ENDOTOXINS 129 



the cellular constituents (receptors) -which bind the haptophure 

 o-roups to the cells, these excessive receptors being secreted into the 

 blood, where they combine with the toxin or enzyme so that it cannot 

 enter into combination with the cells. This "side chain theory" of 

 Ehrlich has been a useful working hypothesis, although it is becoming 

 highly probable that it does not picture the exact method of toxin and 

 antitoxin action."^'* 



Immune substances cannot 1)C produced against ptomdins, or for 

 that matter against the vegetable alkaloids, or against any chemical 

 bodies of knoicn constitution. Another difference between the action 

 of toxins and simpler chemical poisons is, that while with the latter 

 the effects are produced in a very short time after injection, there is 

 a latent period of several hours before symptoms appear after inject- 

 ing toxins. What occurs during this latent period is not fully known, 

 but that there is a latent period suggests a resemblance to enzyme 

 action. An alkaloidal or other chemical poison enters the cell, and its 

 harm is done at once. A toxin combines with the cell, and then, if 

 it produces its effects by an enzymatic alteration of the cellular struc- 

 ture, some time must elapse before the changes are great enough to 

 cause the appearance of symptoms. 



ENDOTOXINS og 



By far the greater number of pathogenic bacteria do not secrete 

 their poisons as toxins into the surrounding medium, although they 

 manifestly cause disease by poisoning their host. Among them are 

 such organisms as the typhoid bacillus, pneumococcus, the pus cocci, 

 cholera vibrios, and many others. If cultures of these organisms are 

 iiltered, the tiltrate will be found to be but slightly toxic (except for 

 the hemolytic poisons), although the bodies of the bacteria after they 

 have been killed by chloroform or other antiseptics are highly poison- 

 ous if injected into an animal. These bacteria, then, produce poisons 

 which do not escape from the cells into the culture-medium, but are 

 firmly held within them. By using various means these intracellular 

 toxins, or endotoxins, can be obtained independent of the bacterial 

 cells. One of these is to grind up the cells, which can be particularly 

 well done if they are first made brittle by freezing at the temperature 

 of liquid air (MacFadyen's method). By very great pressure in the 

 Buchner press the cellular contents can be expressed. They may also 

 be obtained by letting the bacteria autolyze themselves for a short 

 time in non-nutrient fluids (Conradi," et al.) Endotoxins obtained 

 in this way are soluble and highly poisonous, and it is undoubtedly 

 through their action that the characteristic diseases are produced by 

 the bacteria that contain them. Presumably the endotoxins are liber- 



95a See Coca; Jour. Infect. Dis., 1915 (17), 3.51. 



96 See general review by Pfeiffer, Jahresber. d. Innimnitatsforsch.. 1910 (6). 13. 

 97Deut. med. Woch., 1903 (29), 26. 

 9 



