Mechanisms of immunity to Babesia bovis: The role of innate immune mechanisms

Court, Rebecca Ann. (2001). Mechanisms of immunity to Babesia bovis: The role of innate immune mechanisms PhD Thesis, School of Molecular and Microbial Sciences, The University of Queensland.

       
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Author Court, Rebecca Ann.
Thesis Title Mechanisms of immunity to Babesia bovis: The role of innate immune mechanisms
School, Centre or Institute School of Molecular and Microbial Sciences
Institution The University of Queensland
Publication date 2001
Thesis type PhD Thesis
Supervisor A/Prof Paul Prociv
Total pages 158
Collection year 2001
Language eng
Subjects L
300508 Parasitology
730101 Infectious diseases
Formatted abstract
The in vivo innate immune response to infection with the bovine haemoparasite Babesia bovis has not previously been established. To gauge the role of innate immune mechanisms from both primary and secondary B. bovis infection, the studies reported in this thesis aimed to assess the antimicrobial function of monocytes and neutrophils, and the expression of cytokines in peripheral blood leucocytes ex vivo, as opposed to in vitro. Assays measuring phagocytosis, oxidative burst and nitric oxide production were used to investigate the innate antimicrobial capacity of monocytes and neutrophils. The kinetics of this antimicrobial activity were followed from preinoculation (day 0) through to 31 days after inoculation of cattle with both virulent and avirulent strains of parasite. Peripheral blood monocytes were found to display a pronounced oxidative burst, but reduced capacity for phagocytosis during a primary infection. On the other hand, neutrophils exhibited an increased phagocytic capacity and reduced oxidative burst activity during a primary infection. Nitric oxide production was also found to increase during a primary virulent infection. The results presented in this thesis show considerable antimicrobial activity evident in peripheral blood monocytes and neutrophils from cattle exposed to B. bovis as a primary exposure. The elevated antimicrobial activity was coincident with the time that parasite numbers peaked in the circulation and occurred prior to parasite clearance. The production of oxidative burst and nitric oxide were not as pronounced in a secondary exposure as in a primary infection. These results suggest that peripheral blood monocytes and neutrophils are active mediators in the innate response to a primary B. bovis infection, and, most likely, contribute directly to the clearance of parasites prior to the production of antibody. The expression of selected cytokines was studied by RT-PCR during both primary and secondary B. bovis infection. The expression of type 1 inflammatory cytokines, such as IL-l α, IFN- γ, TNF-α and IL-6, increased during a primary infection at peak parasitaemia, and their levels declined thereafter, suggesting that their production was important in the recovery from a primary virulent infection. Their production was not as pronounced in secondary infection. The second aim of this thesis was to conpare the activity of the innate immune system in immunocompetent cattle with that of cattle bred from animals shown to be cases of vaccine failure. Greater inflammatory activity in vaccine failure could be linked with pathological characteristics of vaccine failure, although the results presented here were not conclusive. The findings presented within this thesis suggest that the inflammatory type 1 response and peripheral blood monocytes are involved in successfull recovery from primary B. bovis infection and the development of immunity, yet these responses most likely give way to the antibody response during secondary infection. It may be important that the response during a primary infection involves an early and effective innate response for development of protective immunity, and future design of vaccines to overcome the problem of vaccine failure will most likely need to be multifaceted.
Keyword Natural immunity

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
 
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Created: Fri, 24 Aug 2007, 17:41:04 EST