Includes bibliography. / xv, 257 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the role of polymorphisms in immunoregularatory genes in conferring susceptibility to common variable immunodeficiency. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1998?

Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2002? / Includes list of publications arising from the thesis. Bibliography: leaves 327-341.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph.D.)--York University, 2008. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 243-264). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR51693

The surface molecules (procyclins) of procyclic forms of African trypanosomes (Trypanosoma brucei spp.) are complex mixtures of lipid-anchored glycoconjugates. The procyclins are expressed differentially during the parasite life cycle within the tsetse fly vector. It has been hypothesised that these surface molecules are involved in interactions with molecules of the tsetse fly and may influence differentiation, cell death and tissue tropism. To understand procyclin functions it is necessary to identify and characterise them. This thesis presents a study of the biochemical and immunochemical characteristics of the major surface molecules of Trypanosoma simiae and Trypanosoma congolense, animal pathogens of the subgenus Nannomonas that share the same developmental cycle and tropism within the tsetse vector. Organic solvent extraction, reverse-phase high performance liquid chromatography and enzyme-linked imnunosorbent assay using surface binding monoclonal antibodies were used to isolate membrane molecules of procyclic culture forms (PCF) of both trypanosome species. Gel electrophoresis of the purified molecules revealed two predominant molecular species from each parasite that were broadly similar yet showed different apparent molecular masses and staining characteristics. The molecules were shown to be glycosylphosphatidylinositol-lipid anchored glycoconjugates, comprised mainly of carbohydrates. Each moiety displayed surface-disposed carbohydrate epitopes that were recognised on the surface of both species of trypanosomes by monoclonal antibodies specific for procyclic parasites of the subgenus Nannomonas. The epitopes were previously shown to be displayed on the glutamic acid-alanine rich protein (GARP) of T. congolense, yet neither this protein (as detected either immunologically or by mass spectrometry) nor its encoding gene (as detected by Southern blot analysis) was present in T. simiae. The results indicate that although T. congolense and T. simiae share common carbohydrate surface epitopes, these are displayed on biochemically different molecules. I hypothesise that the surface disposed carbohydrate structures and not the polypeptide moieties are involved in parasite-tsetse interactions since these species have the same developmental cycles in the insect vector. In an attempt to obtain primary sequence information for the T. simiae PCF surface molecules, I identified and characterised an unique open reading frame. This was shown to be expressed as a protein in PCF and is likely a membrane-associated molecule of the subgenus Nannomonas. / Graduate

The major pathologic feature of the human autoimmune disease Systemic Lupus Erythematosus (SLE) and its murine counterpart, murine lupus, is the production of autoantibodies to nucleic acid antigens. In this study, a panel of six murine monoclonal anti-DNA autoantibodies was characterized at both the cellular and molecular levels in order to determine their possible role in the etiology of autoimmune disease. At the cellular level the autoantibodies were found to be highly cross-reactive, binding to three different antigenic forms of DNA as well as to the cell surface of various lymphoid cell lines. Furthermore, the fact that this autoantibody binding could be abrogated by pretreating the cells with either Proteinase K or DNase supports the hypothesis that a DNA binding protein may exist on the cell surface and that DNA bound to this receptor may serve as the target for the anti-DNA autoantibody. At the molecular level, the immunoglobulin (Ig) gene segments (V(H), D, J(H)) used to encode the variable region of the heavy chain of an anti-DNA autoantibody were sequenced. All three gene segments could be identified as members of established Ig gene segment families. In fact, the heavy chain of an antibody directed against the hapten L-glutamine₆₀-L-alanine₃₀-L-tyrosine₁₀ polymer (GAT) was found to utilize the same combination of V(H), D, and J(H) gene segments as the anti-DNA autoantibody. These results clearly indicate that autoantibodies are encoded by gene segments from the same Ig gene families used to encode antibodies to exogenous antigens. However, the discovery that this anti-DNA autoantibody is encoded by the same V(H) gene segment which encodes another anti-DNA autoantibody, derived from a different autoimmune mouse strain, supports the idea that certain V(H) gene segments may, in fact, be preferentially used to encode autoantibodies.

No description available.

Type 1 innate lymphocytes comprise two developmentally divergent lineages, type 1 helper innate lymphoid cells (hILC1s) and conventional NK (cNK) cells. All type 1 innate lymphocytes (ILCs) express the transcription factor T-bet, but cNK cells additionally express Eomesodermin (Eomes). We show that deletion of Eomes alleles at the onset of type 1 ILC maturation using NKp46-Cre imposes a substantial block in cNK cell development. Formation of the entire lymphoid and non-lymphoid type 1 ILC compartment appears to require the semi-redundant action of both T-bet and Eomes. To determine if Eomes is sufficient to redirect hILC1 development to a cNK cell fate, we generated transgenic mice that express Eomes when and where T-bet is expressed using Tbx21 locus control to drive expression of Eomes codons. Ectopic Eomes expression induces cNK cell-like properties across the lymphoid and non-lymphoid type 1 ILC compartments. To investigate if T-bet is sufficient to direct type 1 ILC development into the hILC1 lineage, we also generated transgenic mice in which Tbx21 locus control drives expression of T-bet codons. Enforced T-bet expression, however, does not appear sufficient to induce hILC1-like attributes among type 1 ILCs. Subsequent to their divergent lineage specification, hILC1s and cNK cells possess substantial developmental plasticity elicited by the absence or presence of Eomes.

Typescript (photocopy) / xiii, 209 leaves : ill., (1 col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Genetics, 1983

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