E anti-parasite response major to pathogen manage and clearance (124). Immediately after several rounds of infectionproliferation, a robust antiT. cruzi immune response is developed, which can be able to greatlyreduce parasitemia and tissue parasitism. However, this immune response is unable to provide parasite clearance, as polymerase chain reaction (PCR) and immunocytochemistry assays have shown the presence of parasites in infected tissues in individuals with cardiac (12527) and digestive (128) manifestations. The delayed immune response as well as the inability to clear the parasite could be related towards the massive repertoire of hugely polymorphic and immunogenic surface proteins which are coexpressed by the parasite (82, 123, 129, 130). This antigen arsenal may perhaps deliver suggests of evading immune response that are distinct from the classic antigenic variation employed by parasites including Trypanosoma brucei and Giardia lamblia (13136). Classic antigenic variation is accomplished by the expression of identical antigenic variants around the surface of the majority from the cells in a parasite population when a small subset expresses distinct variants (131, 13739). The immune response targets the parasites expressing the prevalent variant whilst failing to identify PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21357911 these expressing rare variants (137). Long-term infection is accomplished by varying the expressed antigens, top to successive waves of parasitemia and clearance as novel antigenic determinants spread within the parasite population (133, 138, 139). There is certainly no evidence that T. cruzi adopts this type of antigenic variation. Rather, the entire T. cruzi population simultaneously exposes a number of antigenic surface proteins, like mucins, trans-sialidase, and MASPs, encoded by very polymorphic multigene households (22, 80, 82, 129, 130). The coexpression of this diverse antigenic repertoire drives the immune program into a series of spurious and non-neutralizing antibody responses, a mechanism called a smoke screen, which delays the production of high-affinity anti-T. cruzi antibodies and the priming of efficient T-CD8+ cells (22, 82, 140). The presence of a broad range of antigenic motifs may perhaps also be a mechanism to drive the antibody response away from catalytic web sites of crucial parasite surface proteins. In actual fact, a powerful humoral response against the transsialidases C-terminal repetitive motif shed acute phase antigen (SAPA) has been observed, followed by a weak antibody response against many epitopes in the N-terminal catalytic region inside a later stage that was unable to inhibit the enzyme activity (141). Moreover towards the high variability of parasite surface antigens, the presence of parasite-derived B cell order GNF-7 mitogens also causes polyclonal B cell activation and hypergammaglobulinemia, resulting within a delayed parasite-specific antibody response (21, 22, 142, 143). This unfocused response is important for parasite survival, as most of the antibodies made by splenic cells during the initial acute phase don’t target the parasite, and particular anti-T. cruzi antibodies are only created later (22). Interestingly, while the humoral response within the chronic stage shows a preferential IgG2a pattern, the acute infection comprises a broader variety of immunoglobulin isotypes: IgM, IgG1, IgG2a, IgG2b, and IgG3 (22, 144). Furthermore to B cell mitogens, a further driving issue of this polyclonal activation might be the coexpression and shedding of a big repertoire of immunogenic surface proteins, delaying the immune response t.
