antibiotics currently available and so there is ever a need to develop more ~-lactam antibiotics, which are effective and yet safe. A major drawback to the ~-lactams is the degree of immunologically adverse reactions they induce. It was the aim of this study to develop both mechanistic and immunological methods to enable the prediction of a B-lactam's potential to induce an allergic response and to determine if a relationship between these responses and the molecular properties of the ~-lactams was present. In this study a database pertaining to frequency by which 70 p-lactams induce adverse reactions has been compiled and used to produce 27 QSAR models. A highly sensitive assay for the quantitation of cross-reactivity between B-lactams and serum anti-benzylpenicillin antibodies has been developed and used to determine the cross-reactivity potential of 31 ~-lactams and to develop 18 QSAR models. All of the QSARs developed suggest that the shape and electron separation of the ~-lactams are crucial to the development and extent of adverse response or crossreactivity induced by a specific p-lactam antibiotic, new or old. The QSARs developed will enable the design and development of new ~-lactam antibiotics which present a significantly lower risk of inducing immunologically mediated adverse responses when used therapeutically. Two sensitive assays for the quantitative detennination of the cytokines IL2 and IL4 in lymphocyte culture supernatants have been developed, and have been shown to have a potential use in the prediction of the type of immunological response initiated following p-Iactam stimulation of a sensitised individual.

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3

McDonald, Valerie Alexandra. "Evaluating Immunotoxicity of Quaternary Ammonium Compounds". Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/79723.

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Alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) are common quaternary ammonium compounds used as disinfectants in households, medical, and restaurant settings. They cause occupational skin and respiratory hazards in humans, and developmental and reproductive toxicity in mice. They also cause increased secretions of proinflammatory cytokines in cell lines and vaginal inflammation in porcine models; but have not been evaluated for developmental immunotoxicity. We assessed immunotoxicity in-vitro with J774A.1 murine macrophage cell line by analyzing cytokine production and phagocytosis; and evaluated developmental immunotoxicity in CD-1 mice by analyzing antibody production. Additionally, because of the associations between gut microbiome dysbiosis and immune disease, we monitored changes in the microbiome as a result of ADBAC+DDAC exposure. Production of cytokines TNF-alpha and IL-6 increased at low ADBAC+DDAC concentrations, and IL-10 decreased in the murine macrophages with ADBAC+DDAC exposure. The phagocytic function of macrophages was also severely decreased. ADBAC+DDAC altered the mouse microbiome by decreasing the relative abundance of Bacteroides and increases in Clostridia in F0 and F1 generations. IgG primary and secondary responses were altered in F1 male mice; and IgA and IgM production were decreased in secondary response in F2 male mice. Since ADBAC+DDAC show signs of immunotoxicity in mice, further studies are needed to reassess risk for human exposure as ADBAC+DDAC may be contributing to immune disease.
Master of Science

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4

Maliji, Ghorban. "Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat". Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319022.

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5

McDonald, Jennifer C. Venables Barney J. "Bacterial challenge in Lumbricus terrestris a terrestrial invertebrate immunotoxicity model /". [Denton, Tex.] : University of North Texas, 2007. http://digital.library.unt.edu/permalink/meta-dc-3640.

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6

Baken, Kirsten Annika. "Immunotoxicogenomics gene expression profiling as a tool to study immunotoxicity /". [Maastricht] : Maastricht : Universitaire Pers Maastricht ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=9329.

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7

Rabideau, Christine L. "Pesticide Mixtures Induce Immunotoxicity: Potentiation of Apoptosis and Oxidative Stress". Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/34547.

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The three insecticides of interest were lindane (an organochlorine), malathion (an organophosphate) and piperonyl butoxide (PBO; a synergist). Based on minimum cytotoxicity (> LC25), the following concentrations were chosen for the pesticide mixture studies: 70Î¼M lindane (Lind), 50Î¼M malathion (Mal) and 55Î¼M PBO. In the AlamarBlue cytotoxicity assay, individual pesticide and mixtures of malathion/PBO (MP) and malathion/lindane (ML) prompted cytotoxicity with varying intensities (Mal 18.8%, Lind 20.4%, PBO 23.5%, ML 53.6% and MP 64.9%). Cytopathological analysis revealed apoptotic features in treated cells and the DNA Ladder Assay confirmed the presence of DNA fragments. The specific mode of cell death was examined via the 7-aminoactinomycin D (7-AAD) Staining Assay. Apoptosis was detected in each treatment (Mal 6.5%, Lind 12.0%, PBO 13.2%, ML 19.3% and MP 23.4%). Furthermore, 7-AAD staining in combination with fluorescent-labeled monoclonal antibodies, PE-CD45RB/220 and FITC-CD90, was performed. B-cells were more susceptible to Mal and PBO treatments than were T-cells. The pro-oxidant activity of the pesticides was monitored via the Dichlorofluorescin Diacetate assay. Exposure to pesticides for 15 minutes increased H2O2 production above the controls, Mal 21.1%; Lind 10.8%; PBO 25.9%; ML 26.8%; MP 37.8%. The activities of antioxidant enzymes, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were altered by these treatments. GR was significantly reduced for the pesticide mixtures only (control: 51.7; Mal: 48.2; Lind: 50; PBO: 52.3; ML: 40.5; MP: 42 Units/mg). GSH-Px activity was severely reduced for all the pesticide treatments (control: 44.9; Mal: 30.2; Lind: 30.6; PBO: 32.4; ML: 21.1; MP: 21.1 Units/mg). These results indicate that exposure to these pesticide and pesticide mixtures induces apoptosis and oxidative stress.
Master of Science

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8

Olgun, Selen. "Immunotoxicity of Pesticide Mixtures and the Role of Oxidative Stress". Diss., Virginia Tech, 1998. http://hdl.handle.net/10919/11114.

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The immunotoxic effects of multiple pesticide exposure were evaluated. C57BL/6 mouse thymocytes were exposed to lindane, malathion, and permethrin, either separately or in mixtures of two pesticides, in concentrations ranging from 37.5 uM to 1mM. These exposures caused both apoptotic and necrotic cell death in thymocytes as evaluated by 7-aminoactinomycin-D, Annexin-V/PI, and lactate dehydrogenase release assays. When cells were exposed to lindane+malathion, or lindane+permethrin, a significantly greater-than-additive cytotoxicity was observed. The pesticide exposure caused DNA ladder formation with increased laddering in mixtures. Further, the effect of these pesticides on thymocyte oxidative stress was investigated. Thymocytes treated with any of these pesticides generated superoxide and H2O2. The lindane + malathion caused more-than-additive increase in superoxide production compared to single treatments of these pesticides. However, the effect of the lindane + permethrin was not significantly different from individual components of this mixture. The effects of pesticides on antioxidant enzymes were also investigated and only mixtures were found to have significant effects. Alteration in transcription factor NFkB level was measured as an indicator of oxidative stress in thymocytes following 12 h pesticide exposure, in vitro. Only lindane + malathion was found to increase the protein level. Furthermore, the effects of pesticides and their mixtures on immune functions of mice were studied in vivo. Animals (8-12 week old, male mice) were randomly divided into groups of six and injected intraperitoneally with three different doses (one-half, one-third, one-fourth, or one-eight of LD50) of individual pesticides. Exposure to individual pesticides did not alter the thymus/body or spleen/body weight ratios, thymic or splenic cell counts, or CD4/CD8 or CD45/CD90 ratios. However, anti-sRBC plaque forming cell (PFC) counts were significantly lowered with all treatments. Two other groups of animals were injected with lindane + malathion or lindane + permethrin at one-third of the LD50 of each pesticide. Exposure to pesticide mixtures did not alter the CD4/CD8 or CD45/CD90 ratios. However, the thymus/ and spleen/body weight ratios, thymic and splenic cell counts, and PFC counts were significantly lowered. These data indicate that lindane, malathion, and permethrin are immunotoxic and their mixtures can cause higher toxicity compared to individual exposures. In addition, these data support the hypothesis that oxidative stress were induced in thymocytes by exposure to these pesticides in vitro.
Ph. D.

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9

McDonald, Jennifer C. "Bacterial Challenge in Lumbricus Terrestris: A Terrestrial Invertebrate Immunotoxicity Model". Thesis, University of North Texas, 2007. https://digital.library.unt.edu/ark:/67531/metadc3640/.

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A bacterial challenge assay was developed utilizing the earthworm, Lumbricus terrestris, in order to assess potential immunotoxic effects from exposure to specific polychlorinated biphenyl congeners. Earthworms were inoculated with Aeromonous hydrophila, establishing a 10-day LD50. In vitro assays for effects of PCBs on phagocytosis agreed with mammalian studies, demonstrating potent suppression of phagocytosis by the non-coplanar PCB congener 138 and no suppression by the coplanar congener 126. However, when the effects of the two PCB congeners were evaluated for suppression of resistance to a whole animal infection challenge assay, coplanar PCB 126 decreased the ability of L. terrestris to withstand infection while non-coplanar PCB 138 did not.

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10

Mohammadian, Gholamreza. "Immunotoxicity of Chromium Contaminated Soil in the Earthworm, Lumbricus Terrestris". Thesis, University of North Texas, 1993. https://digital.library.unt.edu/ark:/67531/metadc501250/.

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Objective was to assess the toxicity of chromium (Cr) contaminated soil (CS) using the earthworm Lumbricus terrestris. Specific aims were to determine: (1) survival (LC50); .(2) immunotoxicity as indicated by lysozyme activity, coelomocyte counts, secretory (SR) and erythrocyte rosette (ER) formation, and phagocytosis; and (3) compare effects of CS exposure with those of Cr spiked artificial soil (AS) . CS Cr concentration was 8.78 mg/g with 98.2% being Cr^3+ and 1.8% being Cr^6+. Using 14 d AS protocol the LC50 was 6.49% CS: AS mixture. CS concentrations of 0.5, 1.0, 2.5 and 5.0% were sublethal, whereas 6.25, 12.5, 25, 50 and 100% CS were lethal. Sublethal exposure caused no immuno- modulation. Exposure to 50% CS: AS mixture for 5 d caused reduced SR and ER formation. Exposure to AS spiked with 0.27% Cr for 5 d resulted in immunomodulation equivalent to 50% CS: AS mixtures. Results indicated the CS to be acutely toxic.

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11

Neethling, Michelle. "An in vitro study on the immunotoxicity of South African beer". Thesis, University of the Western Cape, 2008. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_5120_1257318050.

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"
Traditionally brewed beers are of cultural and economic importance to many African nations. The presence of mycotoxins in African beer is a topic that needs to be addressed, since most African countries have a climate of high humidity and temperature that favours the growth of moulds. Mycotoxins challenge not only the health of animals and humans, but also the economy, especially in underdeveloped countries where contamination is most likely. Literature proves that mycotoxins depict various effects on the immune system including immunotoxicity. Beer analysis is therefore of utmost importance in order to evaluate organoleptic characteristics, quality, nutritional value as well as safety. The aims of this study involve the analysis and comparison of traditional and commercial beer in terms of physical characteristics, mycotoxin concentrations as well as effects on specific immune pathway biomarkers in order to elucidate possible immunotoxicity..."

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12

Steer, Sarah Jane. "Problems inherent in developing in vitro tests for phototoxicity and immunotoxicity". Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357820.

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13

Kamath, Arati B. "Apoptosis as a Mechanism of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-Induced Immunotoxicity". Diss., Virginia Tech, 1998. http://hdl.handle.net/10919/40094.

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environmental pollutant and is well known for its immunotoxic effects, particularly on the thymus. The exact mechanism by which TCDD induces thymic atrophy is not known. In the current study, we investigated whether TCDD triggers apoptosis in the thymocytes and whether Fas and Fas ligand play a role in TCDD-mediated immunotoxicity. Administration of a single dose of TCDD at 0.1, 1, 5 or 50 mg/kg body weight intraperitoneally into C57BL/6 +/+ mice caused a significant dose-dependent decrease in the thymic cellularity; whereas, in the C57BL/6 lpr/lpr (lpr) (Fas-deficient) and C57BL/6 gld/gld (gld) (Fas ligand-defective) mice, TCDD failed to induce a decrease in thymic cellularity at doses of 0.1-5 mg/kg body weight. In the lpr and gld mice, thymic atrophy was seen only at 50 mg/kg body weight of TCDD. Significant apoptosis was detected within 8-12 hours after injection in the wild type mice, whereas, in the lpr and gld mice apoptosis could not be detected. Upon culturing the thymocytes from TCDD-treated mice for 24 hours in vitro, the wild-type cells showed increased apoptosis when compared to the control; whereas, similar cells from lpr and gld mice did not show apoptosis. Furthermore, TCDD-treatment caused significant alterations in the expression of surface molecules on the thymocytes in the wild-type mice and minimal changes in the lpr or gld mice. Sera from TCDD-treated wild-type mice also exhibited increased levels of soluble Fas ligand. Also, TCDD-induced apoptosis was inhibited both in vitro and in vivo by caspase inhibitors and other inhibitors of apoptosis. Together, the current study demonstrates that TCDD-induced apoptosis plays an important role in thymic atrophy caused by TCDD in vivo. Furthermore, phenotypic changes in the density of thymocyte surface molecules may serve as a useful biomarker for chemical toxicity involving apoptosis. The current study also demonstrates that Fas-Fas ligand interactions play an important role in the induction of apoptosis and immunotoxicity by TCDD.
Ph. D.

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14

Chen, Shing-Chong. "Enzyme Assays Using Earthworms for Assessing Innate and Nonspecific Immunotoxicity of Xenobiotics". Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc277598/.

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Principal objectives of my research were to: (1) report for the first time that coelomocytes are able to reduce NBT dye and confirm the presence of lysozyme-like activity in earthworm; (2) develop a standard methodology for determination of NBT reduction and lysozyme-like activity in earthworms; (3) compare NBT reduction and lysozyme-like activity in earthworms with those of murine and human cells and fluids; and (4) demonstrate the sensitivity of earthworm NBT reduction and lysozyme-like activity as the assays using matrics in refuse-derived fuel fly ash (RDFF) and CuSO4.

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15

Giggleman, Marina A. "Phagocytosis by Earthworm Coelomocytes : A Biomarker for Immunotoxicity of Hazardous Waste Site Soils". Thesis, University of North Texas, 1997. https://digital.library.unt.edu/ark:/67531/metadc278359/.

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Several biomarkers (cell viability and phagocytosis) based on earthworm (Lumbricus terrestris) immune cells (coelomocytes), together with whole-worm mortality (LC/LD50's), were used to assess a bioremediation attempt to reduce pentachlorophenol (PCP) toxicity in a former wood processing hazardous waste site (HWS).

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16

Murray, Stephanie Mae. "Evaluation of Sequential Events in Phagocytosis by Earthworm Coelomocytes as Potential Immunotoxicity Biomarkers". Thesis, University of North Texas, 1998. https://digital.library.unt.edu/ark:/67531/metadc278424/.

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This research evaluated the potential of activation and attachment, as sequential companion biomarkers of phagocytosis by earthworm, Lumbricus terrestris, immunoactive coelomocytes for use in immunotoxicology. The potential was assessed by exposing earthworms to sublethal concentrations of CuSO4 and Arochlor 1254®, chemicals used as reference or standard immunotoxicants.

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17

Harford, Andrew James, i andrew harford@rmit edu au. "The characterisation of Australian freshwater fish immune systems and their response to immunomodulators". RMIT University. School of Medical Science, 2005. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20060307.171411.

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The Murray-Darling basin is the largest river system in Australia with significant economic, social, recreational and cultural value. It supplies water for drinking and agriculture to a large inland area of the eastern and southern states of Australia. It is also the ultimate sink for many environmental contaminants that result from human activities within the catchment. Aquatic organisms live intimately with their environment and may be continuously exposed to these contaminants through the water column or the food chain. Some chemicals are bioaccumulated and biomagnified in tissue to reach high body burdens. Populations of native fish species within the Murray-Darling basin have been in decline since human settlement, yet little is known about the lethal and sublethal effects of environmental pollutants on native freshwater fish and many of the Australian water quality guidelines are based on data from exotic fish species. Researchers have correlated levels of pollution with immune dysfunction and an increased incidence of disease amongst wildlife populations. Many of the pollutants of the Murray-Darling basin have known immunotoxicity in both mammals and exotic fish species. The immune system is a sensitive target organ because, in order to maintain integrity, it requires constant renewal through the rapid proliferation and differentiation of cells. Efforts to increase numbers of native fish in the wild have led to an aquaculture industry that produces fingerlings for the restocking of waterways. In more recent years, this industry has matured and now produces table-size native freshwater fish for local and international markets. Although the industry has researched areas of reproduction, nutrition and stocking, there is little understanding of the immunology or immunotoxicology of Australian freshwater fish. This research project investigated the immunology of three large native fish species (i.e. 2 Murray cod, golden perch and silver perch), which are the basis of the native freshwater aquaculture industry. Additionally, a small fish species native to the basin (i.e. crimsonspotted rainbowfish) was studied as an alternative to the use of large fish. Of the four species, Murray cod possessed characteristics that made it an excellent candidate for ecoimmunotoxicity testing.

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18

Punareewattana, Korawuth. "Immune Function Determination in Mice Dermally Exposed to Permethrin". Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/9868.

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Inhibited immune responses have been observed following occupational, inadvertent, or therapeutic exposure to chemically diverse xenobiotics. In the present studies, preliminary data were generated showing limited but significant systemic immunotoxicity following low-level topical exposure to the pyrethroid insecticide, permethrin (formerly not considered an immunotoxicant). Permethrin was applied to the shaved dorsal interscapular region of C57Bl/6N mice at doses of 0.5, 1.5, or 5.0 μl/day. The highest of these doses was approximately equal to 215 μg/kg/day, which is about seven times the estimated daily human exposure in individuals wearing permethrin treated clothing for insect protection. Mice were thus exposed to permethrin daily for 10 or 30 consecutive days, or every other day for 7 or 14 exposures. Body weight was not affected by the treatment. However thymic weight was decreased and splenic weight increased 2 days after termination of the topical exposure. Histopathology of immune organs showed no significant changes. Splenic macrophages showed significantly depressed chemiluminescent responses up to 10 days following termination of exposure, but macrophage phagocytic activity was not affected. Cell surface markers of thymocytes, splenocytes and bone marrow cells were not affected. Antibody production as shown by plaque forming cell (PFC) assay decreased significantly at 10 days after dosing termination. Taken together, these data indicate that low-level topical permethrin exposure may produce systemic immunotoxicity.
Master of Science

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19

Handy, Andrea Renee. "Acute Toxicity and Immunotoxicity Testing of Total Petroleum Hydrocarbons in Aquatic and Terrestrial Organisms". Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1185910580.

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20

Reid, Lynnda Louise 1949. "Use of staphylococcal enterotoxin A-induced interleukin 2 production as an indicator of immunotoxicity". Thesis, The University of Arizona, 1990. http://hdl.handle.net/10150/278371.

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An in vitro assay measuring IL-2 production as an index of compromised immune function was developed using primary splenocytes from female C57BL/6 mice pretreated with olive oil, 30 mg/kg Cyclosporin A, or 220-880 mg/kg benzene. Splenocytes were mitogen-stimulated to produce IL-2 with SEA, Con A or PHA. Benzene induced inhibition of IL-2 production was demonstrated by incubating the splenocyte culture supernatant fraction with an IL-2 dependent T-lymphocytic cell line. Cell proliferation was measured by blastogenesis and MTT reduction as an index of IL-2 mediated response. Benzene and cyclosporin dosed animals demonstrated a significant decrease in splenocyte proliferation. However, cell proliferation in IL-2 dependent cells was inhibited only with the higher doses of benzene indicative of a dose dependent IL- 2 mediated suppression. Chemically induced impairment of IL-2 mediated immune function may be detected with this assay.

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21

Prater, Mary Renee. "Immunotoxicity of Dermal Permethrin and Cis-Urocanic Acid: Effects of Chemical Mixtures in Environmental Health". Diss., Virginia Tech, 2002. http://hdl.handle.net/10919/11047.

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The present study examined adverse effects of sunlight exposure (mimicked by intradermal cis-urocanic acid, cUCA) on local and systemic immune responses, with or without co-exposure to the immunotoxic insecticide permethrin. A single exposure to cUCA caused diminished splenic macrophage phagocytosis that was persistent up to 30 days post-exposure. Five-day exposure to cUCA subtly increased splenocyte proliferation in response to the T cell mitogen Concanavalin A. Four-week exposure to cUCA caused increased splenic lymphocyte cellularity, thymic hypocellularity, and enhanced hydrogen peroxide production by splenic leukocytes. Single exposure to topical permethrin resulted in decreased thymic and splenic weight and cellularity, and inhibited antibody production by splenic B cells. cUCA worsened the negative effect of permethrin on both thymic weight and cellularity, and depressed splenocyte blastogenesis, hydrogen peroxide production, and antibody production. Five-day exposure to either cUCA or permethrin also caused persistent decreased contact hypersensitivity responses, an effect that became more than additive when the chemicals were administered concurrently. Defects in antigen processing and presentation by cutaneous Langerhans cells were evaluated as possible contributing mechanisms to the cutaneous immunosuppression, using mice with deleted genes. Vehicle-exposed IFNg knockout mice displayed approximately a 22.1% depression in the ear swelling response as compared to control C57BL/6N mice, suggesting that this cytokine may be required for mounting a control-level hypersensitivity response. Ear swelling in cUCA-exposed IFNg knockout mice displayed a 21.4% depressed response as compared to cUCA-exposed wild-type C57BL/6N mice, again suggesting that IFNg is an important cytokine in the contact hypersensitivity (CH) response. TNFaR knockout mice exposed to cUCA displayed 33.9% greater ear swelling than cUCA-exposed wild-type C57BL/6N mice, suggesting that increased TNFa may be involved in inhibited CH by cUCA. TNFaR knockout mice exposed to permethrin displayed 33.9% greater ear swelling than permethrin-exposed C57BL/6N mice, suggesting that increased TNFa may also be involved in inhibited CH by permethrin. C57BL/6N mice exposed to cUCA + permethrin displayed severe reduction of the CH response to 8.7% of the control level. IFNg knockout mice exposed to permethrin + cUCA showed essentially identical depression of the CH response as IFNg knockout mice exposed to either permethrin or cUCA alone. These results suggest that IFNg is required for the greater than additive immunotoxic effect that occurred when these two agents were co-administered. TNFaR knockout mice exposed to cUCA + permethrin displayed 8.7 fold greater ear swelling than similarly exposed C57BL/6N mice, again suggesting that increased TNFa is involved in inhibited CH by both cUCA and permethrin.
Ph. D.

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22

Pryputniewicz, Sarah Jean. "Mechanism of TCDD-Induced Immunotoxicity: The Role of Cell Activation in the Generation of Toxicity". Thesis, Virginia Tech, 1997. http://hdl.handle.net/10919/9691.

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2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin is well known for its immunotoxic effects on the thymus, as well as on B and T lymphocyte functions. Previous studies suggested that TCDD exerted immunotoxic effects only on cells differentiating in response to antigenic challenge. To this date, no work has been done to characterize the long-term effects of TCDD on the activated cells. Additionally, no studies have been done to determine whether TCDD has any effect on resting T cells. In the current study, therefore, we investigated the effects of TCDD on activated and resting cells within the same animal. T cells in the popliteal lymph node cells were activated by rear footpad immunizations with anti-CD3 antibodies. Distally-located axillary lymph nodes were chosen as a source of naive and resting T cells. Our results demonstrate that TCDD acted at the time of cell differentiation to suppress the immune responses of activated T cells, but failed to suppress, and at times, enhanced the immune responses of resting T cells. The TCDD-induced immunomodulations were temporary; responsiveness of both activated and resting T cells from TCDD-treated animals returned to normal by two weeks post-treatment, suggesting that TCDD does not affect memory cells. Futhermore, we provide direct evidence that the TCDD-induced immunosuppression in activated cells is due to increased apoptosis of CD3+ T cells. TCDD also induced significant changes in cell surface markers expressed by naive and activated T cells. Together our data suggested that TCDD suppresses the proliferative responsiveness of only the activated, but not naive, T cells and that this is accomplished by induction of increased apoptosis of activated T cells. These studies shed new light on the mechanism through which TCDD induces increased susceptibility to infections and cancer in the vertebrate host.
Master of Science

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23

Gonon, Alexis. "Impact d'une exposition aux nanoparticules sur les fonctions des cellules présentatrices d'antigènes". Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV078/document.

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Les nanoparticules (NP) ont été introduites en médecine pour développer des médicaments intelligents ou des agents d'imagerie. En raison de leur petite taille (<200 nm), les NP permettent la mise en place de thérapies ciblées, augmentent la diffusion et l’efficacité des drogues, tout en facilitant les modes d’administration et en diminuant les couts de santé publique. Malgré les promesses que présentent les NP pour la médecine, les risques potentiels pour la santé humaine associés à une exposition aux NP restent mal documentés ; en particulier en ce qui concerne leurs effets sur le système immunitaire. Les cellules présentatrices d’antigène (CPA) (comprenant les macrophages et les cellules dendritiques) sont recrutées au site d’inflammation induite par des pathogènes et constituent une ligne de défense majeure pour notre organisme. Les CPA sont dotées d’une activité de phagocytose et endocytose conduisant à une forte internalisation des NP. Ainsi, ces cellules seront parmi les plus affectées par une exposition aux NP et sont un modèle expérimental pertinent pour l’étude du devenir cellulaire des NP et de leurs effets sur l’hôte.Dans cette étude, nous avons étudié si les fonctions de ces cellules pourraient être modifiées par une exposition aux NP. Comme modèles de NP, nous avons choisi l'or (AuNP) et le gadolinium-polysiloxane (GdSi) utilisés comme agent de contraste ou de théranostique, le poly lactic-co-glycolic acid (PLGA) et une nano émulsion lipidique (LNP) développés comme plateforme de délivrance d’antigènes ou de médicaments. Tout d'abord, en utilisant des microsphères fluorescentes comme sonde, nous avons montré que toutes les NP testées n'altèrent pas la capacité de phagocytose de la lignée cellulaire de macrophages J774. Ensuite, l’activation des cellules a été analysée par cytométrie de flux, basée sur l'expression des marqueurs de surface CD-86 et MHC-II. Nous avons établi que l'exposition aux NP n'active pas les cellules dendritiques dérivées de la moelle osseuse (BMDC). Dans le même sens, aucune de ces NP n’induit par elle-même de sécrétions de cytokines par les BMDC. En outre, l’activation de ces cellules par des activateurs connus, tels que le lipopolysaccharide bactérien (LPS) n'est pas modifiée par les NP. Cependant, l'exposition aux AuNP diminue l'expression des cytokines IL-6, IL-12 et IL-23 par les BMDC activées par LPS. Or, ces cytokines sont impliquées dans la polarisation des lymphocytes T CD4 + vers le phénotype T helper approprié (Th). Nous avons analysé si ces modifications de cytokines pourraient modifier la réponse Th. Dans un modèle in vitro de présentation d'antigène, les BMDC ont été incubés avec un antigène modèle (ovalbumine (OVA)) et co-cultivés avec des cellules T spécifiques de l'OVA. L'exposition aux AuNP a conduit à une augmentation des cytokines spécifiques des lymphocytes T: IL-13 (indiquant un déplacement de la balance Th1 / Th2 classique vers Th2) et IL-17 (permettant de diriger les cellules T vers Th17). L'exposition des BMDC aux autres NP de l'étude ne modifie que très faiblement leurs sécrétions de cytokines inflammatoires, et n'a donc pas d'impact sur le destin des lymphocytes T après la présentation de l'antigène.L’ensemble de ces résultats démontrent que GdSi, PLGA et LNP ne modifient pas la phagocytose, l'activation des DC et la présentation antigénique. Cependant, l'exposition aux AuNP modifie les réponses inflammatoires des DC et le devenir des cellules T vers les phénotypes Th2 et Th17. Ces modifications pourraient entraver la physiologie du système immunitaire et contribuer aux maladies chroniques ou à l'auto-immunité
Nanoparticles (NP) have been introduced in medicine to develop intelligent drugs or imaging agents. Due to their small size (<200 nm), NPs allow the development of targeted therapies, increase drug diffusion and effectiveness while facilitating modes of administration and decreasing public health costs. Nevertheless, the potential risks for human health associated to NP exposure remain poorly documented; especially about their effects on the immune system. Antigen-presenting cells (APC) (including macrophages and dendritic cells) are recruited at the site of pathogen-induced inflammation and constitute to the maintenance of body integrity, engulfing pathogens and delivering signals to other components of the immune system. Due to their internalization abilities, APC accumulate NP in their cytoplasm. Thus, these cells will be among the most affected by exposure to NP and constitute a relevant experimental model for the study of the cellular fate of NP and their effects on the host.In this study, we investigated whether the functions of these cells could be modified by an exposure to NP. As models of NP, we selected gold (AuNP) and gadolinium-polysiloxane (GdSi) used as contrast agent for therapeutic and diagnostic applications, and poly lactic-co-glycolic acid (PLGA) and lipid nano emulsion (LNP) developed as a platform for the delivery of antigens or drugs.First, using fluorescent microspheres as probe, we have shown that all of the tested NP did not alter the phagocytosis capacity of the J774 macrophage cell line. Then, cell activation was analyzed by flow cytometry, based on the expression of the surface markers CD-86 and MHC-II. We have established that NP exposure did not activate bone marrow derived dendritic cells (BMDC). In this way, none of these NP induced cytokine secretions by the BMDC. Furthermore, activation of these cells by known activators, such as bacterial lipopolysaccharide (LPS) was not modified by NP.However, in this case, the cytokine response was altered by AuNP exposure, showing reduced inflammatory cytokine production such as IL-6, IL-12 and IL-23. Interestingly, these cytokines are involved in the polarization of CD4 + T lymphocytes to the appropriate T helper phenotype (Th). In a model of antigen presentation in vitro, this cytokine profile resulted into an altered development of specific immune responses. AuNP exposure increased T cell specific cytokines: IL-13 and IL-4 (indicating a shift of classical Th1/Th2 balance towards Th2) and IL-17 (standing for an alteration of T-cell fate towards Th17). The exposure of BMDC to the other NP of the study only very slightly altered their inflammatory cytokine secretions and therefore did not affect the fate of T lymphocytes after antigen presentation.All together, these results demonstrate that GdSi, PLGA and LNP do not modify phagocytosis, DC activation and antigen presentation. However, exposure to AuNP alters the DC induced inflammatory responses and polarizes the T cell fate towards Th2 and Th17 phenotypes. These changes could impair the physiology of the immune system and contribute to chronic diseases or autoimmunity

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24

Liamin, Marie. "Exposition in vitro de lymphocytes T humains aux hydrocarbures aromatiques polycycliques : étude des effets immunotoxiques". Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B060/document.

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Les hydrocarbures aromatiques polycycliques (HAPs), tels que le benzo(a)pyrène (B[a]P), sont des contaminants environnementaux ubiquistes générés lors de la combustion de matière organique. Ces composés ont été associés au développement d'effets toxiques sur la santé humaine, notamment des effets cancérigènes et immunotoxiques, principalement liés à l'activation du récepteur aux hydrocarbures aromatiques (RAh). Parmi les cellules du système immunitaire, les lymphocytes T apparaissent comme des cibles majeures des HAPs. Des résultats antérieurs, obtenus au laboratoire, ont montré que l'activation des lymphocytes T humains en culture primaire conduit à l’augmentation de l'expression et de la fonction du RAh, suggérant la capacité accrue de ces cellules à répondre à une exposition aux HAPs. Nos objectifs sont : (1) de déterminer les effets du B[a]P sur les profils d'expression génique dans les lymphocytes humains normaux en utilisant des approches à haut débit telle que l'analyse transcriptomique sur puce à ADN, (2) d’évaluer les effets génotoxiques et immunotoxiques du B[a]P en mesurant respectivement les dommages à l'ADN induits et leurs actions immunosuppressives et (3) d’analyser la modulation de ces effets en présence d'autres HAPs. Notre travail identifie les lymphocytes T humains normaux comme un bon modèle pour étudier les effets génotoxiques et immunotoxiques des HAPs, et pour prédire les problèmes de santé humaine liés à l’exposition à ces contaminants. Il permet également de mieux comprendre la régulation par les HAPs de la réponse immune et propose de nouveaux biomarqueurs potentiels de l'exposition à ces contaminants environnementaux
Polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B[a]P), are ubiquitous environmental contaminants generated during organic matter combustion. These compounds have been associated with the development of toxic effects on human health, including carcinogenic and immunotoxic effects, mainly related to Aryl hydrocarbon Receptor (AhR) activation. Among the immune system cells, T lymphocytes appear as major targets of PAHs. Previous results, obtained in the laboratory, have shown that activation of primary human T lymphocytes leads to a functional AhR expression increase, suggesting their ability to respond to PAH exposure. Our specific aims are: (1) to determine the effects of B[a]P on gene expression profiles in human normal lymphocytes by using large-scale approaches such as microarray-based transcriptome analysis, (2) to monitor the genotoxic and immunotoxic effects of B[a]P by measuring DNA damage and immunosuppressive actions, respectively and, (3) to analyze the modulation of these effects by the presence of other PAHs. Our work propose primary cultures of activated human T lymphocytes as a good model for studying both genotoxic and immunotoxic effects of environmental contaminants such as PAHs and predicting human health issues. It also gains a comprehensive insight into the immune response regulation after PAH exposure and provides potential new biomarkers of exposure to these environmental contaminants

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25

Holloway, Jennifer C. "Investigation of white blood cell phagocytosis as a potential bio-marker of mercury immunotoxicity in birds". Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33002.

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White blood cell phagocytosis was investigated and used with avian blood, and assessed as a potential biomarker for mercury immunotoxicity in free ranging birds (common loons). Phagocytosis is an essential immunological function and can be measured using flow cytometry. The assay was assessed with in vitro exposure using whole blood and isolated white blood cells (WBC) from domestic chickens, and with in vivo exposure using whole blood from captive doves and wild loons. McHg at 0.1ppm significantly depressed phagocytic capacity of isolated WBCs without affecting their viability, but did not affect phagocytic activity when added to whole blood up to 50ppm. Also, no significant relationship between blood-Hg level and phagocytic capacity of WBCs was observed in ringed turtle doves fed McHg in their diets, nor in wild common loons having a range of blood-Hg concentrations. The phagocytosis assay is a convenient assay for use in field studies of free-living birds, but is not responsive to McHg exposure in birds, and so is not recommended as a biomarker of immunotoxicity in Hg-exposed loons.

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26

Domingues, Alexandre. "Avaliação do potencial imunotóxico do herbicida diuron: estudo de toxicidades de 28 e 90 dias(doses repetidas) /". Botucatu : [s.n.], 2007. http://hdl.handle.net/11449/95906.

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Resumo: Escassas informações são encontradas na literatura a respeito do potencial imunotóxico do Diuron, um herbicida derivado da uréia, utilizado no Brasil e no mundo nas lavouras de café, cana-de-açúcar, algodão, abacaxi, citros, alfafa e trigo. Desta forma, o presente estudo teve por objetivo investigar a toxicidade do Diuron sobre o sistema imunológico. Para isso, foram avaliados parâmetros gerais de toxicidade, bioquímicos, hematológicos, histopatologia de órgãos linfohematopoiéticos e fenotipagem de linfócitos T CD4, T CD8 e B de ratos Wistar machos. Foram utilizados dois protocolos experimentais: I - toxicidade aguda (28 dias) e II - toxicidade subcrônica (90 dias) sendo os animais expostos ao Diuron por via oral (adicionado à ração), nas concentrações de 125, 1250 e 2500 ppm. A exposição ao Diuron resultou em diminuição do ganho de peso corpóreo médio nos grupos 1250 e 2500 ppm aos 28 e 90 dias acompanhada pela redução do consumo de ração. O peso relativo do baço e dos rins foi maior nas três concentrações de Diuron aos 28 dias, e apenas em 2500 ppm, aos 90 dias. O peso relativo do fígado foi maior em 1250 e 2500 ppm aos 28 dias e apenas em 2500 ppm aos 90 dias. Aos 28 dias, os níveis de albumina e proteína total foram maiores nos três grupos expostos e os níveis de creatinina e uréia aumentaram apenas no grupo 2500 ppm. A análise histológica revelou que o Diuron, especialmente na maior concentração levou à depleção de polpa branca no baço, associada a redução do número de linfócitos T CD4+ e aumento de hematopoiese extramedular, deposição de hemosiderina e hiperplasia eritróide na polpa vermelha. Não foram observadas alterações hematológicas importantes. Com relação à análise fenotípica das subpopulações de linfócitos, observamos uma redução de células CD4+... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Few information is available regarding immunotoxic potential of Diuron, a phenylurea herbicide widely used in Brazil and around the world on sugar cane, cotton, coffee, pineapple, citros, alfafa and wheat crops.The objective of the present study was to evaluate the toxicity of Diuron in the immune system. General parameters of toxicity were evaluated and biochemistry, hematology, histologic aspects of lymphohematopoietic organs and CD4+, CD8+ and CD45RA+ splenic lymphocytes subpopulations of male Wistar rats. Two experimental protocols were used: I Acute toxicity (28 days) and II Sub-Chronic toxicity (90 days) and the animals were treated with 125 ppm, 1250 ppm and 2500 ppm of Diuron by feeding. The experimental groups treated with Diuron at 1250 ppm and 250o ppm, showed decreased body weight gain after 28 and 90 days of treatment, corresponding with the reduced food intake. The relative weight of the spleen and kidneys were higher at the three concentrations in the end of 28 days, and only at 2500 ppm after 90 days. The relative weight of the liver was higher at 1250 ppm and 2500 ppm to the 28 days, and only at 2500 ppm to the 90 days of treatment. After 28 days, the albumin and total protein serum levels were higher at the three treated groups and the creatine and urea higher only at 2500 ppm of Diuron. The treatment with Diuron at higher doses causes the depletion of the lymphoid white pulp and increases the hemosiderin deposition in the red pulp. We didn't observed significant hematological alterations between the treated and control groups. Regarding fenotipic analysis of splenic lymphocytes, it was observed a decrease in CD4+ subpopulations at 1250 ppm and 2500 ppm in the end of 28 days, and only at 2500 ppm after 90 days of treatment compared with the control groups values. Concluding, Diuron had a systemic toxic effect and also on lymphohematopoietic organs.
Orientador: Ana Lúcia Tozzi Spinardi-Barbisan
Coorientador: Luís Fernando Barbisan
Banca: Carla Adriene da Silva Franchi
Banca: Isis Machado Hueza
Mestre

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Bolt, Alicia Marie. "Arsenite Alters Lysosome-Mediated Degradation and the Autophagy Process Leading to Immunosuppression in Human B-Lymphoblastoid Cell Lines". Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/222895.

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The immune system is a target of arsenic toxicity. Epidemiological data have shown that arsenic exposure is associated with characteristics of immunosuppression. Human B-lymphoblastoid cell lines (LCL) were used as an in vitro model of immune cell targeting by arsenic to investigate the mechanism of arsenic-induced cytotoxicity, which could provided insight into the mechanism underlying arsenic-induced immunotoxicity leading to the immunosuppression observed in humans. In LCL arsenite-induced cytotoxicity was not associated with apoptosis, but associated with hallmarks of autophagy, a cell stress-responsive process that facilitates the removal of cellular components through lysosome-mediated degradation. At environmentally relevant concentrations, arsenite-induced toxicity resulted in a decrease in cell proliferation that was correlated with hallmarks of autophagy including expansion of acidic vesicles, global induction of lysosomal gene expression, increased flux of the autophagosome marker LC3-II, and increased enzymatic activity of the lysosomal hydrolase cathepsin D. Investigation of the upstream cellular damage leading to the induction of autophagy revealed that arsenite induces proteotoxic damage leading to an accumulation of protein aggregates that may be targeted to the lysosome for degradation. In addition, global gene expression data showed an enrichment of ER stress responsive genes after arsenite exposure. Further evaluation of global gene expression data indicated that the global induction of lysosomal genes occurs before the activation of ER stress genes, suggesting that the induction of autophagy may occur before the generation of ER stress. To investigate the effect of arsenite-induced proteotoxicity and autophagy on normal immune function, the ability of LCL to process and present exogenous antigens onto MHC class II molecules was evaluated. Arsenite decreased antigen presentation of the exogenous antigen HSA. This decrease was associated with decreased lysosomal degradation of the model substrate DQ-Ova, suggesting that arsenite is disrupting lysosome-mediated degradation. In addition, arsenite exposure was associated with an increase in MHC class II protein aggregates, which could render them unavailable to bind peptide fragments. Through the identification that arsenite induces proteotoxicity and autophagy in LCL, it provides novel insight into the mechanisms of arsenic-induced immunotoxicity that could lead to a better understanding of the mechanisms underlying arsenic-induced immunosuppression observed in humans.

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28

Besteman, Elizabeth Gayle. "Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Diethylstilbestrol (DES) in the Fetal Mouse Thymus and Liver". Diss., Virginia Tech, 2006. http://hdl.handle.net/10919/27887.

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Diethylstilbestrol (DES) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been identified as immunotoxicants causing thymic atrophy, thymocyte hypocellularity, phenotypic changes detected by CD4 and CD8 surface antigens, and progenitor T-cell targeting in the fetal mouse. We hypothesized that gestational exposure to these two compounds may lead to comparable histologic and gene expression alterations in the fetal mouse thymus and liver. Treatment of pregnant C57Bl/6 mice with doses of 5 or 10 ug/kg TCDD or 48 ug/kg DES by oral gavage on gestation days (gd) 14 and 16 severely depressed day 18 thymic cellularity. Histologic evaluation of day 18 fetal thymuses showed disruption of normal cortico-medullary architecture after TCDD or DES. Decreased thymocyte density was noted primarily in cortical zones where pyknotic cells were increased by either TCDD or DES treatment. Using day 18 thymocyte suspensions and flow cytometry, 7-AAD showed decreases in viable thymocytes from TCDD- or DES-treated fetal mice, and concomitant increases in thymocytes in early apoptosis. When thymocytes were co-identified with CD4 and CD8 cell surface antigen expression, enhanced apoptosis occurred in CD4+CD8+ phenotype after TCDD treatment. After DES exposure, increased apoptosis occurred in CD4-CD8- and CD4-CD8+thymocytes. Both TCDD and DES increased liver to body weight ratios and decreased ratios of hematopoietic to hepatic cells present. Cytomegaly was seen in hepatocytes of TCDD and DES treated animals, and these cells had more variable features, such as increased cytoplasmic basophilia and more prominent nucleoli. Real time quantitative PCR demonstrated that DES decreased c-jun, Bcl-2, and PKCalpha mRNA expression. These results suggest a shift away from proliferative activity and may reflect alterations noted predominantly in the hematopoietic population. TCDD increased c-jun mRNA expression with modest decreases in PKCalpha, and marked decreases in p53 also noted. Decreases in p53 suggest a pro-proliferative status of hepatic cells, while decreases in PKCalpha may indicate decreases in phosphorylation of substrates required for normal cell cycle progression. The increased c-jun suggests that this gene may play a role in the hepatocyte hyperplasia, as well as the diminution of hematopoiesis.
Ph. D.

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Vemireddi, Vimala. "Immunotoxic and Oxidative Effects of Endosulfan and Permethrin on Murine SPlenocytes, in vitro". Thesis, Virginia Tech, 2004. http://hdl.handle.net/10919/32983.

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Indiscriminate use of pesticides appears to alter immune response in non-target organisms such as humans and other animals. Thus, immune modulation is considered as one of the potential risks and consequences following exposure to these chemicals. Because of the widespread usage, exposure to mixtures of pesticides during the lifetime of individuals is unavoidable and can result in potentiation of the toxic effects. Because immune cells are more susceptible to toxic insults at a lower dose than most other cell types, the effects of pesticides and their mixtures on murine splenocytes were evaluated. C57BL/6 male mouse splenocytes, in vitro, were exposed to permethrin and endosulfan, individually and in-combination (25-200 ÂµM). The immunotoxic potential of these pesticides was monitored using a flow cytometric technique in combination with 7-Amino Actinomycin D (7-AAD) staining. Endosulfan exposures (25-150 ÂµM) resulted in time- and dose-dependent increase in apoptotic and necrotic cell death in murine splenocytes, in vitro. Permethrin exposure (50-200 ÂµM) resulted in neither a time-dependent/dose-dependent loss of splenocyte viability nor induction of apoptosis in splenocytes. With mixtures of permethrin and endosulfan, depressed viability and enhanced early apoptosis and late apoptosis/necrosis were observed. Exposure to mixtures of 50 ÂµM endosulfan with 50 or 100 ÂµM permethrin increased late apoptosis/necrosis compared to exposure to either chemical alone. DNA fragmentation, a hall mark of apoptosis was observed by DNA ladder technique, confirming the occurrence of apoptosis. Morphological observation using cytospun slides was also carried out to further confirm the presence of apoptosis and necrosis. These findings suggest that the immunotoxicity of endosulfan both individually and in mixtures with permethrin is associated with the occurrence of apoptotic and necrotic processes.

Further, the ability of these pesticides to alter the oxidative status of the cells, via reactive oxygen species (ROS) generation and modulation of intracellular antioxidant enzymes levels, was investigated. We monitored the generation of ROS such as hydrogen peroxide (H2O2) with 2Â´, 7Â´- dichlorofluorescin diacetate (DCFH-DA) assay and superoxide anion (O2-) with hydroethidine (HE) assay in combination with flow cytometry. Spectrophotometric techniques were used to measure antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPX). Results of the analyses revealed that individual pesticides increased the production of H2O2 in a time and dose-dependent manner. Both time and dose-dependent increases in O2- production were caused by permethrin; whereas endosulfan exposure resulted in only a dose-dependent increase. However, exposure to mixtures of these pesticides had little or no effect on the generation of H2O2 and O2- radicals as compared to individual pesticides. The levels of SOD and GPX in pesticide-treated splenocytes were found to be not different from solvent control. An increase in GR and CAT levels in cells was noticed with permethrin (100 ÂµM) exposure. These findings suggest that permethrin and endosulfan have the ability to affect the cellular oxidative status and can cause toxicity in immune cells, in vitro.
Master of Science

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30

Fowler, Jodi. "The Assessment of Effects of Carbon Quantum Dots on Immune System Biomarkers Using RAW 264.7 Macrophage Cells". University of the Western Cape, 2020. http://hdl.handle.net/11394/7712.

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>Magister Scientiae - MSc
Nanotechnology is a rapidly growing field of research. Due to major innovations brought about by developments in nanotech, several consumer products are currently available containing nanomaterials. The increase of nanomaterial production and use is accompanied by the increased potential of human, plant and animal exposure to these nanomaterials. As a relatively new nanomaterial, carbon quantum dots (CQDs) are being extensively used and researched due to its unique properties. Although many studies have assessed the toxic potential of CQDs, and found them to exhibit low toxicity, there is lack of work assessing the effects on the immune system. In the present study, RAW 264.7 murine macrophages were used as model to assess the immunomodulatory potential of CQDs. RAW cells exposed to varying concentrations of CQDs (0-500μg/ml), showed that CQDs caused a reduction at cell viability. In the absence of a mitogen CQDs, induced an inflammatory response by stimulating the release of various cytokines and chemokines such as, TNFα, MIP-1α, MIP-1β, MIP-2, IP-10, G-CSF, GM-CSF, and JE.

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Algadi, Hend Emhemed. "Effects of graphene oxide nanoparticles on the immune system biomarkers produced by RAW 264.7". University of the Western Cape, 2019. http://hdl.handle.net/11394/6983.

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Magister Scientiae (Medical Bioscience) - MSc(MBS)
Graphene oxide (GO) is a single carbon layer, oxygen bearing graphene derivative, containing hydroxyl and carboxyl groups. Graphene oxide nanoparticles (GONPs) are promising nanomaterials for a variety of applications such as electrochemical analysis, adsorption of biomolecules, biosensors and drug and vaccine delivery systems. While these newly engineered nanoparticles hold great potential for developments in industry and medicine, the widespread use of these material will inevitably result in GO residues in the environment where they could possibly pose a risk to human and wildlife health. Interaction of the nanoparticles and biota can affect numerous biological processes. In humans they can affect any of the physiological systems such as the immune, endocrine, reproductive and cardiovascular systems. Although studies have indicated that GO exposure cause increased reactive oxygen species in cells, they mechanisms whereby GO act on the cell are still poorly understood. A few studies have investigated the effects of GONP and other graphene nanoparticle derivatives on the immune system. The aim of this study was to investigate the in vitro effects of GONPs on the immune system by the exposure of the murine macrophage cell line, RAW 264.7, to different concentrations of GONPs.

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32

Shoko, Yeukai Phoebe. "The screening of phyto-pesticides for potential adverse effects on human health". Thesis, University of the Western Cape, 2010. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_7861_1328620487.

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Pesticides are designed to control or eliminate pests such as insects, rodents, weeds,
bacteria, and fungi. They are used at a global scale for agricultural produce. Although
pesticides play a significant role in increasing food production and eliminating diseases,
exposure to pesticides may be harmful to non-target organisms. As a result concern over
safety and resistance to pesticides has increased and there is pressure to reduce use and
search for more environmentally and toxicologically safe and efficacious pesticides. Most
pesticides currently in use are synthetic
therefore an alternative to synthetic pesticides is
the use of naturally occurring products/ botanicals with pesticidal properties.

Two plants indigenous to South African with pesticidal properties were chosen for this
study. Dicerothamnus rhinocerotis (D. rhinocerotis) and Galenia africana (G. africana)
have potential antifungal properties thus, may have potential use on agricultural produce
as fungicides. Galenia africana and D. rhinocerotis extracts inhibit growth of B. cinerea
(a fungal pathogen) at concentrations greater than 31.25 mg/ml and 125mg/ml
respectively. A major consideration in approving pesticides for use is whether they pose
an unreasonable risk to humans and to the environment. Toxicity studies are required to
determine the safety of the plant extracts.

The purpose of this study was to evaluate potential toxicity of ethanol extracts of D.
rhinocerotis and G. africana, which is important when designing practices to reduce or
eliminate excess exposure to them. Natural plant products with pesticidal properties could
provide an alternative to synthetic pesticides and may thus effectively reduce resistance
levels.

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Domingues, Alexandre [UNESP]. "Avaliação do potencial imunotóxico do herbicida diuron: estudo de toxicidades de 28 e 90 dias(doses repetidas)". Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/95906.

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Made available in DSpace on 2014-06-11T19:27:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-26Bitstream added on 2014-06-13T20:17:33Z : No. of bitstreams: 1 domingues_a_me_botfm.pdf: 594143 bytes, checksum: 583e125c7a9e0c3c3a4f6516dabc6d61 (MD5)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Escassas informações são encontradas na literatura a respeito do potencial imunotóxico do Diuron, um herbicida derivado da uréia, utilizado no Brasil e no mundo nas lavouras de café, cana-de-açúcar, algodão, abacaxi, citros, alfafa e trigo. Desta forma, o presente estudo teve por objetivo investigar a toxicidade do Diuron sobre o sistema imunológico. Para isso, foram avaliados parâmetros gerais de toxicidade, bioquímicos, hematológicos, histopatologia de órgãos linfohematopoiéticos e fenotipagem de linfócitos T CD4, T CD8 e B de ratos Wistar machos. Foram utilizados dois protocolos experimentais: I - toxicidade aguda (28 dias) e II - toxicidade subcrônica (90 dias) sendo os animais expostos ao Diuron por via oral (adicionado à ração), nas concentrações de 125, 1250 e 2500 ppm. A exposição ao Diuron resultou em diminuição do ganho de peso corpóreo médio nos grupos 1250 e 2500 ppm aos 28 e 90 dias acompanhada pela redução do consumo de ração. O peso relativo do baço e dos rins foi maior nas três concentrações de Diuron aos 28 dias, e apenas em 2500 ppm, aos 90 dias. O peso relativo do fígado foi maior em 1250 e 2500 ppm aos 28 dias e apenas em 2500 ppm aos 90 dias. Aos 28 dias, os níveis de albumina e proteína total foram maiores nos três grupos expostos e os níveis de creatinina e uréia aumentaram apenas no grupo 2500 ppm. A análise histológica revelou que o Diuron, especialmente na maior concentração levou à depleção de polpa branca no baço, associada a redução do número de linfócitos T CD4+ e aumento de hematopoiese extramedular, deposição de hemosiderina e hiperplasia eritróide na polpa vermelha. Não foram observadas alterações hematológicas importantes. Com relação à análise fenotípica das subpopulações de linfócitos, observamos uma redução de células CD4+...
Few information is available regarding immunotoxic potential of Diuron, a phenylurea herbicide widely used in Brazil and around the world on sugar cane, cotton, coffee, pineapple, citros, alfafa and wheat crops.The objective of the present study was to evaluate the toxicity of Diuron in the immune system. General parameters of toxicity were evaluated and biochemistry, hematology, histologic aspects of lymphohematopoietic organs and CD4+, CD8+ and CD45RA+ splenic lymphocytes subpopulations of male Wistar rats. Two experimental protocols were used: I Acute toxicity (28 days) and II Sub-Chronic toxicity (90 days) and the animals were treated with 125 ppm, 1250 ppm and 2500 ppm of Diuron by feeding. The experimental groups treated with Diuron at 1250 ppm and 250o ppm, showed decreased body weight gain after 28 and 90 days of treatment, corresponding with the reduced food intake. The relative weight of the spleen and kidneys were higher at the three concentrations in the end of 28 days, and only at 2500 ppm after 90 days. The relative weight of the liver was higher at 1250 ppm and 2500 ppm to the 28 days, and only at 2500 ppm to the 90 days of treatment. After 28 days, the albumin and total protein serum levels were higher at the three treated groups and the creatine and urea higher only at 2500 ppm of Diuron. The treatment with Diuron at higher doses causes the depletion of the lymphoid white pulp and increases the hemosiderin deposition in the red pulp. We didn't observed significant hematological alterations between the treated and control groups. Regarding fenotipic analysis of splenic lymphocytes, it was observed a decrease in CD4+ subpopulations at 1250 ppm and 2500 ppm in the end of 28 days, and only at 2500 ppm after 90 days of treatment compared with the control groups values. Concluding, Diuron had a systemic toxic effect and also on lymphohematopoietic organs.

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Ponce, Fernando. "Estudo das alterações imunológicas e comportamentais provocadas pelo crack em ratos adultos expostos à droga por via pulmonar". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-15122015-143149/.

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O crack, uma droga de abuso constituída principalmente por cocaína, continua sendo um grande problema social e de saúde pública. Apesar de vários estudos em modelos animais com outras formas de cocaína, raros são os relatos sobre os efeitos da exposição pulmonar ao crack em roedores, devido à dificuldade de realizar a exposição dos mesmos à droga, o que seria de grande valia, uma vez que eliminaria variáveis encontradas em usuários, como o uso de outras drogas. Assim, o propósito do presente estudo foi avaliar os efeitos tóxicos, imunotóxicos e ainda, alterações comportamentais de ratos Wistar machos expostos ao crack pela via pulmonar. Inicialmente, foram realizadas determinações de cocaína nas pedras de crack utilizadas e também, a quantidade de crack e tempo de exposição dos animais para obtenção de níveis séricos de cocaína semelhantes àqueles encontrados na literatura, e os dados obtidos foram de: 67% de cocaína no crack e a queima de 250 mg de crack, com exposição dos animais por 10 minutos acarretou em níveis plasmáticos próximos de 170 ng/mL de cocaína. Assim, em cada experimento foram utilizados 30 ratos divididos em 3 grupos iguais, um controle, um experimental e um grupo pair-fed, já que a cocaína promove efeitos anorexígenos que poderiam interferir nas avaliações comportamentais e imunológicas aqui estudadas, e que foram expostos ou não à fumaça resultante de 250 mg de crack, por 10 minutos, duas vezes ao dia, durante 28 dias. Ao final do período experimental, os animais foram submetidos à eutanásia para realização de avaliações bíoquimicas, hematológicas, histopatológicas, análise de órgãos-linfóides, avaliação das respostas imune inata (inflamatória), humoral e a avaliação da reação de hipersensibilidade do tipo IV. Ainda, ao longo do período experimental, estes mesmos animais foram avaliados quanto a possíveis alterações comportamentais e para tal foram utilizados 3 métodos distintos: avaliação cognitiva em labirinto em T, avaliação geral do comportamento em campo aberto e ainda, a avaliação de preferência ou aversão ao odor da droga. A exposição ao crack não resultou em alterações que caracterizem toxicidade em parâmetros clínicos, bioquímicos, hematológicos e histopatológicos; não foram observadas alterações com significado clínico nas avaliações do peso relativo, celularidade, morfometria de órgãos linfoides e fenotipagem de linfócitos esplênicos de ratos expostos à droga. Não houve efeitos imunomodulatórios nas avaliações do burst oxidativo e fagocitose de macrófagos peritoneais e de neutrófilos circulantes, assim como nas avaliações da produção de anticorpos T-dependentes e na reação de hipersensibilidade do tipo IV. Quanto às avaliações comportamentais, os animais expostos à droga apresentaram aumento da atividade locomotora, e uma maior preferência ao odor característico do crack, aparentemente sem prejuízo cognitivo. Em conclusão, a exposição de ratos 2 vezes ao dia, por 28 dias ao crack não promoveu alterações imunotóxicas; por outro lado, comportamentos clássicos da exposição à cocaína foram observados nos animais expostos, evidenciando que o modelo aqui utilizado será de grande utilidade para outros estudos que envolvam drogas de abuso, como possíveis estratégias terapêuticas e o melhor entendimento da toxicocinética de drogas utilizadas pela via pulmonar
Crack cocaine, a drug of abuse that consists mainly of cocaine, remains as a major social and public health problem. Although several studies in animal models with other forms of cocaine, there are few scientific reports on the effects of pulmonary exposure to crack in rodents, this is due to the difficulty of performing their exposure, which would be of great value, since would eliminate variables observed in users, such as the use of other drugs. Initially, the concentration of cocaine in crack samples, as the amount of crack and time of exposure of the animals to obtain serum levels of cocaine similar to those found in the literature were determined, and the data obtained were: 67% of cocaine in crack, and 250 mg of crack, exposing the animals for 10 minutes resulted in plasma levels close to 170 ng/mL of cocaine. Thus, the purpose of this study was to evaluate the toxic effects, immunotoxic and behavioral changes of male Wistar rats exposed to crack cocaine. Thus, in each experiment were used 30 rats divided into three groups, one control, one experimental and one pair-fed, since it is known that cocaine promotes anorexic effects that may interfere with behavioral and immunological assessments that will be studied here, and who were exposed or not to the burning of 250 mg of crack, for 10 minutes, twice daily for 28 days. At the end of the experiment, the animals were euthanized to perform biochemical evaluation, hematological, histopathological, analysis of lymphoid organs, evaluation of innate immune responses (inflammatory), humoral and the assessment of the type IV hypersensitivity reaction. Still, throughout the experimental period, these same animals were evaluated for possible behavioral changes and were used three different methods: cognitive assessment in T-maze, overall assessment on open field behavior and the evaluation of preference or aversion to the odor of the drug. Exposure to crack cocaine, did not result in changes that characterize toxicity in clinical, biochemical, hematological and histopathological parameters; were not observed clinically meaningful changes in the relative weight ratings, cellularity, morphology of lymphoid organs and phenotyping of splenic lymphocytes from rats exposed to the drug. There was no immunomodulatory effect in the evaluations of oxidative burst and phagocytosis of peritoneal macrophages and in circulating neutrophils, and the assessments of the production of T-dependent antibodies and the type IV hypersensitivity reaction. With regard to behavioral assessments, the animals exposed to the drug showed increased locomotor activity, and greater preference to the characteristic odor of crack cocaine, apparently without cognitive impairment. In conclusion, in the exposure model to crack cocaine used here, immunotoxic changes were not evident; by contrast, classic behavior of cocaine exposure were observed in the animals exposed, indicating that the model used herein will be useful for the study of other parameters involving drugs of abuse, in evaluation of therapeutic strategies and a better understanding of drugs toxicokinetics used by the pulmonary route

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Rahman, Qazi Mousumi. "Immunohepatotoxicity of the persistent environmental pollutants perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS)". Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-63180.

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Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), manufactured for a variety of industrial and consumer applications, are ubiquitous environmental pollutants. Their accumulation in humans and wildlife raises serious health concerns. Here, we examined the potential effects of PFOA and PFOS on the innate immune system in mice. Short-term dietary exposure to high doses reduces the total number and subpopulations of circulating white blood cells. Moreover, production of proinflammatory cytokines by macrophages in the peritoneal cavity and bone marrow, but not in the spleen following exposure to in vitro or in vivo stimulation by bacterial lipopolysaccharides is enhanced. With respect to adaptive immunity, PFOS reduces the total numbers of thymocytes and splenocytes and subpopulations thereof in a dose dependent fashion. Furthermore, comparison of wild-type mice and the corresponding knock-out strain lacking peroxisome proliferator-activated receptor-alpha revealed that these immunological changes are partially dependent on this receptor. Our further studies also show that sub-chronic dietary exposure to an environmentally relevant dose of PFOS does not alter the cellularity of the thymus and spleen and exerts no influence on humoral immune responses. To facilitate examination of the effects of PFOA and PFOS on the hepatic immune system, we developed a procedure for mechanical disruption that yields a larger number of functionally competent immune cells from this organ. In our last study, lower doses of PFOA or PFOS induced hypertrophy of hepatocytes and altered the hepatic immune status. Thus, we find that short-term, high- and low-dose exposure of mice to these fluorochemicals is immunohepatotoxic.
Perfluorooktanat (PFOA) och perfluorooktansulfonat (PFOS) som tillverkas för många olika industri och konsumentprodukter, är globalt förekommande miljögifter. Deras ackumulering i människor och djur ger upphov till en stark oro för hälsoproblem. Vi har granskat effekterna av PFOA och PFOS på det medfödda, ospecifika immunförsvaret. Exponering för höga doser via maten under kort tid minskar det totala antalet cirkulerande vita blodkroppar samt delpopulationerna.. Immunsvaret ökar dock efter stimulering med bakteriella lipopolysaccharider både in vitro och in vivo , dvs produktionen av proinflammatoriska cytokiner av makrofager i bukhålan och benmärgen, men inte i mjälten ökar.. När det gäller adaptiv, specifik immunitet minskar PFOS det totala antalet tymocyter och splenocyter och deras olika subpopulationer. Vid exponering för lägre doser av PFOS induceras hepatomegali utan att påverka tymus eller mjälten. Vi kunde visa att peroxisomal proliferator-aktiverad receptor-alfa medierar effekterna utav PFOS i tymus samt delar av effekterna av PFOS i mjälten genom att använda möss som saknade denna receptor. . Dettastöds av vår studie med subkronisk exponering för en miljömässig dos av PFOS vilken inte ändrade den cellulära sammansättningen i vare sig tymus eller mjälte och inte hade något inflytande på det humorala immunsvaret. För att underlätta studier av hur PFOA och PFOS påverkar immunsystemet i levern utvecklade vi en metod för framrening av immunceller via mekanisk sönderdelning av levern, vilket gavett större antal av funktionella immunceller från detta organ. I vår sista studie kunde vi påvisa att lägre doser av PFOA eller PFOS inducerade hypertrofi av hepatocyter samt en påverkan av leverns immunförsvar.

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Mendes, Patrícia Franciscone. "A cetamina associada ou não ao álcool, quais as consequências toxicológicas e sua influência no estresse oxidativo? Estudo em ratos". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-12122018-113556/.

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O uso recreacional e os efeitos deletérios de drogas lícitas e/ou ilícitas é considerado um problema de saúde pública. Dentre estas drogas destaca-se a cetamina, um anestésico empregado na veterinária e o etanol, a droga lícita mais utilizada. Além dos efeitos centrais, estudos revelam que a cetamina e o etanol possuem propriedades imunomodulatórias. No entanto, poucos estudos são realizados com a associação destas drogas; assim, o objetivo deste estudo foi o de avaliar os efeitos tóxicos, imunotóxicos, o potencial oxidativo e os possíveis efeitos neurotóxicos resultantes do consumo associado ou não das mesmas. Para isso, ratos Wistar foram tratados uma vez ao dia, por até 28 dias, com injeções intraperitoneais (15 ou 30mg/kg/PV) de cetamina (K) ou com etanol a 10% (E) via oral (gavagem ou adicionado a água de bebida), ou ainda em associação (KE). O grupo controle recebeu apenas os veículos dos tratamentos. Ao final do experimento, os animais foram submetidos à eutanásia para realização de avaliações toxicológicas, imunológicas, oxidativas e antioxidativas, e de neurotransmissores centrais. Os resultados revelaram redução no ganho de peso dos animais tratados com KE e aumento de ácido ascórbico urinário. A redução de pH e glicose urinária foi observada nos grupos E e KE. Na bioquímica, todos os grupos apresentaram aumento de HDL, porém a associação das drogas levou a um aumento do colesterol, enquanto no grupo K, observou-se diminuição dos triglicérides e da fosfatase alcalina. Ainda, somente o grupo KE apresentou alterações na função renal. Todos os grupos experimentais exibiram alterações histopatológicas hepáticas e/ou vesicais. Os grupos E e KE apresentaram alterações no número de células mieloides e linfoides concomitantes ao aumento na celularidade de medula óssea. Apenas animais do grupo KE apresentaram alteração na resposta do tipo Th2. Foi observado o aumento da peroxidação lipídica nos animais tratados com K, bem como aumento na atividade de GPx e CAT e do conteúdo de GSSG dos animais tratados com E e/ou KE nos órgãos analisados. Ao nível central, observou-se elevação dos níveis de DA e NOR no hipocampo dos animais do grupo E, e 5HT nos animais do grupo K; além de aumento de DA e 5HT no córtex pré-frontal dos animais dos grupos E e K, respectivamente. Assim, concluímos que a associação KE promove redução do ganho de peso não relacionado ao consumo de ração. O etanol, em associação ou não, promove alterações nos parâmetros urinários; a cetamina promove diminuição nos níveis de FA e as drogas quando em associação alteram o perfil lipídico e renal na dependência da dose e do tempo de administração. Efeitos pró-oxidantes entraram em equilíbrio devido à ação de antioxidantes. O etanol, em associação ou não, promove alterações em células do sistema imune, no entanto, sem promover imunomodulação sobre suas respostas. O etanol e/ou a cetamina também promovem alterações histopatológicas hepáticas, enquanto que a associação ainda promove lesões vesicais. Além disso, ambas as drogas promovem alterações no perfil neuroquímico central; porém, quando associadas não promoveram efeitos sinérgicos sobre os parâmetros avaliados.
The recreational use and the deleterious effects of licit and/or illicit drugs are considered a public health issue. Among these drugs are ketamine, used in veterinary anaesthesia, and ethanol the most commonly licit drug. Besides their central effects, studies have shown that ketamine and ethanol have immunomodulatory properties. However, few studies are conducted with the association of both drugs; thus, we aimed to evaluate the toxic and immunotoxic effects, as well the oxidative potential and the possible neurotoxic effects resulted from the consumption of these drugs associated or not. For this, Wistar rats were treated once daily for up to 28 days with intraperitoneal injections (15 or 30mg/kg/BW) of ketamine (K) or orally with 10% ethanol (E) (gavage or drinking water) or the association of both treatments (KE). Control group received only vehicles. At the end of the experimental period, the animals were euthanized for toxicological, immunotoxicological, oxidative stress and antioxidant status evaluation, and central levels of neurotransmitters. KE animals showed reduced body weight gain and increased levels of urinary ascorbic acid. Reduction of urinary pH and glucose was observed in E and KE groups. Biochemistry analysis showed an increase in HDL levels in all experimental groups; although, KE showed an increase in cholesterol levels, while K group exhibited reduction in triglycerides and alkaline phosphatase (ALP) levels. Only KE group showed renal function alterations. All experimental groups showed hepatic and/or bladder histopathology alterations. E and KE groups exhibited alterations in myeloid and lymphoid cells number with concomitant increased in bone marrow cellularity. Only animals of KE group presented changes in Th2 response. Increased in lipid peroxidation was observed in K-treated animals, as well as GPx and CAT activities and GSSG content of animals treated with E and/or KE. We observed elevation in DA and NOR in hippocampus of E group and 5HT in K group, in addition to an increase in DA and 5HT of the prefrontal cortex of E and K groups, respectively. Thus, we conclude that KE association promotes reduction in body weight gain not related to food consumption. Ethanol, in combination or not, promotes urinary alterations; ketamine reduces ALP levels and the drugs, when in combination, alter lipid and renal profile depending on dose and time of administration. Pro-oxidant effects were balanced due to the action of antioxidants. Ethanol, associated or not, promotes alterations on immune cells without immunomodulatoty responses. Ethanol and/or ketamine also promotes liver histopathological alterations, while this association promotes bladder lesions. In addition, both drugs promote changes in central neurochemical levels; however, when associated do not promoted synergistic effects in evaluated parameters.

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Stetzer, Randy T. "Immunological and Developmental Effects of Polybrominated Diphenyl Ethers (PBDEs) and 2,3,7,8-tetrachloro-p-dioxin (TCDD) in Birds". Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1189789668.

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Rhile, Mark Joseph. "Immunotoxicity of TCDD : role of Fas expression and MHC phenotype on TCDD-mediated thymic artophy and decrease in peripheral T cell responsiveness /". Thesis, This resource online, 1995. http://scholar.lib.vt.edu/theses/available/etd-01312009-063044/.

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Walderdorff, Louise. "Étude comparative de la réactivité des cellules du système immunitaire (invertébrés et vertébrés) vis-à-vis des pesticides". Electronic Thesis or Diss., Université de Lorraine, 2019. http://www.theses.fr/2019LORR0268.

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Les pesticides synthétiques sont de plus en plus utilisés dans la lutte antiparasitaire moderne et dans l'agriculture conventionnelle. Leurs résidus sont fréquemment trouvés dans notre environnement et dans notre alimentation. Le groupe des insecticides les plus couramment utilisés sont les néonicotinoïdes et leurs résidus ont par exemple été trouvés dans les fruits et légumes traités, le pollen et le miel, ainsi que dans l’organisme des abeilles. Même si les concentrations environnementales rencontrées sont plutôt faibles par rapport aux concentrations pour la toxicité aiguë, elles mènent à des effets sublétaux dans l'organisme exposé. Plusieurs études ont montré un affaiblissement de l’effet des néonicotinoïdes sur les pollinisateurs lorsqu'ils sont confrontés à des agents pathogènes. De plus, d'autres pesticides sont liés à plusieurs maladies chez l'homme. Ainsi les pesticides pourraient avoir un impact direct sur le système immunitaire des invertébrés et / ou des vertébrés. Dans les dernières années, un déclin dramatique de pollinisateurs a été rapporté dans le monde entier. De nombreuses hypothèses ont été proposées pour expliquer la cause de cette baisse en mentionnant les agents pathogènes, le changement climatique, la perte de l'habitat et l'exposition aux pesticides. Bien que plusieurs études aient été menées sur les effets des pesticides et l'exposition simultanée des abeilles à des agents pathogènes, seules quelques-unes ont été réalisées en se concentrant sur la réponse spécifique des cellules immunitaires des insectes pollinisateurs comme celles des abeilles et de Drosophila melanogaster. Dans le système immunitaire des invertébrés et vertébrés, les cellules de la réponse primaire ou innée, notamment les cellules phagocytaires, sont comparables du point de vue morphologique et peuvent avoir une réactivité comparable vis-à-vis des polluants de l'environnement. Cette réactivité implique leur mobilité, morbidité ou la production de molécules d'alerte et de défense (cytokines, ROS...), faisant de ces cellules des indicateurs précoces des pollutions environnementales.L'objectif de cette étude est de comparer la cytotoxicité des pesticides et ses métabolites sur les cellules du système immunitaire des invertébrés et des vertébrés
Synthetic pesticides are increasingly used in modern pest control and in conventional agriculture and thus their residuals can be found frequently in our environment and in our food. The most commonly used group of insecticides are the neonicotinoids and residues of them have been found in treated vegetables and fruits, as well as in honey bees, their pollen, and honey. Even if these encountered environmental concentrations are rather small compared to concentrations for acute toxicity they still lead to sublethal effects in the exposed organism. Several studies showed a weakening effect of neonicotinoids on pollinators when confronted with pathogens and other pesticides are linked to several diseases in human. Thus pesticides might have a direct impact on the immune system of invertebrates and/or vertebrates. In recent years a dramatic decline of pollinators has been reported for the northern hemisphere. Many assumptions have been made on the cause of this decline mentioning pathogens, climate change, habitat loss and pesticide exposure, while there is still no evidence that one of these alone might be the ultimate cause. Although several studies have been conducted on the effect of pesticides and the simultaneous exposure of bees to pathogens only few of these have been concentrating on the actual immune response of pollinating insect immune cells like those of honeybees and of Drosophila melanogaster. Innate immune responses in mammals and insects do show several functional similarities. Cells, especially phagocytes, of these innate immune systems are comparable both in terms of morphology and reactivity towards pathogen recognition. This responsiveness involves mobility, morbidity or production of warning and defense molecules (cytokines, ROS...), making these cells early indicators of environmental pollution. The objective of this PhD is thus to compare the cytotoxicity of pesticides and their metabolites on immune system cells of invertebrates and vertebrates

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Lautert, Claudia. "Efeitos de micotoxinas sobre o sistema imunológico de frangos de corte". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/116166.

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Aves domésticas são um dos principais alvos da contaminação alimentar com micotoxinas. O que contribui para o aumento dos prejuízos da indústria avícola devido a problemas como: alta mortalidade, redução do ganho de peso, alteração da conversão alimentar, imunossupressão, anormalidades embrionárias e morte embrionária precoce. Além disso, o acúmulo residual de micotoxinas na carne é uma preocupação da Saúde Pública. Diversos métodos são utilizados para a avaliação da citotoxicidade induzida por agentes tóxicos, incluindo a inibição do crescimento celular, a avaliação da capacidade celular de sintetizar macromoléculas necessárias para a replicação e da capacidade desse agente tóxico para induzir a peroxidação lipídica. Sendo assim, o objetivo geral do presente estudo foi avaliar os efeitos in vitro de ocratoxina A, deoxinivalenol e zearalenona sobre o sistema imunológico de frangos de corte, utilizando como parâmetros, a viabilidade celular, a atividade enzimática e o estresse oxidativo. Realizou-se cultivo primário de linfócitos das aves e o seu isolamento através da técnica de centrifugação por gradiente de densidade. Cada micotoxina foi adicionada ao meio celular, em uma confluência de 80%, em diferentes concentrações (0,001; 0,01; 0,1 e 1 μg/mL), analisando-se viabilidade celular, atividade de ecto-adenosina desaminase e acetilcolinesterase por ensaios colorimétricos e peroxidação lipídica através dos níveis de malondialdeído mensurados pela técnica de substâncias reativas ao ácido tiobarbitúrico. Todos esses parâmetros foram analisados em 24, 48 e 72 h, em triplicata e os resultados expressos como média e erro padrão da média, utilizando nível de significância P<0,05. Os resultados obtidos demonstraram que tanto ocratoxina A como deoxinivalenol induziram proliferação linfocitária e baixa atividade de adenosina desaminase, enquanto zearalenona também induziu proliferação, mas nenhuma alteração na atividade da respectiva enzima. Quanto à avaliação da peroxidação lipídica, demonstrou-se a seguinte relação crescente de citotoxicidade: deoxynivalenol> ocratoxina A> zearalenona; enquanto que na avaliação da atividade de acetilcolinesterase esta relação foi inversamente proporcional. Este é o primeiro estudo in vitro realizado com ocratoxina A, deoxinivalenol e zearalenona sobre o cultivo primário de linfócitos de frangos de corte na avaliação desses parâmetros.
Poultry is one of the main targets of food contamination with mycotoxins. This contributes to the increase in the poultry industry losses due to problems such as high mortality, reduced body weight gain, change in feed conversion, immunosuppression, embryonic abnormalities and early embryonic death. Furthermore, the residual accumulation of mycotoxins in the meat is a public health concern. Various methods are used to assess the cytotoxicity induced by toxic agents, including inhibition of cellular growth, the evaluation of cell ability to synthesize macromolecules necessary for replication and the ability of this toxic agent to induce lipid peroxidation. Thus, the general objective of this study was to evaluate the in vitro effects of ochratoxin A, deoxynivalenol and zearalenone on the immune system of broiler chickens using as parameters, cell viability, enzymatic activity and oxidative stress. It was realized a primary culture of lymphocytes of birds and their isolation through density gradient centrifugation technique. Each mycotoxin has been added to the cell medium, at 80% confluence, at different concentrations (0.001, 0.01, 0.1 and 1 μg/ mL), analyzing cell viability, ecto-adenosine deaminase and acetylcholinesterase activity by colorimetric assays and lipid peroxidation through the malondialdehyde levels measured by thiobarbituric acid-reactive species test. All these parameters were evaluated at 24, 48 and 72 h, in triplicate and the results expressed as mean and standard error of the mean, using P<0.05 as significance level. The results showed that both ochratoxin A and deoxynivalenol induced lymphocyte proliferation and low adenosine deaminase activity, while zearalenone also induced proliferation, but no change in their enzyme activity. The assessment of lipid peroxidation demonstrated the following increasing cytotoxicity relation: deoxynivalenol>ochratoxin A>zearalenone; while in the evaluation of acetylcholinesterase activity this relationship was inversely proportional. This is the first in vitro study performed with ochratoxin A, deoxynivalenol and zearalenone on the primary culture of broiler chicken lymphocytes evaluating these parameters.

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Mendes, Patrícia Franciscone. "Avaliação dos possíveis efeitos tóxicos e imunotóxicos da Uncaria tomentosa em ratos". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-13112014-162653/.

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A Uncaria tomentosa (U. tomentosa), popularmente conhecida como \"Unha-de-gato\", é uma planta medicinal nativa das Américas, mundialmente empregada devido às suas atividades anti-inflamatórias e imunomodulatórias. O consumo desta planta ocorre não apenas na forma in natura, mas principalmente como fitoterápico, sendo muitas vezes utilizada de forma indiscriminada pela população. Apesar de vários estudos revelarem as propriedades terapêuticas da U. tomentosa, poucos são os trabalhos que empregam protocolos estabelecidos por agências regulamentadoras internacionais, para a avaliação dos possíveis efeitos tóxicos e imunotóxicos deste fitoterápico. Assim, o propósito do presente estudo foi verificar se a administração de um extrato seco de U. tomentosa, comercialmente disponível no mercado, poderia ocasionar efeitos tóxicos e imunotóxicos em ratos após 90 dias de tratamento. Para isso, 40 ratos Wistars machos foram tratados oralmente com as doses de 15, 75 ou 150 mg/kg de extrato seco de U. tomentosa comercialmente disponível no mercado, contendo teores de alcaloides de acordo com aqueles valores preconizados em literatura. No final do período experimental, os animais foram submetidos à eutanásia para realização de avaliações bioquímicas, hematológicas, histopatológicas, análise de órgãos linfoides e não-linfoides, avaliação das respostas imunes inata, inflamatória e humoral, bem como teste para determinação de reação de hipersensibilidade do tipo IV. Os resultados revelaram aumento nos níveis de ALT dos animais tratados com a dose de 75 mg/kg, e redução nos índices glicêmicos de ratos tratados com 75 e 150 mg/kg de U. tomentosa. Entretanto, somente os ratos tratados com a maior dose exibiram discreta vacuolização centro-lobular hepática; assim, somente os dados de ALT não são sugestivos de efeitos hepáticos adversos da U. tomentosa após um longo período de tratamento. A redução nos índices sanguíneos de glicose dos ratos, após tratamento com a U. tomentosa, podem representar importante risco para seres humanos diabéticos, susceptíveis ao desenvolvimento de hipoglicemia e que fazem uso da U. tomentosa para outros propósitos. Em conclusão, estes estudos demonstraram que, apesar de a U. tomentosa não promover efeitos tóxicos e imunotóxicos, o uso prolongado da mesma, a altas doses, pode promover redução dos índices glicêmicos.
Uncaria tomentosa (U. tomentosa), commonly known as \"Cat\'s claw\", is a native medicinal plant from America, it is employed worldwide for its anti-inflammatory and immunomodulatory activities. The consumption of this plant occurs not only in natura, but mainly as a phytotherapic, used indiscriminately by the population. Although many researchers revealed the therapeutic properties of U. tomentosa, few studies employing established protocols by international regulatory agencies for the evaluation of the possible toxic and immunotoxic effects of this herbal medicine. Thus, the purpose of the present study was to verify if the dry extract of U. tomentosa could promote toxic and/or immunotoxic effects in rats following 90 days of treatment. For this, forty male rats were orally treated with 15, 75 or 150mg/kg of dry extract of U. tomentosa, commercially available, containing levels of alkaloids according to those values recommended in the literature. At the end of experimental period, the rats were killed for the evaluation of the biochemistry, haematology, histopathology, status of the lymphoid and non-lymphoid organs, evaluation of innate, inflammatory and humoral immune responses, as well as a test to determine the delayed type hypersensitivity. The results revealed an increase in the levels of ALT in the animals treated with 75mg/kg and a reduction in the glycaemic levels of rats treated with 75 and 150mg/kg of U. tomentosa. However, only rats treated with the higher dose showed a slight centrilobular hepatic vacuolation; thus, ALT data alone are not suggestive of a hepatic adverse effect of U. tomentosa following long-term treatment. The reduction in blood glucose levels of the rats, could represent an important risk for diabetic humans, who are susceptible to the development of hypoglycaemia and who might use U. tomentosa for purposes other than anti-diabetes. In conclusion, these studies demonstrated that, while U. tomentosa has no immunotoxic effect, long-term U. tomentosa treatment at high doses can promote reduction in glycemic levels.

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Deak, Kristina L. "Cloning and Characterization of IL-1β, IL-8, IL-10, and TNFα from Golden Tilefish (Lopholatilus chamaeleonticeps) and Red Snapper (Lutjanus campechanus)". Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5416.

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Cytokines are pleiotropic and redundant signaling molecules that govern the inflammatory response and immunity, a critical ecological parameter for organism success and population growth. Produced at the site of injury or pathogen intrusion by a variety of cell types, cytokines mediate cell-signaling in either an autocrine or paracrine manner. The type and magnitude of the cytokine milieu produced subsequently dictates the strength and form of immune response. As the most diverse vertebrate group, with a high sensitivity to contaminants, fish represent an important foci for the evaluation of immune system evolution, function, and alteration upon toxicant exposure. While many cytokines have been identified in teleosts, primary study has been limited to model species (e.g. zebrafish and fugu). However, evidence exists for several variations of cytokine genes within taxa, underscoring the need for species-specific evaluation. In this study, two pro-inflammatory cytokines (IL-1β and TNFα ), one chemokine (IL-8), and one anti-inflammatory cytokine (IL-10) were cloned, sequenced, and characterized for the first time in two commercially relevant Perciformes in the Gulf of Mexico, golden tilefish (Lopholatilus chamaeleonticeps) and red snapper (Lutjanus campechanus). The complete amino acid sequence was obtained and confirmed for IL-β and IL-8 from golden tilefish and for IL-8, IL-10, and TNFα from red snapper, with partial sequences obtained for the remaining proteins. The results indicate high homology among Perciformes for all cytokines studied, but divergence with other teleost orders, and low conservation when compared to birds, amphibians, and mammals. The sequences will be used to create a multi-plexed antibody-based assay for the routine detection of cytokines in teleost serum. This would allow the biochemical response to fish health challenges, such as oil spills and other contamination events, to be monitored at the protein level, building upon the current regime of genetic biomarkers. Thus, this work will aid in the understanding of how oil spills and other contamination events may alter the immune response in fishes.

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Dao, Duy Khiem. "Immunotoxicité des dioxines". Paris 5, 1997. http://www.theses.fr/1997PA05P127.

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Smith, Dorinda Ann. "The Development and Application of a Hemolytic Plaque Forming Cell Assay (PFC) and a Cytotoxic T-Lymphocyte Assay (CTL) in Tilapia (Oreochromis niloticus) for Immunotoxicity Risk Assessment of Environmental Contaminants". Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/36948.

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The prospect of utilizing the cichlid teleost tilapia (Oreochromis niloticus) as an alternative experimental model to mammals for immunotoxicity risk assessment is currently being proposed. As such, the National Toxicology Program's (NTP) standard battery of rodent immunotoxicity assays is being developed for use in this fish species. Included in the testing series are the hemolytic plaque forming cell (PFC) and the cytotoxic T-lymphocyte (CTL) assays, quantitative indicators of antibody production and cell-mediated activity, respectively. The assays were modified in consideration of specific tilapian immune parameters, then tested using fourteen environmental contaminants or drugs, ten of which are classified by the NTP as immunotoxic in rodents. Reduced antibody production via a decrease in plaque number was observed in response to exposure of tilapia to eight of the nine humoral immunotoxicants, and five of the five non-immunotoxicants. Under specific immunization circumstances, immunostimulation (also a response to immunotoxicity) was noted via an increase in plaque number in benzo[a]pyrene (B[a]P) exposed fish using the PFC assay, a result noted in rodents as well. Reduced T-cell recognition and lysis of allogeneic tilapian lymphocytes via a decrease in the percentage of specific 51Chromium (51Cr) release was observed in response to exposure of tilapia to the nine of the ten cell-mediated immunotoxicants, and four of the four non-immunotoxicants. Although the normal teleost immune responsiveness was slightly weaker than seen with mice under comparable conditions (presumably due to differences in antibody structure and decreased cells counts), tilapia were found to exhibit well-defined humoral and cell-mediated immune responses, and responses to immunotoxic and non-immunotoxic chemicals comparable to the rodent model.
Master of Science

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Costa, Leonor Coutinho. "Mechanisms of immunotoxic effects of nanomaterial in fish". Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12616.

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Mestrado em Química - Química Analítica e Qualidade
Information and knowledge related to nanotechnology raise new challenges to the scientific community mainly in terms of human health risks and environmental implications associated to nanomaterials. In this perspective, the contamination of aquatic environments cannot be overlooked since it is an ultimate repository of the contaminants where this emerging appears as part of a cocktail of different classes of contaminants. Thus, the major task of this work was to connect gaps in current knowledge with a comprehensive sequence of biological responses toward environmentally relevant concentrations of engineered nanomaterials (IONM - silica coated iron oxide nanomaterial functionalized with dithiocarbamate group) and their interaction with other conventional anthropogenic contaminant (Hg - mercury), outlining the interaction with the innate immune system of fish. The research was divided into following steps: i) phagocytes macrophages were isolated from peritoneum (P-phagocytes), gill (G-phagocytes), head kidney (HK-phagocytes) and spleen (S-phagocytes) of European eel Anguilla anguilla L. in order to evaluate whether, and how can IONM and its co-exposure to Hg modulate phagocytes status and function; ii) determine the changes in phagocytes activation and their association to peroxidative damage (OBA - oxidative burst activity; LPO - lipid peroxidation); iii) to assess the impact of IONM on phagocytes enzymatic (CAT - catalase; GPX - glutathione peroxidase; GR - glutathione reductase; and GST - glutathione S-transferase) and non-enzymatic (NP-SH - non-protein thiols; and TGSH - total glutathione) antioxidants protection overtime. It was hypothesized that IONM can cause measurable changes in fish immune response and oxidative stress modulation. A period of exposure-dependency was exhibited by IONM alone and IONM+Hg joint exposures accrued impacts on A. anguilla phagocytes. IONM exposure alone lead to an acute response in terms of viability increase in P-phagocytes and modulated phagocytic activity in P-, and S-.phagocytes during 2 hours of exposure; whereas, IONM lead to a chronic immunotoxicity during 72 hours exposure only in S-phagocytes. However, IONM+Hg exposure lead to both acute and chronic response in terms of modulated phagocytic activity with no change in viability in P-, HK- and S-phagocytes only. Increase in the period of exposure to Hg disrupted phagocytic activity of P-, HK- and S-phagocytes, an increase in P- and decrease in HK- and S- phagocytes was perceptible at late hours of exposure. The occurrence of synergism between IONM and Hg was evidenced at 72 hours by significantly increasing trends of phagocytosis increase. A differential extent of OBA and LPO induction at the end of different period of exposure to IONM, Hg or IONM+Hg was also perceptible. The OBA induction and its concomitant association to LPO induction were observed only in gill after exposure to Hg (8 and 48 hours) and IONM+Hg (8 hours). At late hours of exposure, an induction was observed in G- phagocytes (OBA) after exposure to IONM+Hg suggesting that the concomitant exposure was unable to mitigate the Hg-accrued negative impacts. A. anguilla also displayed that the damage was accompanied with a differential modulation of enzymatic and non-enzymatic antioxidants in P, G-, HK- and S-phagocytes. Under IONM alone exposure, no LPO induction along the time was observed probably due to efficient induction of, GR and GST providing a better protection to IONM exposed phagocytes. However, antioxidants protection responses displayed hours of exposure dependency in G- and S-phagocytes where, an insufficiency of elevated CAT, GPX, GST, NP-SH and TGSH was clearly depicted for the maintenance of pro- and antioxidant balance optimum for scavenging ROS and protecting membrane lipids against IONM impact. As increased LPO was observed under IONM alone exposure condition, the joint action of IONM+Hg led to elevated damages to membrane-lipids at 4 and 8 hours (G-phagocytes), 2 hours (HK-phagocytes) and 24 hours (S-phagocytes) of exposure. These responses together, point towards the antioxidants defense failure for the protection of membrane lipids during those periods of exposure to IONM+Hg. However, it is important to underline here that during the late hours of exposure (72 hours), the results imply the positive effect of the concomitant exposure (IONM+Hg) which significantly mitigated the said negative impacts of Hg. Overall, the observations of this study open up new insight into the areas of evaluation of immune defense mechanisms in fish exposed to IONM and recommend that the interactions between IONM and other conventional anthropogenic contaminants should be considered while interpreting the fish immunotoxicity responses to IONM exposure in a multi-pollution state.
Informações e conhecimentos relacionados com a nanotecnologia colocam novos desafios à comunidade científica, principalmente em termos de riscos para a saúde humana e alterações ambientais. A contaminação dos ambientes aquáticos não pode ser ignorada, uma vez que é um repositório final dos contaminantes onde estes aparecem como parte de um conjunto complexo de diferentes tipos. O objetivo principal deste trabalho foi relacionar lacunas no conhecimento atual com uma sequência de respostas biológicas, para concentrações ambientalmente relevantes de nanomateriais (ONM - nanomateriais de óxidos de ferro revestidos com sílica e funcionalizados com grupos de ditiocarbamato) e avaliar a sua interação com outros contaminantes antropogénicos, nomeadamente mercúrio (Hg), na interação com o sistema imunitário de peixes. A investigação desenvolvida foi dividida nos seguintes passos: i) os macrófagos fagocitados foram isolados da cavidade peritoneal (P-fagócitos), das guelras (G-fagócitos), da “cabeça do rim” (HK-fagócitos) e do baço (S-fagócitos) da enguia europeia Anguilla anguilla L., a fim de avaliar como podem os ONM e a sua co-exposição com o mercúrio modular o estado das fagocitoses e a sua função; ii) avaliar as alterações na ativação das fagocitoses e a sua associação ao dano peroxidativo (OBA – atividade respiratória oxidativa; LPO - peroxidação lipídica); III) avaliar o impacto das ONMs ao longo do tempo nos antioxidantes, nomeadamente fagocioses enzimáticas (CAT - catalase; GPX - glutationa peroxidase; GR - glutationa redutase; e GST - Glutationa S-transferase) e não enzimáticas (NP-SH- proteína não-tiol; e TGSH - glutationa total). É apresentada a hipótese de que as ONMs podem causar mudanças na resposta imunológica de peixe e modular o stress oxidativo. Uma dependência do período de exposição foi observada para as ONMs isoladas e também uma sucessão de impactos sobre as fagocitoses da Anguilla Anguilla. A exposição isolada às ONMs parece poder induzir uma resposta aguda em termos de aumento de viabilidade em P-fagócitos e uma atividade fagocítica modulada em P e S-fagócitos após 2 horas de exposição; as ONMs podem induzir imunotoxicidade crónica durante uma exposição de 72 horas, apenas em S-fagócitos. A coexposição a ONM+Hg induziu uma resposta aguda e crónica em termos de atividade fagocítica modulada, com nenhuma mudança na viabilidade em P, HK e S-fagócitos. O aumento do período de exposição a Hg interrompeu a atividade fagocítica de P-, HK - e S-fagócitos. Porém, um aumento de P - e diminuição de HK - e S-fagócitos foi percetível nas 72 horas. A ocorrência de sinergismo entre as ONMs e o Hg foi evidenciado às 72 horas pela tendência do aumento significativo das fagocitoses. Diferença nas induções de OBA e LPO para diferentes períodos de exposição, às ONMs, Hg e ONMs+Hg foi também percetível. Uma indução de OBA paralela à resposta do LPO foi observada unicamente nas guelras por exposição ao Hg (8 e 48 horas) e ONMs+Hg (8 horas). Para períodos mais longos de exposição, foi observada uma indução nas G-fagócitos (OBA) depois da exposição a ONMs+Hg, sugerindo que a contaminação ONMs+Hg é capaz de mitigar os impactos negativos do Hg-acumulado ao longo do tempo. A. Anguilla evidenciou danos ao nível da modulação diferencial de antioxidantes enzimáticos e não enzimáticos em P, G, HK e S-fagócitos. Sob exposição simples às ONMs, não foi observada nenhuma indução do LPO ao longo do tempo, talvez devido à indução eficiente de GR e GST, proporcionando uma melhor proteção para os fagócitos expostos às ONMs. No entanto, as respostas de proteção dos antioxidantes exibiram dependência das horas de exposição em G - e S-fagócitos onde uma insuficiência elevada em CAT, GPX, GST, NP-SH e TGSH foi claramente observada para a manutenção do equilíbrio antioxidante e eliminação de ROS, protegendo os lipídios da membrana contra o impacto das ONMs. A ação conjunta das ONM+Hg conduziu a elevados danos nos lipídios da membrana às 4 e 8 horas (G-fagócitos), 2 horas (HK-fagócitos) e 24 horas (SP-fagócitos) de exposição. Estas respostas conjuntas, apontam para o fracasso da defesa dos antioxidantes na proteção dos lipídios da membrana durante os períodos de exposição com ONM+Hg. De salientar que para exposições de 72 horas, os resultados evidenciam efeitos positivos da exposição concomitante a ONM+Hg o que atenuou impactos negativos do Hg. As observações deste estudo dão novas ideias sobre a avaliação dos mecanismos de defesa imunotoxicológica em peixes expostos a ONMs e indicam que as interações entre ONMs e outros contaminantes antropogénicos devem ser consideradas na interpretação das respostas imunotóxicas de peixe expostos às ONMs em situações contaminação múltipla.

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Hernandez, Denise Marie. "Immunotoxicological Evaluation Of Critical Windows Of Development Following Exposure to 1,2:5,6 Dibenzanthracene in B6C3F1 Mice". VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1605.

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Vi-Fane, Sylvie. "Immunotoxicité du mercure et de ses dérivés". Paris 5, 1993. http://www.theses.fr/1993PA05P135.

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Blot, Christian. "Immunotoxicité des molécules médicamenteuses : mécanismes impliqués dans les différences inter-espèces". Paris 11, 1994. http://www.theses.fr/1994PA114844.

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Bruneau, Audrey. "Immunotoxicité des nanoparticules de Cd/S, Cd/Te et d’Ag sur des espèces modèles". Brest, 2011. http://www.theses.fr/2011BRES2015.

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A l'heure actuelle, l'usage des nanoparticules (NP5) est de plus en plus médiatisé. Elles sont maintenant utilisées à grande échelle dans de nombreux domaines, L’objectif principal de cette thèse était donc d’évaluer l’immunotoxicité des NPs de Cd/S, Cd/Te et d’Ag sur 4 espèces modèles: l’humain, la souris, la truite arc en ciel et la moule bleue, Dans le cadre de ces travaux, nous avons défini quatre sou objectifs: 1) déterminer l’impact des NPs sur différentes cellules et systèmes immunitaires 2) évaluer les facteurs influençant la toxicité des NPs; 3) identifier les atteintes mécanistiques de la réponse immunitaire 4) établir la toxicité des NPs en fonction des stress environnementaux. Les résultats du projet ont démontrés que les NPs induisent des altérations des performances du système immunitaire, selon les espèces. De plus, nous avons aussi démontré que cette toxicité était influencée par la chimie, la nature du métal la taille de la NP. Nos résultats ont aussi indiqué une action mécanistique des NPs. Des phénomènes de stress oxydatif, de production d métallothionéines, d’apoptose et de nécrose ont été observés. Enfin des études in situ, en France et au Québec, ont démontré que des organismes déjà sensibilisés par leur milieu de vie sont encore plus sensibles à une exposition aux NPs. Ce projet a contribué à enrichir les connaissances sur la toxicité des NPs selon différents modèles d’études. Ceci a permis d’évaluer la sensïbilité de chaque espèce et les actions mécanistiques des NPs. Les résultats concemant la sensibilité des différents modéles d’animaux pourront étre utilisés dans les prochaines études de risques
Actually, the usage of nanoparticles (NPs) is more and more mediatized. They are used on a large scale in numerous domains. The mail objective of this thesis was to estimate the immunotoxicity of the NPs of Cd/S, Cd/Te and of Ag on 4 model species: human, mouse, rainbow trout and blue mussel. For the project, we defined four sub-objectives: 1) determine the impact of the NPs on various cells and immune systems; 2) estimate factors influencing the toxicity of the NPs; 3) identify mechanistic achievements of the immunizing answer 4 establish the toxicity of the NPs according to environmental stress. The project results demonstrate that the NPs induced immune system performance changes, according study species. Furthermore, we also demonstrated that this toxicity was influenced by the chemistry, the’ nature of the metal and NPs size. Our results also indicated mechanistic impacts of NPs on immune cells. Oxydative stress phenomena, metallothioneines production, apoptosis and necrosis were observed. Finally in situ studies, in France and in Quebec, demonstrated that organisms already sensitized by their life environment are more sensitive to additional exposure of NPs. This project contributed to improve the knowledge on NPs toxicity according to different models species. This allowed to estimate the sensibility of every species on the NPs toxicity mechanism. The results concerning could be used in the future studies of risk assessment

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Deyo, James A. "Immunotoxicity of the pyrrolizidine alkaloid monocrotaline in C57B1/6 mice". Thesis, 1991. http://hdl.handle.net/1957/36782.

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Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids (PAs). Exposure to PAs can result in liver and cardiopulmonary lesions as well as lymphoid organ atrophy. In the present study C57BI/6 (B6) mice received MCT (0-150 mg/kg/day, po) for 14 days. Overt toxicity was minimal and observed only at highly immunosuppressive doses. Following MCT exposure, significant dose-dependent suppressions were observed in the following immune responses: numbers of antibody producing cells, cytotoxic T- lymphocyte activity, and NK cell cytotoxicity. The antibody responses to the T cell-dependent antigen, SRBC, and the T cell-independent (TI) antigens, DNP-Ficoll and TNP-LPS, were decreased with identical dose response curves. This, along with data showing MCT decreased blastogenesis of B cells more than T cells at the lowest dose level, and that high doses induced significant decreases in the total number of B cells only, suggest that the B cell may be more sensitive than T cells, NK cells , or macrophages. The liver and lung toxicity of MCT is believed to be mediated through its metabolism by mixed function oxidase (MFO) enzymes to reactive pyrroles (monocrotaline pyrrole, MCTP; and dihydropyrrolizine, DHP). Accordingly, it was our hypothesis that the immunotoxicity could be modulated by altering MFO activity. To test this, mice were given a single dose of MCT (100 or 200 mg/kg, po) after MFO induction with phenobarbital; in other experiments mice received the MFO inhibitor chloramphenicol immediately before and 3 hrs after a single exposure to MCT (300 mg/kg, po). However, neither MFO induction nor inhibition significantly altered the immunosuppressive potency of MCT. The antibody and blastogenic responses of splenic lymphocytes directly exposed to MCT (1-3 mM) or MCTP (1-8 μM) in culture were inhibited in a concentration-dependent manner, indicating that both parent and metabolite were immunotoxic. However, the inability to alter the in vivo immunotoxicity by altering MFO activity questions the role this metabolite may play in vivo. In conclusion, the immune system in B6 mice is a sensitive target of MCT toxicity. Inhibition of blastogenesis appears to be one mechanism of MCT-induced immunosuppression. In contrast to other toxic effects of MCT, our results suggest that the parent compound itself plays a significant role in the immunotoxicity.
Graduation date: 1992

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