Date of Award

8-1989

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Professor Brian J. Underdown

Abstract

Giardia muris is an intestinal parasite of mice. It has a simple life cycle and is non-invasive. Therefore, G. muris infection provides a model to study immune mechanisms that operate at mucosal surfaces. Immunocompetent mice eliminate primary G. muris infections. T cell-dependent humoral immune mechanisms are involved in this process.

The CBA/N mouse bears an X-linked immunodeficiency gene (Xid), the expression of which results in defective B cell maturation and consequent impairment of certain humoral immune responses. The antibody responses of CBA/N mice are particularly defective in certain isotypes and specificities.

CBA/N mice fail to eliminate G. muris. The major focus of this dissertation was an attempt to elucidate the basis for chronic giardiasis in this strain.

Cellular reconstitution experiments showed that the ability to eliminate G. muris was transferred to CBA/N mice with lymphoid cells from immunocompetent, CBA/Ca mice. Reconstitution required prior irradiation of recipient mice, and was not effective with semi-purified B cells and T cells. These results indicate that conventional B cells and T cells are insufficient, and that another cell type is also required. This cell may be the Lyl+ B cell.

CBA/N mice make quantitatively deficient serum IgG antibody responses to G. muds infection. Providing CBA/N mice with this antibody failed to induce elimination of the parasite, thus this isotype defect was ruled out as the cause of their susceptibility to chronic giardiasis.

Analysis of G. muris antigen recognition failed to reveal a specificity defect in the antibody response of CBA/N mice. However, a glycolipid component of G. muris bound serum IgM from CBA/J and BALB/c mice, but not serum IgM from CBA/N mice. These results indicate a possible structural defect in IgM from CBA/N mice.

Although unable to eliminate primary G. muris infection, drug-cured CBA/N mice are resistant to reinfection. These results indicate that the immune mechanisms that mediate elimination of G. muris are different from those that mediate resistance to reinfection.

Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS