Evasive Strategies

Intracellular hiding is a very important evasive strategy of T. cruzi, because the blood is the primary battleground of the humoral immune response. If T. cruzi trypomastigotes remained in the blood for a month, this would give the T and B lymphocytes sufficient time to activate very specific IgG immunoglobulins against them. During the acute phase, polyclonal stimulation occurs and parasites are chased into cells. After polyclonal activation subsides, immunosuppression follows, which provides more time for trypomastigotes to enter cells.

Some lesser strategies are evident. Trypomastigotes show rapid surface turnover, capping, shedding, and some interstrain antigenic variation of their coats, but not to the degree exhibited by the T. brucei ‑complex of organisms. If antibodies attach to trypomastigotes, trypomastigotes can shed them if they act quickly enough.

Trypomastigotes are also able to evade host antibodies by binding to the Fc (crystallizable fragment) portion and by fabulation. T. cruzi have a surface component that enables their antigens to bind to the Fc end and not to the FAB (antigen‑binding fragment) end of the immunoglobulin molecule. If antigens bind to the Fc end, then this end is blocked from activating complement, which is necessary to lyse the parasite. This is especially true for antibodies directed specifically at nonsurface epitopes, which they cannot reach, since antigens on the trypomastigote’s surface bind to the Fc portion of IgG. Antibody‑dependent cell‑mediated cytotoxicity (ADCC) and antibody‑dependent complement lysis are both dependent on the Fc portion being exposed. Trypomastigotes become coated with host antibodies clinging to antigens on their surfaces, but with their FAB extended and nonfunctional.

Fabulation is when trypomastigote antigens bind to the FAB end of the molecule and cleave off the Fc portion, which literally disables the antibody. Trypomastigotes have surface proteases (protein‑eating enzymes) that cleave off the Fc end of the antibody. Without its Fc end, the antibody is left with an ineffective little piece of protein dangling from its surface that is unattractive to complement or to cells.

Although it is not surprising that T. cruzi has all these mechanisms for evading the host immune system, African trypanosomes rely most heavily on antigenic variation. African trypanosomes don’t have the need to use anything but antigen variation, which is enough to enable them to avoid the destruction of all their number by host immunity measures. A parasite may have four or five mechanisms for evasion, and then another one appears that is better than the others, but the parasite doesn’t then get rid of the less‑effective ways, at least not for many, many generations. These mechanisms will be selected in those organisms that don’t have the better one. T. cruzi, then, has not attained such a refined mechanism of evasion as antigenic variation, and so it utilizes more than one evasive mechanism. All of which work toward the same end: the survival of the species.