Notes on the Leucocyte-Reaction during the Immunisation of the Horse and Goat with Diphtheria Toxin
Authors: Ledingham J. C. G. 
Published: May 2009

It must be clear then from the above data on the horse and goat that the inoculation of diphtheria toxin produces a definite leucocytic reaction of polynuclear type. In fact the detailed evidence speaks more clearly in favour of a leucocytic reaction than Besredka's own results on the goat which he immunised. The question then arises: How are we to interpret the contradictory conclusions reached by Nicolas and Courmont? Metchnikoff (1905), while referring to the work of these authors in his Immunity in Infectious Diseases, maintains that a slight leucocytic reaction is apparent from their own figures and especially from the figures obtained in the early hours succeeding an injection. Of course, Nicolas and Courmont considered these slight changes to be negligible.It seems to me, that the reason must be sought in the method of immunisation employed.Nicolas and Courmont immunised their animals with very small doses many times repeated, and by such a method it was doubtless possible to reduce local swelling to a minimum. With no local reaction it would seem quite reasonable to expect an absence of general leucocytic reaction, but, as Metchnikoff maintains, such local tumefaction is never absent in horses which are subjected to increasing doses of toxin and which ultimately develop high grade antitoxin.Throughout the immunisation of the animals detailed in the foregoing paper local swelling and oedema invariably followed the injections except in the earlier stages of immunisation when small doses were being given.There is no doubt that, in order to produce a high degree of immunity in an animal, the stimulation must be sufficient. A certain small degree of immunity may always be reached without much leucocytic change, as was apparent in the early stages of “Plug's” immunisation.It must be admitted, however, that, though the leucocytic reaction may be extremely marked after large doses of toxin, it does not necessarily follow that the antitoxin development will be correspondingly influenced.Such a phenomenon was apparent in the case of "Plug," a relatively refractory horse.In the more responsive horses, a parallelism between leucocytic reaction after large doses and increased antitoxin development would certainly be expected, without, however, inferring a causal relationship between these two phenomena. We cannot therefore admit the general applicability of Nicolas and Courmont's views, which merely indicate that cells subjected to small oft-repeated doses lose their power of reaction.On the other hand there is probably no justification for the criticism brought forward by Besredka with regard to the results of Nicolas and Courmont, viz. that in the absence of antitoxin development, an absence of leucocytic reaction was to be expected.We may therefore conclude that the leucocytic reaction of polynuclear type which follows the injection of large and increasing doses of diphtheria toxin is merely an evidence of efficient cellstimulation and may not necessarily be accompanied by increased antitoxin development.