J. p. SIMONDS 773 



fest. They have the quality of inducing the formation of antibodies which neutrahze 

 the toxin. The pathological changes which they induce are of relatively short dura- 

 tion, for with the development of antitoxins in sufficient quantities they cease to be 

 active. Any damage which they have done to the tissues of the body may be com- 

 pletely repaired. These substances, therefore, do not cause chronic disease nor pro- 

 duce structural changes that become permanent. 



The toxic products that are firmly fixed in the bacterial cells must be liberated 

 by autolysis, bacteriolysis, crushing, and grinding or other means before they can 

 become effective. These endotoxins act immediately without the lapse of an incuba- 

 tion period. They do not induce the formation of antibodies which neutralize their 

 toxicity. An animal that has been repeatedly injected with these substances, or a 

 patient who is the subject of a chronic infection with micro-organisms of this type, 

 has not the power of neutralizing the toxic products. The continuous or intermittent 

 presence of these endotoxins in the animal body may, therefore, induce lesions that 

 are chronic. 



In addition to the type of toxin and the size of the dose, the lethality of a given 

 bacterial poison depends upon various more or less unrelated factors: (i) Most 

 bacterial poisons are inactive when administered by mouth. They are destroyed by 

 the digestive ferments and bacteria of the gastro-intestinal tract.' The toxin of B. 

 botidinns, however, is an exception to this general rule, for it is just as effective and 

 produces as severe symptoms when given by mouth as when injected intravenously. 

 (2) Some animals are not susceptible to the action of certain bacterial poisons. The 

 rabbit is far less susceptible to tetanus toxin than the mouse or the guinea pig. The 

 rabbit's spleen has an affinity for this toxin. In this animal, therefore, a large part 

 of the tetanus toxin is fixed in the spleen and the central nervous system is protected 

 against its action. (3) The effect of tetanus toxin also varies with the body tempera- 

 ture of the animal. A frog injected with this poison and kept in an incubator develops 

 symptoms of tetanus in twelve hours; one injected with this toxin may be kept at a 

 low temperature for a week or more without showing any manifestations of the dis- 

 ease, but, upon then being placed in an incubator, will develop tetanus in an hour.^ 

 (4) Animals may be sensitized to bacterial poison so that a dose which, in a normal 

 animal, would be without effect or at most sublethal will cause death in a short time. 

 Koch early showed that a guinea pig infected with tubercle bacilli could be easily 

 killed with a dose of tuberculin that in a normal animal would be quite harmless. 



EFFECTS OF SUBLETHAL INTOXICATIONS 



The effects of sublethal intoxications with bacterial products may be (i) local, 

 due to the direct action of the bacterial products upon the tissues with which they 

 come in contact, and taking the form of necrosis and of varying degrees and types of 

 inflammation; (2) general, manifested either by alterations in the blood, or by changes 

 in the temperature and metabolism of the body of the animal; (3) focal or metastatic 

 effects which occur in organs distant from the place of entry of the toxin, usually in 

 an organ which is concerned with the excretion of the poison, and manifesting them- 



' For detailed data on this point see Courmont, J., and Rochaix, A.: op. cit., pp. 1073-97. 

 * Meyer, H., and Ransom, F.: Arch.f. e.xper. Path. it. Pharmakol., 49, 369. 1903. 



