Date of Award

2001

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Veterinary Medical Sciences - Pathobiological Sciences

First Advisor

Thomas R. Klei

Abstract

To address the role of parasites on subsequent antigenic challenge, humoral, lymphoproliferative and cytokine responses to a single intramuscular injection of keyhole limpet haemocyanin (KLH) were compared between groups of ponies with high, medium or low gastrointestinal parasite burdens. Heavy and moderately parasitised animals showed a trend towards reduced KLH-specific lymphoproliferation and reduced antigen specific total immunoglobulin, IgG(T) and IgA compared to lightly parasitised ponies. The peripheral blood mononuclear cells (PBMC) from medium and heavily parasitised ponies also had significantly lower levels of IL-4. These data indicate that heavily parasitised animals have uniformly decreased cellular and humoral immune responses to soluble protein immunization. The well-defined Strongylus vulgaris helminth naive pony model was employed to investigate the cross-regulation of T-helper (Th1) cytokines on the induction of Th2 cytokines and to demonstrate the importance of Th2 responses in protective immunity to S. vulgaris. Whereas immunization of naive ponies with radiation-attenuated third stage larvae (IrrL3) induces Th2 cytokines and is protective against S. vulgaris infection, soluble adult worm antigen (SAWA) in Ribi adjuvant induces Th1 cytokines and is not protective. Cytokine, humoral, and cellular responses were characterized to determine whether prior immunization with Ribi-SAWA would alter the IrrL3 induced protective immune response to S. vulgaris . Similar to ponies vaccinated only with IrrL3, animals immunized with both Ribi-SAWA and IrrL3 were still protected against challenge even though they demonstrated alterations in the protective immune response. Protection against S. vulgaris was associated with increased mRNA levels of IL-5 and IL-13 within the cecal lymph node cells (CLNC) and increased blood and cecal eosinophil counts. Vaccination with Ribi-SAWA reduced the level of IL-5 in the CLNC and lowered the blood eosinophil count, but failed to alter the protective immune response. Elevated IL-4 and cecal mast cells did not correlate with protection against S. vulgaris. Antibody analysis revealed increased IgG(T), IgGa and IgA responses to L4 and L3 soluble S. vulgaris antigens in protected animals, along with an early IgGa, IgGb and IgG(T) antibody response to the surface of both early and developing L3.

ISBN

9780493562971

Pages

134

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