CELLULAR BASIS FOR IMMUNITY IN MALARIA 
245 
applicable to P. vivax and P. malariae in¬ 
fections in man because they agree with the 
necropsy material as far as the latter go. 
They are also probably applicable to infec¬ 
tions with P. falciparum except for the fact 
that infections with P. falciparum are fre¬ 
quently overlaid with general and particu¬ 
larly with local degenerative changes. 
The main conclusions from the investi¬ 
gations on monkeys are as follows: During 
the initial acute rise of the infection when 
death of the parasites represents a natural 
immunity, the free merozoites and intra- 
corpuscular parasites in all stages of de¬ 
velopment are phagocytosed sluggishly by 
macrophages of the spleen, liver and bone 
marrow (PL I, Fig. 1). At the crisis when 
the initial acute rise is terminated, the 
parasitized erythrocytes are regionally con¬ 
centrated in the splenic cords and are 
probably agglutinated or adhere to the 
macrophages. After a day or so, the para¬ 
sitized erythrocytes are avidly eaten by the 
macrophages of the spleen, liver and bone 
marrow (PI. I, Fig. 2). This phagocytic 
activity is many times greater than that 
observed before the crisis and represents 
the beginning of the heightened activity of 
the immune reaction. Once this immune 
phagocytosis is initiated, the infection is 
generally subdued and held at a compara¬ 
tively low level. The red cells and para¬ 
sites within the phagocytes disappear 
rapidly, but the pigment is not metabolized 
for several months (PI. I, Fig. 3). When 
animals which have recovered from an in¬ 
fection are superinfected with the homolo¬ 
gous strain to which they are immune, the 
sequence of splenic filtration, phagocytosis, 
etc., is initiated within an hour instead of 
several weeks or months as in the initial 
attack. In other words, acquired immu¬ 
nity takes time to develop, but once devel¬ 
oped responds immediately.. 
The limitation of phagocytosis to the 
spleen, liver and bone marrow probably 
follows from the fact that the blood in 
these organs, at least periodically, flows 
slowly and comes into direct contact with 
active macrophages, whereas other organs, 
such as the lymph nodes, lung, etc., which 
are also rich in macrophages, do not have 
this intimate contact with the blood except 
after a hemorrhage due, for example, to in¬ 
farction. The fact that the adrenal is similar 
to the liver and yet is only sporadically 
involved may be due to the richness and 
swiftness of the blood flow. In any case 
there are differences in the activity of the 
macrophages in these various organs. 
Thus, Taliaferro and Mulligan (1937) 
have shown that even in the overwhelming 
infection of P. knowlesi in the rhesus mon¬ 
key in which almost every available cell 
of the lymphoid-macrophage system is 
phagocytic, the same quantitative relation 
is maintained, i.e., the individual macro¬ 
phages of the spleen are most active, those 
of the liver are less active and those of the 
bone marrow are least active 1 while those 
in other organs are only rarely active. The 
generalized character of the malarial infec¬ 
tion and the limitation of the immune reac¬ 
tion to a few organs in which the macro¬ 
phages are oriented to phagocytose material 
from the blood led Taliaferro (1934) to 
suggest that many of the so-called general 
immunities are actually local immunities 
in strategically placed organs. 
The objective histological differences be¬ 
tween acquired immunity and natural im¬ 
munity are: (1) a greatly increased rate 
of phagocytosis by individual macrophages 
and (2) a local increase of macrophages in 
some of the strategically placed organs, in 
particular in the spleen and to a lesser 
extent in the bone marrow. The increased 
rate of phagocytosis by the individual 
macrophages is specific (i.e., is largely 
operative against homologous strains of 
parasites) and is the chief characteristic 
of acquired immunity. It is probably asso¬ 
ciated with the opsonic activity of specific 
antibodies and is considered in detail by 
Coggeshall (this volume p. 250). It sug¬ 
gests a fundamental difference between the 
phagocytosis of natural and acquired im¬ 
munity. Such a conclusion is further 
i Although, the individual macrophages of the 
liver are less active than those of the spleen, the 
total activity of the liver may he greater due to its 
greater size. 
