PRINCIPLES OF ANAPHYLAXIS 223 



bring on characteristic acute symptoms which may terminate fatally. 

 The picture of hypersensitiveness or " serum sickness" in man, as described 

 by v. Pirquet and Schick, is classical. Other investigators who deserve 

 merit for work in this field are Arthus, Otto, Rosenau, Anderson, Kraus, 

 Doerr, Besredka, Weichardt, Wolff-Eisner, Friedemann, Friedberger, H. 

 Pfeiffer, Schittenhelm. 



It is through their efforts that the close relationship between hyper- 

 sensitiveness and immunity is more clearly understood. Like the state of 

 immunity, anaphylaxis is either spontaneous or acquired. It is also specific, 

 that is a guinea-pig made sensitive toward horse's serum will react only 

 when again treated with horse's serum but not when receiving rabbit's or 

 human serum. 



A classical anaphylaxis experiment may be carried out as follows. A 

 guinea-pig receives a subcutaneous injection of o.ooi to o.oi c.cm. of horse 

 serum and after three weeks an intravenous injection of 3 to 5 c.cm. is 

 repeated. This quantity, which under normal conditions has no influence 

 upon the animal, will now produce very alarming symptoms or even death 

 in a couple of minutes. 



There are several factors upon which the occurrence of the anaphylactic 

 phenomena strictly depends. 



(a) The first, preparatory, or sensitizing dose must enter the system 

 in some way other than through the gastro-intestinal tract. Only ex- 

 ceptionally does hypersensitiveness arise if the antigens are given per os. 



(b) The quantity of antigen is of the utmost importance. The smallest 

 amounts of proteid suffice, e.g., o.oooooi c.cm. serum. As aruleo.ooi to 

 o.oi c.cm. are employed. 



(c) An incubation period (the preanaphylactic state) is always neces- 

 sary. This period varies in the widest degree, but depends primarily 

 upon the amount of antigen first injected. 



With guinea-pigs, it is never less than seven days. If o.oi to o.i c.cm. serum is 

 injected, symptoms may usually be stimulated after ten days. Very large doses as 

 well as very minute ones increase the length of the preanaphylactic state very mark- 

 edly (as long as three months). 



(d) The susceptibility of the various animal species differs greatly. 

 The most suitable is the guinea-pig, the rabbit far less so. 



(e) The actual anaphylactic shock is dependent upon the quantity of 

 the second dose injected and the mode of injection. The intravenous path 

 of a massive dose is the most reliable; then comes the intraperitoneal and 

 then the subcutaneous method. While with the intravenous procedure 

 the final result is usually death, this is almost never so with the subcuta- 

 neous injection. Here the anaphylaxis expresses itself in a more marked 

 local inflammation, edema and eventually necrosis. 



