Factors sensitizing the erythrocytes in-vivo during acute
Salmonella gallinarum infection in chickens, the probable mechanism
of the associated haemolytic anaemia,and the respective roles played
by the phenomena of in-vivo erythrocyte sensitization and the haemolytic episode in the overall pathogenesis of this disease syndrome,
Detailed pathological study of the blood during the acute
disease showed that, at the time of death, the infected chicken had
developed a very severe anaemia and leucocytosis. By relating the
reticulocyte response and the absolute haematologic values to the
gross and histopathological changes in the bone-marrow, spleen and
the liver, it was shown that the anaemia observed was not of the
dyshaemopoeitic type; it was, however, macrocytic and normochromic.
It was observed that the erythrocytes regularly became
sensitized in-vivo during infection and this was subsequently shown
to be a common occurring phenomenon in this disease. By examining
the biologic, serologic, immunologic, immunochemical and electrophoretic properties of these in-vivo sensitizing factor(s) it was
conclusively established that these factors were specific bacterial
1ipo-polysaccharide and its homologous antibody.
Examination of the patterns of sensitization revealed 4
types of in-vivo erythrocyte sensitization, which were found to be
intimately related to the severity and mortality of the haemolytic
and the disease syndromes respectively. It was also shown that,
chickens in which erythrocyte sensitization was detected, a characteristic binodal erythrocyte fragility curve could be demonstrated.
Techniques were developed for obtaining from infected
... destruction. It was demonstrated that the sensitized cells
recovered from infected animals may consist of a mixed, heterogeneous cell population of a small minority of •maximally' sensitized erythrocytes and a larger number of non-sensitized reticulocytes .
Normal chicken serum was found to contain a high con¬
centration of heat-stable, non-gamrna globulin components which
inhibit erythrocyte sensitization by bacterial polysaccharide.
These inhibitors, determined to act by either neutralising or
altering the polysaccharide in such a way as to prevent its sub¬
sequent adsorption by the erythrocyte, were also shown to be signi
ficantly decreased in concentration at the peak of the haemolytic
episode during acute fowl typhoid.
A moderately severe imrnuno-haemolytic anaemia could be
induced in chickens by single or multiple injections of endotoxin;
evidence for the unequivocal participation of specific antibody
in the production of this .anaemia was obtained by challenging
endotoxin-injected chickens with homologous anti-endotoxin antibody.
The significance of the anaemia in the overall pathogenesis of this infection was investigated and it was shown that the
anaemia per se did not increase the susceptibility of the chicken
to endotoxin. However, prior intravenous administration of invivo sensitized, homologous or normal, heterologous erythrocytes
markedly decreased the of the subsequently injected endotoxin. This latter increase in susceptibility to endotoxin .
was suggested to be due to a blockaded reticulo-endothelial
system, resulting from increased phagocytosis of the foreign
and altered homologous erythrocytes.
These results were discussed in relation to the immunological basis of the mechanism of the anaemia and the significance
of this anaemia in the overall pathogenesis of this disease syndrome. It was submitted that they were consistent with the
hypothesis that the anaemia is the consequence of an immune reaction, involving the specific bacterial polysaccharide and homologous antibody. Furthermore, the anaemia plays an extremely
important role in the pathogenesis of the fowl typhoid syndrome.
The possibility that similar phenomena and iinnunologic
mechanisms may be occurring in other acute gram-negative bacterial
infections was also stressed.