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| Antibody Repertoire Development and Immune Homeostasis | |||||||
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We utilize fetal and neonatal piglet models to study the development of adaptive immunity during the critical window of immunological development. This is because after birth we have control of maternal factors, colonizing bacteria, pathogens and diet after these precosial offspring are recovered by Caesarian and reared in isolator units. Neonatal life is the critical window of immunological development for all mammals. During this period newborns must develop their adaptive immune system in a homeostatic manner, i.e. develop oral tolerance to dietary antigen and establish equilibrium with commensal gut flora. Such experimental control is not possible using rodent models.
have used the piglet model to:(a) study the fetal development of the pre-immune B cell and T cell repertoires, (b) demonstrate that colonization of the GI tract or contact with microbial-associated molecular patterns (PAMPs) is required to stimulate the development of adaptive immunity and (c) determine the impact of various pandemic viral pathogens on development of the immune system during the critical window. These findings are of evolutionary and developmental importance and also important for vaccine development and management practices for veterinary medicine. e physiological and genetic similarities of swine and humans have generated the CFTR piglet model for cystic fibrosis. The molecular genetic studies of the lab have also made possible the development of B cell knockout piglets that could be invaluable in determining the basis of protective immunity to various pathogens. e laboratory is now engaged in characterizing the humoral immune system of bats. Bats comprise 20% of all mammals, are the major insectivores, and are important for pollination and as vectors for various human pandemic viruses. Specifically we are eventually targeting vaccine development for the fungus responsible for white nose syndrome that is decimating bat populations in Eastern USA. |
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| Selected Publications | |||||||
| Click Here for a Complete List of Articles | |||||||
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Butler J.E., Francis, D., Freeling, J., Weber, P., Sun, J. and Krieg, A.M. Antibody repertoire development in fetal and neonatal piglets. IX. Three PAMPs act synergistically to allow germfree piglets to respond to TI-2 and TD antigens. J. Immunol. 175: 6772-6785, 2005.
Butler J.E. and Sinkora, M. The isolator piglet: A model for studying the development of adaptive immunity. Immunol. Res. 39:33-51, 2007. Butler J.E., Weber, P., Wertz, N. and Lager, K.M. Porcine reproductive and respiratory syndrome virus (PRRSV) subverts development of adaptive immunity by proliferation of germline-encoded B cells with hydrophobic HCDR3s. J. Immunol. 180: 2347-2356, 2008. Butler J.E., Wertz, N., Deschacht, N. and Kacskovics, I. Porcine IgG: Structure, genetics and evolution. Immunogenetics 61: 209-230, 2009. Butler J.E., Lager, K.M., Splichal, I., Francis, D., Kacskovics, I., Sinkora, M., Wertz, N., Sun, J., Zhao, Y., Brown, W.R., DeWald, R., Dierks, S., Muyldermanns, S., Lunney, J.K., McCray, P.B., Rogers, C. S., Welsh, M.J., Navarro, P., Klobasa, F., Habe, F. and Ramsoondar, J. The Piglet as a Model for B cell and Immune System Development. Vet. Immunol. Immunopath.; Special Edition : IUIS Award Review 128:147-170, 2009. |
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| Department/Program Affiliations |
| Microbiology |
| Biosciences |
| Immunology |