Browsing by Subject "Immune response"

Now showing 1 - 3 of 3
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    The effect of antibiotic treatment on Haemophilus parasuis colonization, disease and immunity
    (2015-07) Macedo, Nubia
    Glasser's disease is an important source of economic losses in commercial swine production systems. The success of controlled exposure in the field suggests that early exposure (colonization) with pathogenic H. parasuis protects pigs from Glasser's disease. However, little is known about the immune response that is generated during colonization and how antimicrobials can modulate the immune response to H. parasuis. The overall goal of this PhD dissertation was to investigate the influence of antimicrobial treatment on H. parasuis colonization and infection, and its effect on the development of immune responses against H. parasuis in swine. First, a species-specific ELISA assay and an experimental model of H. parasuis colonization were developed to study the immune response to H. parasuis colonization by a pathogenic strain in conventional pigs. Moreover, the effect of the antimicrobial enrofloxacin in reducing H. parasuis colonization in weaned pigs was assessed. It was demonstrated that enrofloxacin was able to affect H. parasuis colonization by temporarily reducing the bacterial load in the upper respiratory tract. However, enrofloxacin was unable to eradicate the organism. Then, it was demonstrated that the inoculation of pigs with a low dose of pathogenic H. parasuis protected pigs against secondary infection. Most importantly, the timing of enrofloxacin administration in relation to H. parasuis exposure was relevant to develop protection to a subsequent H. parasuis challenge. The protection observed after H. parasuis inoculation was not affected by enrofloxacin given 3 days before inoculation. In contrast, enrofloxacin given 3 days after inoculation with H. parasuis interfered with protection against challenge. Based on the lack of H. parasuis isolation after enrofloxacin treatment, it appeared that the antibiotic quickly inactivated and removed H. parasuis. For the given infectious dose of pathogenic H. parasuis used, more than 3 days of live bacteria exposure is necessary for pigs to seroconvert and be protected against reinfection. Enrofloxacin-induced abridgement of infection on day 3 post inoculation resulted in the absence of serum IgG response and protection.
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    Immunological responses during the incubation period and acute phase of naturally acquired primary Epstein-Barr virus infection
    (2015-07) Dunmire, Samantha
    Epstein-Barr virus (EBV) in a human herpesvirus. It infects about 90% of the human population, and is the main causative agent of infectious mononucleosis. The incubation period, the time between viral acquisition and onset of symptoms, is unusually long in patients presenting with infectious mononucleosis, lasting about six weeks. In addition to causing acute illness, there can also be long-term consequences as the result of acquisition of the virus, including nasopharyngeal carcinoma and lymphoma. Nevertheless, there remains a surprising dearth of knowledge regarding the establishment of and immune response to persistent EBV infection in its natural hosts, especially during the incubation period. We sought to address many of these gaps by studying the incubation period, acute phase, and convalescence of undergraduates experiencing infectious mononucleosis during primary natural EBV infection in a cohort of prospectively studied volunteers. Particular attention was paid to the previously uncharacterized incubation period. Our findings have focused on understanding the immune response that occurs in young adults presenting with infectious mononucleosis, via gene expression changes as observed in peripheral blood mononuclear cells and innate and adaptive immune cells. Using a systems biology approach we discovered that important gene expression changes occur during the immune response to primary EBV infection. A typical antiviral type I interferon response was not observed at onset of infectious mononucleosis symptoms, but rather up to two weeks prior. The gene expression signature at symptom onset was dominated by cell cycle related genes, probably due to the CD8 T cell lymphocytosis, and type II interferon regulated genes. Interestingly, comparison of the EBV signature with other acute viral infections revealed very little similarity. The EBV signature showed the greatest similarity with hemophagocytic syndromes. This result is consistent with the view that infectious mononucleosis is an immunopathologic disease, and is supported by evidence that EBV can cause hemophagocytic lymphohistiocytosis. As an extension of this work, we carefully examined changes in cellular phenotypes and population frequencies to determine if there were significant alterations to certain compartments during the response to primary EBV infection. We observed a type I interferon signature in a larger subset of study participants during the incubation period. This response was concurrent with the transition of virally infected B cells from the oral cavity to the blood, a decline in plasmacytoid dendritic cells from the circulation, and a polyclonal CD8 T cell activation. No EBV specific CD8 T cells activation was observed until the onset of infectious mononucleosis symptoms. A major obstacle to understanding EBV related sequelae has been the lack of an efficient animal model for EBV infection, although progress in primate and mouse models has recently been made. Taken together, the data compiled in this thesis provide important first descriptions of the immune responses that occur during the establishment of a natural persistent infection in humans. Key future challenges are to develop protective vaccines and effective treatment regimens.
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    Regulation of T cell migration and the immune response by phosphoinositide 3-kinase gamma.
    (2007-11) Martin, Amanda Lorene
    Efficient migration of leukocytes is essential to an optimal immune response. The goal of these studies was to determine the role of the PI3K isoform p110γ in T cell migration, activation and the immune response as a whole. Our studies revealed that naïve T cell migration in response to the constitutive chemokines CCL19 and CCL21 in vitro is minimally affected by the loss of p110γ, which correlates with the absence of trafficking defects of p110γ/- T cells into secondary lymphoid organs in vivo . In several models of in vitro activation, p110γ deficiency does not impair naïve T cell activation and proliferation nor does it impact OT-I T cell proliferation and effector cell differentiation in vivo in response to vaccinia virus challenge. In contrast to naïve T cell migration, p110γ plays an important role in CD8 effector T cell migration both in response to inflammatory chemoattractants in vitro and to the inflamed peritoneum following challenge with vaccinia virus. Furthermore, while wild-type mice efficiently cleared vaccinia virus at high viral doses, infection of p110γ/- mice resulted in visible illness and death less than a week after infection. In all, we conclude that p110γ is dispensable for constitutive migration of naïve T cells and subsequent activation and differentiation into effector CD8 T cells, but plays a central role in the migration of effector CD8 T cells into inflammatory sites and in the antiviral immune response.