Antiserum

“ It is, however, also accompanied by the appearance of certain bodies in the blood serum of the animal treated, to which the name of anti-substances is given, and these have been the subject of extensive study. It is by means of them that immunity (passive) can be transferred to a fresh animal. The development of anti-substances is, however, not peculiar to bacteria, but occurs also when alien cells of various kinds, proteins, ferments, &c., are injected. In fact, organic molecules can be divided into two classes according as they give rise to anti-substances or fail to do so. ”

“ Why and how does one attack of a certain disease protect against another? When a person is taken sick with one of these diseases, the cells of his body immediately begin to make a substance called antitoxin. We learned something about antitoxin when we were studying diphtheria. In diseases like scarlet fever, measles, and smallpox, in which one attack protects against another, the antitoxin that is formed in the body when you are sick stays there for a long time, in some cases as long as you live. While this antitoxin is present in the blood, the cause of the disease cannot live in the body ”

“ In the third group, the anti-substance, after it has combined with the antigen, leads to the union of a third body called complement (alexine or cytase of French writers) , which is present in normal serum. As a result of the union of the three substances, a dissolving or digestive action is often to be observed. This is the mode of action of the anti-substances in the case of a haemolytic or bacteriolytic serum. So far as bacterial immunity is concerned, the anti-serum exerts its action either on the toxin or on the bacterium itself ”

“ At the end of twenty days’ injections they found they could obtain such a large quantity of anti-rabic substance in the serum of an animal, that even 1 part of serum to 25,000 of the body weight would protect an animal. This process differs from that of Pasteur in so far as that in place of promoting the formation of the antidote within the body of the patient, by a process of vaccination with progressively stronger and stronger virus, this part of the process is carried on in an animal, Babes using the dog and Centanni the sheep, the blood serum of which is injected. ”

“ In order that it may exert this power it requires the presence of a substance normally present in the serum known as “complement.” The development of these “anti-bodies,” though it has been studied mainly in connexion with bacteria and their toxins, is not confined to their action, but can be demonstrated in regard to many other substances, such as ferments, tissue cells, red corpuscles, &c. In some animals, for example, the blood serum has the power of dissolving the red corpuscles of an animal of different species ”

“ When the infectious disease is the expression not of the combined effects of poison and bacteria but of the poison chiefly which enters the blood, the bacteria remaining without as in diphtheria, then the blood changes characterizing the immune state are simpler and consist in the accumulation there of antitoxins that constitute the most perfect antidote to poisons that are known. The condition of immunity produces no demonstrable change in the properties of the phagocytes through which they are better enabled to overcome the poisonous bacteria. ”

“ The increased ingestion of bacteria in active immunity would seem to depend upon the presence of immune opsonins in the serum. These, as already explained, are true anti-substances. Thus the apparent increased activity of the leucocytes is due to a preliminary effect of the opsonins on the bacteria. We have no distinct proof that there occurs in active immunity any education of the phagocytes, in Metchnikoff’s sense, that is, any increase of the inherent ingestive or digestive activity of these cells. ”

“ The question of the value of preventive inoculation is, however, still an open one. So also are other applications of the principles of immunity, as the production of anti-sera for snake-venom, and for the irritant (and perhaps intoxicating) vegetable agent causing hay fever.
I have earlier in this lecture referred to methods of serum diagnosis depending on agglutination or solution of bacteria or on the precipitation of protein. Immunology has recently contributed to medicine another diagnostic method of great value. ”

“ All immunological studies are based on the known fact of the reinforcement of natural resistance to disease, as illustrated by serum therapy in diphtheria and by vaccine therapy in anthrax. The attempts to elucidate the principles underlying these two methods have led to the development of many fruitful hypotheses and theories, and many diagnostic and curative procedures of great value. It was early evident that the explanation of resistance to infection, either natural or acquired, must be sought in the cells or fluids of the body and especially of the blood. ”

“ Here we have the first steps in the direction of serum-therapy, that new treatment of disease which during the last few years has been so prominently before the public in the cure of diphtheria, tetanus, and other maladies, and for the development of which we owe so much to the labours of Behring, Roux, Kitasato, and other investigators.
The astounding fact that the blood of animals which have been trained to artificially withstand a particular disease becomes endowed with the power of protecting other animals from that disease is only in the earliest stages of its application. ”

“ In modern medicine at its best, some substance, such as the diphtheria antitoxin, that is already present in the blood in quantity sufficient under ordinary circumstances to prevent infection, is reënforced in an emergency by more of the same substance prepared in the blood of the horse. Or if that cannot be done, the next best thing is to inject some serum that by a natural reaction will stimulate the body to prepare in excess its own antitoxin or excite the phagocytes to greater exertions in overcoming their enemies. ”

“ His great notebook of observations lay unopened on the library table, and his little gold syringe of anti-fever serum—a clever device of his own, with a self-contained reservoir, attached to a broad gold finger ring, and single-pressure action peculiar to itself—rested idly in a small leather case beside it. Vigor, ambition, and the desire for study and observation seemed to have died within him; and he made no inquiries about his clinic, where hundreds of germ cultures stood in their orderly phials awaiting his attention. ”

“ But in certain directions, notably in regard to the relations with micro-organisms, changes in the blood-plasma can be made out, though they are not associated in all cases with changes in the formed elements which float in it, nor with any obvious microscopical or chemical alterations.
The phenomena of immunity to the attacks of bacteria or their toxins, of agglutinative action, of opsonic action, of the precipitin tests, and of haemolysis, are all largely dependent on the inherent or acquired characters of the blood serum. It is a commonplace thatImmunity. ”

“ Guinea-pigs' serum is that most frequently employed for experimental work.
Hæmolysin (immune body, copula, sensitising body, amboceptor) is a thermostable antibody formed in response to the injection of red cells which although in itself inert is capable of linking up complement present in the normal serum to the red cells of the variety used as antigen—a combination resulting in hæmolysis.
Hæmolysin is obtained by collecting fresh blood serum from a suitably inoculated animal and exposing it to a temperature of 56° C. (to destroy the thermo-labile complement) for 15 to 30 minutes before use. ”

“ As is well known, blood serum possesses, as a rule, a bactericidal power upon most micro-organisms, and we have every reason to believe in the existence of specific substances in the serum which exert some influence upon the growth and development of micro-organisms, and also upon the toxic products they tend to elaborate. These protective substances—the alexins of Buchner—appear to be proteid in nature, resembling globulins, since they are precipitated from serum by the action of certain strong solutions of alkali salts, as sodium sulphate. ”

“ Antibodies in the Blood in Disease.—It is part of the new understanding we have of many diseases that we are able to recognize them by finding in the blood of the sick person substances which the body makes to neutralize or destroy the poisons made by the invading germs, even when we cannot find the germs themselves. These substances are called antibodies, and the search for antibodies in different diseases has been an enthusiastic one. If we can by any scheme teach the body to make antibodies for a germ, we can teach it to cure for itself the disease caused by that germ. ”

“ Such serums are injected subcutaneously in diphtheria, tetanus, streptococcic infections, plague, snake-poisoning, cholera and other similar diseases. They do not as a rule harm healthy men even in large quantities, but when repeated they often cause serious symptoms due to the body becoming more sensitive to the action of the horse-serum in which they are contained. ”

“ It is also accounted for by the germicidal properties of the blood serum.
The resistance of the tissues may in some cases be due to the absence from them of some particular element necessary to the growth of a particular microorganism. This refractoriness varies in every species of animal in its relation to every form of germ. Different individuals of one species also vary in their susceptibility, and even different parts of the body vary in the same individual. The lower animals offer a greater resistance to pyogenic bacteria than do human beings. ”

“ The facts at our command point to the great potential power of the normal organism to resist infection and indicate that the normal body possesses the capacity, on demand, to increase this power beyond the mean value, chiefly by opposing intending infection by hyperleucocytosis and also, probably, by the strengthening of its plasmatic defensive action through the additional soluble alexin substances thrown off by the augmented leucocytes. This defensive mechanism acts in the same manner on all bacterial invaders and is not specially adapted for any one or group of bacteria. ”

“ Antidiph.) , Antidiphtheric Serum, U.S.P. (Diphtheria Antitoxin) .—Serum from a horse properly immunized against diphtheria toxin; has a potency of not less than 250 antitoxic units per Cc.
Action and Uses: Curative and prophylactic agent in diphtheria. The possibility of serum disease must be remembered. Caution should be exercised when antidiphtheric serum is administered to persons who have had asthma, and, above all, “horse asthma.” ”

“ The treatment of diphtheria in man by the antitoxic serum thus obtained has proved to be remarkably successful. Furthermore, if a susceptible person who has been exposed to the infection of diphtheria, is injected with a small dose of antitoxic serum, he becomes temporarily immune, and does not fall a victim to diphtheria. This is a most important point especially for young children, who may already be incubating a disease which but for this prophylactic injection might occur and prove fatal. ”

“ Willmore and Savage think one obtains the best results by injecting from 80 to 120 cc. of a polyvalent serum into the subcutaneous tissues of the flank or abdomen or intravenously. They think that anaphylaxis is less liable to follow a massive initial dose of serum.
In the use of serum Shiga recommends a dose of 10 cc. for a mild case or two injections of 10 cc. at intervals of ten hours for cases of medium severity, while in very toxic cases he uses 60 cc. in 3 daily doses of 20 cc. each. It is important to use serum early as it has little or no effect if used after the 7th day (Klein) . ”

“ The organism has still other ways and means of defending itself. At the time of bacterial infection, certain germ-killing substances are developed in the blood serum. Science has named these defensive proteins ~alexins.~ It has also been found that the phagocyte and tissue cells in the neighborhood of the area of irritation produce antipoisons or natural antitoxins, which neutralize the bacterial poisons and kill the microorganisms of disease. ”

“ The amboceptors so necessary for the destructive action of the serum are produced by the body cells, particularly the leucocytes. The serum assists in pagocytosis by the action on bacteria of substances called opsonins which are contained in it, and the formation of which can be very greatly stimulated. Again, not all inclusion of bacteria within leucocytes is indicative of phagocytosis; in many cases the bacteria seem to find the best conditions for existence within the leucocytes, and these and not the bacteria are destroyed. ”

“ At present the trend of allopathic medical science is undoubtedly toward the serum, antitoxin and vaccine treatment. Practically all medical research tends that way. Every few days we see in the daily papers reports of new serums and antitoxins which are claimed to cure or create immunity to certain diseases. ”

“ The utmost precaution should be observed whenever it become necessary to inject a therapeutic serum in a patient who has been injected with serum before, who is subject to asthma, hayfever, or who shows an idiosyncrasy to horses. The best treatment of this kind, in my opinion, is the vaccination procedure of Besredka. In this method a very small quantity of horse serum is given subcutaneously or even rectally and time allowed for its absorption. The amount absorbed at any time will be too small to cause serious symptoms and yet enough to produce anti-anaphylaxis. ”