Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1990. / Vita. Abstract. Includes bibliographical references (leaves 111-123). Also available via the Internet.

Thesis (M.D.)--University of Adelaide, Dept. of Paediatrics, 1991. / Includes bibliographical references (leaves 287-310).

Bibliography: leaves 287-310 / 311 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Paediatrics, 1991

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2008. / Title from title screen (site viewed Aug. 14, 2008). PDF text: 208 p. : ill. (some col.) ; 3 Mb. UMI publication number: AAT 3297662. Includes bibliographical references. Also available in microfilm and microfiche formats.

The roles of humoral and cell mediated immune responses in murine brucellosis were investigated in this study.B. abortus strain 19, the current vaccine strain, is known to induce an antibody as well as cell mediated immune responses, both of which protect mice against smooth strain 2308. B. abortus rough strain RB51 does not induce an o-side chain specific antibody response and yet protects mice against smooth strain 2308. Passive transfer experiments using serum and nylon wool enriched T cells obtained from micevaccinated with strain 19 and strain RB51 were carried out. Immune senum from strain 19 vaccinated mice protected against challenge with strain 2308 but not strain RB51. Nylon wool enriched T cells from strain 19 vaccinated mice protected recipient mice against challenge with both strains RB51 or 2308. Serum obtained from RB51 vaccinated mice did not protect recipient mice against challenge with either strain RB51 or strain 2308. Nylon wool enriched T cells from the same vaccinated mice, however, protected mice against challenge with both strains. Thioglycollate elicited mouse peritoneal macrophages could be activated by recombinant gamma-interferon to kill ingested B. abortus. This was true for both the rough strain RB51 and smooth strain 2308, although RB51 exhibited greater susceptibility to killing. Macrophages already invaded by either strain RB51 or strain 2308 retained their responsiveness to gamma-interferon activation am could kill either strain of B. abortus following activation by gamma-interferon. Results obtained in this investigation indicate that strain RB51 protects mice against strain 2308 by probably inducing a cell mediated immune response. / Ph. D.

D.Litt.et Phil. (Psychology) / According to Cunningham (1978) there is a fair amount of controversy that surrounds the possible causes of auto-immune diseases. According to him there are two conflicting categories of causes of which psycho-social causes is one and abnormalities of the immune system is the other. Although a substantial amount of studies concerning the relationship between psychological factors and immune functioning have been done, the results have been inconclusive. The reason for this seems to be that there is a vast amount of mediating factors. A further aspect that needs to be taken into account is that psychoneuroimmunological research has focused mainly on adults. Schleifer, Scott, Stein and Keller (1986) is of the opinion that extensive research is required to study the effects of the central nervous system and behaviour during the early development of a person. The study attempted to identify possible psycho-social factors that could contribute to pediatric diseases such as rheumatoid arthritis. In order to identify factors that are unique to auto-immune diseases four groups were compared i.e, emotional disorders, behavioral disorders, auto-immune diseases and a "normal" group.

The dysregulation of immune system function has been centrally implicated in numerous age-related and neurodegenerative disorders, including Alzheimer’s disease (AD). Genetic susceptibility studies have positioned microglia, brain-resident immune cells, as critical actors in the development and the progression of the disease. Microglia are highly plastic cells with diverse functions across many modalities, and the appropriate regulation of their activities are a prerequisite for central nervous system homeostasis and cognitive health. Aging and pathogenic contexts are posited to modify microglial behavior, inhibiting their neuroprotective function and promoting a dysfunctional state that drives disease. However, the mechanisms underlying these pathogenic alterations in microglial state and function are complex and poorly understood. This thesis identifies three elements that are altered in the AD brain and investigates how these mechanisms may serve as triggers producing microglial dysregulation in AD. Chapter 3 examines the role of expression of the transposable element LINE-1 in AD-related microglial dysfunction. Chapter 4 explores the regulation of PLCG2, which encodes a critical AD-associated signaling enzyme. Chapter 5 investigates the role of the AD-linked sorting receptor SORL1 in microglia. Together, these data expand our understanding of mechanisms driving altered microglial pathophysiology in AD and illuminate pathways of interest with potential therapeutic applications meriting deeper exploration.

Thesis (M. Tech. (Biomedical technology)) - Central University of technology, Free State, 2013 / INTRODUCTION: The renal effects of Tenofovir Disoproxil Fumarate (TDF) and antiretroviral treatment (ART) outcomes remain under-reported in African settings. The study sought to assess immunological outcomes and to compare renal function outcomes between patients exposed to TDF and unexposed patient group. METHODS: Phase 1 of the study was a retrospective case control analysis of serum creatinine data for 312 ART naïve adult patients exposed to TDF and 173 unexposed patients enrolled on ART between Dec 2006 and Jan 2011 at Roma Health Service Area in Lesotho. Sub-optimal renal function outcomes were serum creatinine clearance values <50 ml/min calculated using the Cockcroft-Gault equation. Phase 2 was based on re-sampling of the study population and analysis of CD4 counts of 516 adult naïve HIV-positive patients. Univariate logistic regression (p<0.1) and multivariate analyses (p<0.05) were performed using STATA® version 11 software. RESULTS: Overall, 153 (31.5%) patients had moderate baseline (30-60 ml/min) renal insufficiency. Renal function improved by +2 ml/min at 24 months. Almost 18% (n=312) of the patients on TDF were erroneously put on TDF. The use of TDF was a marginally significant factor (p=0.054) associated with CrCl<50 ml/min outcomes in univariate analysis but was insignificant (p=0.122) in multivariate analysis. Female gender (p=0.016), high blood pressure (p=0.009), ages over 60 (p=0.004), and underweight (p<0.001) were significantly associated with CrCl<50 ml/min outcomes. The proportion of patients who developed immunological failure in this study was low (6.8%, n=516). The mean CD4 count increased significantly after treatment (p<0.001). Baseline CD4 count below 50 cells/mm3 (p=0.049) and male gender (p=0.005) were significantly associated with sub-optimal immunological outcomes. CONCLUSIONS: TDF is a weak contributing factor associated with renal impairment outcomes compared to other variables such as hypertension, older age, underweight and female gender. More research on long term effects of TDF is recommended. Baseline renal function screening should be improved to minimise leakages of patients contraindicated of TDF. Although the patients’ immunological status generally improved, males and patients with low baseline CD4 counts should be monitored closely while on ART.

Os fagócitos contêm uma nicotinamida adenina dinucleotídeo fosfato (NADPH) oxidase associada à membrana, que gera superóxido e outros reativos intermediários do oxigênio. Defeitos nesta oxidase em seres humanos resultam na doença granulomatosa crônica (DGC). Mutações próximas aos sítios de splicing que interferem com o processamento do RNA mensageiro, acarretando deleção de um ou mais exons, são cada vez mais freqüentes na literatura científica, nesses casos, os mecanismos moleculares que levam a DGC nem sempre são totalmente esclarecidos, assim como o efeito do IFN-g, seja sobre o processamento da mensagem ou estabilidade dos transcritos. Com base nessas informações o objetivo geral deste trabalho é investigar o efeito do IFN-g sobre a regulação do sistema NADPH oxidase fagocítico humano. Através dos resultados obtidos, não se pode constatar melhora na produção de ânions superóxido após o tratamento com IFN-g em pacientes com defeito de splicing, no entanto detectou-se aumento da expressão do gene CYBB através de PCR convencional e através de real-time PCR além de um aumento na marcação de proteínas do spliceossoma através do FAN. / Phagocytes have a nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) associated to plasmatic membrane that generates superoxide and other oxygen reactive intermediates. Defects on this oxidase in humans result in a disorder called Chronic Granulomatous Disease (CGD). Mutations next to splicing sites that interfere with the mRNA processing leading to deletion of one or more exons, are even more frequent on scientific literature, in these cases, the molecular mechanisms causing CGD are not always completetly clear, as well as the effect of IFN-g on the mRNA processing or on the stability of transcripts. Based on this information our aim is to investigate the effect of IFN-g on the regulation of the human NADPH oxidase phagocyte system.. With the obtained results it wasnt possible to see an increase in anion superoxide production after the IFN-g treatment in patients with splicing defects, however it was detected an increase on the expression of CYBB gene by conventional and real-time PCR besides an increase in the marking of spliceossomal proteins by FAN.

HIV-1 specific CD4+ T cell activity in clade C infected subjects has not been studied. CD4+ T cells play a vital role in controlling infectious diseases and there is a need to augment our knowledge of HIV immunology to aid vaccine design. We therefore embarked on a study to characterize HIV-1 specific CD4+ T cell activity in both adults and infants; assess the relationship between CD4+ and CD8+ immune responses; and the relationship between CD4+ T cell activity and markers of disease progression (viral loads and CD4 counts). Our study revealed that the magnitude of CD8+ T cell responses correlated significantly with CD4+ T cell responses, but that the percentage of CD8+ T cells directed against HIV-1 was always greater than that of CD4+ T cells. Gag was the frequently targeted HIV-1 protein by CD4+ T cells and had the highest density of epitopes targeted by CD4+ T cells. Patients with either a dominant CD4 or CD8 T cell response against Gag had significantly lower viral loads than patients in whom non-Gag proteins were the main target (p< 0.0001 for CD4 activity and p= 0.007 for CD8 responses). Single IFN- producing CD4+ T cells were present in significantly higher numbers than cells producing both IFN- and IL-2 simultaneously (p=0.009). Gag also dominated the CD4+ T cell response in acutely infected infants with IFN- production detected more frequently than IL-2 or TNF- . Longitudinal analysis of infants receiving early ARV treatment and then ceasing after 12 months revealed that early treatment conferred no protection against increasing viremia and disease progression. CD4+ T cell responses were detected sporadically in untreated infants indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia. Taken together, the data reveal that a vaccine inducing Gag specific CD4+ T cell responses has the potential to confer some degree of protection, but other immunological parameters need to be investigated especially in infants. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.