Typescript (photocopy). / Digitized by Kansas Correctional Industries

The immune system relies on the collaboration of heterogeneous cell types to respond to infection, develop immunological memory, and to maintain immunological tolerance. In response to infection, naïve lymphocytes must divide and give rise to differentiated effector cells while also regenerating a population of memory cells that may respond more efficiently to future infection. It has been demonstrated in B cells and T cells that the generation of these cell types may be accomplished simultaneously through asymmetric cell division. The second chapter of this thesis focuses on what factors may drive the divergence of cell fates in asymmetric cell division of CD8+ T cells. We demonstrate unequal expression of transcription factor TCF1 between cytokinetic sibling cells, which may be driven by unequal transduction of nutrient-sensitive PI3K/AKT/mTOR signaling. In chapter three, we extend our interrogation of asymmetric cell division in lymphocytes to the development of regulatory T cells, which are important for the maintenance of immunological self-tolerance. It has been shown that there is some overlap in the T cell receptor repertoires of Tregs and conventional CD4+ T cells. We propose that this overlap may be a result of an asymmetric cell division, giving rise to one Treg and one conventional CD4+ T cell. We demonstrate asymmetric Foxp3 expression between cytokinetic sibling cells found in the thymus as well as from an in vitro Treg induction model. We also show that in vitro upregulation of Foxp3, the major Treg-associated transcription factor, is inhibited by cell cycle inhibitors, further linking the act of cell fate divergence to a divisional event.

No description available.

Doctor of Philosophy / Profound perturbation of epithelial structure is a characteristic feature of the immunopatholoical response to bacterial antigens considered to be central in the pathogenesis of the destructive lesion of periodontitis. The pathological basis for the disturbance of epithelial structure is not understood. It was demonstrated that the structural integrity and functional differentiation of the lining epithelium is compromised in relation to inflammatory changes associated with destructive periodontitis. In the pathological lining epithelium of the periodontal pocket there was a marked reduction of epithelial cadherin important in intercellular adhesion, of involucrin, a marker of terminal differentiation, and of the gap junction connexions that form intercellular communication channels. These changes were associated with alterations of filamentous actin expression, collectively indicating profound perturbation of epithelial structure. The data reported support the concept that the ability of the pathological lining epithelium to function as an effective barrier against the ingress of microbial products into the tissues is severely compromised (Ye et al., 2000). In addition, a recent study (Ye et al., 2003) by Western analysis of serum IgG from all 22 patients with chronic periodontitis tested indicated recognition of multiple epithelial components in individual patterns. In contrast, subjects with a healthy periodontium displayed only trace recognition of epithelial antigens. Levels of epithelial-reactive antibodies were significantly correlated with attachment loss as an indication of disease activity. To investigate a possible relationship between the bacterial flora adjacent to the diseased sites and the presence of epithelial-reactive antibodies, subgingival plague samples were taken from deep periodontal pockets and cultured anaerobically. Gram positive bacteria containing antigens potentially cross-reactive with epithelial cells were reproducibly isolated by probing membrane colony lifts with affinity-isolated (epitheial-specific) antibodies. The bacteria were identified as streptococci (S. mitis, S. constellatus and two S. intermedius strains) and Actinomyces (A. georgiae, and A. sp. oral clone) by 16S rDNA sequence homology. Recognition by affinity-isolated antibodies of antigens from the captured organisms was confirmed by Western analysis. Conversely, absorption of affinity-isolated antibodies with bacterial species specifically reduced subsequent recognition of epithelial antigens. To identify the auto-antigens, a human keratinocyte cDNA expression library in Lambda phage was probed using a pooled sera. Groups of responders were detected for CD24 (a recently described adhesion molecule also known as P-selectin ligand), antioxidant protein 2 (a newly recognised member of the thiol-dependment anti-oxidant proteins), lavtate dehydrogenase A, the transcription factor NFAT5, and for three genes encoding novel proteins. Six identified bacteria, especially S intermedius were demonstrated to absorb antibodies reaching with identified auto-antigens in patterns varying between individuals. This evidence indicated that during the course of periodontits, subjects develop increased levels of antibodies to common oral bacteria amongst which are included tissue cross-reactive antigens. Periodontitis could therefore present a risk for the subsequent initiation or exacerbation of a broad spectrum of disease processes including autoimmune, inflammatory, proliferative and degenerative disorders.

Typescript Includes bibliographical references

Typewritten ms. Includes bibliographical references

Bibliography: leaves 113-144. Investigates the functions of the maternal, protein secretions of the endoparasitoid wasps Venturia canescens Gravenhorst regarding their role in providing protection against the host's immune system. Also investigates mucinous protein secretions on the egg surface and coagulation reactions and their role in protecting eggs against host cellular attacks.

Bibliography: leaves 183-228

Bibliography: leaves 136-157 / x, 157 leaves, [1] leaf of plates : ill ; 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, 1983

Bibliography: leaves 154-185 / iv, 185 leaves, [15] 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. / Thesis (Ph.D.)--University of Adelaide, Dept. of Science, 1987