Bibliography: leaves 172-214. Interleukin-12 (IL-12) is a heterodimeric cytokine composed of two disulphide-linked subunits, p35 and p40, which form biologically active p70. IL-12 is able to induce IFN-y production from T and NK cells, and promote the proliferation of mitogen-activated T cells. It is thought that IL-12 may be an important cytokine in the initiation and progression of allograft destruction. This thesis describes the characterisation of ovine IL-12.

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

published_or_final_version / abstract / toc / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Bibliography: leaves 172-214. / 214 leaves, [41] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Interleukin-12 (IL-12) is a heterodimeric cytokine composed of two disulphide-linked subunits, p35 and p40, which form biologically active p70. IL-12 is able to induce IFN-y production from T and NK cells, and promote the proliferation of mitogen-activated T cells. It is thought that IL-12 may be an important cytokine in the initiation and progression of allograft destruction. This thesis describes the characterisation of ovine IL-12. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2000

Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 2000. / Bibliography: leaves 172-214.

Each year, between 300 and 500 million people develop malaria. Close to 3 million people die as a result. Due to resistance there are now few drugs left which are effective against malaria; one is a Chinese herbal remedy called qinghaosu (artemisinin). A section of this thesis represents an attempt to understand further the mode of action of this antimalarial agent. Several mechanisms involving iron have been proposed and the main categories reviewed (chapter 3). Techniques including ESR spectrometry, fluorescence and absorbance measurements were used to further probe the mode of action of qinghaosu. The findings of these studies provide support for a mechanism proposed by Wu et al., involving cleavage of the peroxy bridge in qinghaosu with the ferrous ion as opposed to antimalarial activity being due to the generation of high valent iron-oxo species. The ether derivative of qinghaosu, arteether has been studied using 2D NMR in order to provide further insight into the unusual structure of this compound (chapter 4). A comparison of the sp2 lactone functionality in qinghaosu with the sp3 ether group in arteether was performed. Evidence is presented for different conformations and chemical shift values. The immune system protects the human body from invasion by foreign substances or cells. A key part of this immune response comes from cellular components known as macrophages. The killing process of macrophages appears to involve nitric oxide. However, this natural defence mechanism is not very efficient as the body is susceptible to invasion by microbes. The term microbe includes both parasites and bacteria. The toxicity of nitric oxide (NO) and NO donor compounds has been investigated using the bacterium E. coli (chapter 5). In addition, studies have been performed using parasites. Malarial parasites (Plasmodia) are difficult to culture, therefore Leishmania parasites which cause the tropical disease leishmaniasis were used as a model (chapter 6). Evidence is presented for the toxic nature of NO donor compounds towards both parasites and bacteria. However, qinghaosu and its derivatives did not prove effective against Leishmania mexicana parasites in contrast with their reported antimalarial activity. The conclusions of this study suggest that qinghaosu possesses a toxicity mechanism selective for malarial parasites.

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy

Thesis (Ph. D.)--University of Chicago, Pritzer School of Medicine, Committee on Immunology, June 2000. / Includes bibliographical references. Also available on the Internet.

Thesis (M.S.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains vii, 73 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 60-66).

Coccidioidomycosis is a growing problem in the United States. There is still an incomplete understanding of the immunological response associated with human coccidioido-mycosis, although previous studies have indicated that cell-mediated immunity (CMI) is critical in the control of this disease. We have examined necrotizing pulmonary coccidioidal granulomata using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-?). Discrete perigranulomatous lymphocytic clusters were identified containing roughly equal numbers of T (CD3+) and B (CD20+) lymphocytes. While the number of cells expressing IL-10 was similar in the mantle and in the perigranulomatous clusters, there were significantly more cells expressing IFN-? in the mantle compared to the clusters (P = 0.037). Confocal microscopy revealed that CD4+ T lymphocytes and B lymphocytes are associated with IL-10 production. CD4+CD25+ T lymphocytes were also identified in the perigranulomatous clusters but were not associated with IL-10 production. This is the first report noting perigranulomatous lymphocyte clusters and IL-10 in association with human coccidioidal granulomata, suggesting a down-regulation of cellular immune response.IL-12 is critical in driving a T helper type 1 (Th1) immune response. To understand the mechanism associated with hyporesponsiveness to IL-12 stimulation seen in some anergic patients with disseminated coccidioidomycosis, IL-12 receptor expression and function were determined in PBMCs from immune and nonimmune healthy donors. By using a relative quantitative RT-PCR technique, we found that IL-12R?1 is constitutively expressed in PBMCs and is equally up-regulated by coccidioidal antigen preparation T27K in both immune and nonimmune donors. On the other hand, the IL-12R?2 expression level is increased by T27K only in PBMCs from immune but not nonimmune donors. In addition, the increased IL-12R?2 expression in immune PBMCs is correlated with Stat4 activation and the induction of IFN-? production by IL-12. These data suggest that the IL-12R?2 expression and signal transduction is functional in host immunity against Coccidioides infection. Subsequent research, which involved the stimulation of lymphocytes with autologous dendritic cells (DCs) pulsed with T27K, revealed that the up-regulation of IL-12R?2 expression and signal transduction is associated with the induction of IFN-? production by DCs pulsed with T27K.