246 
malaria 
/strengthened by the work of Gingrich 
(1934, 1941). He found that blockade with 
foreign red cells markedly affects acquired 
and not natural immunity of birds to P. 
cathemerium. The local increase of macro¬ 
phages in strategic sites has been noted 
repeatedly in man, chiefly in the spleen and 
bone marrow. Experimental work with 
animals indicates that it varies in extent 
and is nonspecific, i.e., it is not necessarily 
associated with acquired immunity. If the 
initial attack is long enough, it may begin 
before the immune reaction is initiated. 
Before considering specifically the origin 
of new macrophages, certain proliferations 
should be mentioned. In the bone marrow, 
a myeloid hyperplasia may occur which 
involves an increase in the cells of the ery¬ 
throcyte and heterophil elements (see re¬ 
parative proliferations). In the spleen, 
which is the lymphatic organ most affected 
by malaria, lymphoid hyperplasia charac¬ 
teristically occurs and involves the mitotic 
proliferation of, chiefly, the medium 
lymphocyte and, to a lesser extent, the large 
tissue lymphocyte (the lymphoblast of 
some hematologists) and is a characteristic 
part of the development of the enlarged 
“chronic” (as contrasted with the early 
hyperemic) spleen of malaria. Various 
proliferations and accumulations of lymph¬ 
ocytes may take place in the liver, bone 
marrow and other organs, but are not as 
characteristic of man as of the monkey. 
Whenever lymphoid hyperplasia occurs in 
lymphatic tissue or myeloid hyperplasia 
occurs in the bone marrow, the reticular 
cells of the stroma proliferate. These cells 
are macrophages and their mitotic prolifer¬ 
ation supplies new macrophages. In the 
fresh tissues of monkeys, however, which 
have been particularly studied, the number 
of mitoses in lymphocytes is many times 
that found in reticular cells and, as will be 
pointed out below, the lymphocytes are the 
source of the majority of the new macro¬ 
phages. Both the reticular cell and lymph¬ 
oid hyperplasias form a prominent part of 
Siegmund’s “mesenchymal activation.” 
(2) Mobilization and formation of mac¬ 
rophages. As pointed out by Taliaferro 
and Mulligan (1937), many macrophages 
are available for malarial defense from the 
beginning of the infection. Chief among 
these are (1) the fixed and free reticular 
cells in the spleen and bone marrow and 
(2) the littoral cells of the sinuses or sinu¬ 
soids of the spleen, liver, bone marrow and 
adrenal. In addition, new macrophages 
replacing those which go to pieces as a re¬ 
sult of the malarial infection and account¬ 
ing for the “hyperplasia of the reticulo¬ 
endothelial system” so characteristic of 
malaria, particularly in the spleen, arise 
both homoplastically and heteroplastically. 
Homoplastically, macrophages arise by 
the mitotic division of (1) a few engorged 
macrophages in the spleen, liver and bone 
marrow, (2) a few littoral cells, particu¬ 
larly of the liver, and (3) large numbers 
of outstretched unengorged reticular cells. 
Bruetsch (1927, 1932a, 1932b) has studied 
Plate II 
Comparative histology of a venous sinus of the spleen (1) of a normal rhesus monkey and (2) of a 
rhesus monkey infected with P. cynomolgi in which intense heteroplastic eytogenesis of macrophages from 
lymphocytes is seen, x 1400. From Taliaferro and Mulligan. 
Fig. 1. A portion of a venous sinus and of a Billroth cord in the red pulp of the spleen from an un¬ 
infected monkey. Note within the sinus the typical nongranular leucocytes and within the cord the 
rounded macrophages and the typical reticular cells with indeterminate cytoplasm. 
Fig. 2. A comparable region from the spleen of a monkey killed 10 days after infection and 7 days 
after parasites appeared in its peripheral blood. The animal underwent a typical infection and was 
killed at about the time of the crisis. The sinus contains many lymphocytes with an increased amount 
of cytoplasm and many large phagocytic cells which do not occur in the normal spleen. In addition, it 
contains a progressive series of mononuclear cells from lymphocyte to macrophage as is indicated by 
Polyblasts 1—5. Polybl. 1 has a lymphocyte type of nucleus, but contains one piece of malarial pigment, 
whereas at the other end of the series Polybl. 5 is a typical macrophage. Within this series of cells, the 
extent of phagocytosis varies approximately with the size of the cell. The same intermediate stages 
can be found in the cords. Med. Lym. 1 possesses a typical lymphocyte nucleus and contains two small 
granules of malarial pigment in its cytoplasm. 
