Made available in DSpace on 2014-10-09T12:49:26Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:35Z (GMT). No. of bitstreams: 1 10197.pdf: 3419296 bytes, checksum: e271656d34b0cc65fff142154edf6b74 (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo

Made available in DSpace on 2014-10-09T12:54:15Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:07:40Z (GMT). No. of bitstreams: 1 12717.pdf: 5471144 bytes, checksum: 872c913b90fcce0e4a41c9eb08fb65a9 (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo, Sao Paulo

Made available in DSpace on 2014-10-09T12:54:18Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:21Z (GMT). No. of bitstreams: 1 12722.pdf: 558008 bytes, checksum: 01284590d84b5a596a55c0b0b7177695 (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo, Sao Paulo

Made available in DSpace on 2014-10-09T12:49:26Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:35Z (GMT). No. of bitstreams: 1 10197.pdf: 3419296 bytes, checksum: e271656d34b0cc65fff142154edf6b74 (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares, IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo

Made available in DSpace on 2014-10-09T12:54:15Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:07:40Z (GMT). No. of bitstreams: 1 12717.pdf: 5471144 bytes, checksum: 872c913b90fcce0e4a41c9eb08fb65a9 (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo, Sao Paulo

Made available in DSpace on 2014-10-09T12:54:18Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:21Z (GMT). No. of bitstreams: 1 12722.pdf: 558008 bytes, checksum: 01284590d84b5a596a55c0b0b7177695 (MD5) / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP; Faculdade de Odontologia, Universidade de Sao Paulo, Sao Paulo

[Truncated abstract] Infectious and allergic diseases of the respiratory tract are major contributors to global mortality, morbidity and economic burden. Bacterial infections such as pneumonia and otitis media are important diseases, especially in children, while allergic diseases such as asthma and allergic rhinitis afflict up to 30% of the world's population. A confounding aspect of respiratory disease is the evidence of a complex relationship between respiratory allergy and respiratory infection, with infection suggested to both promote and prevent the pathogenesis of allergic disease. Additionally, allergy is a risk factor for bacterial infection such as otitis media, pneumonia and sinusitis, while respiratory infection can exacerbate allergic symptoms. Given the burden of bacterial respiratory disease and respiratory allergy, the development of preventative treatments for these diseases is needed and will benefit from clearer knowledge of the underlying immune mechanisms. This thesis aimed to to extend current knowledge by using Pasteurella pneumotropica, a similar bacteria to the human pathogen nontypeable Haemophilus influenzae (NTHi), to study respiratory infection and protective anti-outer membrane protein (OMP) immunity as well as the interaction of respiratory infection and allergic inflammation. Homologues of the important NTHi vaccine candidates P4, P6, P26 and D15 were found to be encoded by P. pneumotropica and a high level of amino acid sequence identity was noted between the different P. pneumotropica strains, as well as between other Pasteurellaceae members. ... In contrast, anti-P6his serum antibodies transferred to naïve mice did not confer protection. These results suggested that T-cell–mediated mechanisms were involved in P6his-mediated protection, and showed that the P. pneumotropcia model was useful for elucidating protective mechansims. The interaction of P. pneumotropica infection and papain-induced allergy was studied to investigate immune mechanisms underlying respiratory infection and allergy. Mice with ongoing allergic inflammation were intranasally challenged with bacteria and exhibited reduced pulmonary bacterial numbers, prolonged eosinophilia in the lungs and the induction of Th2 cytokines in the BALF, compared to nonallergic, infected mice. This suggested a protective role for allergic inflammation in this model. The effect of papaininduced inflammation on mice colonised by P. pneumotropica was also examined and allergic inflammation appeared to worsen infection in colonised mice. This suggested that allergic inflammation may also have a role in promoting infection in this model. In conclusion, this thesis explored mechanisms involved in vaccine-mediated immunity and the interaction of respiratory infection and allergy using a P. pneumotropica infection in its natural host. It was shown that intranasally administered recombinant P6 and P4 protected mice from lung infection, which justifies the inclusion of these OMPs as NTHi vaccine candidates. Additionally, it was demonstrated that the interaction of allergy and respiratory infection modulated immune responses. Overall, these results emphasize that a clearer understanding of the complex mechanisms underlying these interactions is required, and may be aided by the development of suitable animal models.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 1, 2010). Vita. Thesis advisor: Habib Zaghouani. "May 2008" Includes bibliographical references.

Thesis (MScMedSc (Pharmacology))--University of Stellenbosch, 2005. / In this thesis, research results are reported on the role of natural and synthetic surfactants on the in vitro permeability characteristics of various chemical compounds across porcine (buccal, bronchial, arterial, venous and rectal) and human (vaginal) tissues. The permeability flux values of the different compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin, oxytocin, zidovudine and isoniazid) were determined using a continuous flow-through diffusion system. Mean steady state flux values were compared statistically by means of a t-test at a significance level of 5% as well as an F-test using whole curve comparisons. The results indicated that the synthetic pulmonary surfactant Biopolsurf is an effective enhancer for the permeation of chemical compounds through most of the tissues tested and that molecular weight, electrostatic charge, partitioning of the molecules in surfactant and surfactant concentration play an important role in trans membrane diffusion. In addition the epithelial permeability of the different types of tissues for various chemical compounds (arecoline, 17β-estradiol, hydrocortisone, dexamethasone, vasopressin and oxytocin) across the above tissues were compared. The results obtained showed that the permeability flux values of the compounds across porcine bronchial and human vaginal tissues were consistently similar and that porcine buccal tissue had the lowest permeability of all tissues tested. This was in agreement with previous in vitro studies. It was concluded that a wide variation in the permeability characteristics of different epithelia exists and that the pulmonary epithelium, due to its high permeability, is probably the most effective epithelium for drug delivery purposes, especially for drugs that undergo extensive gastrointestinal or hepatic first-pass metabolism.

Knowledge of human T cell responses and the pathways for their differentiation and maintenance from development into adulthood remains largely sparse. Much of what is known concerning the adaptive immune response in humans derives from analysis of peripheral blood, even though the majority of T cells within the body reside in tissue sites. We have established a protocol with LiveOnNY, the organ procurement organization of the New York metropolitan area allowing us access to healthy tissues from individual organ donors of a diverse background. Through novel analysis of lymphoid and mucosal tissues from infant and adult organ donors, we reveal how naïve, regulatory, and memory T cells dynamically populate and are maintained in tissues and circulation over the human lifespan. An initial multidimensional, quantitative analysis of human T cell compartmentalization involving 56 organ donors of a broad age range revealed that distribution of naïve, effector, and memory T cell subsets is largely dependent on tissue localization and differentiation state. Furthermore, T cell homeostasis driven by cytokine or TCR-mediated signals is dependent on CD4+or CD8+ T cell subset. Examining whether T cell subset distribution was set at birth, we compared T cell populations from a cohort of pediatric organ donors in the first two years of life to tissues from young adult donors aged 15-25 years. Results show a dynamic compartmentalization of naïve and regulatory T cells in all tissues early in life that is rapidly replaced with effector memory T cells (TEM) especially in mucosal sites further revealing the importance of a local adaptive immune response. Interestingly, the proportion and distribution of these T cell populations in tissue sites show varying levels of reliance on thymic output. Further evidence for the compartmentalization of the adaptive immune response and mechanisms for T cell maintenance throughout life can be shown through the analysis of T cell receptor sequences. We examined naïve and TEM populations in lymph nodes and spleen as a function of thymic output revealing low sharing of the naïve T cell repertoire between tissue sites with higher amounts of overlapping clones seen in TEM populations, especially with CD8+ T cells. These differences highlight potentially different roles for CD4+ and CD8+ T cells in the response to pathogen and their maintenance with age.