90% of Human Immunodeficiency Virus (HIV) infections are acquired across the genital or gastrointestinal mucosa, and infection leads to profound depletion of CD4+ lymphocytes. Antiretroviral therapy can restore blood CD4+ T cells. However, immune dysfunction and defects in mucosal antimicrobial defence persist. Some CD4+ T-subsets, particularly antimicrobial Th17 cells, show enhanced susceptibility to HIV infection and are also preferentially depleted in the course of HIV infection; the latter may allow microbial translocation into the bloodstream. Genital infections have been shown to have direct mucosal immune effects and to increase susceptibility to HIV; however, the effect of systemic infections, such as Malaria (which is holo-endemic in some HIV prevalent regions) is unknown. Understanding the relationship between HIV, highly susceptible immune cells, immune activation and malaria infection on mucosal tissues has been the main focus of my thesis. In HIV-infected individuals, I explored whether HIV antiretroviral therapy restores gut Th17 populations and improves gut antimicrobial defences. Therapy restored gut Th17 populations in some, but not all individuals, but antimicrobial defence remained impaired. I then piloted a novel mucosal-optimized PCR assay to measure cervical immune gene responses, as standard mucosal assays are inadequate. I succeeded in measuring mitogen-induced, but not HIV-specific, cervical immune responses in HIV-infected individuals. Next, using this PCR platform I examined mitogen-induced cervical immune responses in individuals demonstrating reduced susceptibility to HIV, and found that they had reduced production of both Th17-associated and pro-inflammatory cytokines from cervical cells. Finally, in a murine model I found that malaria caused genital and gastrointestinal mucosal immune activation, and increased both the expression of mucosal HIV susceptibility immune markers, and mucosal T cell immune activation. In summary, insufficient gastrointestinal Th17 cells restoration does not underlie persistent mucosal immune activation and microbial translocation in HIV-infected people on therapy. A reduced frequency of highly susceptible Th17 cells in the cervix of HIV-exposed but uninfected individuals was identified as a correlate of reduced HIV susceptibility. Malaria, a common systemic infection in HIV-endemic countries, may enhance susceptibility to HIV through increasing putative immune markers of HIV susceptibility and immune activation in potential mucosal sites of HIV exposure.

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / Rhinosinusitis is a common condition that is chronic in up to 18% of the general population. If intensive medical treatment fails, then surgery may be required. Currently the accepted form of surgery is endoscopic sinus surgery. This technique involves opening the natural ostia of the sinuses to restore aeration and mucociliary drainage. The most frequent complication of this surgery is the development of postoperative adhesions. Their formation represents a failure of the healing process. To prevent the formation of adhesions, nasal packing is often used. To date the effect of nasal packing on the healing process has not been studied with rigorous scientific control. The sheep has been chosen as the most suitable animal model to investigate the healing process. The sheep is suitable in terms of size, histology, physiology, and pathology. The sheep's nasal cavity is also suitable for nasal endoscopy and surgery. Research conducted previously in the sheep model has demonstrated that unpacked full-thickness wounds take longer than three months to heal. The research in this thesis sought to determine if the use of different packing materials influenced healing. This thesis has compared the healing process that follows the use of three different nasal packing materials. These are a polyvinyl acetate based pack, a hyaluronic acid-based pack, and the hyaluronic acid-based pack with Insulin-like growth factor-I incorporated into it. Assessment was made using light microscopy, immunofluorescence, and electron microscopy. The results demonstrate that the use of a polyvinyl acetate sponge a dissolvable hyaluronic acid based pack confers no significant benefit to the healing process when compared to controls. However, the incorporation of insulin-like growth factor-I into the hyaluronic acid based pack resulted in a statistically significant (p<O,05) improvement in re-epithelialisation at day 28 (89% for Insulin-like growth factor-I versus 44% for controls). Attempts to assess the effect of this pack on the rate of adhesion formation was unsuccessful due to the inability to produce a replicable animal model of adhesion formation. It is concluded that the use of Insulin-like growth factor-I in the hyaluronic acid based packs confers an important benefit to the healing process after full-thickness injury. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1218836 / Thesis (Ph.D.) -- University of Adelaide, Medical School, 2005

Diss. Linköping : Univ., 2001.

Diss. (sammanfattning) Umeå : Univ., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (M.D.)--University of Adelaide, Depts. of Gastroenterology and Haematology/Oncology, 1998. / Copy of author's previously published article inserted. Bibliography: leaves 210-234.

Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999. / Errata & addenda tipped in behind back end paper. Copies of author's previously published articles in pocket on back end-paper. Bibliography: leaves 147-194.

Thesis (M.S.)--Eastern Illinois University, 2009. / Includes bibliographical references (leaves 80-84).

Thesis (M. Phil.)--University of Hong Kong, 1980. / Also available in electronic format. Also available in print.