124 CHEMISTRY OF BACTERIA AND THEIR PRODUCTS 



identical processes, which consist in an overproduction of the cellular 

 constituents (receptors) which bind the haptophore groups 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 combi- 

 nation" with the cells. This "side chain theory" of Ehrhch 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 be produced against ptoma'ins, or for 

 that matter against the vegetable alkaloids, or against any chemical 

 bodies of known 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 injecting 

 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 enz3'matic alteration of the cellular struc- 

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

 cause the appearance of symptoms. 



Endotoxins" 



By 'far the greater number of pathogenic bacteria do not secrete their poisons 

 as toxins into the surrounding medium, aUhough they manifestly cause disease by 

 poisoning their host. Among them are such organisms as the typhoid bacilhis. 

 pneumococcus, the pus cocci, cholera vibrios, and many others. If cultures of 

 these organisms are filtered, the filtrate will be found to be but slightly toxic 

 (except for the hemolytic i)oisons). although the bodies of the bacteria after they 

 have been killed by chloroform or other antiseptics are highly poisonous if injected 

 into an animal. These bacteria, then, produce poisons which do not escape from 

 the cells into the culture-medium, but are firndy 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 particu- 

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

 liquid air (MacFadyen's method). By very great ])ressure in the Buchner press 

 the cellular contents can he expressed. They may also be obtainctl by letting the 

 bacteria autolyze themselves for a short time in non-nutrient fluids (Conradi,^" 

 et ai). 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 liberated in the 

 body either by autolysis, or by heterolysis by the enzymes of the body cells and 

 fluids, and there is some (luestion as to whether they are preformed specific con- 

 stituents of the bacteria, or merely the jjoisonous ])roduct of enzymatic disintegra- 

 tion of the ba(!terial i)roteins, similar to the "anaphylatoxins."^' 



Endotoxins differ from the true toxins in one imj)ortant respect: namely, it is 

 difficuU or impossible to obtain an antitoxin for endotoxins by immunization of 



<« See Coca, .lour. Infect. Dis., 1915 (17), ;J51. 



*• See general r(>view by I'feifTer, Jahresber. d. Immunitatsforsch., 1910 (ti), 13. 

 "0 Deut. med. Woch., \\)0A (29), 2ti. 



"See Dold and llanau, Zeit. Immunitat., 1913 (19), 31; Zinsser, "Infection 

 and Resistance," N. W, 1911, ("Iim]). xvii. 



