Analysis of the immune responses against influenza and vesicular stomatitis virus (VSV) using bispecific antibodies (BsAbs) and cytokines.
Item
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Title
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Analysis of the immune responses against influenza and vesicular stomatitis virus (VSV) using bispecific antibodies (BsAbs) and cytokines.
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Identifier
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AAI9820530
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identifier
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9820530
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Creator
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Fernandez-Sesma, Ana Maria.
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Contributor
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Adviser: Thomas M. Moran
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Date
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1998
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Microbiology | Health Sciences, Immunology
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Abstract
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The immune response against virus infections is dictated by the way viral antigens are presented to the cells of the immune system and by the cytokine context in which the infection takes place. Th1 or inflammatory immune responses in which infected cells are eliminated by T cells are believed to be optimal to clear virus infections, while Th2 immune responses are not believed to be responsible of fighting viruses. BsAbs which bind some molecule on the T cell receptor of T cells with one arm and a viral protein on the other arm can be used to redirect T cells not specific for that particular virus to kill virus infected cells.;In this thesis I show results using bispecific antibodies that bind the T cell receptor on T cells and proteins of either influenza virus or VSV to inhibit virus replication. This system allowed me to study inhibition of virus replication by non virus specific T cells which can clear virus infections without standard antigen presentation. Both BsAbs worked in vitro, and one of them, 526, could redirect superantigen activated T cells to prolong the life of mice lethally infected with VSV.;The study of the immune response in Stat1 KO mice after influenza virus infection, showed a mixed response which was slightly biased towards Th2. These mice were unable to clear virus infection.;I also studied the generation of immunity by mice infected with influenza virus under different cytokine treatments. When IL-4 was added at the time of infection, mice could not generate cytotoxic T cells against influenza virus and the cytokine profile in supernatants from spleen cultures was clearly of the Th2 type.;When different cytokines were used in combination with either live or inactivated influenza viruses for vaccinations the Th1 response generated by live virus could be reversed to Th2 by the addition of IL-4, unprotective upon challenge with live virus. The addition of IL-12 to inactivated virus switched the response of vaccinated mice from a clear Th2 to a more Th1 type, protective after challenge.;This work proves the importance of generation of an adequate immune response against viruses for efficient clearance of viruses, and how limitations that may exist in some organisms can be overcame to efficiently fight these infections.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
