Figure 2.

Immunosuppression tactics in the human host. Schistosomes travelling through employ different immune evasion methodologies depending upon their location and life cycle stage. (A) As cercariae penetrate the skin, numerous proteases of different families help facilitate the cleavage of host molecules. The degradation of key structural components such as numerous collagens and elastin by these proteases helps the parasite descend through the epidermis, penetrate through the basement membrane, and eventually navigate the dermis in the search for a nearby venule. The invading larvae also release numerous immunosuppressants such as Sm16 and prostaglandins which alter leukocyte function in an attempt to avoid cell mediated death by creating a favorable immune environment. (B) Adults can also release molecules to reduce blood clotting in the area immediately surrounding a mated pair. This wide variety of molecules may be involved in the degradation of host plasma components to facilitate feeding, but their capacity to act as anti coagulants also implies the creating of a milieu in which the worms are able to move freely without fear of being killed by the coagulation of the blood in which they are emersed. (C) Adult worms in the mesenteric blood vessels incorporate host molecules into their tegument. Many of these molecules are important immune factors, which are bound in such a way as to prevent proper opsonization. IgG is found via its Fc portion, making in unrecognizable to cell found Fc receptors. Complement component C3 is also bound, although the effects of this association are not completely understood. Finally host MHCI can also be found bound to adult worms via its β2-microglobulin domain. The worm also targets mammalian factors not only for capture, but also for inactivation, as evidenced by schistosome paramyosin inhibiting membrane attack complex formation. (D) Schistosomes release a wide variety of parasite derived factors into their environment to create tolerable conditions for their survival. These molecules perform many different tasks, including the inhibition of cysteine proteases (Sj cysteine protease inhibitor), the blocking of neutrophil elastase (SmKI), and the alteration of antigen processing in macrophages (SjTpx). (E) Schistosome eggs release several factors which is key in skewing the T cell response towards the Th2 phenotype necessary for migration through the intestinal wall. These include α-1, which causes TH2 type granuloma formation through basophil mediated IL-4 production, and Ω-1, which brings about M2 polarization by altering dendritic cell antigen presentation. The chemokine binding protein SmCKBP is also present and reduces recruitment of varying leukocytes.