Download (direct link):
Antibody production appears to be protective during infection with Babesia. A study of B. bovis-infected cattle demonstrated that those animals which did not produce a serologic response to the parasite died after primary or secondary challenge. All cattle that mounted a serological response survived primary and secondary challenges with B. bovis (Goff et al.,
1982). IgG titers produced during an anamnestic response to B. microti in a mouse model correlated well with protection against infection (Meeusen et al., 1985).
In contrast, in a study of adoptive transfer of immunity to B. rodhaini in mice, protection from challenge by the parasite was maintained despite irradiation of the adoptively transferred cells at a radiation dose which would be expected to suppress antibody production. This led the investigators to suggest that antibody production is of minor if any importance in protecting against B. rodhaini infection (Zivkovic et al.,
Studies with monoclonal antibodies have identified Babesia antigens that are important for successful infection. Winger et al. (1987) developed a monoclonal antibody to a 50-60kDa protein from B. divergens merozoites; the presence of the antibody in cultures prevented the invasion of bovine erythrocytes by B. divergens. Immunization of gerbils with the antigen provided partial immunity when the animals were later challenged with parasitized erythrocytes. Those animals which survived were found to have a strong serological response to the 50-60 kDa antigen (Winger et al., 1989). In similar studies, monoclonal antibodies to a 17 kDa antigen isolated from B. divergens inhibited parasite growth in vitro (Precigout et al., 1993). The same group later demonstrated that a 37 kDa glycoprotein present on the membrane of B. divergens merozoites induced a
strong antibody response, which was felt to be protective (Carcy et al., 1995). These and other antigens from Babesia that might be important in successful infection of erythrocytes have not been identified, nor has their function been elucidated. Antigenic variation of Babesia-derived components has been observed, which can only complicate the study of important structures on the surface of Babesia and infected erythrocytes (Allred et al., 1994).
Phagocytosis of Babesia as a means of immune protection has been studied. Phagocytosis of B. bovis-infected erythrocytes and of cell-free parasites occurred in the presence of antibody raised against a particular fraction of the parasite. However, in the presence of immune serum, phagocytosis did not occur (Jacobson et al.,
1993). In another study, phagocytosis of B. rodhaini-infected erythrocytes or cell-free forms occurred in the presence of hyperimmune serum. Phagocytosis was not enhanced and perhaps was reduced in the presence of complement (Parrodi et al., 1991). Both studies suggest that phagocytosis of opsonized erythrocytes and parasites might be an important means of immune protection during Babesia infection.
T lymphocyte responses also appear to be important in the development of immunity to Babesia infection, although the topic has not been thoroughly examined. Mice depleted of T lymphocytes and infected with B. microti displayed higher parasitemias than control mice. The natural degree of resistance could be restored by reconstitution of the T lymphocyte-depleted mice by transfer of B lymphocyte-depleted spleen cells (Ruebush and Hanson, 1980). In a murine model, depletion of T lymphocytes with a cytotoxic/ suppressor phenotype resulted in increased resistance to B. microti infection, whereas depletion of CD4+ T lymphocytes resulted in increased susceptibility to infection. The converse was true for B. rodhaini infection (Shimada et al., 1996),
suggesting that cellular immunity to Babesia infections is complex. The results of other studies suggest that antibody-independent, T lymphocyte-mediated mechanisms are important in the resolution of acute infection of mice with B. microti (Cavacini et al., 1990).
Further studies of the T lymphocyte response to Babesia antigens have been conducted recently. A 77kDa protein, isolated from
B. bovis produced during natural infection in cattle and thought to be an apical complex-associated protein, was cloned. The recombinant protein elicited the proliferation of CD4+ and CD8+ T lymphocyte cell lines (Tetzlaff et al.,
1992). Two epitopes capable of stimulating CD4+ T lymphocyte clones were identified. The epitopes from the B. bovis-derived protein appeared to preferentially stimulate the Th1 subset of CD4+ T lymphocytes (Brown et al.,
1993). Studies on y/8 T lymphocyte lines suggested that these cells might be important in modulating the CD4+ T lymphocyte response to Babesia antigens (Brown et al., 1994). Subsequent studies have identified five different antigenic groups of B. bovis merozoite proteins which stimulate proliferation of Th clones. The authors suggest that these antigens are potentially useful for the construction of a vaccine (Brown et al., 1995).