A Novel Approach Towards Induction and Evaluation of Anti-infeclious and Anti-inflanmmatory Immune Response against Schistosomiasis Mansoni
| dc.contributor.advisor | Petros, Beyene(PhD) | |
| dc.contributor.author | Lakew, Mekuria | |
| dc.date.accessioned | 2021-12-15T06:43:00Z | |
| dc.date.accessioned | 2023-11-08T16:33:56Z | |
| dc.date.available | 2021-12-15T06:43:00Z | |
| dc.date.available | 2023-11-08T16:33:56Z | |
| dc.date.issued | 1998-07 | |
| dc.description.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. | en_US |
| dc.identifier.uri | http://etd.aau.edu.et/handle/123456789/29310 | |
| dc.language.iso | en | en_US |
| dc.publisher | Addis Abeba, Ethiopia | en_US |
| dc.subject | A Novel Approach Towards Induction and Evaluation | en_US |
| dc.title | A Novel Approach Towards Induction and Evaluation of Anti-infeclious and Anti-inflanmmatory Immune Response against Schistosomiasis Mansoni | en_US |
| dc.type | Thesis | en_US |