To see the other types of publications on this topic, follow the link: Mice – Immunology.
Dissertations / Theses on the topic 'Mice – Immunology'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Mice – Immunology.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Riley, E. M. "The immunology of experimental Echinoccus granulosus infection in mice." Thesis, University of Liverpool, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332701.
Full text
2
Rottinghaus, Erin Kay. "Pulmonary Innate Immune Mechanisms in Old Mice." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1237473771.
Full text
3
Peugh, W. N. "The genetics and immunology of cardiac allograft rejection in inbred mice." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375315.
Full text
4
Manoukian, Raffi. "The microenvironmental organization of early B cell precursors in the femoral bone marrow of mutant SCID mice, SCOD/myc transgenic mice and alternate fraction x-irradiated endocolonized mice /." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=57003.
Full textAbstract:
The in situ microenvironmental organization of early precursor B cells in mouse bone marrow has been studied using three experimental models: (1) mutant mice with severe combined immunodeficiency (SCID), which develop pro-B cells but no pre-B and B cells; (2) SCID/myc transgenic mice having expanded pro-B cell populations, but no pre-B and B cells; (3) x-irradiated C3H/HeJ mice during early stages in the regeneration of pro-B cells in bone marrow seeded from a shielded marrow site. The in vivo localization of B220$ sp+$ cells was revealed by the binding of i.v. injected $ sp{125}$I-mAb 14.8 detected by light and electron microscope radioautography of femoral marrow sections. Many B220$ sp+$ pro-B cells were located in peripheral regions of SCID and SCID/myc bone marrow, often in clusters, associated with an electron dense extracellular matrix and with the processes of stromal reticular cells. Many B220$ sp+$ cells were associated with macrophages which contained numerous ingested bodies. Macrophage associations were more numerous in SCID/myc than in SCID mice, especially in the peripheral marrow regions. 3-5 day post-irradiation endocolonizing marrow contained increasing numbers of B220$ sp+$ cells in subosteal and peripheral regions, situated both within sinusoids and extravascularly, associated with stromal reticular cell processes and often close to nerve fibers. The results demonstrate that early B220$ sp+$ precursors begin to differentiate in peripheral marrow regions and develop intimate associations with reticular cells and macrophages. These findings suggest that through these associations, the bone marrow reticular cells promote the early development of the B cell lineage, while the bone marrow macrophages play a role in the elimination of aberrant precursor B cells.
5
Huang, Dennis Shihchang. "Immunological changes in retrovirus-infected mice." Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186463.
Full textAbstract:
Acquired Immune Deficiency Syndrome (AIDS), a progressive immunodeficiency induced by Human Immunodeficiency Virus (HIV), frequently sets the stage for life-threatening tumors and opportunistic infections. The proposed study focuses on the immunological changes associated with HIV infection. Often superimposed diarrhea, causing malabsorption and malnutrition, leads to further immunosuppression and accelerated deterioration in many patients. The pathomechanism of Cryptosporidium-induced diarrhea is poorly understood and its relation to AIDS urgently requires investigation. We used LP-BM5 murine leukemia virus (MuLV)-infected C57BL/6 mice to model AIDS and thereby study the immunological changes in human retrovirus infection. Production of Th1 cytokines (IL-2 and IFN-γ) was suppressed, whereas Th2 cytokine production (IL-4, IL-5, IL-6, and IL-10) was enhanced in spleen and mesenteric lymph nodes (MLN) during retrovirus infection. However, increased secretion of IFN-γ in the MLN of retrovirus-infected mice may represent incremental production and release by non-Th1 cells. Lymphoid cell population changes in gut-associated lymphoid tissues (GALT) were documented 4 months after retrovirus infection. Total lymphoid cell numbers decreased in Peyer's patches and CD4⁺ cell numbers decreased in the intestinal lamina propria (ILP). Total lymphoid cell numbers increased in MLN but the relative percentages of surface IgA⁺, cytoplasmic IgA⁺ (cIgA⁺), and cIgM⁺ cells were decreased. Cryptosporidium infestation in retrovirus-infected mice decreased following the administration of pooled bovine colostrum containing a high titer of antibody demonstrating the potential efficacy of passive humoral immunity. Changes in the host cellular immune apparatus, following Cryptosporidium infection, were as follows: (1) increased γδ-TCR⁺ cells in the ILP 6 and 10 days post-infection, (2) decreased CD4⁺ cells in the ILP and intraepithelium 10 days post-infection, (3) reduced IgA⁺ and IgG⁺ cells in the ILP 6 and 10 days post-infection, and (4) increased IgE⁺ cells 6 days post-infection. This altered cellular profile indicates the potential for aberrant cytokine production which may be responsible for the compounded immunodeficiency during retrovirus infection. Overall, the findings underscore the importance of understanding both humoral and cell-mediated immunological influences before the rational development of a therapy against opportunistic cryptosporidial infection in AIDS patients can be undertaken.
6
Andrén, Maria. "The Role of Fc Gamma Receptors in Experimental Arthritis." Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4724.
Full textAbstract:
Induction of collagen-induced arthritis (CIA), an animal model for human rheumatoid arthritis, is dependent on anti-collagen type II (CII) antibodies. The effector mechanism by which autoantibodies contribute to inflammatory reactions in autoimmune diseases is not well understood. In this thesis I have studied the effector pathways used by IgG anti-CII antibodies to initiate arthritis, namely the IgG Fc receptors (FcγRs) and the complement system. We have found that FcγRIII is crucial for development of CIA, as CII-immunized mice lacking this receptor do not develop arthritis and IgG1 and IgG2b anti-CII antibodies require FcγRIII to trigger arthritis when transferred to naïve mice. The antibody-mediated arthritis was further enhanced in mice deficient in the inhibitory FcγRIIB, indicating that FcγRIIB regulates the activation of FcγRIII. Furthermore, we demonstrate that FcγRIII exist as three distinct haplotypes in mice, FcγRIII:H, FcγRIII:V and FcγRIII:T. Mice expressing the FcγRIII:H haplotype are more susceptible to CIA than mice expressing the FcγRIII:V haplotype, indicating that certain FcγRIII haplotype predisposes for CIA. We also show that the most likely FcγRIII-expressing effector cell in CIA is the macrophage, since FcγRIII-expressing macrophages exclusively can induce arthritis in FcγRIII-deficient mice challenged for CIA.
The complement system was also investigated in development of CIA. We found that this effector pathway is also necessary for onset of arthritis, as CIA was inhibited by treatment with anti-complement factor 5 (C5) antibodies. C5-deficient mice could neither develop CIA unless provided with C5-containing sera.
Taken together, the work presented in this thesis indicates that FcγRs and the complement system are crucial for the induction of experimental arthritis. These findings are important for understanding the mechanisms behind rheumatoid arthritis and blocking of these effector pathways may in the future be used as treatment of rheumatoid arthritis.
7
Mathai, Lalitha. "Studies of proteoglycan induced arthritis in BALBc mice." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61247.
Full textAbstract:
Studies of proteoglycan-induced arthritis in mice revealed two previously unidentified features: polymorphonuclear leucocytes in knee joint cavities and sacroiliac joint involvement. Immunological studies of cellular responses to the proteoglycan revealed a lack of response prior to arthritis which was produced by a further injection. Further studies revealed that depletion of suppressor/cytotoxic T cells in vitro led to an increased response to antigen. Cellular responses in immune and preimmune mice involve helper T lymphocytes. The preimmune but not immune responses wee inhibited by mouse serum and involved a helper T cell dependent response. It did not involve detectable cell death or suppressor/cytotoxic T lymphocytes. Bacteria isolated from mice did not produce arthritis and showed no immune cross-reactivity with proteoglycan.
8
Macht, Lisa. "Human autoantibody production in SCID mice." Thesis, University of Bristol, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335368.
Full text
9
Dehlawi, M. S. "Mast cell responses to intestinal nematodes in mice." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376170.
Full text
10
Madison, Sharon L. "THE EFFECTS OF PM2.5 ON ALLERGIC INFLAMMATION IN MAST CELL DEFICIENT MICE." NCSU, 2002. http://www.lib.ncsu.edu/theses/available/etd-05082002-132938/.
Full textAbstract:
MADISON, SHARON LYNN. The effects of PM2.5 on allergic inflammation in mast cell deficient mice. (Under the direction of Bruce Hammerberg.) Animal models of asthma have confirmed epidemiological findings that exposure to fine particulate matter (PM2.5) can enhance asthmatic symptoms, including eosinophilic inflammation and airway hyperresponsiveness. Critics have dismissed the possibility that these studies utilizing artificial exposure scenarios, like intratracheal instillation (i.t.), can be legitimately extrapolated to human risk largely due to the fact that the doses required for this type of model exceed the normal ambient concentrations of PM2.5. In order to improve the credibility of the findings from previous animal studies utilizing the i.t. method for delivery of aqueous particle suspensions to the lung, and to determine the biological mechanisms responsible for the observed enhancement of allergic inflammation following PM2.5 exposure, large-scale air samplers have been developed making it possible to directly expose wild type (WT) and genetically altered mice to fine, concentrated ambient particles (CAPs). In this study allergic asthma was modeled in both WT and mast cell deficient (MCD) mice by local (L) or systemic (S) sensitization to ovalbumin (OVA). Two weeks later mice were challenged with OVA (day 0) and then exposed to CAPs (day 0 & 1) with numerous endpoints collected (day 0-2). Overall, there was a temporal difference in the bronchoalveolar lavage cell profile between L and S sensitized mice, and the contribution of mast cells (MC) to this differential response was best observed for neutrophils at day 0 and day 1. Compared to air exposed mice, CAPs depressed total inflammatory cell infiltrates in the bronchoalveolar lavage fluid at day 0 and day 1 after OVA challenge for all groups. This overwhelming difference of limited cellular infiltration of monocytes and neutrophils in the bronchoalveolar lavage fluid following CAPs exposure, and the significant difference between the L and S sensitization protocols, confound interpretation for all of the factors examined. However, the specific finding that CAPs can enhance eosinophil recruitment by day 2 after OVA challenge indicates that the results from previous animal studies utilizing i.t. PM2.5 exposures do in fact support the epidemiological associations linking PM2.5 exposures with the enhancement of allergic inflammation indicative of the asthmatic phenotype. Given the strict regulation of immunological tolerance at mucosal surfaces like the lung, the genetic variability of different mouse strains, and the daily changes in ambient PM2.5 composition, the findings of this study prompt many unique questions. However, the bottom line is that this study demonstrates that ambient PM2.5 does alter Th2-like responses in mice by enhancing pulmonary BAL eosinophils in the late phase response (day 2), and that mast cells are critical to their recruitment.
11
Li, Samantha. "The importance of the intracytoplasmic domain of CD3 epsilon in thymocyte development /." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116027.
Full textAbstract:
The development of T cells in the thymus is a tightly regulated process. Any defect in thymic differentiation could result in autoimmune disorders, inability to ward off infections or neoplasm. Early thymocyte development requires signals mediated through the preTCR complex by the associated CD3 chains (gamma, delta, epsilon, and zeta). Research conducted towards this project has revealed that signaling modules within the intracytoplasmic domain of CD3epsilon is absolutely required for this process. Interestingly, our results emphasized the importance of the proline-rich sequence motif in preTCR mediated signaling events, such as the proliferation of double negative thymocytes and the regulation of TCR surface expression on double positive thymocytes in a stage-specific manner. The outcomes of this project may provide a better understanding of the mechanism of preTCR-mediated thymocyte differentiation and the role of CD3 chains in these processes.
12
Myburgh, Elmarie. "Lymphocyte-specific reconstitution of IL-4Ra-deficient mice : characterization and infectious disease studies." Doctoral thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/3114.
Full textAbstract:
Includes bibliographical references (leaves 114-142).Lymphocyte-specific reconstitution of IL-4Ra was recently established by intercrossing lymphocyte-specific human IL-R4a transgenic mice with mIL-4Ra-deficient mice. Human IL-4Ra may bind to mouse yc resulting in a chimeric receptor specific for human IL-4 but not mouse IL-4. This provides us with and inducible IL-4 system. The aim of this study was to investigate in vitro and in vivo characteristics of our novel hlL-4Ra Tg/mIL-4Ra+/- mouse model.
13
Olivier, Martin. "Studies on the immunobiology of experimental visceral leishmaniasis in mice." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74363.
Full textAbstract:
The immunobiology and the control of experimental visceral leishmaniasis were studied in susceptible (C57BL/6J) and resistant (C57L/J) strains of mice. It was found that the resistant/susceptibility phenotype for infection with L. donovani is expressed only by liver macrophage in vitro; the resistant/susceptible phenotypes were transfered reciprocally by bone marrow radiation chimeras. It was also found that the phagocytic activity of macrophages is reduced by the infection and that liver and peritoneal macrophages reflect their specific resistance/susceptibility phenotype following protective or curative treatment with lymphokines: macrophages from resistant C57L/J mice responded better to lymphokine activation. The production of IL-1 by spleen and peritoneal macrophages is inhibited by the infection. Immunosuppression with cyclosporin A (CsA) exacerbated the infection, without affecting phenotype; both CsA-treated strains of mice heal the infection in the absence of IL-1 and IL-2. There were more infected liver macrophages in normal or CsA-treated susceptible C57BL/6J mice and a greater number of amastigotes per cell than in normal or CsA-treated resistant C57L/J mice. CsA treatment did not affect the responsiveness of macrophages to lymphokine activation. IL-2-treated spleen and blood leucocytes from infected animals reduced infection in macrophages infected in vitro. Adoptive immunotherapy in vivo with IL-2-treated spleen cells from infected animals showed significant specific reduction of the parasite load in the liver; daily injections of IL-2 enhanced cure. T lymphocytes are the cells involved in cure; cure is mediated by soluble factors produced by the treated cells, and is specific to Leishmania infection.
14
Gallimore, Barbara. "Characterization of experimental Staphylococcus epidermidis peritonitis in chronically uremic mice." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75686.
Full textAbstract:
A mouse model of surgically induced renal failure was utilized to investigate the pathogenesis of Staphylococcus epidermidis peritonitis which is a frequent and serious complication of continuous ambulatory peritoneal dialysis (CAPD). Compared to sham-operated controls, chronically uremic mice were more susceptible to intraperitoneal S. epidermidis inoculation, presenting decreased survival time and survival (10$ sp9$ cfu, 10$ sp8$ cfu), delayed bacterial clearance and attenuated peritoneal inflammatory response (10$ sp6$ cfu). In mice bearing a peritoneal catheter implant, the catheter was a preferred site for peritoneal bacterial persistence up to one month after intracatheter inoculation. Despite in vitro cytotoxicity of commercial peritoneal dialysis solutions toward peritoneal leucocytes, repeated peritoneal instillation of dialysis solutions did not influence S. epidermidis recoveries following inoculation. Although the mouse preparation did not undergo peritoneal dialysis, these studies nevertheless demonstrate that chronic uremia and the peritoneal catheter may be important etiological factors in the development and persistence of CAPD peritonitis.
15
Barkhuizen, Mark. "Determination of the role of cytokines using gene deficient mice in African trypanosomiasis infection." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3119.
Full textAbstract:
Includes bibliographical references.African trypanosomiasis encompasses diseases caused by pathogenic trypanosomes, infecting both humans and animals alike. To determine the immunological role of IL=12 family members in Trypanosoma brucei brucei, Trypanosoma evansi and Trypanosoma congolense infections, IL-12p35¯/¯, IL-12p40¯/¯ and IL-12p35¯/¯/p40¯/¯ mice were used. While the two latter mouse strains lack all IL-12 homologues, IL-12p35¯/¯ mice still produce IL-12p80 homodimers and IL-23. In infection with T.b. brucei and T.evansi; IL-12p35¯/¯, IL-12p40¯/¯ or IL-12p35¯/¯/p40¯/¯ mice were susceptible to both these pathogens, demonstrated by increased mortality compared to wild type C57BL/6 mice. The different IL-12 deficient mouse strains showed similar mortality kinetics, suggesting that IL-12p70 but not the IL-12p80 homodimer or IL-23 plays a crucial role in survival. Similarly, parasitemia control was reduced in the absence of IL-12p70. While plasma levels of IgM and IgG2c were similar between IL-12 deficient mice and wild type mice, IF-γ production. As IFN-γR¯/¯ mice were also highly susceptible to both T.b. brucei and T. evansi, IL-12p70-dependent IFN-γ production seems to be important mechanism involved in resistance against both these pathogens.
16
Wahid, Faisal Numman. "Immunogenetics of Heligmosomoides polygyrus (Nematospiroides dubius) in mice." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280098.
Full text
17
Khalili, Saeed. "A novel cell therapy for xerostomia in non-obese diabetic mice." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106445.
Full textAbstract:
Sjögren's syndrome is a chronic autoimmune disease that involves primarily the exocrine glands, resulting in their functional loss. Sjögren's syndrome typically manifests as dry mouth (xerostomia) and dry eyes (xerophthalmia). In many patients, all the salivary secretory tissue is lost, and no pharmaco-therapy is effective, as they depend on the stimulation of residual acinar cells. Given the long gap between the initiation of disorder and its clinical manifestation, SS is usually diagnosed in its late stage, making it challenging to study and to treat. The NOD mouse is a commonly used animal model to study Sjögren's syndrome and type I diabetes. NOD mice suffer from a proteasome defect that results in improper T lymphocytes negative selection. As a result, autoreactive T-cells are released into the blood. The proteasome defect also impairs NF-κB and increases the autoreactive T-cells susceptibility to induced TNF-α apoptosis. The aim of this thesis was to apply an intervention that relies on a two-pronged therapy on NOD mice. An injection of CFA, to increase TNF-α levels to eradicate autoreactive T-cells through apoptosis, is the first prong. Transplantation of matched MHC-I spleen or bone marrow cells that re-select autoreactive T-cells, is the second prong. The result demonstrates that the saliva flow of NOD mice treated with CFA and spleen or bone marrow cells increased up to one year post-therapy, whereas saliva flow deteriorated in non-treated NOD. Saliva composition (e.g. total proteins, amylase, EGF, and electrolytes) was comparable to those prior to disease. Furthermore, treated NOD mice were protected from type I diabetes. To identify the cell fraction that restores salivary gland function, CD45-/TER119- cells was isolated and transplanted. In addition to salivary flow improvement, the numbers of lymphocytic infiltrates in salivary glands of cell-treated NOD were lower than that of non-treated NOD. Gene expression of TNFα and TGFβ1 were downregulated, while EGF, FGF-2, IGF-IR and AQP5 were upregulated in cell-treated NOD. Finally, the timing for administration of this novel cell therapy was compared (i.e. early stage versus advanced stage of Sjögren's syndrome). The therapy was more effective when applied in the early stage of Sjögren's syndrome. This research presents evidence that salivary gland function can be preserved prior to disease and/or the gland dysfunction can be halted in advanced stages. An endogenous regeneration may have occurred in the salivary glands.Le syndrome de Sjögren (SS) est une maladie auto-immune inflammatoire chronique qui affecte principalement les glandes exocrines, résultant en une perte de fonction. SS se manifeste typiquement par le symptôme de sécheresse de la bouche (xérostomie) et des yeux (xérophtalmie). Du fait de la longue durée qui s'écoule entre le début de la maladie et sa manifestation clinique, SS est habituellement diagnostiqué à un stade avancé, ce qui rend son étude et son traitement difficiles. Dans de nombreux cas, le tissu de sécrétion salivaire est détruit et aucun traitement pharmaceutique n'est efficace, car ce type de traitement nécessite une stimulation des cellules acineuses restantes, et peu de ces cellules sont encore présentes. La souris NOD contracte la maladie lorsqu'elle est âgée d'environ 8 semaines et manifeste une production insuffisante de salive. Les patients atteints du SS souffrent d'un défaut du protéasome un complexe enzymatique multiprotéique, qui donne lieu à une sélection négative des lymphocytes irréguliers et l'échappement des cellules T auto-réactives. Ce défaut du protéasome atteint également le facteur de transcription NF-κB, qui permet la maturation des lymphocytes et la production des cytokines. Le défaut de NF-κB augmente la susceptibilité des cellules T auto-réactives à l'apoptose induite par les molécules TNF-α. L'objectif de cette thèse est d'appliquer une intervention qui repose sur une thérapie à deux volets sur les souris NOD. Le premier volet consiste en une injection de CFA, dans le but d'augmenter les niveaux de TNF-α afin d'éradiquer les cellules T autoréactives par l'apoptose. La transplantation des cellules MHC-1 de la rate ou de la moelle osseuse qui re-sélectionnent les cellules T autoréactives, représente la deuxième étape du traitement. Nos résultats démontrent que la sécrétion salivaire, des souris NOD traités avec le CFA et des cellules de la rate ou de la moelle osseuse, augmente jusqu'à un an après la thérapie, alors que la quantité de salive conitnue de se détériorer dans les souris non traitées. La composition de la salive (par exemple, protéines totales, l'amylase, l'EGF, et électrolytes) était comparable à celle d'avant la maladie. Par ailleurs, les souris NOD traitées ont été protégées contre le diabète de type I. Pour identifier la fraction de cellules qui restaure la fonction des glandes salivaires, les cellules CD45-/TER119- ont été isolées et transplantées. En plus de l'amélioration de la quantité de salive, le nombre d'infiltrats lymphocytaires dans les glandes salivaires des souris NOD traitées ont été inférieurs à ceuxl des NOD non-traités. L'expression des gènes du TNFa et TGFβ1 ont diminués, tandis que l'EGF, le FGF-2, l'IGF-IR et AQP5 étaient surexprimés dans les souris NOD traitées. Le temps propice pour l'administration de cette nouvelle thérapie cellulaire a été comparé (ie stade précoce par rapport au stade avancé du SS). La thérapie est plus efficace lorsqu'elle est appliquée à un stade précoce du SS. Cette recherche présente des preuves que la fonction des glandes salivaires peuvent être conservés avant la maladie et / ou le dysfonctionnement de la glande peut être arrêtée à un stade avancé. Une régénération tissulaire endogène peut avoir eu lieu dans les glandes salivaires.
18
Kornbluth, Murray. "T cell differentiation in the thymus of graft-versus-host mice." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68191.
Full textAbstract:
We have investigated the effects of graft-versus-host disease on T cell differentiation in the murine thymus. Flow cytometry analysis of L3T4 and Lyt-2 antigen expression on thymocytes along with immunofluorescence microscopy were employed to assess T cell phenotypes in thymuses of GVH mice. GVH reactions were induced by injecting 40 $ times$ 10$ sp6$ C57BL/6 (B6) or A strain lymphoid cells into C57BL/6 $ times$ A F$ sb1$, (B6AF$ sb1$) mice. Thymocyte populations were quantitated on different days after GVH induction. Our results demonstrate that single positive L3T4 cells are present in the murine GVH thymus, yet they have not acquired cortisone resistance, a trait normally attributed to this mature thymic subset. It appears that the GVH dysplastic thymus can support the differentiation of L3T4$ sp{+}$Lyt-2$ sp{-}$ cells however, such a thymus is unable to confer cortisone resistance upon this population.
19
Boespflug, Nicholas. "ATF3 regulates neutrophil migration in mice." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382372804.
Full text
20
Oliver, Kevin Russell. "Consequences of neurotropic virus infections of developing and adult mice." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389959.
Full text
21
Zhu, Lei 1980. "Perturbed B cell development in young B7.2 transgenic mice." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84090.
Full textAbstract:
The best-characterized costimulation system for naive T cell activation is the interaction between CD28 and B7.1 or B7.2 ligands expressed on antigen-presenting cells such as activated B cells. Unexpectedly, transgenic mice with constitutive expression of B7.2 on B lymphocytes do not develop systemic autoimmune diseases, but rather exhibit a reduction of the B cell compartment that involves a defect in B cell maturation occurring very early in the ontogeny. In this study, we show that the early B cell loss is accompanied by splenomegaly and lymphoadenopathy that are due to a dramatic and transient increase in eosinophils. This immune response leads to disturbed splenic architecture, and is mediated by CD4+ T cells. In the absence of CD4+ T cells, early B cell maturation is nevertheless perturbed. Thus, our findings indicate that both T cell subsets participate in the elimination of B cells, but through different mechanisms.
22
Gravitte, Amy, Jen Kintner, Stacy Brown, Benjamin Kennard, Allison Cobble, and Jennifer Hall. "Estrogen treatment protects mice from C. muridarum infection." Digital Commons @ East Tennessee State University, 2021. https://dc.etsu.edu/asrf/2021/presentations/16.
Full textAbstract:
Chlamydia is the most commonly reported sexually transmitted infection in the US, with an estimated 4 million new cases in 2018 alone. In addition to humans, Chlamydia infects other animals including mice, and mice have become a popular model for the study of Chlamydia infection. Female sex hormones (FSH) estrogen (E2) and progesterone (P4) rise and fall in a cyclic fashion in both humans and mice, and it is well established that these hormones affect the establishment and progression of genital chlamydial infection. Prior studies that used a co-culture model of human endometrial epithelial cells (IK cells) grown on extracellular matrix-coated inserts over human stromal cells (SHT cells) showed that E2 treatment enhanced initial chlamydial infection and production of progeny Chlamydia compared to hormone free (HF), P4 or combination E2’E2/P4 treatment. This led to the hypothesis that the treatment of ovariectomized (OVX) mice with E2 would enhance chlamydial infection compared to mice treated with no hormone, P4, or a combination of E2 and P4. We ordered OVX mice from Jackson Laboratories and surgically implanted silastic capsules that contained E2, P4, E2/P4, or no hormone diluted in sesame oil. A gas chromatography method was developed to test E2 and P4 concentration in mouse serum, ensuring that hormone levels were physiologically relevant. 8 days after the implantation of the capsules, mice were vaginally-inoculated with C. muridarum¸ a chlamydial species that mimics human chlamydial infection in mice. Every 3 days post infection (pi), for 21 days, we vaginally swabbed mice to determine how much C. muridarum each mouse shed and created a graphical representation of chlamydial shedding. A subset of mice were sacrificed on day 10pi so that presence and identity of immune cells could be analyzed by flow cytometry. Surprisingly, E2 alone and E2/P4 treatment completely protected mice from chlamydial infection. HF-treated mice peaked in chlamydial shedding on day 3pi, and P4-treated mice peaked on day 9pi. Flow cytometry data showed that E2-treated mice had a significantly reduced T cell presence in the genital tract. Thus far, our data suggest that FSH affect chlamydial infection in mice differently than in humans. This observation could have important implications for a field that is heavily reliant on murine studies.
23
Liu, Dien. "Effects of R294C mutation on expression and stability of interferon regulatory factor-8 in BXH-2 mice." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116090.
Full textAbstract:
Interferon regulatory factor-8 (Irf-8), a hematopoietic transcriptional regulator, controls myeloid-cell proliferation and coordinates innate and adaptive host immune responses. Mice from the BXH-2 recombinant inbred strain carry an endogenous R294C mutation in Irf-8. This loss-of-function mutation induces clonal infiltration of undifferentiated Mac-1+/Gr-1 + granulocytic precursors in BXH-2 mice, extramedullary hematopoiesis, and splenomegaly similar to those seen in human chronic myeloid leukemia. It also renders the host permissible to the otherwise avirulent Mycobacterium bovis (BCG), and negatively affects survival or recovery of these mice to other infectious pathogens. Here, we generated a polyc1onal anti-Irf-8 antibody to better characterize the effects of the R294C mutation on Irf-8 protein expression, stability, and inducibility in hematopoietic and non-hematopoietic tissues. We found that mutant Irf-8C294-expressing tissues consistently displayed reduced Irf-8 abundance compared to their wild-type counterparts in both primary splenocytes and following transfection into heterologous cells, presumably due to decreased stability or increased rate of degradation of the mutant isoform. Results also indicate that native Irf-8 is also expressed in the heart, and to a lesser extent, in the kidneys. Since neither of these organs is well-known to be associated with hematopoietic or immune functions, this finding strengthens the possibility that Irf-8 may exert additional regulatory functions in other cellular contexts. Taken together, our study provides a better understanding about the molecular features of the mutant Irf-8 C294 protein and contributes to a growing body of evidence in support of Irf-8 expression in non-hematopoietic tissues.
24
Ben-Smith, Anne. "Mechanisms of expulsion of primary infections of Heligmosomoides polygyrus in mice." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284027.
Full text
25
Luu, Rachel. "Characterization of the CD8 T cell response to Salmonella typhimurium infection in mice." Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27474.
Full textAbstract:
Salmonella typhimurium (ST) causes gasteroenteritis in humans and typhoid-like disease in mice. Since CD8 T cells facilitate acquired immunity, we evaluated the development and function of the CD8 T cell response against ST. Responses were compared to the acute intracellular pathogen, Listeria monocytogenes (LM). Because ST replicates within phagosomes and causes chronic infection, it was hypothesized that CD8 T cell priming may be muted and dysfunctional. While LM-induced CD8 T cells differentiated rapidly and displayed a mainly central-memory phenotyope in the long-term, CD8 T cells failed to become activated rapidly during ST infection and differentiated mainly into an effector/effector-memory phenotype. While the CD8 T cells induced against ST were functional, owing to the delay in CD8 T cell activation during ST infection, even conventional memory CD8 T cells failed to respond rapidly. Thus, the phagosomal lifestyle may allow escape from CD8+ T cells, conferring a survival advantage to the pathogen.
26
Bowie, Laura Elizabeth Stuart. "The role of CD8'+ T cells in IDDM in non obese diabetic mice." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388762.
Full text
27
Gough, Lucy. "The proteolytic activity of the mite allergen Der p 1 enhances IgE synthesis : studies in mice showing a link between allergenicity and cysteine protease activity." Thesis, University of Nottingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342508.
Full text
28
Xu, Jialin, and 徐嘉林. "B lymphocyte development and function in leptin receptor-deficient mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45011096.
Full text
29
Huang, Dennis Shihchang 1957. "Canthaxanthin and tumor growth in mice." Thesis, The University of Arizona, 1990. http://hdl.handle.net/10150/291428.
Full textAbstract:
Canthaxanthin (CX), a non-provitamin A carotenoid, has been shown to exert a variety of effects on cells of the immune system and to have tumor-specific cytopathic effects in vivo and in vitro. In the present study, CX was shown to inhibit the in vitro growth of three murine tumor cell lines, JB/MS melanoma, B16F10 melanoma, and PYB6 fibrosarcoma. This effect was dose-dependent up to a concentration of CX of 10⁻⁴M. In contrast, the growth of NIH-3T3 fibroblasts was enhanced following a 96 hr incubation with 10⁻⁴M CX. A dietary supplement of 1% CX retarded tumor growth in LP-BM5 retrovirus-infected female C57BL/6 mice after tumor challenge, but had no effect on tumor growth in normal, uninfected animals. Although, NK activity and T and B subpopulations were not modified by dietary CX after tumor challenge, irrespective of whether mice had been virus-infected, there was a slight enhancement of mitogen-stimulated IFN-τ production by virus-infected murine spleen cells when compared with non-infected cells. We suggest that CX has potential as a modifier of cancer cell growth, especially in situation where impairment of the immune system has occurred as a result of viral infection.
30
Mayeku, Jukie K. "The Effects of Aldehydehydrogenase1A1 on Immunoglobulin Production in Mice." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281035253.
Full text
31
van, der Ventel Michelle. "The role of IL-4Ra signalling in gene deficient mice during asexual-stage Plasmodium chabaudi AS infection." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3438/.
Full textAbstract:
BALB/c mice infected with P. chabaudi AS develop immunity to erythrocytic-stage infection with early Th1 responses followed by a switch towards Th2 responses later to mediate protection during chronic disease. In order to determine the importance of the Th2 cytokines, IL-4/IL-13, in inducing protective immunity, the course of P. chabaudi infection was monitored in IL-4Rα-deficient mice. Interestingly, an early delay in the onset of peak parasitaemia in IL-4Rα-/- compared with WT control BALB/c mice was evident. Consequently, we demonstrated that IL-4Rα deficiency resulted in mice becoming more susceptible to chronic P. chabaudi infection with increased recrudescence, mortality and an impaired Th2 immune response compared with WT control mice. Similar results in the overall disease and immunological profiles between IL-4Rα-/- and wild-type mice were obtained whether male or female mice or the AJ or AS strains of P. chabaudi were used to infect mice. Thus, the protective role of IL-4Rα signalling during chronic disease was not parasite strain-specific or host gender dependent. However, males were significantly more susceptible than female mice and consequently further studies involving cell-type IL-4Rα-/- mice, utilized female mice to identify functional targets of IL-4/IL-13 protection. Abrogated IL-4Rα expression on macrophages/neutrophils (LysMcreIL-4Rα-/lox) mice had minimal effect on the outcome of P. chabaudi AS chronic infection and was comparable to WT mice implicating no major role for alternatively activated macrophages during chronic infection. In contrast, CD4+ T-cell-specific IL-4Rα-/- (LckcreIL-4Rα-/lox) mice infected with P. chabaudi AS developed increased recrudescence, increased mortality and impairment of Th2 immunity during the chronic infection similar to that of the global IL-4Rα-/- mice. This highlights the importance of signalling via CD4+ T-cells signalling via IL-4Rα for protective immunity during chronic infection. Paradoxically, CD4+CD8+ T-cell-specific IL-4Rα-/- (iLckcre IL-4Rα-/lox) mice displayed a similar disease profile to WT control mice but manifested a delayed Th2 phenotype during the latter stage of the disease with enhanced splenomegaly in comparison to the WT and IL-4Rα-/- mice. Thus while protection during chronic infection with P. chabaudi AS appears dependent on CD4+ T-cells responsive to IL-4, CD8+ T cells responsive to IL-4 have a more complex and more difficult role to interpret.
32
Goulet, Marie-Line. "Differential immune responses and hematopoiesis in mice deficient for Ly49Q, a plasmacytoid dendritic cell receptor." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101715.
Full textAbstract:
Plasmacytoid dendritic cells (pDCs) are members of the innate immune system and are particularly important in anti-viral immunity since they are the most potent producers of type I interferon (IFN). The objective of this research project is to analyze the phenotype of knockout mice for Ly49Q, a cell surface receptor expressed on pDCs. In vivo, KO mice with PGK-Neor insertion control early murine cytomegalovirus (MCMV) infection better, but no difference could be detected in mice with recombined LoxP sites. Thus, we observed differential immune response in KO mice with the PGK-Neor insertion and recombined LoxP sites. In mice with PGK-Neor insertion, we found enhanced hematopoiesis of some populations of the myeloid lineage and lower activation of pDCs following treatment with particular Toll-like receptors (TLR) ligands, which translates into diminished T cell stimulatory capacity. This suggests a role for Ly49Q in regulating hematopoiesis and pDC activation potential.
33
Gowdy, Kymberly Mae. "Increased Susceptibility and Severity of Influenza in Mice Exposed to Diesel Exhaust." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-11202008-100143/.
Full textAbstract:
Epidemiological studies have noted an increase in adverse health effects with increasing levels of air pollution. One major area of concern is the incidence of respiratory infections, specifically influenza. An air pollutant that has raised concern in recent years is diesel exhaust (DE) due to an increase the amount of diesel engines in use. Previous laboratory studies have reported that DE exposure prior to an influenza infection increases viral titers but the mechanism of how this occurs is still unknown. Herein, studies were designed to investigate three main areas associated with DE enhanced influenza infection. 1) Assess whether DE affects host defense responses against pathogens, 2) Determine if pre-exposure to DE increases susceptibility to influenza in vivo, 3) Investigate whether exposure to DE increases the severity of an ongoing established influenza infection. DE exposure alone increased proinflammatory cytokines, adhesion molecules, decreased expression and production of surfactant proteins (SP)-A and D as well as clara cell secretory protein (CCSP). The molecules downregulated by DE are important for binding viral and bacterial pathogens therefore making the lung more susceptible to infection. This was confirmed when mice were exposed to DE and then subsequently infected with influenza A. One day post infection mice pre-exposed to DE had a significant increases in influenza induced inflammation and viral titers that were associated with a decrease in SP-A and SP-D. Mice exposed to DE during an established influenza infection also had a significant increase in viral titers and pulmonary inflammation throughout the course of infection. This DE-enhanced influenza infection was associated with an upregulation of the Th2 cytokine IL-4 which has previously been shown to delay clearance. However with antioxidant treatment to combat the oxidative stress induced by DE, pulmonary inflammation and IL-4 expression returned to baseline levels. Taken together these data indicate that exposure to DE either before or during influenza infection has immunomodulatory effects that can be detrimental to the host with increased viral proliferation and morbidity associated with the disease.
34
Lai, Yeuk-yu. "Characterization of lymphocyte development in young and aged mice." Click to view the E-thesis via HKUTO, 2003. http://sunzi.lib.hku.hk/hkuto/record/B31971076.
Full text
35
Novak, Susan Marie. "Gastrointestinal cellular and humoral immune responses in BALB/c mice infected with Cryptosporidium parvum." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185563.
Full textAbstract:
Immunohistochemical analysis of intestinal tissue from infected and uninfected neonatal mice was performed to determine immune responsiveness to Cryptosporidium parvum at the gut level. Infected mice showed a significant increase in T cell (T helper/T cytotoxic/suppressor) populations (p < 0.001), macrophages (p < 0.001), IL-2R positive cells (p < 0.001 at 16 days PI), and IgA positive cells (p < 0.001 at 16 days PI) compared to control (uninfected) animals. No differences between the two groups of animals existed for B cell populations of the IgG (p = 0.264) and IgM (p = 0.646) isotype. Cellular immunity seems to be primarily responsible for clearing cryptosporidial infection from infected animals. Humoral immunity mediated by B cells of the IgA isotype could be a secondary (delayed) factor which aids in the recovery of the animal. Neonatal mice were also infected with C. parvum to describe the susceptibility dynamics in this animal model. Percent infectivity of the animals (infected at various days of age beginning on day 4 and ending at day 18) began to decrease at 10 days of age (33% infectivity). Infectivity percentages varied up until 14 days of age and older when all of the animals inoculated were refractory to infection. Why this refractiveness to infection occurs as the animals age is still unknown. In another study neonatal mice infected at 4 days of age continued to be positive for parasites up until 25 days of age (21 days PI). Percent infectivity began to vary at 20 days of age (16 days PI) which meant that only a certain percentage of the mice tested at that time point were positive for C. parvum. Prior to 20 days of age 100% of the animals tested were infected. Proliferative responses of spleen cells from infected and control mice to C. parvum antigen were measured. Spleen cells from infected animals responsed to C. parvum antigen in vitro (stimulation index (SI) = 14.52 (infected mouse #1); 14.23 (infected mouse #2)) whereas cells from uninfected mice did not (SI = 1.12 (control mouse #1); 1.07 (control mouse #2)). The spleen seems to be one organ involved in the immune circuitry responsible for clearance of cryptosporidiosis in neonatal mice.
36
Elkovich, Andrea J. "Mast Cells In Kainate Receptor Knockout Mice." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3944.
Full textAbstract:
Kainate receptor knockout mice have unique differences within their immune system. They exhibit an attenuated TH2 branch, while maintaining a robust TH1 response. Specifically, blocking the formation of functional kainate receptors affects mast cells and their related pathologies. While they seem to develop and activate normally in vivo and in vitro, KAR KO mast cells release more inflammatory mediators upon degranulation. These mice experience severe anaphylactic shock due to two compounding abnormalities. First, KAR KO mast cells release significantly more histamine in vivo upon IgE-mediated activation. Second, the animals over-respond to exogenous histamine with drastic temperature drops compared to WT. This report shows that the kainate receptor plays an important role in mast cell-mediated immune responses.
37
Getahun, Andrew. "Antibody Feedback Regulation : From Epitope Masking to T Helper Cell Activation." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4580.
Full text
38
Bartley, Paul Murdoch. "Host-parasite interactions of Neospora caninum." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/23592.
Full textAbstract:
The papers included in this thesis examine the host–parasite relationship in small and large animals following experimental challenges with Neospora caninum. This apicomplexan parasite is a major cause of abortion and reproductive losses in cattle worldwide. Economic and welfare issues make the development of a vaccine against the transplacental transmission of Neospora highly desirable. This thesis evaluates the host-parasite interactions in a non-pregnant mouse model examining whether the actively multiplying stage of the parasite (tachyzoite) could be attenuated through prolonged in vitro cultivation (passage) and used as a live vaccine. We show that continued maintenance of tachyzoites in tissue culture produced significantly reduced levels of morbidity and mortality in the mice following challenge, compared to mice receiving virulent parasites. Inoculation with a sub-lethal dose of tachyzoites was shown to protect against a subsequent lethal challenge of virulent parasites. Mice showing higher levels of cell mediated immunity (CMI) (antigen-specific splenocyte proliferation and interferon-γ (IFN-γ) production) had lower parasite burdens compared to mice with less pronounced CMI responses. Combined, these works show that it is possible to protect against a lethal challenge using attenuated tachyzoites and that a strong T-helper Type-1 CMI response is involved in protection and in reducing clinical disease severity. As the most commonly known route of infection with N. caninum is transplacental, from dam to foetus, we also wanted to examine the host-parasite relationship in pregnant cattle. This was done through the serial examination of the maternal and foetal immune responses of experimentally challenged cattle under controlled conditions at different stages throughout pregnancy. These works show the importance of the timing, location and magnitude of multiple components of the host immune response in determining foetal survival and also whether vertical transmission occurs. We show that both the maternal and foetal immune responses are critical in determining the clinical outcome of infection. A strong maternal CMI response was shown to aid foetal survival by reducing the numbers of parasites reaching and thus damaging the placenta. Due to the syndesmychorial nature of the ruminant placenta, any foetal responses observed are as a result of foetal infection. These experiments show that as pregnancy progresses the foetus goes from being immunologically immature and incapable of mounting a protective immune response (70 days of gestation (dg)) to becoming capable of mounting parasite-specific humoral, innate and CMI responses from around 140dg onwards. The experiments in pregnant cattle confirm the importance of parasite-specific proliferation and IFN-γ production, in reducing the magnitude of the parasite challenge reaching the maternal–foetal interface and aiding foetal survival. We also examined the immunodominant parasite peptides expressed in HPLC fractionated tachyzoite antigen, which are recognised by the cellular immune response of experimentally challenged cattle. Through LC-ESI-MS/MS, 6 Neospora proteins (including SAG1, SRS2 and GRA2) and a number of Toxoplasma gondii orthologues were identified and found to be recognised by CD4+ T-cells. These works collectively demonstrate the complexity of the host-parasite interaction in Neospora infections and show the importance of a CMI response in protection against the parasite.
39
Mehdizadehkashi, Zahra. "Variation in Plasma Prostaglandin E2 Level in Mouse During Infection with Trichinella spiralis and Trichinella pseudospiralis." PDXScholar, 1995. https://pdxscholar.library.pdx.edu/open_access_etds/5194.
Full textAbstract:
Polymorphonuclear leukocytes infiltrate tissues in response to an inflammatory stimulus such as endotoxin or parasite products. Previous studies have shown an extensive cellular infilteration about the parasitized skeletal muscle of mouse infected with the nematode, Trichinella spiralis. Infection of the host with Trichinella pseudospiralis, on the other hand, is associated with a dramatic suppression of inflammatory cellular response. Prostaglandin Bi is a product of arachidonic acid metabolism and is synthesized by variety of cell types. Prostaglandins of the E series have been generally known to suppress inflammatory responses. In the present study, I have investigated the possible relation between plasma prostaglandin Bi levels and host cellular response in infected mice. Concentrations of prostaglandin Bi in mice plasma were measured at 5, 11, and 21 days after infection with larvae of either nematode species by enzyme immunoassay. There were noticeable elevations in the concentrations of prostaglanding Bi in samples of mice infected with Trichinella pseudospiralis compared to controls. Conversely, decreased levels of prostaglandin Bi were observed in samples from the mice infected with Trichinella spiralis. These results suggest that the differences observed in the host inflammatory response to infection with Trichinella spiralis versus Trichinella pseudospiralis might be associated with recognized properties of prostaglandin Bi· In this connection, I have suggested three possible mechanisms by which the differences of inflammatory response in relation to PGEi production may be explained.
40
Poswayo, Sibongiseni Kwakho Luntukazi. "The role of Cysteinyl leukotriene type 1 receptor (CysLTR1) during Listeria monocytogenes infection in mice." Master's thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/32970.
Full textAbstract:
South Africa recently experienced a Listeriosis outbreak, which was responsible for over 180 deaths, caused by an intracellular, rod-shaped bacilli called Listeria monocytogenes (LM). LM can infect both phagocytic and non-phagocytic cell types and induces its uptake by expressing internalin A and B, then secretes listeriolysin O (LLO), a virulence factor forming pores on the phagosome membrane to escape into the cytosol. Macrophages can phagocytose invading pathogens and induce innate inflammatory responses. Production of cytokines and eicosanoids by antigen presenting cells activates the adaptive immunity. Eicosanoids (epoxyeicosatreinoic acids, prostanoids and leukotrienes) are generated from metabolites of 20-carbon chained polyunsaturated fatty acids and arachidonic acid. Leukotrienes (LTs) are generated from 5- lipoxygenase-metabolism of arachidonic acid to LTB4 and cysteinyl LTs (cysLTs). CysLTs are pro-inflammatory lipids that have pathobiological functions in asthma. CysLTs function through three G-protein coupled receptors (CysLTR1, CysLTR2 and GPR99). The CysLTR1 and its ligands function has been well elucidated in asthmatic and allergic responses however, its role in bacterial infections is unknown. The aim of our study was to elucidate the role of CysLTR1 on disease progression in mice and macrophages infected with LM. In this study, we showed that CysLTR1 mRNA expression is upregulated by LM infection in WT macrophages and mice. Mice deficient of CysLTR1 had no defects at homeostasis. During time kinetic experiments with LM, CysLTR1 knockout mice displayed increased neutrophil recruitment and decreased lymphocyte cells at 3dpi, however, bacterial burdens were comparable to wild-type mice. In addition, macrophages deficient of CysLTR1 have no effect on the intracellular growth of LM. In conclusion, CysLTR1 signalling plays a role in lymphoid cell activation and neutrophilic recruitment during early LM infection, however, further studies are required to better understand the role of CysLTR1 during inflammatory responses.
41
Gerarduzzi, Casimiro. "Poly IC induced antiviral responses of type I IFNs alter thymopoietic processes in mice : an apoptotic liaison." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97960.
Full textAbstract:
Type I IFNs modulate the onset of immune responses against viruses through the activation of numerous rapid signaling pathways. Although beneficial on specific infected cells, administered IFNs were shown to decrease thymic cellularity. Herein, we developed a murine model treated with polyinosinic:polycytidylic acid (Poly IC) to dissect the mechanisms and the role of in vivo produced IFNs on the thymus. Treatment induced thymic atrophy, while having no effect on the lymph nodes. However, under chronic conditions, we observed a complete thymic replenishment. These findings should be the result of a LPS contamination, since the use of a new certified LPS-free Poly IC induced a maintained thymic atrophy in time. DP (CD4+CD8+) cells were mostly affected, where part of this decrease was contributed by apoptosis. T cell receptor excision circle (TREC) levels, produced during T cell receptor (TCR) rearrangements, were unaffected, suggesting no alteration of this diversity factor. Additionally, measured up-regulation of MHC class I expression could result in aberrant thymic selections with a modification of selection ranges. Finally, using Caspase 3 KO mice, we showed that DP apoptosis was Caspase-3 independent.
42
Flaczyk, Adam. "Induction of the epithelial polarizing cytokine interleukin-33 by the fungus «Cryptococcus neoformans» in genetically susceptible mice." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107706.
Full textAbstract:
With the progression of the AIDS epidemic, understanding the host responseto the opportunistic fungal pathogen Cryptococcus neoformans, responsible forapproximately 650,000 deaths in Sub-Saharan Africa each year, has become animportant topic of research. Current knowledge suggests that susceptibility tocryptococcal pneumonia in both mice and humans proceeds via an allergic (TH2)pattern of lung inflammation, while resistance is attributable to a TH1 response in thelungs. The epithelial polarizing cytokines thymic stromal lymphopoietin (TSLP),interleukin-25 (IL-25) and IL-33 have been implicated in TH2 mucosal andrespiratory inflammation caused by allergens and helminths; however, their rolesduring C. neoformans infection are not known. We demonstrated that in vitrostimulation of the mouse lung epithelial cell line (MLE-12) with both the acapsularmutant C. neoformans CAP64 and the highly virulent C. neoformans H99, resulted indose- and time-dependent increases in both Il25 and Il33 mRNA expression.Correspondingly, intranasal infection of susceptible Balb/c mice with C. neoformansH99 showed time-dependent IL-33 mRNA and protein in the lungs. Furthermore,moderately virulent C. neoformans 52D induced differential Il33 mRNA expressionamong susceptible and resistant strains of mice, with susceptible C57BL/6 micedeveloping a significant increase in lung Il33 mRNA compared to resistant CBAmice. Finally, Balb/c mice lacking the IL-33 receptor T1/ST2 had significantlyreduced lung, spleen and brain fungal burdens following intratracheal instillation ofC. neoformans. These observations support a role for IL-33 in polarization of the hostinflammatory response that facilitates progressive pulmonary C. neoformansinfection.Avec la prevalence de l'épidémie du SIDA, comprendre la reaction de l'hôte au champignon opportuniste pathogène Cryptococcus neoformans, responsable de 650,000 décès chaque année en Afrique sub-saharienne, est devenu un sujet de recherche profonde. Les connaissances actuelles suggèrent que la susceptibilité à la pneumonie de cryptocoque chez les souris et les humains se produit par l'intermédiaire des réponses allergiques de type TH2 d'inflammation pulmonaire, alors que la résistance est attribuableau développent d'une réponse TH1 dans les poumons. Les cytokines épithéliales polarisatrices comme thymic stromal lymphopoietin (TSLP), l'interleukine-25 (IL-25) et IL-33 sont impliqués dans l'inflammation allergique TH2 respiratoire, mais leur rôle pendant l'infection C. neoformans reste inconnu. Nous démontrons que la stimulation invitro des cellules épithéliales de poumons de souris (MLE-12) par la souche C. neoformans sans-capsule CAP64 ou la souche C. neoformans très virulente H99, révèleune augmentation sélective de doses de l'expression d'ARNm d'Il25 et d'Il33.Corrélativement, l'infection intranasale de souris susceptible Balb/c au H99 a montré l'induction en fonction du temps de l'ARNm et du protéine de l'IL-33 dans les poumons.Par ailleurs, l'utilisation de la souche de C. neoformans modérément virulente 52D, adémontré une expression de l'Il33 différente entre les souches de souris susceptibles et résistantes. La souche C57BL/6 a connu une augmentation significative de l'ARNm de l'Il33 dans les poumons comparée à la souche résistante CBA. Enfin, les souris Balb/cknockout qui manquaient le récepteur T1/ST2 pour l'IL-33, avaient une charge fongique réduite dans les poumons, les spleens et les cerveaux suite à l'infection par C. neoformans. Ces observations suggèrent un role désavantageux de l'IL-33 dans la polarisation de la réponse inflammatoire pendant l'infection C. neoformans pulmonaire.
43
Lee, Jeongmin. "The immunomodulatory effect of antioxidants in murine retrovirus-infected mice: Treatment opportunity." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284082.
Full textAbstract:
The acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by the human immunodeficiency virus (HIV) that induced severe immunosuppression, rendering the body highly susceptible to opportunistic infection. As HIV-infected persons survive previously life-threatening infection through the use of effective medical therapies, malnutrition has become central issues in the health care plan of long-term survivors. Nutrition is a fundamental intervention in the early and ongoing treatment of HIV disease. Nutrition therapy, in coordination with other medical interventions, can extend and improve the quality and quantity of life in individuals infected with HIV and living with AIDS. A murine AIDS (MAIDS) model, induced by LP-BM5 murine leukemia virus, has been an effective tool to investigate mechanisms of retrovirus-induced immunodeficiency. The MAIDS animal model displays a number of the features of human AIDS, including progressive lymphoproliferation and increasing severe immunodeficiency. The present studies suggested that micronutrient deficiency resulted in premature death and immune dysfunction beyond immune suppression induced by LP-BM5. Chronic EtOH consumption in murine retrovirus-infected mice caused deleterious effects on host defense, immune response, cytokine release, oxidative stress, and nutritional status. This immune dysfuction happened more severely with aging. Supplementation with antioxidants prevented retrovirus-induced suppression of immune response and prolonged the survival of retrovirus-infected mice. It maintained nearly normal cytokine production. This occurred simultaneously with restoration of tissue vitamin E and T- and B-cell proliferation. DHEAS accentuated the effects of antioxidants and maintained cytokine production, T- and B-cell proliferation, and hepatic vitamin E close to the activity level of the uninfected mice.
44
黎若愚 and Yeuk-yu Lai. "Characterization of lymphocyte development in young and aged mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B31971076.
Full text
45
Rosean, Timothy Robert. "The tumor microenvironment is critical for the development of plasma cell neoplasia in mice." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/1497.
Full textAbstract:
Plasma cell neoplasms (PCN), including multiple myeloma, are tumors of terminally differentiated B cells. Despite a significant research effort, and numerous advances in therapy, most tumors of this B cell lineage remain incurable. To this end, understanding factors which are critical for the development of PCN may lead to new avenues for therapy. Interleukin-6 (IL-6) is a pleiotropic, pro-inflammatory cytokine which supports the growth, proliferation, and survival of myeloma cells.
We found that inflammation, and in particular, IL-6 is critical for the development of PCN. In order to determine if tumor microenvironment (TME) or B cell-derived IL-6 was more important in PCN development, we utilized an adoptive transfer system of tumor formation. By adoptively transferring premalignant B cells into recipients, and then providing the B cells with an inflammatory microenvironment through the use of pristane, we were able to generate donor tumors in recipient mice. Utilizing this method, a series of adoptive transfers were performed to determine the primary source of IL-6 in murine PCN development. We discovered that TME-derived IL-6, and not B cell-derived IL-6, is most critical for PCN development.
Furthermore, in studying the lesions in B cell development which lead to tumor formation, we discovered that IL-6 collaborates with the proto-oncogene c-Myc in spontaneous germinal center (GC) formation. The spontaneous GCs were accompanied by a robust follicular T helper cell response. In characterizing the genetic lesions which lead to the GC formation, we discovered that Myc-transgenic mice develop a significant increase in the population of B1a B cells. Furthermore, these B1a B cells infiltrate the spontaneous GCs of double transgenic Myc/IL-6 mice. Lastly, utilizing our adoptive transfer method, we determined that the germinal center response is necessary for the development of PCN in mice.
Lastly, we focused our efforts on another oncogene which collaborates with IL-6, BCL-2. Double transgenic BCL-2/IL-6 mice develop PCN and spontaneous GCs. Of interest however, the adoptive transfer of BCL-2/IL-6 B cells results in tumor formation without the use of pristane. Furthermore, the adoptive transfer recipients develop bone lesions, hind limb paralysis, and a monoclonal gammopathy. This model closely recapitulates many of the pathophysiological features seen in human PCN. This new model promises to be important for future studies into PCN development and treatment.
46
Hoyeck, Edward. "The effects of moderate swimming exercise on immune system function in C57 BL/6(B6) mice /." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33288.
Full textAbstract:
The purpose of this study was to separate acute and chronic effects of moderate exercise on the immune system by analyzing three sets of experimental and control groups; (1) 72 hours, (2) 1 week, (3) 2 weeks post exercise. Mice swam 5 days per week for 3 weeks accumulating a total of 125, 225, and 225 minutes of exercise in weeks 1, 2, and 3, respectively. Moderate swimming exercise did not result in a significant increase in SDH levels (p > 0.05). There was no change in tissue cell responses as measured by mitogen responsiveness, nor in splenic and thymic cell counts in response to the training regimen at any time point (p ≥ 0.05). Total, CD4, CD8, and T cell counts in the lymph nodes were significantly suppressed at 72 hours and 2 weeks post exercise (p ≤ 0.05). It appears that chronic exercise resulted in an increased trafficking of lymphatic cells, which could be interpreted as a sign of heightened immune reactivity.
47
Padda, Ranjit. "Impairment of iron homeostasis and lipid metabolism in Hemojuvelin knockout (Hjv-/-) mice in response to high fat diet." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119742.
Full textAbstract:
Hemojuvelin (HJV) is a membrane protein that controls the body iron metabolism. HJV mutations lead to juvenile hemochromatosis (JH), which arises from uncontrolled absorption of dietary iron from intestine and deposition of the metal into liver parenchymal cells. Hepatic iron overload progressively leads to inflammation, fibrosis or hepatocellular carcinoma. The molecular mechanisms responsible for iron induced liver injury are not fully characterized. Here, we investigated the potential contribution of hemojuvelin ablation to hepatic iron, lipid metabolism and its role in the pathogenesis of liver fibrosis. Wild-type (WT) and Hemojuvelin knockout mice (Hjv-/-) on C57BL/6J background were fed either a standard chow, a high fat, or a high-fat with 2% supplemented iron diet (HFD + Fe) for a time course experiment (0, 3, 6, 9, 12 weeks). Comparatively, Hjv-/- animals developed higher serum iron indices, liver iron deposition, and diminished hepcidin levels. Likewise, dramatic changes were observed between levels of iron uptake protein TfR1 and iron storage protein ferritin. Interestingly, HFD + Fe group showed significant reduction in body weight irrespective of genotype. Further, qPCR data revealed significant downregulation of Adiponectin receptor 2 (AdipoR2) in this group, in addition to upregulation of cholesterol biosynthesis with excess iron. Hjv-/- animals also develop higher serum titer for transaminases (ALT, AST), common markers of liver injury. However, animals failed to develop liver fibrosis. We speculate that this is related to the strain of the mice, which is genetically resistant to liver injury.L'hémojuvéline (HJV) est une protéine membranaire qui contrôle le métabolisme systémique du fer. Les mutations de HJV conduisent à l'hémochromatose juvéline, qui découle de l'absorption incontrôlée du fer de l'alimentation et des dépots de ce métal dans les cellules parenchymateuses du foie. La surcharge hépatique en fer mène progressivement à l'inflammation, la fibrose et le carcinome hépatocellulaire. Les mécanismes moléculaires responsables des dommages au foie qui sont attribuables au fer ne sont pas entièrement caractérisés. Nous avons donc étudié la contribution potentielle de l'ablation de HJV sur le fer hépatique, le métabolisme des lipides et son rôle dans la pathogénèse de la fibrose hépatique. Des souris de type sauvage (WT) et déficiente pour HJV (Hjv-/-) dans la souche C57BL/6J ont été nourries avec un régime normal, riche en gras ou riche en gras et supplementé en fer (HFD + Fe) pour différentes périodes (0, 3, 6, 9, 12 semaines). Comparativement, les animaux Hjv-/- développent des indices de fer sérique plus élevés, des dépots de fer dans le foie, et une diminution de niveaux de hepcidine. Des changements dramatiques sont également observés entre les niveaux de la protéine de capture du fer, TfR1, et la protéine de stokage du fer, la ferritine. De manière intéressante, le groupe HFD+ Fe montre une réduction significative de la masse corporelle des animaux quel que soit leur génotype. De plus, les données de qPCR revèlent la régulation à la baisse significative du récepteur 2 de l'adiponectine (AdipoR2) dans ce groupe, en plus de la régulation à la hausse de la biosynthèse de cholestérol avec un excès de fer. Les animaux Hjv-/- montrent un titre sérique plus élevé de transaminases (ALT, AST), marqueurs communs de dommages du foie, bien que les animaux ne développent pas la fibrose hépatique. Nous spéculons que ceci est dû à la souche des souris qui est résistante aux dommages du foie.
48
Rahim, Mir Munir Ahmed 1975. "Pathogenesis of HIV-1 nef in adult mice." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115698.
Full textAbstract:
Development of a suitable animal model of AIDS is much needed in AIDS research to study infection and pathogenesis as well as to evaluate methods of prevention and treatment of HIV infection. Small animals such as rodents are attractive candidates for AIDS research due to the availability of various inbred and genetically engineered strains, extensive knowledge or their immune system, especially in mice, and the relative ease of breeding and maintaining animal colonies. Transgenic small animal models carrying entire HIV genome or selected genes have been instrumental to understand functions of HIV genes in vivo and their role in HIV pathogenesis. The type of cells in which HIV genes are expressed seems to be an import prerequisite for the study of HIV gene functions in transgenic mice. Mice constitutively expressing the entire HIV-1 genome or HIV-1 nef gene in CD4 + T cells and in the cells of macrophage/dendritic lineage develop an AIDS-like disease very similar to AIDS disease in humans. Similarly, expression of Nef in adult mice, using inducible system, results in the AIDS-like disease. This disease is characterized by thymic atrophy, impaired thymocyte maturation, loss of CD4+ T cells, increased activation and turnover of T cells, which can occur in the absence of lymphypenia, and non-lymphoid organ disease involving the lungs and kidneys. Susceptibility of adult mice to the pathological effects of Nef suggests that the AIDS-like disease in the constitutively expressing Nef Tg mice is not due to developmental defects caused by early expression of Nef. This model highlights the important role of Nef in HIV-1 pathogenesis. The high similarity in the disease in these Tg mice with human AIDS strongly suggest that these mice are a relevant model to study AIDS. This study further evidence that mouse cells can support functions of Nef and these Tg mice represent a unique model to study Nef functions in vivo in the context of the primary immune system. Moreover, the inducible Nef Tg model has given us the ability to control the level and time of expression of Nef which was impossible to do in the previously reported constitutive Nef Tg mouse models. These mice will be useful to study immune reconstitution since Nef expression can be turned off after withdrawal from dox.
49
Salwa, Taneem. "Citrobacter rodentium infection in mice to dissect host pathogen relationship in the gut." Thesis, Queen Mary, University of London, 2016. http://qmro.qmul.ac.uk/xmlui/handle/123456789/23654.
Full textAbstract:
Citrobacter rodentium is a gut pathogen, which infects the distal colon of mice. It has many similarities to human Enteropathogenic and Enterohemorrhagic E.coli in terms of mechanisms of pathogenicity and methods of transmission. Like many other gram negative bacteria, C. rodentium has developed a complex and highly specialised protein secretion system, known as type three (T3SS), to deliver bacterial proteins into eukaryotic cells. By injecting effector proteins into host cell cytoplasm, the pathogens are able to modulate host cellular functions to facilitate their own survival and replication. There is growing evidence that Attaching Effacing (AE) pathogens can inject effector proteins into gut epithelial cells, which dampen pro-inflammatory responses. There is also evidence that EPEC, Yersinia and Shigella can inject effectors into immune cells and also modulate their function. The objective of this work was to visualise and identify the host cells targeted for type III secretion by C. rodentium, and consequently determine the effect on host immune responses. The method chosen to detect cells targeted for effector protein delivery was the β-lactamase reporter system, where cells loaded with the fluorogenic substrate CCF2-AM emit a green FRET signal upon excitation by UV light, but emit a blue signal when cleaved by β-lactamase. By creating reporter strain of C.rodentium expressing fusion proteins between NleD effector and β-lactamase, I was able to show that C.rodentium is capable of injecting NleD in a wide variety of murine cell lines including Swiss 3T3 fibroblasts, J774 macrophages, CMT93 epithelial cells and BW715 T cells in a dose and time dependent manner in vitro. In addition, I found that C.rodentium has the ability to inject proteins into the cytoplasm of immune cells isolated from mouse lymphoid tissues including the spleen, mesenteric lymph nodes and Peyer's patches. Detailed analysis of the types of cells injected with effectors in vitro showed that NleD- injected cells represented B cells, dendritic cells and T cells. After inoculation of mice with the reporter strain of CitropACYCnleD, the plasmid encoded reporter fusion remained stable throughout infection and was able to inject cells in vitro after passage through the mouse gut. Unfortunately under the conditions described in this study, we were unable to visualise any gut cells targeted for protein delivery by C. rodentium in vivo, thus highlighting the complex nature of the host pathogen relationships in the gut. Although there is a need to develop better strategies to visualise effector translocation in vivo, our study has demonstrated, for the first time, the ability of C. rodentium to target immune cells for effector injection in vitro.
50
Shahbazian, Lotfollah Masoud. "Dietary ethanol modulates immune responses, and alter resistance to Streptococcus pneumoniae in LP-BM5 retrovirus infected mice." Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186594.
Full textAbstract:
A murine model of acquired immunodeficiency syndrome (AIDS) was developed by infecting C57BL/6 mice with murine leukemia retrovirus LP-BM5. Murine AIDS shares many features with human AIDS. Murine and human AIDS cause impairment of cell-mediated and humoral immune responses, and increase risk of opportunistic infection such as Streptococcus pneumoniae. Cofactors such as ethanol may determine the severity of the retrovirus infection and the rate of progression to AIDS. Changes in nutritional status due to retrovirus infection or ethanol consumption, can play an important role in immunomodulation in the animal. Immunomodulation observed in animals with chronic ethanol ingestion is associated with age of the animal, the nutritional composition of the diet, and the amount of ethanol consumed. Young mice are more sensitive to the immunomodulating effects of ethanol and diet than mature mice. The percentage of B cells in mature mice was significantly increased with consumption of nutritionally superoptimal diet containing ethanol while ethanol ingestion with a nutritionally inadequate diet severely decreased the percentage of B cells when compared to control or pair-feeding. Cytokine secretion, and natural killer cell and phagocytic activities were modulated by ethanol as well as by the nutritional quality of the diet. Both retrovirus infection and ethanol consumption affected survival rate after Streptococcus pneumoniae infection in mice. Chronic ethanol consumption, but not retrovirus infection resulted in significant reduction in serum level of anti pneumococcal polysaccharide antibody which in combination with complement system make up an important part of host defense against S. pneumoniae. However, retrovirus infection significantly reduced resistance to S. pneumoniae. Retrovirus infected mice fed a diet containing a high concentration of ethanol for short term exhibited a greater resistance to S. pneumoniae infection than mice fed diets with low concentration or no ethanol. S. pneumoniae antigen immunization improved survival of the mice infected with S. pneumoniae. In conclusion, ethanol and nutritional adequacy of diet induced immunomodulation of the host. Ethanol consumption during retroviral infection may accelerate the progression of murine AIDS through changes in the lymphoid cells and resistance to S. pneumoniae infection.