72 



inoculated in the peritoneum together with a minimum 

 îethal dose, showed quite definite protective properties 

 "He concludes from his experiments that in a phase of 

 Immunisation the lencocytes, and specially the 1 neutro 

 philes play a part in the production or modification of- 

 special cellular substances; the demonstration of these 

 substances is easy when they are freed suddenly and 

 violently from the leucocytes, but in the circulating blood 

 they are probably secreted in a certain quantity. One 

 nay deduct that the production of these special immu- 

 nising leucocytic substances and their appearance in the 

 circulation being more prompt and intense, is a result 

 of the leucoljsis following every Icucocytosis. 



METALNIKOW and OASCHEN (1922) attribute an 

 important part in the formation of antibodies in inver- 

 tebrates (Galeria larvae) to various cells of the blood 

 of these insects. 



ROBERTSON and ROUS (1922) assert the existence 

 of intercellular agglutinins in the red blood-corpuscu- 

 les of the rabbit, and declare them to be easily demons- 

 trable in the watery extracts of dried corpuscles. 



4o) The antibodies are formed by 

 hematopoietic organs ; 



PFEIFFER and iVlARX (189S) titrating simultaneous- 

 ly bactericid antibodies in serum and leucocyte-extracts, 

 demonstrated that the leucocyte-extracts showed no 

 excess of antibodies as compared to the serum and as- 

 certained besides a decided accumulation of antibodies 

 i» certain organs of the rabbit (spleen, bone-marrow, 

 lymphatics glands, and to a lesser extent, the lungs) 

 during the first days of immunisation. The spleen sho- 

 wed, already on the second d iy, a perceptible quantity 

 of protective substances against cholera, although the 

 blood showed no sign of a specific alteration. They 

 thought the hematopoietic organs to be the point of 

 origin of the antibodies, and that any excess of antibo- 

 dies in these organs would represent an excess of pro- 

 duction not accompanied by an equally rapid elimination 

 into the blood. 



DEUTSCH (1899) ascertained that splenectomy pre- 

 ceding an immunising injection does not prevent the for- 

 mation of agglutinins ; carried out 3-5 days after the in- 

 jection it prevents quite clearly the formation of anti- 

 bodies. 



V. EMDEN (1899) immunising rabbits with B. nefo- 

 genes and searching for agglutinins in the blood and 

 various organs verified that sometimes spleen extracts 

 have a higher agglutinating titre than the blood ; agglu- 

 tinin-formation is hindered by splenectomy, but even so 

 continues; he therefore admits that besides the spleen 

 other organs, specially lymphoid organs are able to ela- 

 borate agglutinins. 



WASSERMANN (1899) studied the action of sera 

 and extracts of different organs of rabbits immunised 

 ■with virulent pneumococci on the course of experimen- 

 tal pneumococcus infection. The extracts of bone-marrow 

 showed greater quantities of antibodies than any other 

 organ, and, in the first stages of immunisation the pro- 



tective power of bone-marrow and of other blood for- 

 ming organs exceded that of the serum. He thinks that 

 the bone-marrow is the seat of the production of anti- 

 bodies and that the lymphatic glands, the thymus and 

 spleen are simply reservoirs. 



JATTA (1900) ascertained that the agglutinating titre 

 (B. typhi) of spleen extracts, between second and fourth 

 day of immunisation, is considerably superior to that of 

 the blood, equal to it on the fourth day, and considera- 

 bly inferior to it on the eight day. 



HEKTOEN (1909-1910) pointmg out the irregularity 

 of the graphics of the production of different antibodies 

 in the same animal suggested that they are distinc 

 substances, the production of which depends on a si- 

 milar but not identical mechanism. 



LIPPMANN (1911) after immunising animals with 

 repeated inoculations of killed cultures of B. typhi, left 

 them for 4 months during which the agglutinating titre 

 decreased gradually to a constant mean figure ; then 

 injected them with 0,1 gr of arsacetin, a substance who- 

 se stimulating influence on the blood forming organs is 

 well known and applied in the treatment of anemia. He 

 ascertained a rapid rise in the titre of the agglutinins 

 which attained its maximum at the and of 6-9 days. 



HEKTOEN (1916) verified a reduction in the forma- 

 tion of antibodies in animais intoxicated with benzol to- 

 gether with severe lesions of the bone-marrow, leuco- 

 penia and other lesions characteristic of benzol-intoxi- 

 cation. He found also a reduction of the phagocytic pro- 

 perties of the leucocytes. In dogs, small doses of benzol 

 which produce leucocytosis, increase the production of 

 antigoat hemolysins. 



Benzol acts on the elements which elaborate antibo- 

 dies and the leucocytogenic centres take part in this ela- 

 boration. This is demonstrated in rabbits by the redu- 

 ction in number of the leucocytes and in quantity of the 

 antibodies, which does note take place when the benzol 

 is given at the time when the production of antibodies 

 is nearly at its height ; in dogs by the increased forma- 

 tion of lysins which is accompanied by leucocytosis. 



CARREL and INOEBRIGSTEN (1912) ascertained 

 that fragments of bone-marrow and of lymphatic glands 

 cultivated outside the organism are able to produce an- 

 tibodies (hemolysins). 



LUDKE (1912) ascertained the production of agglu- 

 tinins and hemolysins in bone-marrow and pieces of 

 spleen taken from guinea-pigs and rabbits 24, 48 and 

 60 hours after the intravenous injection of killed cultures 

 of B. typhi and B. dysenteriae and kept aseptically in 

 saline solution, solution of RINGER, and normal rabbit 

 and guinea-pig serum at 37o— 40o C. At the 5th day of 

 cultivation the spleen emulsion agglutinated up to 1:160 

 and bone-marrow 1 : 320. 



Inoculating directly in the bone-marrow and killing 

 the animal at the end of 36-48 hours, amputating the fe- 

 mur and cultivating it in the above-mentioned culture 

 media, he was also able to verify the existence of bacte- 

 ricid antibodies and agglutinins in the emulsion of bone- 

 marrow. 



TSURUMI and KOHDA (1913) came io the conclu- 



