110 
ANNALES DE L’INSTITUT PASTEUR 
confronting the lherapeutist is not alone to search for curative 
agents but also to devise ihe means of bringing such remedies 
into intimate relation with the local lésions of disease [1]. 
Expérience lias shown lhat the causes of microbic disease 
are most readily and certainly brought under the influence of 
healing agencies when the parasiles are widely disseminated 
throughout the blood. The operation of quinine against the 
malarial parasites is such an example ; while mercury and 
salvarsan are most effective against syphilitic infection at that 
period in which Treponema pallidum is widely distributed 
throughout the body. Indeed, once the spirochaetae hâve 
become aggregaled into local lésions or in situations lhat are 
more remote from the circulating blood, they are destroyed wilh 
far less certainty. In other words, curative agents dépend for 
their action on aceessibility to the microbic causes of disease. 
Even when the severe elfecls are caused not by the microôr- 
ganisms themselves but by their toxic products, the same rule 
holds true. Diphtheria toxin is readily neutralized by 
diphtheria antiloxin, because it exhibits low affmity for organic 
cells that withdraw it from the blood and awayfrom the sphere 
of action of the antitoxin ; while tetanus toxin, being quickly 
and firmly bound by nerve cells, is far more difficult to bring 
under the neutralizing etfects of tetanus antitoxin. 
The process of destruction of microbes takes place chiefly 
within the tissue spaces and lymph cavities which are eut off 
from direct communication with the blood. Hence ail the 
défensive and curative principles that are contained within the 
blood must leave that fluid in order to reach the true seat of 
disease. This fact is equally true of the phagocytes and of 
dissolved immunity principles or drugs. The phagocytes 
escape from the blood into the local lésion through émigration, 
and the dissolved principles by transudation, two processes 
which are accelerated as the resuit of inflammation that occurs 
about the lésion. But both are nevertheless Jimited by condi¬ 
tions which on the one hand détermine the local qualily of the 
lymph and on the other the supply and extent of émigration of 
the phagocytes. 
The lymph is poorer in protein constituents tlian is the 
plasma of the blood and it is notidentical in composition in the 
