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the other, the theory of serum immunity. The mass of experimental work which poured from the laboratories of the two countries in attack and defence became so great that it could not easily be followed. It had a good influence because, without the stimulation of this national rivalry, the knowledge which gradually arose from this work would not have been so quickly acquired. It is interesting that the mode of action of the serum in destroying bacteria was demonstrated not by a German but by Bordet, a French observer and a pupil of Metschnikoff. He showed that the serum contained two distinct substances, each necessary for the destructive action. The separate action of these substances can be studied since one is thermolabile, or destroyed by heating the serum to one hundred and thirty-three degrees; the other thermostabile, or capable of withstanding a greater degree of heat. These substances are known only by their effect, they have never been separated from the serum. The thermostabile substance, or amboceptor, as it is generally called, has in itself no destructive action on the bacteria; but in some way so alters them that they can be acted on by the thermolabile substance called complement whose action is destructive. The amount of amboceptor may increase in the course of infection and its formation stimulated, the amount of complement remains unchanged. The action of the amboceptor is specific, that is, directed against a single species of bacterium only; the destructive power of the blood may be very great against a single bacterium species and have no effect on others. There seem naturally to be many different amboceptors in the blood, and the number may be very greatly increased. It has been shown as a result of the work of many investigators that the shield has two faces,—there is destruction both by cells and fluids and there is interaction by both. 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.

So far it has been shown that the best defence of the body is, as is the best defence in war, by offensive measures, as illustrated by phagocytosis and destruction by the serum. Both of these actions can be increased by their exercise just as the strength of muscular contraction can be increased by exercise, and the facility for doing everything increased by habit. Certain of the infectious diseases are, as has been said, essentially toxic in their nature, and in cultures the organisms produce poisonous substances. By the injection into the tissues of such substances the same disturbances are produced as when the bacteria are injected. Such a disease is diphtheria. In this there is only a superficial invasion of the tissues. The diphtheria bacilli are located on the surface of the tonsils or pharynx or windpipe, where, as a result of their action, the membrane so characteristic of the disease is produced. The membrane may be the cause of death when it is so extensively formed as to occlude the air passages, but the prominent symptoms of the disease, the fever, the weakness of the heart and the great prostration are due not to the presence of the membrane, but to the action of toxic substances which are formed by the bacteria growing in the superficial lesions and absorbed. Tetanus, or lockjaw, is another example of these essentially toxic diseases. The body must find some means of counteracting or destroying these injurious toxic substances. It does this by forming antagonistic substances called antitoxines, which act not by destroying the toxines, but by uniting with them, the compound substance being harmless. It has been found that the production of antitoxine can be so stimulated by the injection of toxine that the blood of the animal used for the purpose contains large amounts of antitoxine. The horse is used in this way to manufacture antitoxine, and the serum injected into a patient with diphtheria has a curative action, a greater amount being thus introduced than the patient can manufacture.

Fig. 18—Diagram To Illustrate Ehrlich'S Theory Of Antitoxine Formation. The surface of the cell (n) is covered with receptors some of which (b) fit the toxine molecule, (a) allowing the toxine to act upon the cell. Under the stimulus of this the cell produces these receptors in excess which enter into the blood and there combine with the toxine as in a^1 b^1, thus anchoring it and preventing it from acting upon the cells. The receptors c and d do not fit the toxine molecule.

Fig. 18—Diagram To Illustrate Ehrlich'S Theory Of Antitoxine Formation. The surface of the cell (n) is covered with receptors some of which (b) fit the toxine molecule, (a) allowing the toxine to act upon the cell. Under the stimulus of this the cell produces these receptors in excess which enter into the blood and there combine with the toxine as in a^1 b^1, thus anchoring it and preventing it from acting upon the cells. The receptors c and d do not fit the toxine molecule.

A very ingenious theory which well accords with the facts has been given by Ehrlich in explanation of the production of antitoxine and of the reaction between toxine and antitoxine (Fig. 18). This is based on the hypothesis, which is in accord with all facts and generally accepted, that the molecules which enter into the structure of any chemical substance have in each particular substance a definite arrangement, and that in a compound substance each elementary substance entering into the compound molecule has chemical affinities, most of which may be satisfied by finding a suitable mate. Ehrlich assumes that the very complex chemical substances which form the living cells have many unsatisfied chemical affinities, and that it is due to this that molecules of substances adapted for food can enter the cells and unite with them; but there must be some coincidence of molecular structure to enable the union to take place, the comparison being made of the fitting of a key into a lock. The toxines—that produced by the diphtheria bacillus being the best example—are substances whose molecular structure enables them to combine with the cells of the body, the combination being effected through certain chemical affinities belonging to the cells termed receptors. Unless the living cells have receptors which will enable the combination with the toxine to take place, no effect can be produced by the toxine and the cells are not injured. This is the case in an animal naturally immune to the action of the diphtheria bacillus or its toxines. In the case of the susceptible animal the receptors of the cells of the different organs combine with the toxine to a greater or less extent, which explains the fact that different degrees of injury are produced in the different tissues; the toxine of tetanus, or lockjaw, for example, combines by preference with the nervous tissue, that of diphtheria with the lymphatic tissue. It is known that in accordance with the general law of injury and repair, a loss in any part of the body stimulates the tissue of the same kind to new growth and the loss is thus repaired; it is assumed that the cell receptors which combine with the toxine are lost for the cell which then produces them in excess. The receptors so produced pass into the blood, where they combine with the toxine which has been absorbed; the combination is a stable one, and the toxine is thus prevented from combining with the tissue cells. The antitoxine which is formed during the disease, and the production of which in the horse can be enormously stimulated by the injection of toxine, represents merely the excess of cell receptors, and when the serum of the horse containing them is injected in a case of diphtheria the same combination takes place as in the case of receptors provided by the patient. In the case of the destruction of bacteria in the blood by the action of amboceptor and complement, the amboceptor must be able to combine with both the bacterial cell and the complement which brings about its destruction, and just as antitoxine is formed so new amboceptors may be formed.

Few hypotheses have been advanced in science which are more ingenious, in better accord with the facts, have had greater importance in enabling the student to grasp the intricacies of an obscure problem, and which have had an equal influence in stimulating research. The immunity which results from disease in accordance with this theory, is due not to conditions preventing the entrance of organisms into the body, but to greater aptitude on the part of the cells to produce these protective substances having once learned to do so. An individual need not practise for many years, having once learned them, those combinations of muscular action used in swimming; but the habit at once returns when he falls into the water.

Infectious diseases and recovery are phases of the struggle for existence between parasite and host, and illustrate the power of adaptation to environment which is so striking a characteristic of living matter.

Chapter VIII

Secondary, Terminal And Mixed Infections.—The Extension Of Infection In The Individual.—Tuberculosis.—The Tubercle Bacillus.—Frequency Of The Disease.—The Primary Foci.—The Extension Of Bacilli.—The Discharge Of Bacilli From The Body.—Influence Of The Seat Of Disease On The Discharge Of Bacilli.—The Intestinal Diseases.—Modes Of Infection.—Infection By Sputum Spray.—Infection Of Water Supplies.—Extension Of Infection By Insects.—Trypanosome Diseases.—Sleeping Sickness.—Malaria.—The Part Played By Mosquitoes.—Parasitism In The Mosquito.—Infection As Influenced By Habits And Customs.—Hookworm Disease.—Inter-Relation Between Human And Animal Diseases.—Plague.—Part Played By Rats In Transmission.—The Present Epidemic Of Plague.

The infectious diseases are often complicated by secondary infections, some other organism finding opportunity for invasion in the presence of the injuries produced in the primary disease. In many diseases, such as diphtheria, scarlet fever and smallpox, death is frequently due to the secondary infection. The secondary invaders not only find local conditions favoring a successful attack, but the activity of the tissue cells on which the production of protective substances essentially depends has suffered by the primary infection, or the cells are occupied in meeting the exigencies of this. The body is in the position of a state invaded by a second power where all its forces and resources are engaged in repelling the first attack.

What are known as terminal infections occur shortly before death. No matter what the disease which causes death, in the last hours of life the body usually becomes invaded by organisms which find their opportunity in the then defenceless tissues, and the end is often hastened by this invasion.

There are also mixed infections in which two different organisms unite in attack, each in some way assisting in the action of the other. The best known example of this is in the highly infectious disease of swine known as hog cholera. It has been shown that in this disease two organisms are associated,—one an invisible and filterable organism, and the other a bacillus. It was first supposed that the bacillus was the specific organism; it was found in the lesions and certain, but not all, the features of the disease were produced by inoculating hogs with pure cultures. The disease so produced is not contagious, and the contagious element seems to be due to the filterable virus.

The modes of transmission of infectious diseases are of great importance and are the foundation of measures of public health. In the preceding chapter we have seen that in the infected individual the disease extends from one part of the body to another. There is a primary focus

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