Doctoral Dissertations

Date of Award

6-1988

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Comparative and Experimental Medicine

Major Professor

Robert N. Moore

Committee Members

M.A. Breider, F.M. Hopkins, A.T. Ichiki, C.J. Wust

Abstract

Pasteurella haemolytica is a leading cause of pneumonia in cattle. At present there is no suitable vaccine for the prevention of this economically important disease. The purpose of this investigation was to determine if pulmonary immunity to P haemolytica can be induced in cattle by stimulation of the gut-associated lymphatic tissue (GALT) by live bacteria or leukotoxin. In addition, the role of endotoxin and leukotoxin of P haemolytica in the pathogenesis of P haemolytica was investigated.

Immunogens were delivered to GALT through catheters surgically implanted in the proximal duodenum of calves. Immune responses of calves were subsequently boostered by a subcutaneous (SO) inoculation of killed P haemolytica or leukotoxin. Leukotoxin neutralizing antibodies (LNA) in serum and pulmonary lavage fluids were detected by a vital stain uptake assay using BL-3 cells. Serum IgG and IgG and IgA in pulmonary lavage fluids were detected by ELISA.

Live P haemolytica administered intraduodenally (ID) to calves resulted in increases in serum LNA, pulmonary LNA, IgG and IgA following a SC booster inoculation of killed bacteria. The ID administration of leukotoxin resulted in increases in pulmonary LNA and IgA. Subsequent SC inoculations of leukotoxin resulted in further increases in antibody titers but also resulted in an endotoxic shock reaction in calves.

The role of ID priming, endotoxin, and leukotoxin in the pathophysiology of pasteurellosis was determined by inoculating calves ID with leukotoxin and endotoxin (LE) or RPMI-1640 and boostering them SC with LE or heat treated LE. Results indicated that calves inoculated SC with heat treated LE had less pathophysiological changes than calves inoculated SC with LE regardless of previous ID exposure.

The results of these experiments suggest that endotoxin and leukotoxin of P haemolytica act in a separate but additive manner in inducing the pathophysiology of pasteurellosis. The production of oral vaccines to stimulate GALT appears to be an effective way to induce LNA and reduce the lesions of pasteurellosis in calves.

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