6 THE PRINCIPLES OF IMMUNOLOGY 



tricate, and whilst at present we are disposed to regard the aggressins 

 as extracts of the bacterial proteins and their split products, as well, 

 perhaps, as exotoxic in nature, further study may offer more com- 

 plete and satisfactory explanation of the problem. 



Production of Poisonous Substances. -The virulence of organ- 

 isms depends, to a certain extent, upon the poisonous substances which 

 they produce. Nevertheless, virulence is not necessarily parallel to 

 the capacity for production of these toxic substances. The poison- 

 ous bacterial products may be divided into four groups, namely, the 

 ptomains, which are the result of decomposition of the media upon 

 which the bacteria grow ; the exotoxins or true toxins, which are 

 soluble poisons produced by the life activities of the bacteria and 

 easily absorbed and diffused in the body of the host ; the endotoxins, 

 which develop within the bodies of the bacteria and are liberated 

 probably only upon the death and disintegration of the bacteria ; and 

 poisonous bacterial proteins, which result in large part from the break- 

 ing down of the protein molecules which go to constitute the 

 bacterial substance. 



The ptomains are formed from the decomposition of the media 

 upon which bacteria grow, provided these media are nitrogenous in 

 nature. The ptomains are basic substances formed not from the 

 bacteria themselves, but from the decomposition products of those 

 media which contain nitrogenous material, especially proteins whose 

 nitrogen is in the form of amino-acids. Most ptomains are combina- 

 tions simply of carbon, hydrogen, and nitrogen, and they may be 

 divided into three groups, the first of which includes methylamine, 

 dimethylamine, and trimethylamine ; the second group somewhat 

 more complex, contains putrescin and cadavarin; the third group, 

 the so-called cholin group, contains, in addition to cholin, neurin, 

 muscarin, and betain. The cholin group are derivatives of lecithin. 

 Cholin itself is found in extremely minute amounts in body cells and 

 has a relatively low degree of toxicity. It is a substance which has 

 been the subject of much experiment and hypothesis, but there is 

 no very good reason for believing that it has any great pathologic 

 importance. Neurin may be transformed from cholin, and although 

 somewhat similar chemically, it is highly poisonous. Muscarin is a 

 crystalline alkaloid obtained from poisonous mushrooms, but is also 

 formed by the decomposition of fish; its chemical composition is 

 very closely similar to that of neurin, and it may be prepared syn- 

 thetically from cholin. Both neurin and muscarin produce definite 

 toxic symptoms in man following subcutaneous injection of i to 3 

 milligrams, but when given by mouth approximately ten times this 

 amount are required, indicating that probably the liver breaks up 

 and detoxifies that which is absorbed from the intestine. Betain is 

 a constituent of plant tissues and has a toxicity from one-tenth to 

 one-twentieth that of neurin and muscarin. The simpler ptomains 

 are not extremely toxic. The ptomains as a group are not specific in 

 any sense, except in so far as they are dependent on the chemical 



