Pasteur and the bacteriologists of his time discovered that bacteria cease to grow in artificial culture media after a time, because of the exhaustion of the food material in some cases and because of the injurious action of their own products in other instances. These facts were brought forward to explain immunity shortly after bacteria were shown to be the cause of certain diseases. Theories based on these observations were called (1) “Exhaustion Theory” of Pasteur, and (2) “Noxious Retention Theory” of Chauveau respectively. The fact, soon discovered, that virulent pathogenic bacteria are not uncommonly present in perfectly healthy animals, and the later discovery that immunity may be conferred by the injection of dead bacteria have led to the abandonment of both these older ideas. The (3) “Unfavorable Environment” theory of Baumgartner, i.e., bacteria do not grow in the body and produce disease because their surroundings are not suitable, in a sense covers the whole ground, though it is not true as to the first part, as was pointed out above, and is of no value as a working basis, since it offers no explanation as to what the factors are that constitute the “unfavorable environment.” Metchnikoff brought forward a rational explanation of immunity with his (4) “Cellular or Phagocytosis Theory.” As first propounded it based immunity on the observed fact that certain white blood corpuscles, phagocytes, engulf and destroy bacteria. Metchnikoff

has since elaborated the original theory to explain facts of later discovery. Ehrlich soon after published his (5) “Chemical or Side-chain Theory” which seeks to explain immunity on the basis of chemical substances in the body which may in part destroy pathogenic organisms or in part neutralize their products; or in some instances there may be an absence of certain chemical substances in the body cells so that bacteria or their products cannot unite with the cells and hence can do no damage.

PLATE VI

PAUL EHRLICH

At the present time it is generally accepted, in this country at least, that Ehrlich’s theory explains immunity in many diseases as well as many of the phenomena related to immunity, and in other diseases the phagocytes, frequently assisted by chemical substances, are the chief factors. Specific instances are discussed in Pathogenic Bacteriologies which should be consulted. It is essential that the student should be familiar with the basic ideas of the chemical theory, not only from the standpoint of immunity, but also in order to understand the principles of a number of valuable methods of diagnosis.

The chemical theory rests on three fundamental physiological principles: (1) the response of cells to stimuli, in this connection specific chemical stimuli, (2) the presence within cells of specific chemical groups which combine with chemical stimuli and thus enable them to act on the cell, which groups Ehrlich has named receptors, and (3) the “over-production” activity of cells as announced by Weigert.

1. That cells respond to stimuli is fundamental in physiology. These stimuli may be of many kinds as mechanical, electrical, light, thermal, chemical, etc. The body possesses groups of cells specially developed to receive some of these stimuli—touch cells for mechanical stimuli, retinal cells for light, temperature nerve endings for thermal, olfactory and gustatory cells for certain chemical stimuli. Response to chemical stimuli is well illustrated along the digestive tract. That the chemical stimuli in digestion may be more or less specific is shown by the observed differences in the enzymes of the pancreatic juice dependent on the relative amounts of carbohydrates, fats, or proteins in the food, the specific enzyme in each case being increased in the juice with the increase of its corresponding foodstuff. The cells of the body, or certain of them at least, seem to respond in a specific way when substances are brought into direct contact with them, that is, without having been subjected to digestion in the alimentary tract, but injected directly into the blood or lymph stream. Cells may be affected by stimuli in one of three ways: if the stimulus is too weak, there is no effect (in reality there is no “stimulus” acting); if the stimulus is too strong, the cell is injured, or may be destroyed; if the stimulus is of proper amount then it excites the cell to increased activity, and in the case of specific chemical stimuli the increased activity, as mentioned for the pancreas, shows itself in an increased production of whatever is called forth by the chemical stimulus. In the case of many organic chemicals, the substances produced by the cells under their direct stimulation are markedly specific for the particular substance introduced.

2. Since chemical action always implies at least two bodies to react, Ehrlich assumes that in every cell which is affected by a chemical stimulus there must therefore be a chemical group to unite with this stimulus. He further states that there must be as many different kinds of these groups as there are different kinds of chemicals which stimulate the cell. Since these groups are present in the body cells to take up different kinds of chemical substances, Ehrlich calls them receptors. Since these groups must be small as compared with the cell as a whole, and must be more or less on the surface and unite readily with chemical substances he further speaks of them as “side-chains” after the analogy of compounds of the aromatic series especially. The term receptors is now generally used. As was stated above, the effect of specific chemical stimuli is to cause the production of more of the particular substance for which it is specific and in the class of bodies under discussion, the particular product is these cell receptors with which the chemical may unite.

3. Weigert first called attention to the practically constant phenomenon that cells ordinarily respond by doing more of a particular response than is actually called for by the stimulus, that there is always an “overproduction” of activity. In the case of chemical stimuli this means an increased production of the specific substance over and above the amount actually needed.