The role of cytokines and inflammatory mediators in immunity to Plasmodium chabaudi chabaudi as infection

Balmer, Paul (1997) The role of cytokines and inflammatory mediators in immunity to Plasmodium chabaudi chabaudi as infection. PhD thesis, University of Glasgow.

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Immunity to an asexual erythrocytic Plasmodium chabaudi chabaudi AS infection in NIH mice is mediated sequentially by Th1 and Th2 cells. The predominantly Th1 mediated response is responsible for the control of the acute phase of infection and there is then a switch to predominantly Th2 mediated response(s). Cytokines and inflammatory mediators are important molecules involved in the parasiticidal mechanisms induced by Th1 and Th2 cells during the course of a P. chabaudi infection. IFNy (Th1 associated cytokine) and IL-4 (Th2 associated cytokine) production during a P. chabaudi infection reflects the sequential involvement of Th1 and Th2 cells. IL-6 is a cytokine which is involved in Th2 mediated responses but can also stimulate the production of inflammatory mediators such as acute phase proteins. The actual role of individual cytokines during the course of experimental malaria infection can be investigated by depletion of the cytokine by antibody treatment or addition of exogenous cytokine and observing the outcome of the infection. Studies were performed, utilising cytokine or cytokine receptor gene deficient mice to investigate the role of individual cytokines during the course of P. chabaudi infection. The induction of inflammatory mediators, such as nitric oxide (NO) and acute phase proteins, by cytokines is an important aspect of the protective immune response to P. chabaudi AS infection but it is unclear where and how these molecules can mediate a protective response. During P. chabaudi infection, mature asexual erythrocytic stage parasites sequester to the liver, making this non-lymphoid organ a potential site of a protective immune response. Serum amyloid P (SAP) and NO are two inflammatory mediators that are synthesised in the liver and may participate in parasiticidal mechanisms. IFNgamma receptor (IFNgammaR) deficient mice are more susceptible to a P. chabaudi infection than intact mice. A high mortality rate was observed in the IFNyR deficient mice whereas none of the control mice died. The IFNgammaR deficient mice consistently had a higher peak primary parasitaemia compared to the control mice but this was never statistically significant. Total IgG2a and parasite-specific IgG responses in the serum of IFNgammaR deficient mice were reduced compared with control mice, whereas both groups had similar total IgG1 levels in their serum. Interestingly, a large total IgE response was observed in the serum of the IFNgammaR deficient mice. Control mice had negligible levels of total IgE in their serum, which is the normal IgE response during a primary P. chabaudi infection. Analysis of leukocytes present in the spleen and liver during the course of infection revealed that there was a reduction in the numbers of lymphoid cells in the spleen at peak parasitaemia and a reduction of lymphoid cell, monocyte and polymorphonuclear (PMN) cell numbers present in the liver of P. chabaudi infected mice during the acute phase of the infection. This study demonstrated the importance of IFNgamma mediated responses during a primary erythrocytic P. chabaudi infection. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Immunology, parasitology.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Phillips, Professor
Date of Award: 1997
Depositing User: Enlighten Team
Unique ID: glathesis:1997-72532
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 17 Oct 2022 08:28
Thesis DOI: 10.5525/gla.thesis.72532

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