Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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2011 - 20122

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    Generating memory cytotoxic T lymphocytes through repetitive peptide boosting
    (2012) Smyth, Kendra; Xiao, Zhengguo; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Cytotoxic T lymphocytes (CTLs) play a critical role in controlling intracellular pathogens and cancer cells, and induction of memory CTLs holds promise for developing effective vaccines against critical virus infections. However, generating memory CTLs remains a major challenge for conventional vector-based, prime-boost vaccinations. Thus, it is imperative that we explore nonconventional alternatives, such as boosting without vectors. We show here that repetitive intravenous boosting with peptide and adjuvant generates memory CD8 T cells of sufficient quality and quantity to protect against infection in mice. The resulting memory CTLs possess a unique and long-lasting effector memory phenotype, characterized by decreased interferon-gamma but increased granzyme B production. These results are independent of the specific adjuvant applied and are observed in both transgenic and endogenous models. Overall, our findings have important implications for future vaccine development, as they suggest that intravenous peptide boosting with adjuvant following priming can induce long-term functional memory CTLs.
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    The activation of memory B cells to generate high affinity antibody responses in vitro and in vivo
    (2011) Richard, Katharina; Song, Wenxia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Immunological memory is the hallmark of the adaptive immune system. The humoral branch of the immunological memory is mediated by memory B-cells (mB). Memory B cells are marked by longevity, expression of antibodies with high affinity, and ability to generate robust antibody responses upon reencountering pathogens. However, requirements for the activation of mB cells and the induction of humoral memory responses are not well understood. This thesis examines the role of Toll-like receptors (TLRs) in mB activation using an immunized mouse model. TLRs are a family of receptors that recognize common molecular patterns of microbial pathogens and stimulate innate immune responses. Our study found that mouse mB expressed TLR9 and 4, and responded to their agonists in vitro by differentiating into high affinity IgG secreting plasma cells. However, TLR agonists alone were not sufficient to activate memory B cells in vivo. Antigen was required for the clonal expansion of antigen-specific memory B cells, the differentiation of mB cells to high affinity IgG secreting plasma cells, and the recall of high affinity antibody responses. The Ag- specific B cells that had not yet undergone isotype switching showed a relatively higher expression of TLR4 than memory B cells, which was reflected in a heightened response to its agonist, but in both cases of TLR4 and 9 yielded mostly low affinity IgM secreting plasma cells. When immunized together with the antigen, TLR agonists not only boosted the antigen-specific titers, but also increased affinity and isotype switching of the immunoglobulin. Thus, while TLR agonists alone are unable to activate mB in vivo, they can enhance humoral memory responses induced by the antigen.