J. p. SIMONDS 775 



Some bacterial toxins, on the other hand, may repel leukocytes as shown by Vaillard 

 and Rouget' and others. For example, when tetanus bacilli were injected subcutaneously 

 along with their toxin, leukocytes did not collect at the place of injection; but if these bacilli 

 were washed free from toxin and then injected, the leukocytes did gather and engulf the 

 bacilli. 



Tubercle bacilli also give rise to substances which cause local necrosis of tissues. But 

 they do not produce a positively chemotactic substance. The}', therefore, induce a character- 

 istic type of coagulative necrosis, known as "caseation." In the absence of leukocytes there 

 are no proteolytic ferments in any abundance and the necrotic material of the tubercle is 

 not digested and liquefied. 



Thus although both staphylococci and tubercle bacilli, by the action of their toxic 

 products, cause necrosis of tissues in which they are growing or into which certain of their 

 products have been injected, the type of necrosis in the two cases differs. This is largely be- 

 cause of the difference in their power to attract leukocytes into the tissues affected. The 

 characteristic lesion of the staphylococcus is, thus, a liquefaction necrosis or abscess forma- 

 tion; while the tubercle bacilli induce a coagulative necrosis, or caseation. 



Most bacterial toxic products, whether true soluble toxins or endotoxins, cause a dilata- 

 tion of the capillaries in the tissues with which they come in contact, and probably also alter 

 their walls in such a manner as to render them more permeable. This gives rise to two of the 

 phenomena of the local reaction. In the first place, the dilatation results in a hyperemia or 

 increase in the amount of blood in the affected area. Second, a greater quantity of fluid 

 escapes from these capillaries into the surrounding tissues resulting in edema. Both of these 

 conditions are the basis of the local swelling and redness which follow the injection of 

 bacterial toxic products into the subcutaneous tissues. The irritating effect of these sub- 

 stances on the sensory nerve endings in the inflamed area is one of the causes of the pain 

 which is a constant symptom of inflammation. 



The local effects of sublethal doses of toxic bacterial products depend in part upon the 

 degree of sensitization of the animal to the particular product used. The tuberculin test em- 

 ploj^ed for purposes of diagnosis depends upon this principle.^ 



GENERAL EFFECTS 



Sublethal intoxications with bacterial products produce general effects upon (a) the 

 blood, and (b) upon temperature and metabolism. 



The injection of an animal with sublethal doses of soluble bacterial toxin or of the bodies 

 of killed bacteria, or of bacterial proteins obtained from them by the various means used for 

 this purpose, is foUowed sooner or later by an increase in the number of leukocytes in the 

 circulating blood. But the reaction to such injections varies with the size of the dose and, 

 to a less extent, with the type of micro-organism used. Holmes,^ Ledingham,'' and others 

 have observed this phenomenon after injections of diphtheria toxin. The chemotactic proper- 

 ties of dead bacteria were apparently first observed by Leber in 1888. But it has been shown 

 by Simonds and Baldauf,^ Glintschikoff,* and others that the first effect of intravenous injec- 

 tions of bacteria is a leukopenia. In sublethal injections this leukopenia is only transitory 



' Vaillard, L., and Rouget, J.: Ann. de Vlnst. Pasleur, 6, 3S5. 1892. 

 " See chap, bcxvi in this volume. 



3 Holmes, T. E.: Guy's Hosp. Rep., 59, 155. 1905. 



4 Ledingham, J. C. G.: J . Hyg., 7, 65. 1907. 



5 Simonds, J. P., and Baldauf, L. K.: /. Infect. Dis., 6, 38. 1908. 



' Glintschikoff, W. J.: Virchow's Anh.f. path. Anat., 212, 461. 1913. 



