Date of Graduation

12-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Rhoads, Douglas D.

Committee Member

Durdik, Jeannine M.

Second Committee Member

Rosenkrans, Charles F. Jr.

Third Committee Member

Wideman, Robert F. Jr.

Keywords

Biological sciences; Applied sciences; Health and environmental sciences; Adaptive immunity; Growing feather; Innate immunity; Iron oxide nanoparticles; Memory immune response; Primary immune response

Abstract

The applications of nanoparticles are growing, but little is known about their interactions with the immune system as most studies did not use suitable in vivo test systems. The purpose of these studies was to investigate the utility of chicken growing feathers as an in vivo test site for iron oxide nanoparticle (IONP) interactions with the immune system. The first objective of this study was to monitor leukocyte infiltration into the growing feather pulp upon the administration of IONP and IO-mIgG preparations. The second objective was to test the utility of IONPs as vaccine adjuvants by monitoring primary and memory immune responses in the growing feathers upon intramuscular injection of treatment preparations. For the first objective, three feather injection studies were conducted. The IONP treatment alone elicited similar responses as the IO-mIgG treatment, suggesting that IONPs can elicit immune responses without the presence of an antigen. The IO-mIgG treatment elicited a significantly higher heterophil response, p = 0.009, and MHCII+ macrophage response, p = 0.0027, compared to the Alum-mIgG group. However, Alum-mIgG elicited significantly higher adaptive immune responses compared to IO-mIgG. It is possible that IONPs were taken up by the innate immune cells before they could activate the adaptive immune cells, but the analyses of organ tissue is an ongoing study that will further clarify this finding. For the second objective, four intramuscular injection studies were conducted using IONPs, Alum-mIgG, and mIgG treatments. The mIgG concentration in Study A was 20-fold lower in the IONP group compared to the other groups. IO-mIgG elicited significantly higher MHCII+ B cell+,  T cell+ CD8+, and  T cell+ CD8- feather pulp infiltration compared to the other groups. When the mIgG concentration for all treatment groups was matched in Study B, the IO-mIgG group elicited similar or significantly lower responses compared to the other groups. These findings suggest that growing feathers in chickens can be used to monitor immune responses to treatments periodically in one subject. The clinical utility of IONPs as vaccine adjuvants is promising, but further research is necessary to improve the knowledge of IONP biointeractions and toxicity.

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