Immunological responses associated with morbidity in human schistosoma mansoni infection
Abstract
A study was carried out to investigate the cellular and
humoural immune responses to S.mansoni antigens and mitogen
concanavalin A in relation to the presence or absence of
hepatosplenic disease in human schistosomiasis mansoni. This
study was also aimed at determining whether anti-idiotypic
responses with specificity for egg stage antigens was associated
with morbidity in S.mansoni infected patients in Kenya.
Study patients were recruited from two schistosomiasis
foci, Kambu and Miu in Machakos district, Kenya. A total of fifty
six patients were recruited into the study. For cellular and
humoural studies, patients were divided into three categories
based on their area of residence, age, egg count and morbidity
status as assessed by the presence or absence of hepatosplenic
disease. The categories were:, group 1 - patients without
morbidity from Miu, a low morbidity schistosomiasis mansoni
foci, group 2 - patients without morbidity from Kambu, a high
morbidity foci" group 3 - patients with hepatosplenic disease
from Kambu. Patients 'in, the three groups were closely matched
for age and egg load.
Blood was collected from the patient-s and processed to
recover peripheral blood mononuclear cell? (PBMC) and plasma for
in vitro stimulation and humoural assays respectively. The
S.mansoni antigens used for stimulation were soluble worm
antigen (SWA), soluble -7..gg .antigen (SEA), glutathione-Stransferase
(P28), and concanavalin A-binding and non-binding
fractions of SEA. Concanavalin A was used as a mitogen.
Suqernatants from antigen and mitogen stimulated cultures were
collected after 2 and 4 days and assayed for cytokines, Tumour
necrosis factor (TNF), InterleukinS (lLS) and Interferon gamma
(IFNy). No supernatants were collected from cultures stimulated
with concanavalin A-binding and non-binding fraction of SEA.
Results of proliferative responses showed that patients
with morbidity produced higher values in responses to S.mansoni
antigens(SWA, SEA) and concanavalin A and lower values in
response to P28. Patients without morbidity produced
significantly higher proliferative values(p<O.OS, Oneway anova)
compared to values for patients with morbidity in response to
stimulation of PBMCswith non-conA binding fraction of SEA.
On comparing the cytokine production between the two time
points at which the supernatants were collected, higher levels of
TNFwere produced in 2 compared to 4 day supernatants in antigen
stimulated cultures. In contrast, peak levels of TNF were
produced in 4 day supernatants in cultures stimulated with
concanavalin A. For IFNy, and ·ILS higher levels were found in 4
compared to 2 day supernatants. The highest level of TNF was
produced in response to SEA followed by SWA, P28 and
concanavalin A:
When proliferative and cytokine responses were correlated,
significant positive correlation coefficients were obtained
between proliferation to concanavalin' A with IFNy and TNF cytokine levels. While proliferation and~LSproduction to P28
were significantly correlated (p<O.OS), proiiferation to SWA and
SEA did not show any significant correlation with peak levels of
either TNF, ILS or IFNy.
Analysis of cytokine production in the three categories
showed that patients with hepatosplenic disease (group 3),
Citation
Ph. D ThesisSponsorhip
University of NairobiPublisher
Department of human pathology, University of Nairobi.
Description
Master of Science Thesis