Specific and nonspecific mechanisms of immunity in toxoplasmosis

Chronic experimental toxoplasmosis can be produced in the guinea pig and closely simulates the commonest form of toxoplasmosis in man. It is characterized by the development of humoral antibodies to toxoplasma and delayed hypersensitivity as evidenced by the skin test. Macrophage migration inhibition factor, an in vitro corollary of delayed hypersensitivity, is also produced during experimental toxoplasmosis in guinea pigs injected with lyophilized toxoplasma extract emulsified with complete Freund's adjuvant. However, antigen sensitized animals, in contrast to previously infected guinea pigs, do not acquire resistance to toxoplasmosis, despite the presence of delayed hypersensitivity. Antigen sensitive lymphocytes can be found in the circulation of infected guinea pigs by the lymphocyte transformation test. Their number diminished as the levels of humoral antibody increased, suggesting that they may disappear from the bloodstream during antibody production. Cultures of lymphoid cells from spleen, lymph nodes, peritoneal exudates and peripheral blood taken from normal guinea pigs support the growth of toxoplasmas. Equivalent tissues from infected animals fail to support toxoplasmal growth. The cells responsible for inhibition of toxoplasmal growth are the adherent mononuclears, probably macrophages. Lymphocytes of infected guinea pigs kill viable toxoplasmas. They also cause release of the isotope from mouse mastocytes coated with purified toxoplasma antigen. Both specific and nonspecific lymphocyte cytotoxicity could be discerned. T lymphocytes from normal and toxoplasma infected animals seem to be toxic for toxoplasma coated mastocytes if a lymphocyte target cell ratio of 12.5:1 is used. On the other hand, B cells from infected animals are nonspecific in their cytotoxic actions on mastocytes, perhaps through release of a lymphocyte product that is toxic for mastocytes. The summation of these two nonspecific actions of lymphocytes provides what appears to be a relatively specific effect of lymphocytes of immune guinea pigs for toxoplasma antigens.