Both adult and larval, contain toxins of great virulence, though in.
In 1904 he delivered at the university of California a course of lectures, the object of which was to illustrate the application of the methods of physical chemistry to the study of the theory of toxins and antitoxins, and which were published in 1907 under the title Immunochemistry.
It has been proved that the pyo-genic bacterial toxins, if not too concentrated, will attract the polymorpho-nuclear leucocytes, but if concentrated, may have a repelling influence.
This splitting up of the fats previously combined with albumin in the cell by the action of natural ferments - lipases - and the setting free of the fats under the influence of toxins represent the normal and the pathological process in the production of so-called fatty degeneration.
Hyaline degeneration is found in certain acute infective conditions; the toxins specially act on these connective-tissue cell elements.
Massart and Bordet, Leber, Metchnikoff and others have studied the phenomenon in leucocytes, with the result that while there is evidence of their being positively chemiotactic to the toxins of many pathogenic microbes, it is also apparent that they are negatively influenced by such substances as lactic acid.
What occurs with snake venom takes place also when the toxins are formed by microbes, and a new method of treatment by anti-toxic serums has been introduced of late years with great success.
Amongst these may be mentioned the neutralizing of the toxins in cases of diphtheria, tetanus and poisonous snake-bite; " serum therapeutics "; and treatment by " vaccines."
By the continuous injections under the skin, in increasing doses, of the toxins of certain pathogenic micro-organisms, such as that of diphtheria, an animal-usually the horse-may be rendered completely refractory to the disease.
Of such probably are the toxins and antitoxins of certain infections, which, anchoring themselves not by any means indiscriminately, but to particular and concerted molecules, by such anchorage antagonize them or turn them to favourable or unfavourable issues.
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.
In the mutual behaviour of such cells, toxins, and antitoxins, and again of microbes themselves, we may demonstrate even on the field of the microscope some of the modes of such actions, which seem to partake in great measure at any rate of a chemical quality (agglutinins, coagulins, chemotaxis).
It forms a valuable treatment in diabetic coma and eclampsia, acting by diluting the toxins in the blood.
The toxins produced by microbes, if too weak to destroy the leucocytes, induce them to secrete antitoxins, which not only act as antidotes to the toxins and are injurious to the microbes, but also increase the phagocytic power of the leucocytes (opsonius of Wright).
The presence of toxins in the blood not only affects the brain, causing delirium, but also other organs, the heart and lung, and may cause fatal syncope or respiratory failure.
Weir Mitchell and others have shown that serpent venom consists chiefly of albumoses, and the toxins formed by infective bacilli have a somewhat similar chemical nature.
In one, Haffkine employs the toxins obtained by growing plague bacilli in broth for five or six weeks, and then heating the whole to 65° or 70° C. so as to destroy the bacilli.
Although the anti-toxins which are used in the cure of infective diseases are not dangerous to life, yet they sometimes cause unpleasant consequences, more especially an urticarial eruption almost exactly like that which follows eating mussels or other shell-fish.
Another condition which is probably due to toxins is high pressure within the arteries.
This and similar facts have suggested that some toxins are only produced in the living body.
At once they proceed to make good their hold on the position they have secured by secreting and throwing out toxins which cause more or less injury to the tissues in their immediate neighbourhood.
Lardaceous disease, however, here and in other regions, now appears to be due to the specific toxins of pyogenetic micro-organisms. In stone of the kidney a great advance has been made in treatment by operative means, and the formation of these stones seems to recent observers to depend less upon constitutional bent (gout) than upon unhealthy local conditions of the passages, which in their turn again may be due to the action of microorganisms.
The microbes appear in many cases to attract the leucocytes (positive chemiotaxis), but when very virulent they usually repel the leucocytes (negative chemiotaxis) and excrete toxins which kill the leucocytes.
These facts, and the further knowledge that many bacteria never observed as parasites, or as pathogenic forms, produce toxins or poisons as the result of their decompositions and fermentations of organic substances, have led to important results in the applications of bacteriology to medicine.
Little is known of the mode of action of bacteria on these plants, but it may be assumed with great confidence that they excrete enzymes and poisons (toxins), which diffuse into the cells and kill them, and that the effects are in principle the same as those of parasitic fungi.
Though subsequent researches have on the whole confirmed these results, it is still a matter of dispute whether these proteids are the true toxins or merely contain the toxic bodies precipitated along with them.
Immunity against toxins also became a subject of investigation, and the result was the discovery of the antitoxic action of the serum of animals immunized against tetanus toxin by E.
Though the causal relationship of a bacterium to a disease may be completely established by the methods given, another very important part of bacteriology is concerned with the poisons or toxins formed by bacteria.
These toxins may become free in the culture fluid, and the living bacteria may then be got rid of by filtering the fluid through a filter of unglazed porcelain, whose pores are sufficiently small to retain them.
In other instances the toxins are retained to a large extent within the bacteria, and in this case the dead bacteria are injected as a suspension in fluid.
At this temperature the bacterial bodies are extremely brittle, and are thus readily broken up. The study of the nature of toxins requires, of course, the various methods of organic chemistry.
Brain and kidneys, it may now be stated as an accepted fact that all the important results of bacteria in the tissues are due to poisonous bodies or toxins formed by them.
In the case of the tetanus and diphtheria bacilli, the production of soluble toxins can be readily demonstrated by filtering a culture in bouillon germ-free by means of a porcelain filter, and then injecting some of the filtrate into an animal.
Such toxins being set free in the culture medium are often known as extracellular.
The toxins are here manifestly contained within the bodies of the bacteria, i.e.
The action of these intracellular toxins has in many instances nothing characteristic, but is merely in the direction of producing fever and interfering with the vital processes of the body generally, these disturbances often going on to a fatal result.
In other words, the toxins of different bacteria are closely similar in their results on the body and the features of the corresponding diseases are largely regulated by the vital properties of the bacteria, their distribution in the tissues, &c. The distinction between the two varieties of toxins, though convenient.
Although the formation of toxins with characteristic action can be shown by the above methods, yet in some cases little or no toxic action can be demonstrated.
This, for example, is the case with the anthrax bacillus; although the effect of this organism in the living body indicates the production of toxins which diffuse for a distance around the bacteria.
Regarding the chemical nature of toxins less is known than regarding their physiological action.
The methods used in the investigations were, however, open to objection, and it is now recognized that although organic bases may sometimes be formed, and may be toxic, the important toxins are not of that nature.
A later research by Brieger along with Fraenkel pointed to the extracellular toxins of diphtheria, tetanus and other diseases being of proteid nature, and various other observers have arrived at a like conclusion.
It may also be mentioned that many toxins have now been obtained by growing the particular organism in a proteid-free medium, a fact which shows that if the toxin is a proteid it may be formed synthetically by the bacterium as well as by modification of proteid already present.
With regard to the nature of intracellular toxins, there is even greater difficulty in the investigation and still less is known.
Many of them, probably also of proteid nature, are much more resistant to heat; thus the intracellular toxins of the tubercle bacillus retain certain of their effects even after exposure to ioo° C. Like the extracellular toxins they may be of remarkable potency; for example, fever is produced in the human subject by the injection into the blood of an extremely minute quantity of dead typhoid bacilli.
Certain toxins resemble enzymes as regards their conditions of precipitation and relative instability, and the fact that in most cases a considerable period intervenes between the time of injection and the occurrence of symptoms has been adduced in support of the view that enzymes are present.
The action of toxins is little understood.
It is important that these two essential factors should be kept clearly in view, since the means of defence against any disease may depend upon the power either of neutralizing toxins or of killing the organisms producing them.
In such diseases the bacteria, when introduced into the subcutaneous tissue, rapidly gain entrance to the blood stream and multiply freely in it, and by means of their toxins cause symptoms of general poisoning.
.In still another class of diseases the bacteria are restricted to some particular part of the body, and the symptoms are due to toxins which are absorbed from it.
The effects produced by bacteria may be considered under the following heads: (I) tissue changes produced in the vicinity of the bacteria, either at the primary or secondary foci; (2) tissue changes produced at a distance by absorption of their toxins; (3) symptoms. The changes in the vicinity of bacteria are to be regarded partly as the direct result of the action of toxins on living cells, and partly as indicating a reaction on the part of the tissues.
The action of toxins on various glands, producing diminished or increased functional activity, has a close analogy to that of certain drugs.
A third method is by injections of the separated toxins of a bacterium, the resulting immunity being not only against the toxin, but, so far as present knowledge shows, also against the living organism.
In the development of toxin-immunity the doses, small at first, are gradually increased in successive inoculations; or, as in the case of very active toxins, the initial injections are made with toxin modified by heat or by the addition of various chemical substances.
Immunity of the same nature can be acquired in the same way against snake and scorpion poisons, and against certain vegetable toxins, e.g.
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.
Natural immunity against toxins must be taken into account, and, if Ehrlich's view with regard to toxic action be correct, this may depend upon either the absence of chemical affinity of the living molecules of the tissues for the toxic molecule, or upon insensitiveness to the action of the toxophorous group. It has been shown with regard to the former, for example, that the nervous system of the fowl, which possesses immunity against tetanus toxin, has little combining affinity for it.
Pharmacology is a branch of biology; it is also closely connected with pathology and bacteriology, for certain drugs produce structural as well as functional changes in the tissues, and in germ diseases the peculiar symptoms are caused by foreign substances (toxins) formed by the infective organisms present in the body.
Ludwig Brieger then discovered the toxins of certain infections; and Emil A.