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ANALYZING THE HOST IMMUNE RESPONSE TO PNEUMOCYSTIS UTILIZING TWO RAT MODELS

THULLEN, TIMOTHY DAVID
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1066676759

Abstract Details

2003, PhD, University of Cincinnati, Medicine : Pathobiology and Molecular Medicine.
Pneumocystis is an opportunistic fungal pathogen that causes pneumonia in patients with HIV+, cancer patients, organ transplant patients, and other immunocompromised individuals. Although information about Pneumocystis pneumonia has increased due to its propensity to infect AIDS patients, there is much that needs to be understood about the interaction between the host and Pneumocystis, and the host’s ability to defend against the organism. Mouse models of Pneumocystis pneumonia have revealed valuable information about host defense, yet the corticosteroid- treated Pneumocystis pneumonia rat model shows similarities to HIV+ patients infected with the organism. Two approaches were made to study host defense to Pneumocystis in the rat model. The first was the adoptive transfer of immune donor splenocytes sensitized to the Pneumocystis antigen, major surface glycoprotein, to corticosteroid- treated rats with Pneumocystis pneumonia. This study was designed to study the cytokines that were involved in the clearance of Pneumocystis pneumonia. Splenocyte adoptive transfer was successful in these studies, resulting in significant Pneumocystis reduction. However, some rats developed a hyperinflammatory reaction following adoptive transfer, and this was associated with increases in the proinflammatory cytokines (TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6), Th1 cytokine IFN-gamma, and Th2 cytokines (IL-5 and IL-10). These studies also revealed a differential effect of splenocyte adoptive transfer on the Pneumocystis morphological forms. The second approach to study host defenses was the development of a CD4- depleted rat model of Pneumocystis pneumonia. The non- depleting W3/25 antibody and depleting OX-38 antibody were both capable of reducing CD4+ expressing T lymphocytes and rendering rats susceptible to Pneumocystis infection. This rat model avoids the immunosuppressive effects of corticosteroids and serves as an additional rat model to test host defenses to the organism and other host/ Pneumocystis interactions. The two different approaches to Pneumocystis host defense in the rat presented in this dissertation have both strengthened the hypothesis that the CD4+ T lymphocyte is the principal effector cell in defense and demonstrated cytokines that are important for organism clearance and possibly detrimental to the host. These two Pneumocystis pneumonia rat models will allow further insight into important immune factors of humans infected with Pneumocystis.
Dr. Peter D. Walzer (Advisor)
171 p.
pneumocystis; adoptive transfer; CD4-depletion; rats; cytokines

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Citations

  • THULLEN, T. D. (2003). ANALYZING THE HOST IMMUNE RESPONSE TO PNEUMOCYSTIS UTILIZING TWO RAT MODELS [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1066676759

    APA Style (7th edition)

  • THULLEN, TIMOTHY. ANALYZING THE HOST IMMUNE RESPONSE TO PNEUMOCYSTIS UTILIZING TWO RAT MODELS. 2003. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1066676759.

    MLA Style (8th edition)

  • THULLEN, TIMOTHY. "ANALYZING THE HOST IMMUNE RESPONSE TO PNEUMOCYSTIS UTILIZING TWO RAT MODELS." Doctoral dissertation, University of Cincinnati, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1066676759

    Chicago Manual of Style (17th edition)

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© 2003, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.