HUMORAL IMMUNITY IN MALARIA 
251 
action when administered to rhesus mon¬ 
keys against infections by the same parasite 
(Coggeshall 1940b). However, the serum 
of these same individuals before the infec¬ 
tion is without effect. 
These studies seem to furnish ample evi¬ 
dence that neutralizing antibodies are 
found during an attack of malaria and, 
although not experimentally proved, it 
seems probable that they are concerned 
with the specificity of the disease. This 
assumption was given strong support by 
the studies of Boyd et al. (1938), who 
showed that paretics with induced P. vivax 
malaria had a complete immunity against 
the Floridian strain of the parasite, with 
which they were initially inoculated, yet 
were readily susceptible to Panamanian 
and Cuban strains of P. vivax. The fact 
that an immune host can resist reinfection 
following massive doses of the homologous 
organism, yet react as a normal when in¬ 
jected with a closely related strain, indi¬ 
cates that some factor other than a highly 
active cellular defense mechanism is re¬ 
sponsible for the marked degree of speci¬ 
ficity encountered with malarial infections. 
The behavior of the protective antibody 
during the long latent period of malarial 
infection has not been thoroughly studied, 
although there is evidence to support the 
belief that the concentration fluctuates 
with the changes in the rate of multiplica¬ 
tion of the parasite. For example, prelimi¬ 
nary studies in this laboratory have shown 
that serum obtained immediately before a 
parasitic relapse in P. knowlesi infections 
contains practically no protective anti¬ 
bodies, while serum obtained after the 
spontaneous termination of the relapse in 
the same animal often has an extremely 
potent effect when used in a protection 
test. It seems probable that recovery from 
malaria is accompanied by a gradually 
increasing titer of protective antibodies re¬ 
sulting from a series of relapses (during 
which parasites may or may not be found 
in the circulating blood stream) until even¬ 
tually a complete cure is attained. Experi¬ 
mental evidence supporting this conclusion 
comes from the finding that the titer of 
serum from monkeys with chronic P. 
knowlesi infections can be enhanced con¬ 
siderably by repeated injections of massive 
doses of living parasites (Coggeshall and 
Kumm 1938). Undoubtedly the occurrence 
of spontaneous relapses is a mechanism of 
autohyperimmunization which results in a 
more efficient humoral immune mechanism. 
The exact role of the protective antibody 
in malarial immunity has not been clearly 
demonstrated, although a likely possibility 
is that it sensitizes the parasite and renders 
it more susceptible to phagocytosis. A 
greater protective effect in protection tests 
in monkeys and chicks is obtained with 
serum that has been incubated at 37° C 
with the inoculating dose of parasites in¬ 
stead of merely allowing the immune serum 
and parasites to come in contact before 
inoculation of the mixture or the separate 
injections of the two components (Cogge¬ 
shall and Eaton 1938b; Taliaferro and 
Taliaferro 1940). There is a union be¬ 
tween the protective antibody and the 
parasite because the protective effect of an 
immune serum can be removed by absorp¬ 
tion with an excess of living parasites. 
These and other related experiments where 
immune serum renders viable parasites 
noninfectious indicate that an immune ma¬ 
laria serum can act upon the asexual plas- 
modia, although the removal of the circu¬ 
lating parasites from an infected host is 
undoubtedly the function of the macro¬ 
phages (Taliaferro, this volume, p. 239). 
Although the above mentioned findings are 
suggestive, further studies are necessary to 
elucidate clearly the exact mechanisms of 
action of the protective antibody. 
Complement-Fixing Antibodies 
A specific complement fixation reaction 
for malarial infections has been the object 
of many studies, and a summary of the re¬ 
sults up to 1927, although contradictory, 
indicates the presence of complement-fixing 
antibodies in the serum of patients with 
chronic malaria (Taliaferro 1929). The 
most significant work was that of Kings¬ 
bury in 1927 who used infected P. falci¬ 
parum blood from internal organs in an 
