The goal of this study was to access the possibility that a vigorous physical regimen is suppressive to the immune system and that conditioning to the exercise minimizes the immune suppression. The following groups of fifteen rats each were used: (i) control rats. (ii) rats exposed to one bout of swimming for two to three hours (exercise-stressed), and (iii) rats which were conditioned to the exercise by swimming two hours daily for two months (exercise-conditioned).FINDINGS1. Exercise-stressed rats were immune suppressed as compared to control rats. In contrast, exercise-conditioned rats were only slightly immune suppressed.2. The immune reactivity of spleen cells from exercise-stressed rats and from exercise-conditioned rats was restored by the addition of indomethacin, a prostaglandin synthesis inhibitor.3. Exercise-stressed rat spleen cells were more sensitive to the immune suppressive effectsPGE than were the control or excercise-conditioned rat spleen cells.4. The nonadherent spleen cells from both exercise-stressed and exercise-conditioned rats were immune suppressive as compared to control rat nonadherent spleen cells. However, immune stimulatory activity was prominent in the nonadherent spleen cells from the excercise-conditioned rats. Immune stimulatory activity was negligible in the adherent spleen cell fractions from exercise-stressed rats.CONCLUSIONSThe results of this study showed that, extreme physical exercise was immune suppressive while conditioning to the exercise minimized the suppression.The immune suppression in the exercise-stressed rats resulted from an increased sensitivity to the immunosuppressive effects of PGE and from immune suppressor activity of nonadherent lymphoid cells. The minimal extent of immune suppression in the exercise-conditioned rats resulted from a reduced sensitivity to immune suppression by PGE and from immune stimulatory activity of adherent macrophages.

The complement system is considered as the chief recognition and effector component of innate immunity; it is involved in inflammation and enhances the adaptive immune response. Factor I (fI) is a heterodimeric serine protease consisting of a heavy (HC) and a light-catalytic (LC) chain; it circulates in an active form regulating complement by selectively cleaving only C3b or C4b in the presence of a cofactor such as factor H (fH), CR1, MCP or C4bp. The cleavage of C3b occurs through a ternary complex formed between fI, C3b and a cofactor like fH and yields iC3b, a major opsonin. The structural and functional properties of fI were investigated. The interchain disulphide bond formed between C³⁰⁹-C⁴³⁵ tnat links the HC and LC of fI as well as the composition of the TV-linked carbohydrates of fI were determined. By using two independent assays, the proteolytic and amidolytic assays, the catalytic properties of human fI were characterised in detail. The catalytic subunit, the SP domain, was shown to have a native conformation that accommodates substrate recognition and cleavage, fI has specificity similar to thrombin, but exhibits lower catalytic activity. fI amidolytic activity reaches optimum at pH 8.25 and is insensitive to ionic strength. This is in contrast to its proteolytic activity within the fI-C3b-fH reaction, in which the pH optimum for C3b cleavage is <5.5 and the reaction rate is highly dependent on ionic strength. The rate of cleavage of tripeptide AMC substrates by fI was unaffected by fH or C3(NH₃) at optimum pH. fI and the isolated SP domain were found to have similar amidolytic activities, but strikingly different proteolytic activities on C3(NH 3 ). fl did not cleave C3(NH₃) in the absence of fH, but cleaved it rapidly at two sites in its presence. The SP domain however, cleaved C3(NH₃) slowly in the absence of fH, at more than two sites. Cleavage by the SP domain was inhibited, not stimulated, by fH. These results suggested that the HC domains and/or the cofactor must orient the natural substrates and restrict cleavage by fI to the two sites which yield iC3b. The implications of these findings are discussed.

The effect of dietary vitamin E and dietary lipids on growth and immune parameters of juvenile turbot (Scophthalmus maximus) were investigated in a series of experiments. The aims of the studies were to maximise immune function through dietary modulation to counteract stress induced immunodepression resulting from high stocking densities. In the first experimental trial, the vitamin E requirement for an optimum immune response was studied and revealed that vitamin E depletion induced poor health status, lower growth with some mortalities occurring at the end of the trial. However, supplementation of the diets with high levels of α-tocopherol although ensuring better growth did not significantly enhance most of the parameters measured at the end of the trial. The second trial aimed to test regimes coupling fresh or oxidised oil and low or high vitamin E supplementation. The results showed that vitamin E had a role in preventing peroxidation as high vitamin E supplementation improved some of the immunological parameters measured compared to fish fed with the same oxidised oil but low levels of vitamin E. By contrast low levels of vitamin E did not induce pathological conditions in fish fed with fresh oil showing the importance of dietary lipid in the evaluation of vitamin E requirements. Following this investigation another feeding trial was designed to look at the interaction of polyunsaturated fatty acids (PUFAs) and α-tocopherol on the immune parameters of juvenile turbot. Although liver lipid composition was affected by the diets and growth was enhanced by high vitamin E levels and a high ratio of (n-3)/(n-6) PUFAs no significant differences could be attributed to the lipid quality in the immunological parameters measured. Vitamin E supplementation enhanced the proliferation of kidney leucocytes when stimulated with lipopolysaccharide. These studies give some information on the requirements for vitamin E and lipid quality of juvenile turbot.

No description available.

Fowlpox viruses (FPV) are attractive platform vaccine vector candidates because their capacity for insertion of multiple heterologous genes makes them favourable for genetic modification. They also have strong adjuvant activity in their own right. As FPV does not replicate in mammalian cells, there is significantly less opposition associated with their clinical application, with a number already in use. However, a thorough understanding of the immunological relationship between FPV and the mammalian immune system is still lacking. The aim of this thesis was to construct a series of recombinant FPV vectors that co-expressed the nominal antigen chicken ovalbumin (OVA), (FPV[subscript]OVA), and/or murine interleukin-4 (mIL-4). These constructs were used for the characterisation of the relationship between FPV and the mammalian immune system and how this is altered by the co-expression of mIL-4. Immunisation with FPV[subscript]OVA resulted in rapid and highly localized OVA expression which induced strong CD8⁺ cytotoxic T cell (CTL) activity but only weak CD4⁺ T helper and antibody responses. In addition, presentation of FPV-derived antigen and the priming of antigen-specific CTL responses required a permissive bone marrow (BM)-derived cell as the antigen presenting cell (APC). Co-administration with FPV[subscript]mIL-4 resulted in a dramatic reduction in CTL activity that remained largely non-functional throughout the infection and a skewing of the T helper (Th) response towards Th2 with a reduction in interferon (IFN)-γ production by OVA-specific Th cells. These findings provide a sound basis for further characterization of how FPV interacts with the innate and adaptive arms of the immune system, how these can be manipulated via the co-administration of cytokines, and discovering if future rationally designed modifications result in FPV vectored vaccines that induce durable cellular and humoral immunity. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352466 / Thesis (M.Med.Sc.) - University of Adelaide, School of Medicine, 2009

Thesis (PhD)--University of South Australia, 2003.

Fowlpox viruses (FPV) are attractive platform vaccine vector candidates because their capacity for insertion of multiple heterologous genes makes them favourable for genetic modification. They also have strong adjuvant activity in their own right. As FPV does not replicate in mammalian cells, there is significantly less opposition associated with their clinical application, with a number already in use. However, a thorough understanding of the immunological relationship between FPV and the mammalian immune system is still lacking. The aim of this thesis was to construct a series of recombinant FPV vectors that co-expressed the nominal antigen chicken ovalbumin (OVA), (FPV[subscript]OVA), and/or murine interleukin-4 (mIL-4). These constructs were used for the characterisation of the relationship between FPV and the mammalian immune system and how this is altered by the co-expression of mIL-4. Immunisation with FPV[subscript]OVA resulted in rapid and highly localized OVA expression which induced strong CD8⁺ cytotoxic T cell (CTL) activity but only weak CD4⁺ T helper and antibody responses. In addition, presentation of FPV-derived antigen and the priming of antigen-specific CTL responses required a permissive bone marrow (BM)-derived cell as the antigen presenting cell (APC). Co-administration with FPV[subscript]mIL-4 resulted in a dramatic reduction in CTL activity that remained largely non-functional throughout the infection and a skewing of the T helper (Th) response towards Th2 with a reduction in interferon (IFN)-γ production by OVA-specific Th cells. These findings provide a sound basis for further characterization of how FPV interacts with the innate and adaptive arms of the immune system, how these can be manipulated via the co-administration of cytokines, and discovering if future rationally designed modifications result in FPV vectored vaccines that induce durable cellular and humoral immunity. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352466 / Thesis (M.Med.Sc.) - University of Adelaide, School of Medicine, 2009

No description available.

No description available.

No description available.