Studies of the Host Response and the Induction of Immunosuppression in Murine Malaria

Abstract

Various fractions were separated from Plasmodium berghei infected erythrocytes and tested for suppression of the immune response to SRBC. Membranes containing fractions Peak I (C), Peak I (G), and the sodium deoxycholate void volume all act as a vaccine against Plasmodium infection and are all without immunosuppressive activity as assayed by the plaque technique. Immunosuppressive activity was found in association with the sedimented parasite fragments (E), detergent-insoluble components (N), and Sephadex G-200 eluate fractions (H(,1), D(,1)).

The daily injection of suppressor factor derived from P. berghei infected erythrocytes was found to suppress the immune response to Plasmodium berghei infection in mice. One, two, or three injections of this factor did not suppress the immune response.

Suppressor factor-free partially purified fractions were used in combination with suppressor factor and without suppressor factor to study the effect of suppressor factor during vaccination. One injection of Peak I (G) and sodium deoxycholate void volume sediment without any adjuvant were very effective against P. berghei challenge. Three injections of Peak I, II, III, and IV from the 6 M guanidine column did not have a significant effect on the patency or mortality rate of mice following P. berghei challenge. However, daily injection of Peak III gave significantly more protected animals as compared to the controls.

Immunosuppressive activity was observed with unfiltered supernatant from PRBC-stimulated spleen cells and with supernatant of PRBC alone in medium (no spleen cells). Filtration of these two supernatants fluids removed the immunosuppressive activity. The supernatant from unstimulated spleen cells was not immunosuppressive.

The effects of PABA, methionine, threonine, and protein dietary levels on the immune system of mice infected with P. berghei were also studied. Methionine had no effect on the parasitemia levels of mice infected with P. berghei. The protein dietary level seems not to be as important to the immune response as is the ratio of supplemental methionine to the threonine.