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of the tissue about the infecting organisms. In most cases the sum of the changes are so characteristic that from them the nature of the infection is easily determined, and these changes often give names to the disease; thus tuberculosis is a disease characterized by the formation of tubercles or little nodules in the body. The situation of the foci of disease is determined by many conditions, the most important being the varying resistance of the different organs of the body to the growth of bacteria. Certain organs, such as the central nervous system, the muscles, the testicles and the ovaries, have a high resistance to the growth of bacteria. The disease may be localized in certain organs because only in these do the bacteria find favorable conditions for growth. In spite of a high general resistance to infection the lesions in chronic glanders are most marked in the muscles, those of poliomyelitis in the spinal cord. There are few bacterial diseases which are localized in the blood, but many of the diseases caused by protozoa have this localization. In every infection some organisms enter the blood, which acts as a carrier and deposits them in the organs.

Bacteria cause disease by producing substances called toxines which are poisonous to the cells, and of which two sorts are distinguished. One form of toxines is produced by the bacteria as a sort of secretion, and is formed both in the body and when the bacteria are growing in cultures. Substances of this character, many of them highly poisonous, are produced both by animals and plants. They may serve the purpose both of offence and defence, as in the case of the snake venom, and in other cases they seem to benefit their producers in no way whatever, and may even be injurious to them. After the different cereals have been grown for succeeding years in the same place, growth finally diminishes not from the exhaustion of the soil, but from the accumulation in it of substances produced by the plants. Beneath certain trees, as the Norway maple, grass will not grow, and it has been shown that the tree produces substances which inhibit the growth of grass. When bacteria are grown in a culture flask, growth ceases long before the nutritive material has been consumed, from the accumulation of waste products in the fluid. The other class of toxic substances, called endotoxines, are not secretion products, but are contained in the bacterial substance and become active by the destruction and disintegration of the bacteria. They can be artificially produced by grinding up masses of bacteria, and in the body the destruction and solution of bacteria which is constantly taking place sets them free. The toxines and the endotoxines are of an albuminous nature, and act only when they come in contact with the living cells within the body. When taken into the alimentary canal they are either not absorbed or so changed by the digestive fluids as to be innocuous. Many of the ordinary food substances, even a material apparently so simple as the white of an egg, are highly injurious if they reach the tissues in an unchanged form.

By means of these substances the bacteria produce such changes in their environment within the body that this becomes adapted to their parasitic existence. In symbiosis the bacteria probably undergo changes by which they become adapted to the environment, and in parasitism the environment becomes adapted to them. In the same way man can change his immediate environment by means of clothing, artificial heating, etc., and adapt it to his needs; or by hardening his body he can adapt it to the environment. The pathogenic bacterium finds the living tissue hostile, its cells devour him, the tissue fluids destroy him, and by means of the toxines he changes the environment from that of living to dead tissue, or in other ways so alters it that it is no longer hostile. The parasite has also means of passive defence comparable to the armor of the warrior in the past. It may form a protective mantle called a capsule around itself, which serves to protect it from the action of the body fluids. Such capsule formation is a very common thing in the pathogenic organisms, and they are found only when these are growing in the body and do not appear in cultures (Fig. 17-c).

It is evident that just as the parasite has his weapons of offence and defence so has the host, otherwise there would be no recovery from infectious diseases. Although many of the infectious diseases have a high mortality, which in rare instances reaches one hundred per cent, the majority do recover. In certain cases the recovery is attended by immunity, the individual being protected to a greater or less degree from a recurrence of the same disease. The immunity is never absolute; it may last for a number of years only, and usually, if the disease be again acquired, the second attack is milder than the primary. Probably the most enduring immunity is in smallpox, although cases are known of two and even three attacks; the immunity is high in scarlet fever, measles, mumps and typhoid fever. The immunity from diphtheria is short, and in pneumonia, although there must be a temporary immunity, future susceptibility to the disease is probably increased. In certain cases the immunity is only local; the focus of disease heals because the tissue there has evolved means of protection from the parasite, but if any other part of the body be infected, the disease pursues the usual course. A boil, for example, is frequently followed by the appearance of similar boils in the vicinity due to the infection of the skin by the micrococci from the first boil, which by dressings, etc., have become spread over the surface.

The natural methods of defence of the host against the parasites have formed the main subject in the study of the infectious diseases for the last twenty years. Speculation in this territory has been rife and most of it fruitless, but by patient study of disease in man and by animal experimentation there has been gradually evolved a sum of knowledge which has been applied in many cases to the treatment of infectious diseases with immense benefit. Research was naturally turned to this subject, for it was evident that the processes by which the protection of the body was brought about must be known before there could be a really rational method of treatment directed towards the artificial induction of such processes, or hastening and strengthening those which were taking place. Previous to knowledge of the bacteria, their mode of life, their methods of infection and knowledge of the defences of the body, most of the methods of prevention and treatment of the infectious diseases was based largely on conjecture, the one brilliant exception being the discovery of vaccination by Jenner in 1798.

The host possesses the passive defences of the surfaces which have already been considered. The first theories advanced in explanation of immunity were influenced by what was known of fermentation. One, the exhaustion theory, assumed that in the course of disease substances contained in the body and necessary for the growth of the bacteria became exhausted and the bacteria died in consequence. Another, the theory of addition, assumed that in the course of the disease substances inimical to the bacteria were formed. Both these theories were inadequate and not in accord with what was known of the physiology of the body. The most general mode of defence is by phagocytosis, the property which many cells have of devouring and digesting solid substances (Fig. 16-p). Although this had been known to take place in the amoebæ and other unicellular organisms, the wide extent of the process and its importance in immunity was first recognized by Metschnikoff in 1884 and the phagocytic theory of immunity advanced and defended by a brilliant series of experiments by Metschnikoff and his pupils conducted in the Pasteur Institute. Metschnikoff's first observations were made on the daphnea, a small animalcule just visible to the naked eye which lives in fresh water. The structure of the organism is simple, consisting of an external and internal surface between which there is a space, the body cavity; daphneæ are transparent and can be studied under the microscope while living. Metschnikoff observed that certain of them in the aquarium gradually lost their transparency and died, and examining these he found they were attacked by a species of fungus having long, thin spores. These spores were taken into the intestine with other food; they penetrated the thin wall of the intestine, passed into the body cavity, multiplied there, and in consequence the animal died. In many cases, however, those penetrating became enclosed in cells which the body cavity contains and which correspond with the leucocytes of the blood; in these the spores were digested and destroyed. The daphneæ in which this took place recovered from the infection. Here was a case in which all the stages of an infectious disease could be directly followed under the microscope, and the whole process was simple in comparison with infections in the higher animals. The pathogenic organism was known, the manner and site of invasion was clear, it was also evident that if the multiplication of the parasite was unchecked the animal died, but if the parasite was opposed by the body cells and destroyed the animal recovered. The studies were carried further into the diseases of the higher animals, and it was found the leucocytes in these played the same part as did the cells in the body cavity of the daphnea. The introduction of bacteria into certain animals was followed by their destruction within cells and no disease resulted; if this did not take place, the bacteria multiplied and produced disease. Support also was given the theory by the demonstration at about the same time that in most of the infectious diseases the leucocytes of the blood became increased in number,—that in pneumonia, for instance, instead of the usual number of eight thousand in a cubic millimeter of blood, there were often thirty thousand or even fifty thousand. At about the same time also chemotaxis, or the action of chemical substances in attracting or repelling organisms, excited attention, and all these facts together became woven into the theory. It was soon seen, however, that this theory, based as it was on observation and supported by the facts observed, was not, at least in its first crude form, capable of general application. Many animals have natural immunity to certain diseases; they do not have the disease under natural conditions, nor do they acquire the disease when the organisms causing it are artificially introduced into their tissues by inoculation. Such natural immunity seemed to be unconnected with defence by phagocytosis, for the leucocytes of the animal might or might not have phagocytic reaction to the particular organisms to which the animal was immune. It was also seen that recovery from infection in certain diseases was unconnected with phagocytosis. It had also been demonstrated, by German observers chiefly, that the serum of the blood, the colorless fluid in which the corpuscles float, was itself destructive, and that in an animal rendered immune to a special bacterium the destructive action of the serum on that organism was greatly increased. In this hostile serum the bacteria often became clumped together in masses, the bodies became swollen, broken up, and finally disintegrated. This property of the serum was described as due to a substance in the serum called alexine, which in the immune animal became greatly increased in amount. It was even denied by some that phagocytosis of living bacteria took place, and that all those included in the cells were dead, having been destroyed in the first instance by the serum. The strife became a national one between the French and Germans,—on the one side in France the phagocytic theory was defended, and in Germany, on

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