TOXINS AND ANTITOXINS 41 



that they have demonstrated in pneumonic exudates a pneumococcus 

 toxin. A number of other organisms produce lytic bodies for red 

 blood-cells or hemotoxins, such as staphylolysin and megath- 

 eriolysin, capable of inducing the formation of antilysins. A lytic 

 body for leucocytes is also produced by staphylococcus aureus. 



The pathological effects of toxins are fundamentally seen in the 

 production of cloudy swelling and even fatty degeneration of the 

 parenchymatous viscera, heart, vascular muscle, liver, kidney, and 

 secreting glands. Local inflammation at the site of injection, some- 

 times leading to necrosis, is a frequent rinding. Diphtheria toxin 

 may show, in cases of paralysis, myelin sheath degeneration or in- 

 flammation of nerves, and in guinea-pigs usually shows marked 

 congestion or hemorrhage in the adrenals. Botulinus toxin leads to 

 meningeal and even cerebral thrombosis and small hemorrhages. 

 Both botulinus toxin and tetanus toxin have a marked affinity for 

 the nervous system, but the effects are seen in the form of func- 

 tional disturbance rather than morphologically demonstrable change, 

 except for the vascular changes produced by botulinus toxin. 



Formation of Antitoxins. Antitoxins are produced by the re- 

 peated parenteral injection of the toxin. Parenteral injection signi- 

 fies introduction into the body by routes other than absorption 

 through the alimentary canal. The selection of the species of 

 animal to be used depends in part on its demonstrated ability to 

 produce antitoxin and in part in commercial establishments on the 

 possibility of obtaining large volumes of immune serum. It is often 

 found desirable to select a species which has natural immunity to 

 certain toxins and by inoculation raise that immunity to a higher 

 degree. This may be accomplished with less difficulty than if a 

 susceptible species were used. This is true of the use of the horse 

 in producing gas bacillus antitoxin. The same principle is employed by 

 Kyes in using fowl for the production of an anti-pneumococcus 

 serum, although in this case it is not clear that the serum is an anti- 

 toxic serum. Kyes states that the antiserum is antibacterial, i.e., 

 agglutinating and bacteriolytic. Especially in the case of suscep- 

 tible animals and also in relatively immune animals it may be neces- 

 sary either to dilute the toxin to a very high degree or to attenuate 

 it by other means, and thus consume considerable time in develop- 

 ing a high degree of immunity. For immunizing guinea-pigs against 

 diphtheria toxin Behring and Kitasato used iodine terchloride, 

 and Roux and Martin, Lugol's solution. Frankel heated the 

 toxin to 60 degrees. Behring in the case of tetanus toxin used 

 a neutralized mixture of toxin and antitoxin, gradually reduc- 

 ing the amount of antitoxin, and finally using unmodified toxin. In 

 a sense this latter method has been employed by Behring and by 

 Park for producing active immunity to diphtheria in children, al- 

 though here it has been found unnecessary to use pure toxin with- 

 out antitoxin to attain the desired result. It is believed that after 

 injection there is a dissociation of the mixture, which permits the 



