A Novel Approach Towards Induction and Evaluation of Anti-infeclious and Anti-inflanmmatory Immune Response against Schistosomiasis Mansoni
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Date
1998-07
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Addis Abeba, Ethiopia
Abstract
In humans, mucosal stimulation, like in systemic immunization, results in a transient
appearance of B-cells capable of spontaneously producing antibodies. These cells are cells
en rOlUe to their final destinations. They primarily go to the sites they were initially
stimulated but also to other se lected effector sites within the common mucosal Immune
system. During the migration , they express specific su rface molecules that represent the
sequence of developmental events taking place in the cells. Using these phenotypic cell
markers B•cells have been divided into discrete populations that span the developmental
stages. On the basis of these phenotypic markers, the migratory B•cells are sorted into
functional groups. To achieve this, a novel approach that combines immunomagnetic beads
with ELIS POT was developed. This method was applied to characterize the phenotypes,
activation pattern and homing commitments of B-cells after oral (Cholera Toxin CT) and
systemic (Tetanus Toxoid• IT) vaccination. Following its success in the known systems, CT
and IT vaccines, it was used to describe immunity in ch ron ically infected patients with
diseases such as leishmaniasis, tuberculosis and schistosomiasis, whose pathology involves
immunological hypersensitivity reaction (DTH). This method was shown to be capable of
describing the immune status of an infected individual in terms of the phenotype and function
of antibody secreting cells (ASC). The fact that the distinction could be made between
mucosally and systemically activated B-cells by differential expression of homing receptors
(L-selection, CD44 and a4(37) is an additional tool to evaluate the contribution of Mucosal
associate Lymphoid tissue (MALT) in disease causation and modulation of the immune
system under natural infections. The comparison of mucosal immune responses following
different routes of immunization was facilitated by the development of the cellular di spe rsion
technique. The technique made the parallel analysis of cellular composition of lymphoid
ti ssue such as the tonsil feasible. Induction from oral , intra-nasal, tonsillar and rectal routes
of immunizations were compared . The intra-tonsillar and intra-nasal routes of immunizations
were found to be capable of acting as induction sites for local and distant 8-cell responses.
The peroral and parenteral immunization of activated B-cells into the circulation, intraton
sillar vaccination is hi gh ly localized. In the study of schistosomiasis, the C019 surface
marker was used for functional characterization of the types of antigen specific
immunoglobulin sec reting cells. Acco rdingly , IgM > IgA > fgG secreting cells were found in
the infected, while the reverse was characteristic of the control group. IgM dominance in
acutely infected individuals was statistically significant (P<O.OI). Analysis of the result by
age and intensity of infection revealed IgA secreting cells to be dominant in older age (>
15 years) and in those with light infections while in those that are under 15 years of age,
IgM secreting cells to be dominant. Attempt to use the tonsils as induction sets to the
common mucosal immune system resulted in highly localized response making it less
interesting in this respect. Instead the intranasal route was found to be convenient to reach
distantly related mucosal sites. In the immunological characterization of S. mansoni in the
BALB/c mice, it was shown that following mucosal immunization with CTB•Sm28GST
vaccine, parasite induced pathology, number of eggs and worms were reduced by more than
50%,84% and 66%, respectively. This strongly suggested a strategy for induction of anti•
infectious and anti•inflammatory immune response which could lead to development of a
vaccine•mediated control measure. Such a strategy may be applicable not only to
schistosomiasis but also to other diseases such as leishmaniasis, leprosy, and tuberculosis,
that induce similar delayed type high resistivity (DTH) responses as an immunopathological
mechanism. This work has improved the technique of assessing the effect of vaccines, and
has evaluated the means of delivery of antigens that induce either stimulation and/or tolerance
at systemic and mucosal levels. The technique is of a broader application to chronic disease
with similar immunologic responses on mechanisms of pathogenesis.
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A Novel Approach Towards Induction and Evaluation