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|Title: ||Significance of cross-reactive antibody responses and isotype bias in malaria- helminth co-infection|
|Authors: ||Fairlie-Clarke, Karen Jane|
|Supervisor(s): ||Graham, Andrea|
|Issue Date: ||24-Nov-2011|
|Publisher: ||The University of Edinburgh|
|Abstract: ||The socio-economic and geographical distribution of malaria overlaps with that of
many parasitic helminths and in these areas co-infections are common. Co-infection
with helminths can influence disease outcome causing either exacerbation or
amelioration of malaria. Understanding the complex host-parasite interactions that
lead to these different disease outcomes is important for the success of control
programmes aimed at these parasites.
The immune system has evolved diverse types of response (e.g. T-helper 1 (Th1) and
T-helper 2 (Th2)) to efficiently combat infection with ‘microparasites’ and helminths
respectively. When faced with co-infection however, the need for the host to multitask
means it must manage these counter-regulatory responses. In this study a murine
model of malaria-hookworm (Plasmodium chabaudi- Nippostrongylus brasiliensis)
co-infection was utilised to investigate how changes in T-helper bias affect malaria
disease outcome. Antibody isotypes were used as indicators of Th1/Th2 bias and
revealed that helminth co-infection reduced the malaria-specific Th1 response.
Counter-intuitively this resulted in ‘protection’ from malaria with co-infected mice
having reduced peak P. chabaudi parasitaemia and suffering less severe anaemia.
In addition to providing a measure of Th1/Th2 bias, analysis of antibody responses
revealed the occurrence of cross-reactive antibodies. The potential for these crossreactive
antibodies to influence disease outcome was investigated but in this murine
model resource-mediated mechanisms of parasite regulation appear to be responsible
for the ‘protection’ that co-infection affords.
The question of why cross-reactive antibodies are produced has important
immunological and ecological implications. Cross-reactive responses may arise
through some physiological constraint on the immune mechanisms that usually result
in antibody-specificity. However experiments designed to investigate if the
specificity of antibodies is constrained by availability of antigen suggest that this is
not the case in the model system used here. There is also the possibility that
production of cross-reactive antibodies represents an evolutionary optimal strategy
for a host faced with unpredictable exposure to a variety of parasites. However a
major finding of this study indicates these two taxonomically distinct parasite species
share antigens, which in itself is crucial to understanding host-parasite interactions in
a co-infection setting.
The main findings of this thesis are relevant to co-infection studies in general and the
implications for both evolutionary and applied biology are discussed.|
|Sponsor(s): ||Biotechnology and Biological Sciences Research Council (BBSRC)|
Princeton programme grant
University of Edinburgh Staff Scholarship scheme.
|Appears in Collections:||Biological Sciences thesis and dissertation collection|
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