220 THE PRINCIPLES OF IMMUNOLOGY 



symptoms identical with those from anaphylatoxin. Bordet found that 

 the action of fresh serum upon agar in solution produces a similar 

 toxic substance. Novy and De Kruif have published very extensive 

 studies upon toxic materials in a measure similar to the anaphylatoxin. 

 It is found that the action of serum upon agar intensifies the toxic 

 power of the agar. They have shown that agar and other non-protein 

 colloids produce anaphylactoid symptoms. 



The poison, if there be such in anaphylaxis, is not dependent on the 

 presence of any antibody or other substance within the cells of the sensi- 

 tized animal, because it can be produced in vitro; neither is it dependent 

 on antigen, inasmuch as barium sulphate and kaolin serve a similar pur- 

 pose; nor is it dependent on complement, for, as Doerr has shown, it 

 can be produced without the action of fresh serum. Besredka maintains 

 that the anaphylatoxin produces no symptoms by sub-dural injection 

 and that it kills only upon intravenous injection. Besredka has found 

 that pepton does not interfere with true anaphylaxis in the guinea- 

 pig, but that it does inhibit the action of anaphylatoxin. Furthermore, 

 the state of anti-anaphylaxis which protects an animal against a massive 

 dose of the antigenic substance and therefore prevents anaphylactic 

 shock has no such protective influence upon anaphylatoxin. These 

 arguments as well as those presented in the subsequent section on the 

 cellular theories of anaphylaxis serve to show that there is prob- 

 ably no poison, which can be produced in -vitro, that leads to the 

 development of a condition identical with true anaphylaxis. Certain 

 features of this discussion will be referred to under the heading of 

 Anaphylactoid Phenomena. 



Cellular Theories. The conflicting views are that either a poison 

 is produced within cells, or that some disturbance of cells appears inde- 

 pendently of the production of a poisonous substance. Gay and 

 Southard, influenced perhaps by the prevailing conceptions of immune 

 reactions and impressed by the cellular degenerations seen in their 

 animals, emphasized the intracellular character of the reaction. They 

 assumed that the injected protein contains a substance, anaphylactin, 

 which is eliminated from the body extremely slowly, in contrast to the 

 fairly rapid elimination of the other constituents of the protein. " The 

 anaphylactin, however, remains and acts as a constant irritant to the 

 body cells, so that their avidity for the other assimilable elements 

 of the horse serum (or protein), which have accompanied the ana- 

 phylactin, becomes enormously increased. At the end of two weeks of 

 constant stimulation on the part of the anaphylactin, and of constantly 

 increasing avidity on the part of the somatic cells, a condition has 

 arrived when the cells, if suddenly presented with a large amount of 

 horse serum, are overwhelmed in the exercise of their increased assim- 

 ilating functions and functional equilibrium is so disturbed that local 

 or general death may occur." This theory was supported by their 

 statement that the sensitizing fraction of serum is contained in the 

 globulin fraction and that the other elements of serum may serve to 

 produce shock. They could not produce a toxic body by mixing the 



