224 ANTITOXINS 



properties of a serum do not always run parallel with its prophylactic pro- 

 perties. To quote a classical instance : antidiphtheria serum is both 

 prophylactic and curative, but antitetanus serum while exhibiting very 

 marked prophylactic properties has no curative properties. These pro- 

 perties of immune serums will be referred to again in more detail, each serum 

 being dealt with in connexion with its corresponding organism. 



SECTION II. ANTITOXINS. 



If an animal be inoculated with progressively increasing doses of a micro- 

 organic toxin it will ultimately become immunized against this toxin, and 

 will be able to tolerate without suffering any inconvenience doses infinitely 

 greater than those which if given in the first instance would have proved 

 fatal (Behring and Kitasato). 



To this general rule there are however a few exceptions and these have been 

 described by Richet as cases of anaphylaxis. 



Richet showed that if a dog were inoculated with a small dose of actino-con- 

 gestine (the poison in the tentacles of sea anemones) it exhibited no ill-effects ; 

 but if 10-20 days after the first inoculation it were re- inoculated with the same or 

 even with a smaller dose than that which before proved harmless the animal 

 quickly died. This result cannot be explained on the theory of an accumulation of 

 toxin because the whole quantity given in the two doses is very much less than that 

 which would be required to produce a fatal result if given in the first instance, and 

 further if the second inoculation be given from 16 days after the first, the animal 

 does not die : the phenomena of anaphylaxis do not appear until about the tenth 

 day. The serum of an anaphylactic dog inoculated into a normal dog produces a 

 condition of hypersensibility immediately after inoculation, and hence the serum 

 of anaphylactic animals contains the substance whatever its nature causing the 

 phenomena of anaphylaxis (Richet). 



Other instances of anaphylaxis may be quoted. If an animal be inoculated once 

 with the serum of another species it is only rarely and then inconstantly that any 

 untoward symptoms develop, but if successive re-inoculations be made the result 

 is quite different, the reaction on the part of the inoculated animal being then very 

 violent and likely to terminate fatally (Arthus). This phenomenon is seen for 

 example when rabbits or, better, guinea-pigs, are repeatedly inoculated with horse 

 serum. According to von Pirquet and Schrick the grave symptoms occasionally 

 observed in the human subject after injections of antidiphtheria serum are of 

 an anaphylactic nature. 



Anaphylaxis in connexion with tuberculosis has also been the subject of experi- 

 mental observation. The reaction to tuberculin is an anaphylactic phenomenon : 

 the inoculation of a trace of tuberculin into man or an animal affected with tuber- 

 culosis sets up a severe reaction (vide Tuberculosis) and numerous methods of 

 diagnosis are based on this reaction. 



Still further examples of anaphylaxis could be given but it must suffice here to 

 have drawn attention to the existence of this phenomenon. To investigate the 

 mechanism of anaphylaxis and to discuss the theories which have been advanced in 

 explanation of it would be altogether beyond the scope of the present work. 



The serum of animals which have survived the inoculation of repeated and 

 increasing doses of toxin has acquired antitoxic properties. 



Antitoxin, like toxin, has its nature altered by being heated, is precipitated 

 by alcohol, and is carried down by precipitates formed in the liquid in which 

 it is in solution. In suitable quantities it saturates toxin both in the tissues 

 and in vitro. In mixtures in vitro toxin is not destroyed by antitoxin but is 

 simply disguised ; the toxin-antitoxin mixture is nevertheless harmless to 

 animals, though under certain conditions the poisonous nature of the toxin may 

 be made to reappear ; thus, if a neutral mixture of snake venom and anti- 

 venomous serum be heated to 70 C. the antitoxin is destroyed but not the 

 toxin so that the mixture is now no longer harmless. 



