Assessment in vitro of immunity against Toxoplasma gondii.

Abstract

Studies have been made on humoral and cellular immune respones in mice immunized with an attenuated strain of Toxoplasma gondii. Heat-inactivated antitoxoplasma serum did not cause morphologic changes in the organisms, but did markedly influence their interactions with host cells. Toxoplasma exposed to antibody were no longer capable of entering fibroblasts or HeLa cells. They were readily engulfed by macrophages, but the antibody treatment strikingly altered the intracellular fate of the parasites leading to killing and digestion of the toxoplasmas in phagolysosomes. Addition of antitoxoplasma antibody immediately after infection of macrophages in vitro had no effect on intracellular multiplication of the organism. The division time of virulent toxoplasmas in mouse peritoneal macrophages in vitro was markedly prolonged in cells from immunized mice. During the first 2-3 mo after immunization, the macrophages harvested from the peritoneal cavity demonstrated this cellular immunity directly; thereafter exposure of the macrophages to immune lymphocytes and toxoplasma antigen, or to supernates from such an interaction was required for induction of the maximal capacity to inhibit growth of toxoplasmas. Induction of the alternation in macrophages by the lymphocyte product was detectable in 6 h and maximal at 18-24 h. Cultivation in vitro of macrophages from immunized animals for periods longer than 48 h rendered the cells nonresponsive to the immune lymphocyte-toxoplasma product. Macrophages from the peritoneal cavities of normal, nonimmunized mice were also incapable of developing the capacity to inhibit growth of toxoplasmas in response to this product. The nonresponsiveness of normal macrophages, or of macrophages cultured for several days in vitro was not changed by exposure of the cells to antitoxoplasma serum.

Experimental Encephalitozoonosis in Neonatal Dogs

“…The macrophage as an element in host-parasite interactions is by no means unique to encephalitozoonosis but is a common participant in other intracellular protozoal infections, especially toxoplasmosis. 16 In both toxoplasmosis and encephalitozoonosis, the quiescent macrophage does not kill the p a r a~i t e~~,~~ but requires activation through lymphokine p r o d u~t s~l ,~~ or parasite opsonization by antibody. 1,35, 48 Although not addressed within these experiments, sensitized canine lymphocytes most likely do produce soluble products when exposed to E. cuniculi antigens.…”

Association of Symptomatic Human Infection with Toxoplasma gondii with Imbalance of Monocytes and Antigen-Specific T Cell Subsets

“…Soluble antigen was prepared from the RH strain of T. gondii as previously described [10]. All five subjects studied were pretested in an eight-day lymphocyte transformation assay with the antigen to determine the optimal dose for maximal proliferation.…”

Some Physicochemical Characteristics of an Immune Lymphocyte Product Which Inhibits the Multiplication of Toxoplasma within Mouse Macrophages

“…At present, the mechanism whereby the macrophages incubated with Toxo-GIF inhibit multiplication of Toxoplasma is unknown. Several workers reported that Toxoplasma-immune macrophages showed a prolonged lag phase and increased generation time compared to nonimmune macrophages (2,11,23). Our unpublished observations indicated that by incubation with Toxo-GIF, glycogen-induced nonimmune macrophages showed prolonged lag phases (18-22 hr) compared to those of control macrophages (10-1 1 hr).…”

“…Recent studies with Toxoplasma infection have shown that cell-mediated immunity plays a major role in resistance to infection with this obligate intracellular pathogen (2,5,8,11,18). Lymphocytes from immunized donors produce in response to antigenic stimulation a variety of biologically active substances which have been collectively termed "lymphokines".…”