Font Size: a A A

Studies on the mechanisms of Teania soluim larval stage adherence to host tissue

Posted on:2011-02-02Degree:Ph.DType:Thesis
University:The Johns Hopkins UniversityCandidate:Verastegui, Manuela ReneeFull Text:PDF
GTID:2444390002450317Subject:Health Sciences
Abstract/Summary:
The mechanisms of adherence and penetration in the host used by T. solium oncospheres have not been studied. This thesis is focused on the development of an in vitro model defining those adherence mechanisms to intestinal epithelium cells, and identifying the potential binding receptors that might be involved in the process of host cell recognition and attachment. In addition, we tested the ability of sera to inhibit T. solium oncosphere adherence in both patients infected with T. solium or other cestodes and sera from animals immunized with different cestode antigens.;This study showed that activated T. solium oncospheres adhered in vitro to Porcine Intestinal Mucosal Scraping, Porcine Small Intestinal Mucosal Explants, and monolayer cells (CHO, CaCo2 and HCT 8). When using monolayer CHO cells, the adherence was most easily measured. Sera increased the number of activated T. solium oncospheres adhered to CHO cells (p<0.05). We differentiated activated oncospheres with and without oncospheral membrane by using indirect immunofluorescence. We also demonstrated that T. solium oncospheres attach to cells with elongated microvilli.;Laminin and fibronectin increase activated T. solium oncosphere adherence. At low concentrations (10ug/ml to 100ug/ml), laminin exhibited a dose response effect, however at high concentration (1000ug/ml) it decreased the adherence. Polyclonal antibody to laminin or fibronectin inhibited the oncosphere adherence to laminin or fibronectin substrate.;The oncospheral adherence inhibition was statistically significant higher in individuals with T. solium tapeworm (53%) and those with Cyst Echinococcosis (75%) as compared with the control group (healthy individuals, 23%) (p<0.009 and p<0.0001, respectively). This suggests that sera from individuals with Cystic Echinococcosis have cross reactive antibodies against T. solium oncosphere. Individuals with T. saginata adult tapeworm also inhibited T. solium oncosphere adherence (53%) but it was not statistically significant. Additionally, hyperimmune rabbit sera against T. solium, T. saginata oncosphere and the enzyme cathepsin L isolated from T. solium cysts all had high rates of inhibition. The finding that antibodies against T. solium oncospheres inhibited the oncosphere adherence to the host cells suggests there may be new options for vaccine protein candidates.
Keywords/Search Tags:Adherence, Solium, Host, Mechanisms, Cells
Related items