It may be stated that while in certain instances the union of toxin and antitoxin may be reversible, all the facts established cannot be explained on this simple hypothesis of reversible action.
Still another view, advocated by Bordet, is that the union of toxin and antitoxin is rather of physical than of strictly chemical nature, and represents an interaction of colloidal substances, a sort of molecular deposition by which the smaller toxin molecule becomes entangled in the larger molecule of antitoxin.
In view of the fact that antitoxin has a direct action on toxin, we may say that theoretically this may take place in one of two ways.
He found, however, that if he took the largest amount of toxin which was just neutralized by a given amount of antitoxin, much more than a single dose of toxin had to be added before a single dose was left free.
(a) The action of antitoxin on toxin, as tested by neutralization effects, takes place more quickly in concentrated than in weak solutions, and more quickly at a warm (within certain limits) than at a cold temperature.
For example, if 'co doses of toxin were neutralized by a unit of antitoxin (v.
Supra) it might be that 12 5 doses would need to be added to the same amount of antitoxin before the mixture produced a fatal result when it was injected.
Its serum in course of time is found to contain something (antitoxin) which has the power of neutralizing the toxin secreted by the organism when parasitical upon the body.
Toxins may thus become so closely keyed into their corresponding atom groups, as for instance in tetanus, that they are no longer free to combine with the antitoxin; or, again, an antitoxin injected before a toxin may anticipate it and, preventing its mischievous adhesion, dismiss it for excretion.
(The tetanus antitoxin should invariably be employed as well.) Sir Thomas Fraser differs from nearly all other authorities in regarding the drug as useless in cases of strychnine poisoning, and the question must be left open.
In recent years the relations of toxin and antitoxin, still obscure, have been the subject of much study and controversy.
In the earlier experiments on smaller animals the potency of the toxin was modified for the first injections, but in preparing antitoxin for therapeutical purposes the toxin is used in its unaltered condition, the horse being the animal usually employed.
The unit of antitoxin in Ehrlich's new standard is the amount requisite to antagonize i oo times the minimum lethal dose of a particular toxin to a guinea-pig of 250 grm.
(b) Antitoxin acts more powerfully when injected along with the toxin than when injected at the same time in another part of the body; if its action were on the tissue-cells one would expect that the site of injection would be immaterial.
Kanthack and Cobbett, that in certain instances the toxin can be made to pass through a gelatine membrane, whereas the antitoxin cannot, its molecules being of larger size.
His view as to the dual composition of the toxin molecule has already been mentioned, and it is evident that if the haptophorous or combining group has its affinity satisfied by union with antitoxin, the toxin will no longer combine with living cells, and will thus be rendered harmless.
One other important fact in support of what has been stated is that a toxin may have its toxic action diminished, and may still require the same amount of antitoxin as previously for neutralization.
Accordingly, the most actively toxic molecules will be neutralized first, and those which are left over, that is, uncombined with antitoxin, will have a weaker toxic action.
Arrhenius, who hold that the union of toxin and antitoxin is comparatively loose, and belongs to the classof reversible actions, being comparable in fact with the union of a weak acid and base.
If such were the condition there would always be a certain amount both of free toxin and of free antitoxin in the mixture, and in this case also considerably more than a dose of toxin would have to be added to a " neutral mixture " before the amount of free toxin was increased by a dose, that is, before the mixture became lethal.
The origin of antitoxin is of course merely a part of the general question regarding the production of anti-substances in general, as these all combine in the same way with their homo logous substances and have the same character of g toxin.
There are three chief possibilities: (a) that the antitoxin is a modification of the toxin; (b) that it is a substance normally present, but produced in excess under stimulation of the toxin; (c) that it is an entirely new product.
In such a case it has been shown that, without the introduction of fresh toxin, new antitoxin appears, and therefore must be produced by the living tissues.
In antitoxin production this combination takes place, though not in sufficient amount to produce serious toxic symptoms. It is further supposed that the combination being of somewhat firm character, the side-chains thus combined are lost for the purposes of the cell and are therefore thrown off.
It has, moreover, been found that the serum of various animals has a certain amount of antitoxic action, and thus the basis for antitoxin production, according to Ehrlich's theory, is afforded.
In specific germ diseases a similar antitoxin forms, and in cases which recover it counteracts the toxin, while the germs are destroyed by the tissues.
The facts with regard to passive immunity were thus established and were put to practical application by the introduction of diphtheria antitoxin as a therapeutic agent in 1894.
It has been found, for example, that a toxin may pass through such a filter while an antitoxin may not.
The laws of antitoxin production and action are not confined to bacterial toxins, but apply also to other vegetable and animal toxins, resembling them in constitution, viz.
The production of antitoxin is one of the most striking facts of biological science, and two important questions with regard to it must next be considered, viz.
As, however, most of the work has been done with regard to antitoxin production we may consider here the theoretical aspect of the subject.
Ultimately the regeneration becomes an over-regeneration and free side-chains produced in excess are set free and appear in the blood as antitoxin molecules.
In other words the substances, which when forming part of the cells fix the toxin to the cells, constitute antitoxin molecules when free in the serum.
There is therefore strong evidence that antitoxin molecules do exist as part of the living substance of nerve cells.
The development of the immune body with specific combining affinity thus presents an analogy to antitoxin production, the difference being that in lysogenesis another substance is necessary to complete the process.
In those cases due to Shiga's bacillus the ideal treatment has been put at our disposal by the preparation of a specific antitoxin; this has been given a trial in several grave epidemics of late, and may be said to be the most satisfactory treatment and offer the greatest hope of recovery.
Retically there are two possible modes of action: antitoxin may act by means of the cells of the body, i.e.
The probable explanation is that an antitoxin is developed within them.
How does the antitoxin Action of act ?
The explanation generally given is that the nerve and other cells become accustomed to the drug, so that they cease to react, or that an antitoxin is formed which antagonizes the poison, or that the poison is rapidly destroyed in the body.
If, however, toxin be mixed with antitoxin for some time, it can no longer be passed through, presumably because it has become combined with the antitoxin.