Semester

Spring

Date of Graduation

2003

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Rosana Schafer.

Abstract

The environment that we live in is composed of many different chemicals, Because of this, all chemical exposures, whether environmental or industrial, are exposures to mixtures. These mixtures have the potential to affect the immune system in a manner that is qualitatively or quantitatively different from the response to the individual components of the mixture. My experiments examine the effects of in vivo exposure to a mixture of herbicides on immune cell populations and on the humoral immune response to immunization with heat killed, whole-cell, Streptococcus pneumoniae (HKSP). The herbicide propanil (3,4-dichloropropionanilide) is sold as a mixture with the herbicide 2,4-D (2,4-dichlorophenoxyacetic acid). In vivo exposure to the mixture of propanil and 2,4-D increases cell loss in the thymus and bone marrow to a greater extent than would be predicted from the cell loss caused by exposure to the individual herbicides. To determine whether the lymphocyte cell number decreases depress the functional immune response, I examined the T-independent (phosphorylcholine, PC) and T-dependent (pneumococcal surface protein A, PspA) antibody response to Streptococcus pneumoniae (SP) immunization after single-herbicide and herbicide-mixture exposure. Mice were exposed to propanil, 2,4-D or a mixture of propanil and 2,4-D and immunized i.p. with HKSP. Exposure to the mixture, in contrast to the individual herbicides, increased the number of IgM and all isotypes of IgG spot forming cells (SFC) responding to PC and PspA antigen as determined by ELISPOT following immunization with HKSP. Exposure to HKSP on day 4 after herbicide treatment resulted in smaller fold antibody increases suggesting that events that occur within the first 4 days after exposure are critical in the response. These results highlight the importance of studying the effects of mixtures on the immune system and contribute to the understanding of the potential connection between exposure to chemicals and disease.

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