73 



■sion that the spleen is the most important site of pro- 

 duction of complement fixing antibodies and that it al- 

 ready contains them 20 hours after immunisation ; the 

 production in bone-marrow and lymphatic glands is not 

 as pronounced as in the spleen, and the quantity found 

 later is also less. 



LIPPMANN (1914) studied the influence of thorium 

 X, and arsenical compounds on the graphics of antibo- 

 dy production. In animals previously immunised and 

 allowed a month's rest, he found an increase of the 

 agglutinins (B. typhi) in the serum surpassing the pre- 

 viously attained maximum after an application of thorium 

 X (about 1 1/2 electrostatic units per kilogramm of weight). 

 This he attributes to a stimulating influence of thorium 

 on the bone-marrow. Entirely similar researches carried 

 out with antibodies of the nature of amboceptors (hemo- 

 lysins^ gave negative results ; neither by the application 

 of thorium X, nor by the application of salvarsan, which 

 has also a distinctly stimulating action on bone-marrow, 

 did he obtain any modification in the graphics of hemo- 

 lysin production. Animals (mice) injected with bone-mar- 

 row-stimulating substances ("salvarsan and thorium X) 

 resist an infection (cultures of pneumococcus) lethal to 

 controls. 



SIMONDS and JONES (191ÓS made researches on 

 the influence of benzol on the production of antibodies; 

 this substance exerts a decidedly noxious action on the 

 blood forming organs, specially on the bone-marrow 

 They noticed a lowering in the graphics of the produ- 

 ction of hemolysins, agglutinins and opsonins as compa- 

 red with controls ; this reduction was most accentuated 

 in the case of hemolysins and least in that of opsonins. 



SIMONDS and JONES (1915) investigated the modi- 

 fications in the production of antibodies, on the one 

 hand in rabbits subjected to the action of X rays, which 

 have a specific destructive action for lymphadenoid 

 tissue, on the other hand on animals treated wifli benzol, 

 which exerts a specific destructive action on the bone- 

 marrow. The action of X rays is not as specific as was 

 supposed; since HEINKE demonstrated that it also pro- 

 duced lesions in the bone-marrow, a fact which ought 

 to be taken into account when reading SIMONDS and 

 JONES results. These are as follows : a) the formation 

 of agglutinins in animals exposed to X-rays is marke- 

 dly reduced, though not as much as in rabbits inocula- 

 ted with benzol; b) bacteriolysin-formation does not ap- 

 pear to be much influenced by exposure (o x-rays ; c) 

 there is no perceptible modification in the contents of 

 the se rum in opsonins and of the complement-fixing 

 power in rabbits exposed to X —rays. 



HEKTOEN (1918), who stands for the formation of 

 the antibodies by the blood forming organs, ascertained 

 that the esposure of animals to X- rays harmed consi- 

 derably and sometimes even prevented entirely the for- 

 mation of antibodies, when carried out at the time of 

 the injecting of antigen, having, on the contrary, no 

 effect wlien the injection was made at the time when 

 the production of antigens was at its height ; a similar 

 resistance was shown by animals inoculated with benzol 

 ni tlie period of active production of antibodies. 



Experiments of HEKTOEN (1920) seem to indicate 

 clearly that, after the process of formation of aniibodies 

 is well on its way, splenectomy has little or no influen- 

 ce of the contents of the serum in antibodies, although 

 at times, its effect was uncertain and variable ; thus in 

 a rabbit after the injection of a big dose of sheep blood, 

 splenectomy has little or no effect on the production of 

 antibodies ; on the other hand if it is carried out on the 

 same animai, even many weeks beforehand, it has an 

 influence on the formation of precipitins. 



MORESCHI and VOTKY and HOWELL (1920) 

 observed the absence of agglutinin and opsonin forma- 

 tion (HOWELL) in patients of leukaemia in which lesions 

 of the bone-marrow are intense. 



An argument in favour of the formation of aggluti- 

 nins by haematopoietic organs and specially by the bone- 

 marrow, consists in the regeneration of the blood pro- 

 voked in immunised animals, by repeated bleedings and 

 accompanied by an increased production of anybodies. 

 This fact was establiahed by HAHN and LANGER ; the 

 authors who reproduced their technic did not confirm 

 their results. It seems, however, that these depend on 

 the oppoituness of the bleeding, for JOTTEN (1920/., 

 who was unable to obtain any results with HAHN and 

 LANCER'S technic obtained an increase of 40 to lOO 

 times (according to wheth.er the results were read after 

 2 or after 24 hours) ou the title of the serum in agglu- 

 tinins (B. typhi), by bleeding rabbits of 5 or of 20 cc, 

 from the second day of inoculation. 



Intravenous injei tions of chlorides of manganese, ni- 

 ckel, cobalt aud zinc produce a marked and rapid in- 

 crease in the concentration of agglutinins and diphteri* 

 antitoxin (WALBUM, 1921). 



5") Organs other than the blood- 

 forming ones also influence the produc- 

 tion of antibodies. 



M'GOWAN (1909), studying the lesions of the organs 

 of rabbits inoculated with chicken red-blood corpuscles, 

 noticed an acunmlation of theses injected corpuscles in 

 tha sinusoids of the liver, to a greater extent than in 

 any other organ and lasting much longer ; he thought 

 this accumulation in the Hver, together with the known 

 phagocitic activity of the hepatic cells and their well- 

 known action on the products of digestion, reinforced the 

 idea that the liver was the seat of the formation of anti- 

 bodies. These are very imsubstantial facts to siipporj 

 such an assertion. 



NOLF and .MULLER (1911) are of the opinion that 

 natural cytolysins (normal alexins and amboceptors^ have 

 their origin somewhere about the liver. Their principa! 

 experiments try to demonstrate the prompt disappearan- 

 ce of natural complement and amboceptors after the 

 suppression of the hepatic circulation, and their persis- 

 iance after an extreme traumatism, sucli as the extirpa- 

 tion of all the abdominal organs with the exception of 

 the liver, provided the Utter remain physiologically (fun- 

 ctionally) intact, as also the poEsibility of increasing the 



