644 Immunity and Resistance 



very severe with some species of Plasmodium. In other cases, a natural 

 tolerance may be eliminated by splenectomy. Much the same effects have 

 been produced by blockading techniques. 



In natural resistance — that is, in the normal animal — phagocytosis ap- 

 pears to be non-specific. Circulating phagocytes seem to take little part 

 in destruction of the parasites and the macrophages show only sluggish 

 phagocytosis. In the early stages of infection, the phagocytes possibly 

 ingest only moribund parasites (78, 84). 



As the infection progresses, some degree of immunity is developed. 

 Previous experience of monkeys with malaria, involving activation of 

 lymphoid-macrophage cells, apparently facilitates the development of 

 immunity against a new strain (118). Cellular responses in the spleen 

 of monkeys (177) include both multiplication of lymphocytes in the 

 splenic nodules, followed by their migration into the red pulp, and later 

 multiplication of lymphocytes and their transformation into macrophages 

 in the pulp. The result is a marked increase in the number of phagocytes. 

 The reproduction of macrophages as such apparently occurs only to a 

 minor extent. As would be expected, such agents as X-rays in heavy 

 dosage (185) and nitrogen mustard (183), which destroy lymphocytes, 

 retard the development of immunity. 



In addition to the increase in number of phagocytes, the phagocytosis 

 of homologous parasites is specifically stimulated. This response suggests 

 the influence of an opsonin (47, 199). It is now widely believed that the 

 appearance of such opsonins, or "protective antibodies," is characteristic 

 of malarial immunity. In inonkeys, corpuscles invaded by P. knoivlesi 

 become coated with a precipitate which is selectively ingested by phago- 

 cytes (98a.) This phenomenon implies stimulation of phagocytes rather 

 than a harmful action of opsonins on the parasites. Phagocytosis occurs 

 principally in regions where the blood flows relatively slowly and comes 

 into close contact with the phagocytes. Such regions are represented 

 particularly by the liver, bone marrow, and spleen. Acquired immunity 

 to malaria, in the phraseology of Taliaferro, is thus expressed primarily 

 as an intensified and specific phagocytosis in such strategically located 

 organs as the spleen. The sluggish and non-specific phagocytosis of the 

 normal animal usually can not prevent establishment of an infection, 

 but the development of immunity increases phagocytosis to such an 

 extent that the infection is brought more or less under control. 



The malaricidal mechanism, particularly after development of a potent 

 immunity, probably plays a significant part in the net results of chemo- 

 therapy. This conclusion is indicated, for example, by the results of 

 splenectomy in chickens infected with P. gaUinaceum (184). Direct inter- 

 ference with the lymphoid-macrophage cells throws more than the usual 

 load on a malaricidal drug in the elimination of infections. A similar 

 situation may exist in therapy following a low-grade immunological re- 



