Page images
PDF
EPUB

severe blows against the theory of phago- ever, that when an injection of foreign cytosis.

Since the bacteria which liberate a soluble toxin seem to be but few in number, it had become evident from much work done along these lines that antitoxin immunity could be accomplished in but a few of the diseases, the lines of research being indicated more towards the formation of bacterialysins or substances which would cause a solution of the bacteria themselves. Hence, Pfeiffer's work was especially valuable. He found that bacteriolysis could be made to take place in the peritoneal cavity of a non-immune guinea pig if a small amount of immune serum (and which could not cause this lysis alone) was added. Immune serum. which has been robbed of its power in this direction by heat could also be reactivated in the peritoneal cavity of the non-immunized guinea pig. Pfeiffer concluded that this reactivation was due in some manner to the endothelial cells of the peritoneal cavity.

Metchnikoff soon afterwards showed that Pfeiffer's phenomenon could be made. to take place in vitro and thus independent of the peritoneal cavity, and Bordet notably increased the knowledge of this subject by showing that this bacteriolytic action was due to the presence of two substances, one present in the serum of the immunized animal and one present in the serum of the healthy animal. In one case Bordet added a drop of human serum to the immune serum of the guinea pig and thus completed the bacteriolysis.

This demonstration that a bacteriolytic serum is composed of two parts neither of which is active without the other marks the next great advance in bacterial immunity.

The ocular demonstration of bacterialysis without the intervention of the leucocytes, seemed to have given the death blow to the theory of phagocytosis. Metchnikoff was soon able to show, how

liquids was made into the peritoneal cavity, it caused the leucocytes to mass together on the omentum and that many of them were severely injured and had allowed their digestive fluid to escape into the peritoneal liquid. To this injury of the phagocytes he applies the term phagolysis. The digestive fluid he called cytase, microcytase or marcocytase as the case may be. It is the equivalent of Ehrlich's compliment or Bordet's alexin as we shall see later. According to Metchnikoff, it is the extracellular working of the digestive ferment of the leucocytes which causes the bacteriolysis in Pfeiffer's phenomenon. He further showed by using some experiments of Issaef's that when the phagolysis is suppressed or at least diminished, as it may be by a previous injection of physiologic salt solution or bouillon, that then the cholera spirilla which were injected were promptly englobed and digested by the leucocytes.

Broadly speaking, pathogenic bacteria may be divided into two classes in reference to their secretion of toxins; first, those which secrete a soluble toxin the absorption of which leads to the production in the body of the host of antitoxin, of which there are but four examples,-— tetanus, diphtheria, boutoulism and pyocyaneus infections-(this latter of experimental interest only) and secondly those bacteria which contain endotoxins or toxins which are so bound up in the bacterial protoplasm that all attempt to create antitoxins for this class of bacteria have failed up to the present time. This latter classification includes practically all of the pathogenic bacteria except the four mentioned above.

For the practical application of bacterial immunity as apart from antitoxin immunity, it is of paramount importance to know what effect an active bacteriolytic serum would have on the human system. In causing a solution of its specific bac

teria, would it set free the endotoxins and thus add to the patient's burden or would these thus liberated endotoxins be neutralized? Pfeiffer in his second communication on these antibodies showed that a too sudden and great disintegration of the cholera spirillum killed these animals; i. e., cholera serum which is bacteriacidal does not protect against cholera toxin. But as this bacteriacidal property is developed to some extent in human subjects convalescent from cholera it would seem to play a part, at least, in acquiring immunity.

Whether the endotoxin bacteria act by secreting a toxin which is soluble in the animal system and not in any of the known media of the laboratory is a question not yet settled. Pfeiffer has demonstrated in the cholera spirilla certain toxins which are liberated only when the spirilla die, and the theory has been advanced that the death and disintegration of these bacteria with the consequent liberation of endotoxin is what causes the systemic damage. If this be true, when the therapeutic application of bacteriolytic sera comes into play, it will be necessary to have an antitoxin serum as well to neutralize the liberated endotoxins.

When more light has been thrown on this complex problem, it may be found that the substance termed by Metchnikoff the preventive substance plays a very important part in bacterial immunity.

Before leaving the subject of bacterial immunity, it is in order to state that Wright and Douglas claim that phagocyton is always preceded by the action of certain humoral substances called by them opsonins which act on the bacteria themselves and thus prepare them for englobement and digestion by the phagocytes. We have not yet heard from Metchnikoff on this subject.

While this work was being executed with reference to bacteriolytic serum Ehrlich had in the meantime turned his

[merged small][merged small][ocr errors][merged small][merged small][merged small][merged small][merged small][merged small][merged small]

function it is normally to assimilate nourishment. This assimilation occurs by means of certain atom groups in the nourishment molecule which exactly fit or correspond to the receptor cell to which it becomes anchored. Ehrlich assumes toxins to be divided into two groups, a haptophore or joining group and a toxophore or poisoning group. He further assumes that the receptor cells above mentioned are likewise provided with a haptophore or combining molecular group which fits exactly with the haptophore group of the toxin molecule (Fig. 1). When the haptophore group of the toxin has united with the haptophore group of the receptor cell the poison of the toxin. is carried within the cell to destroy it, or it may be but to damage it. In the latter case, according to Weigert's theory of tissue equilibrium and repair which Ehrlich accepts as fundamentally true, the damaged cell is stimulated not only to a

instance Bordet applied the term sensabilizing substance to the specific body formed during immunization and used Buchner's old term alexin to designate the normally present substance which he regards as a sort of ferment with digestive powers.

Ehrlich, taking into consideration the above facts, together with the deductions.

Zymotox Group.
Compliment
-Haptophore roup.

re-production of the damaged haptophore Receptor

group but to an over-production of the same. This surplus of haptophore groups thrown into the circulation is what Ehrlich regards as antitoxin.

This theory was originally devised by Ehrlich to explain antitoxin immunity but was further extended by him to elucidate the action of bacteriolytic and other cytolytic sera. The pioneer work in the production of a hæmolytic serum had been done by Belfanti and Cambone who showed that when a horse was injected with the blood cells of a rabbit, the horse serum became toxic for the rabbit, and particularly by Bordet, who showed that if the blood cells of one animal were injected into another, the serum of this latter animal became hemolytic or dissolved the blood cells of the former animal. Bordet further showed that this dissolving action was due to two specific components, just as he had shown was the case with the bacteriolysins of cholera in Pfeiffer's phenomenon. In the present

cell.

Immune Body
Amboceptor or
Interbody.

Compliment.

-com

om plimento plule Ambocept group. cy tophile group Haptophgroup

Bacterium

FIG. 2.

Receptor of the third order. Schematic representation of how compliment is linked to bacterium or cell. After Ehrlich.

from a series of the most profound researches as to the nature of hæmolysins made by himself and Morgenroth, further extended his receptor theory to account for the production and action of these specific antibodies. For the term sensabilizing substance, Ehrlich substituted the words immune body or amboceptor when

this substance was formed by specific immunization, using the term inter body or intermediary body to apply to the normally present substance which link the foreign cell and the compliment in some cases. of natural hæmolysis. For the term alexin, Ehrlich substituted the word compliment.

When a foreign cell, e. g., the red blood cells of one animal, animal A, is introduced into the body of an animal of another species, animal B, the haptophore cell group of the invading blood corpuscle unites with the haptophore group of certain receptor cells and stimulates them to a production of the antibodies called by Ehrlich amboceptors. Instead of being a body with a single combining affinity as in the case of the antitoxins, this substance in the case of the cytolytic or hæmolytic sera has a double combining affinity, joining on the one hand with the haptophore group of the blood cell and on the other hand with the haptophore group of the compliment. Or, to express it in the nomenclature of modern immunity, we say the amboceptor has cytophilic and complimentophilic affinities. (See Fig. 2.)

The compliment, or the body which actually causes the solution, is normally present in the serum. This body according to Ehrlich's theory is divided into a haptophore group and a zymotoxic group (Fig. 2). The latter group constituting the actual dissolving power of the compliment. The compliment is not increased. during immunization, but to repeat, is the substance normally present in the plasma, although Flexner and others have shown that the amount of compliment may vary greatly under certain circumstances, which fact has a direct bearing on resistance to infections.

To go back to the injection of the red cell. When enough injections have been made to stimulate the production of an abundance of amboceptors in the body of animal B the blood of this animal is said.

[ocr errors]

to be hæmolytic for that of animal A. That is, it will dissolve its corpuscles either in the test tube, or, if the blood of animal B is injected into animal A, animal A dies, owing to a solution of its corpuscles intra vitam. The amboceptors formed during immunization have joined the ever present ferment-like compliment with the haptophore group of the blood cells and thus caused their destruction. Thus, according to this theory of Ehrlich's, we have a rational explanation of the mechanism of immunity in Pfeiffer's phenomenon of bacteriolysis. The immunizing process has resulted in the production of amboceptors against the cholera spirillum and these amboceptors uniting the haptophore group of the compliment with the haptophore group of the cholera spirillum, thus enables the zymotoxic group to be brought into play.

Not only may red blood cells be immuinzed against, but there has been a most astonishing array of other body cells and tissues for which these cytotoxic sera have been prepared. Metchnikoff and Delezenne prepared a serum which was solvent for the leucocytes of animals, leucotoxin, by injecting of bone marrow and mesenteric glands. It may be of interest to recall that Metchnikoff believes the atrophy of old age to be due to the activity of the macrophages or the phagocytes chiefly concerned in attacking animal cells, and to overcome this he tried to make a leucotoxin against these phagocytes, but a leucotoxin which acted on the macrophages was found to act on the microphages or the phagocytes chiefly concerned in attacking the bacterial cell as well, so this method of attempting. to counteract this malevolent phagocytosis had to be abandoned. The unusual activity of the macrophages in senile atrophy is attributed by Mechnikoff to the absorption of certain toxic substances for the alimentary canal.

Cytotoxins for spermatazoa and epi

thelium have been prepared and Wasserman suggests that in antiepithelial sera we may eventually construct cytoxic sera for pathologic epithelium as in carcinoma.

Cytotoxins against liver, kidney and brain cells have been prepared. The neuretoxins, e. g., of Metchnikoff and Dele"zenne were obtained by injecting emulsion or dog's brain and cord into ducks. The serum of these ducks injected intra cerebrally into dogs caused their death at once in half c. c. doses; more diluted doses caused paralysis and epileptiform convulsions.

Before leaving this phase of the subject, it may be stated that by immunizing with the various cytotoxins thus obtained anti-cytotoxins may be evolved which will inhibit or neutralize the action of the various cytotoxins.

ing committee: Drs. P. F. Gildea, Will H. Swan and W. A. Campbell.

There being no further business, the members gave attention to a very excellent talk by Dr. Charles A. Powers of Denver, under the title "Remarks on the Surgery of the Bile Passages," which was very ably discussed by Drs. W. A. Campbell, P. O. Hanford, D. P. Mayhew, Charles F. Stough, George A. Boyd, P. F. Gildea and H. W. Hoagland.

After the meeting lunch was served in the private dining room of the hotel.

M. P. REYNOLDS, Secretary.

The Las Animas County Medical Society met March 2 at the office of Dr. D. F. Dayton, with nearly all members present.

The meeting was one of the most interesting which has been held for some time, being marked by the great number of cases reported and spirited discussions entered into by every member present.

Dr. A. Freudenthal, the essayist of the evening, read a paper entitled "Points of Greatest Interest to the General Practitioner in Urinary

discussed the subject, especially those of common use and their importance in diagnosis.

BEN B. BESHOAR, Secretary.

Furthermore, when normal serum which contains compliment, is injected Examinations," in which he very thoroughly into animals, anticompliment is formed. This anticompliment when mixed with a hæmolytic serum will prevent its action. because it joins with the compliment present, making the so-called deviation Ablenkung-of the compliment.

(CONCLUDED NEXT MONTH.)

CONSTITUENT SOCIETIES

The regular monthly meeting of the El Paso County Medical Society was held at the Antlers, Colorado Springs, on Wednesday evening,

March 14, 1906.

There was an excellent attendance of members and several visitors.

The following named were elected to membership in the Society: Drs. John H. Ferguson, Paul M. Lennox and Elmer Lee Timmons.

In compliance with the request of the Committee on Scientific Work of the State Society, contained in their letter of March 10, regarding the appointment of a committee to select representatives of each society for a place on the program of the state meeting, to be held in October, the President appointed the follow

Larimer County Medical Society. Regular meeting convened in City hall. Present, Drs. McHugh, Kickland, Kerlin, Gilbert, Replogle, Upson, Sadler and Stuver; also Drs. Call and Ringle of Greeley, representatives of the Weld County Medical Society. Dr. Upson, Vice President, occupied the chair.

After reading and approval of the minutes, the application of Dr. A. W. Roth for membership in the Society, was considered, and Dr. Roth unanimously elected. The committee on Local Medical Directory, to be published in our city papers, reported that a rate of one hundred dollars a year had been received from each of the three city papers, for a column space each week, the column to be under complete control of the medical society. This proposition was accepted, and Dr. Stuver was elected editor and authorized to name two associate editors. He named Drs. Roth and Upson.

Drs. Call and Ringle, representatives of the Weld County Medical Society, then presented a series of papers on the state medical licensure law of Colorado and the way in which it is being carried out by the State Board of

« PreviousContinue »