Date of Award:

5-1983

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Department name when degree awarded

Toxicology

Committee Chair(s)

S. G. Oberg

Committee

S. G. Oberg

Committee

M. C. Healey

Committee

R. P Sharma

Committee

R. P. Warren

Abstract

Cell-mediated immunity (CMI) in the lung has not been well characterized due to the lack of applicable tests. A major objective was to define pulmonary CMI serially in immunized and control lung lobes using the leukocyte procoagulant (LPCA) assay in young adult dogs. This was compared to a standard, but less reproducible CMI assay, macrophage migration inhibition facet (MIF). The CMI response, as measured by the LPCA assay, peaked in the blood 7 days after lung immunization. The pulmonary CMI response measured with cells obtained by bronchial lavage from the immunized and control lung lobes peaked at 9 to 12 days after intrapulmonary immunization with 10xx sheep red blood cells (SRBC). This peak pulmonary immune response corresponded with the day of lymphocyte influx into the lung.

An attempt was made to increase the level of CMI in the lung by administration of muramyl dipeptide by two different routes. The administration of the adjuvant muramyl dipeptide (MDP) into the lung or given intravenously suppressed the CMI response in the lung after instillation of antigen (10xx SRBC).

Four dogs were exposed to 239Pu02 when the dogs were one year old. When the dogs were 6 to 7 years old the pulmonary CMI was evaluated after lung immunization. Age-matched control dogs were immunized for comparisons. The noticeable difference between the control and plutonium-exposed dogs was the dramatic cellular chancres produced in the control and immunized lung lobes of the plutonium-exposed dogs. Inhalation or plutonium in addition to sequential lavages produced high numbers of neutrophils to be recruited to the lung. However, the effects of inhaled 239Pu02 on pulmonary CMI of 6 to 7-year-old dogs were obscured by the low pulmonary immune response in the age-matched control dogs. The age-matched control dogs showed no cellular changes in either the saline lung lobe or the immunized lung lobe. This result was attributed to the age of the dogs. The control dogs produced high amounts or immunoglobulins as measured in the serum, however, they could not recruit these serum immunoglobulins into the lung. The plutonium-exposed dogs showed a similar immunoglobulin immune response.

The effects of naturally occurring tumors or those produced by inhaled radioactive compounds were evaluated tor their effects on the procoagulant activity assay and spontaneous macrophage migration. The procoagulant activity of the lung is significantly increased if a tumor is present in the lung. The migration area of the cell population lavaged from the tumor-bearing lung lobe was significantly increased over control lobe migration areas.

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