Semester

Summer

Date of Graduation

2006

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Rosana Schafer.

Abstract

As pesticide use rises in the US annually, the need for extensive characterization of the risks associated with these substances also increases. Herbicides represent the most frequently used type of pesticides. 3,4-dichloropropionanilide (propanil) and 2,4-dicholorophenoxyacetic acid (2,4-D) are two of the most commonly used herbicides. These experiments evaluated the effects of propanil and 2,4-D on the humoral immune response in C57BL/6 mice following heat-killed Streptococcus pneumoniae (HKSP) immunization. Intraperitoneal exposure of 150 mg/kg propanil on the same day as HKSP immunization enhances the splenic T-independent type 2 antibody response to phosphorylcholine (PC) antigen 4-6-fold. Maximal PC enhancement occurs 7 days post-exposure. Propanil exposure 9 days following HKSP immunization enhances the T-dependent antibody response to the pneumococcal surface protein A (PspA). 2,4-D exposure decreases the PC-specific antibody response in the bone marrow and the antibody serum titers 10 days post-exposure. Mixture exposure to the herbicides did not produce any synergistic effects. In addition, aspiration of the mixture of herbicides did not affect the antibody response. Ovariectomy and inhibition of ovarian steroid synthesis abrogates the PC-specific antibody enhancement in propanil-treated mice. Several studies examined the direct and indirect estrogenic activity of propanil. Interestingly, propanil enhances the PC-specific splenic antibody response independent of an estrogenic mechanism. Although male mice also had enhanced antibody responses following propanil exposure, orchiectomy did not affect the enhancement. Finally, propanil exposure did not enhance survival following a suboptimal immunization to a virulent strain of S. pneumoniae. Altogether, these results provide a number of findings that contribute to our understanding of the regulation of the humoral response to HKSP.

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