College of Veterinary Medicine

Veterinary Microbiology and Pathology

Wendy Brown


Wendy Brown,
MPH, PhD Professor
Regents Professor

Dr. Wendy Brown is a Professor of Immunology in the Department of Veterinary Microbiology and Pathology, Washington State University. Her research focuses on understanding the bovine helper T cell response to vector-borne hemoparasites and defining protective immune mechanisms and targeted protein antigens. Because Babesia bovis and Anaplasma marginale reside exclusively within erythrocytes, the focus is on priming of MHC class II-restricted, CD4+ T cell responses, IgG responses, and activation of antigen presenting cells including dendritic cells and macrophages. One current program is on the immunological control mechanisms of bovine Babesia infections (B. bovis and B. bigemina), on defining helper T lymphocyte responses, on defining T cell responses to conserved and variable regions of apical complex proteins, on using helper T lymphocytes from immune cattle to identify protective antigens that can be used in a subunit or nucleic acid based vaccine, and on ways of modulating immune responses, such as co-administration of CpG oligodeoxynucleotides or IL-12 with antigens.  link to World Class Research...

A second active program is on using combined genomic and proteomic approaches to identify novel outer membrane proteins of A. marginale present in this protective bacterial fraction. Proteins separated by 2D-electrophoresis or by 1D-continuous flow electrophoresis are tested for antigenicity or the ability to elicit recall T helper cell responses from immunized cattle, and the proteins identified by tandem mass spectrometry. We are testing the hypothesis that antigens selected by the ability to stimulate ex vivo Th1-like responses in cattle protected against challenge infection will stimulate protective immunity in vivo. We are also defining conserved Th cell epitopes on outer membrane proteins of A. marginale that stimulate strong anamnestic Th cell proliferative and IFN-γ responses in immunized or persistently infected cattle. Immunodominant and conserved epitopes that are recognized by multiple class II alleles would be ideal candidates for vaccines to protect a large population against infection. As part of this program, we are defining the role of antigenic variation in helper T cell epitopes in persistent infection of cattle.

A third program focuses on immune modulation by Babesia bovis and Anaplasma marginale. We have characterized the activation of innate immune responses (enhanced B cell proliferation and IgG secretion and macrophage activation) by B. bovis and DNA derived therefrom. We are also currently studying the role of T regulatory cells in maintaining persistent infection with the ehrlichial pathogen, A. marginale. Cattle infected with A. marginale remain persistently infected for life once acute infection has been controlled by the immune response. We hypothesize that a balance between host immune response and pathogen proliferation keeps both the immune response and pathogen in check, facilitating pathogen persistence. We recently showed that strong memory T cell responses specific for two different A. marginale outer membrane proteins and induced by immunization disappeared following challenge with virulent organisms. Ongoing studies are attempting to define the mechanism of this immune regulation by A. marginale and how this relates to the ability of the organism to persist.

A fourth research program is identification of protective antigens of the zoonotic agent of Q fever, Coxiella burnetii. We are taking a similar genomic and proteomic approach to identify proteins that stimulate protective, IFN-γ producing CD4+ T cell responses in a guinea pig aerosol challenge model.

Finally, an additional area of research emphasis is on understanding the role of γδT cells in the bovine immune response to the vector -borne pathogens under study. This multidisciplinary program which involves collaborative studies with Montana State University, University of Massachusetts, and the University of Minnesota has made use of a large-scale functional genome analysis of the biochemical activities of bovine γδ T cells in their resting and activated state, and in their response to tick-borne pathogens.

All of these areas of research emphasis provide opportunities for graduate students to study immune mechanisms against different types of parasitic pathogens in an outbred species, and provide a unique training environment that combines molecular and cellular approaches towards understanding the host-parasite interaction that results in protective immunity or successful parasitism.

Publications

Last Edited: Jul 22, 2009 4:18 PM   

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