In this way secondary abscesses, secondary tubercle glanders and nodules, etc., result; in typhoid fever there is secondary invasion of the mesenteric glands, and clumps of bacilli are also found in internal organs, especially the spleen, though there may be little tissue change around them. In all such cases there is seen a selective character in the distribution of the lesions, some organs being in any disease much more liable to infection than others. 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. Thus in cholera the bacteria are practically confined to the intestine, in diphtheria to the region of the false membrane, in tetanus to some wound. In the last-mentioned disease even the local multiplication depends upon the presence of other bacteria, as the tetanus bacillus has practically no power of multiplying in the healthy tissues when introduced alone.

The effects produced by bacteria may be considered under Tissue changes. the following heads: (1) 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. (Many such changes are usually grouped together under the heading of "inflammation" of varying degree - acute, subacute and chronic.) Degeneration and death of cells, haemorrhages, serous and fibrinous exudations, leucocyte emigration, proliferation of connective tissue and other cells, may be mentioned as some of the fundamental changes. Acute inflammation of various types, suppuration, granulation-tissue formation, etc., represent some of the complex resulting processes. The changes produced at a distance by distribution of toxins may be very manifold - cloudy swelling and fatty degeneration, serous effusions, capillary haemorrhages, various degenerations of muscle, hyaline degeneration of small blood-vessels, and, in certain chronic diseases, waxy degeneration, all of which may be widespread, are examples of the effects of toxins, rapid or slow in action.

Again, in certain cases the toxin has a special affinity for certain tissues. Thus in diphtheria changes in both nerve cells and nerve fibres have been found, and in tetanus minute alterations in the nucleus and protoplasm of nerve cells.

The lesions mentioned are in many instances necessarily Symptoms. accompanied by functional disturbances or clinical symptoms, varying according to site, and to the nature and degree of the affection. In addition, however, there occur in bacterial diseases symptoms to which the correlated structural changes have not yet been demonstrated. Amongst these the most important is fever with increased protein metabolism, attended with disturbances of the circulatory and respiratory Systems. Nervous symptoms, somnolence, coma, spasms, convulsions and paralysis are of common occurrence. All such phenomena, however, are likewise due to the disturbance of the molecular constitution of living cells. Alterations in metabolism are found to be associated with some of these, but with others no corresponding physical change can be demonstrated. The action of toxins on various glands, producing diminished or increased functional activity, has a close analogy to that of certain drugs. In short, if we place aside the outstanding exception of tumour growth, we may say that practically all the important phenomena met with in disease may be experimentally produced by the injection of bacteria or of their toxins.

The result of the entrance of a virulent bacterium into the Susceptibility. tissues of an animal is not a disease with hard and fast characters, but varies greatly with circumstances. With regard to the subject of infection the chief factor is susceptibility; with regard to the bacterium virulence is all-important. Susceptibility, as is well recognized, varies much under natural conditions in different species, in different races of the same species, and amongst individuals of the same race. It also varies with the period of life, young subjects being more susceptible to certain diseases, e.g. diphtheria, than adults. Further, there is the very important factor of acquired susceptibility. It has been experimentally shown that conditions such as fatigue, starvation, exposure to cold, etc., lower the general resisting powers and increase the susceptibility to bacterial infection. So also the local powers of resistance may be lowered by injury or depressed vitality. In this way conditions formerly believed to be the causes of disease are now recognized as playing their part in predisposing to the action of the true causal agent, viz. the bacterium.

In health the blood and internal tissues are bacterium-free; after death they offer a most suitable pabulum for various bacteria; but between these two extremes lie states of varying liability to infection. It is also probable that in a state of health organisms do gain entrance to the blood from time to time and are rapidly killed off. The circumstances which alter the virulence of bacteria will be referred to again in connexion with immunity, but it may be stated here that, as a general rule, the virulence of an organism towards an animal is increased by sojourn in the tissues of that animal. The increase of virulence becomes especially marked when the organism is inoculated from animal to animal in series, the method of passage. This is chiefly to be regarded as an adaptation to surroundings, though the fact that the less virulent members of the bacterial species will be liable to be killed off also plays a part. Conversely, the virulence tends to diminish on cultivation on artificial media outside the body, especially in circumstances little favourable to growth.