rVFlIOII) BACILLUS 'Mu 
l)la(l<ler from wliich sites escape to the exterior is readily aceomplished. 
From the gall-bladder the organisms pass in irregular numbers into 
the intestinal tract; occasionally in sufficient numbers to be demcm- 
strable in the feces. A considerable proportion of operations for 
cholecystitis and gall-stones— the greater majority being among women 
—give positiA'e typhoid cultures when the contents are examined 
bacteriologically. 
Pathogenesis in Animals.— W\ animals, except possibly anthropoid 
apes, are naturally immune to typhoid fever, and inoculation of old 
laboratory cultures of typhoid bacilli into laboratory animals is usu- 
ally without noteworthy effect; virulent cultures of typhoid bacilli, 
particularly those produced by repeated passage through laboratory 
animals, may produce peritonitis and death w^hen they are introduced 
into the animals by the intraperitoneal route. The infection, how- 
ever, does not resemble typhoid fever. The lesions observed post- 
mortem are marked congestion of the abdominal organs, particidarly 
the spleen, kidneys and liver, as well as involvement of the intestinal 
lymph apparatus; the thoracic organs are less involved as a rule. 
The organisms may be recovered from the peritoneal fluid, the 
blood stream, and from various abdominal organs. Gay and Claypole^ 
have succeeded in inducing with great regularity the carrier state in 
rabbits by injecting into them typhoid bacilli which have been grown 
for se\'eral successive transfers on agar overlaid with fresh defibrin- 
ated ral)bit's blood. They found that the typhoid bacilli localize 
themselves in the gall-bladders of the rabbits, and that they may 
from time to time invade the blood stream. In a more recent com- 
munication- they have shown that the carrier state occurs much less 
frequently if the animals are immunized with their dried sensitized 
vaccine. 
Antibody Pnxhiction.—Aniuiah may l)e immunized by repeated 
injections of typhoid bacilli to such a degree that they will success- 
fully resist several times the original fatal dose of these organisms.'^ 
Successive injections of typhoid bacilli stimulate antibody formation 
in horses, ral)bits, guinea-pigs and other animals. Of these anti- 
bodies, the lysins and agglutinins may be produced in high potency if 
the injections are continued long enough. Other antibodies, opsonins 
and preci})itins particularly, are also produced. (Jay and Olaypole"* 
have produced experimental evidence indicating that the titer of 
the specific agglutinins which develop during the process of immun- 
izati(m of rabbits affords no indication of the degree of ])r()tection 
attained by the immunizing process. 
Protective Immunization.— As a rule, one attack of typhoid fever 
confers innnunity; sul)se(iuent attacks are unusual. 
During the last few years, definite progress has been made in the 
1 Arch. Int. Med., 1913, 12, 01.3. ^ Ihid., 1<»14, 14, 671. 
' See Gay and Claypole (Arch. Int. Med., 1!)14, 14, 671; for essential details. 
* Loc cit- 
