|
These bodies of ours and the bodies of all other living things, plants and animals, parasites and all, have lived in a certain relationship for years which no one is able to number. During these ages beyond history, there have been many changes in the manner of life of these structures in answer to the changes in their environment. Since
these exert various effects upon the environment of one another, it is
evident that a change in the metabolism of one group of organic life may
affect the metabolism of other groups with which it is associated. Climatic
conditions may affect one group, these in turn may affect some other group,
and so on. Organisms subject to parasitic invasion may develop an
armor of defense, or they may form substances toxic to the invaders.
The parasites may in turn develop organs of defense, as the hooks of certain
parasitic worms, or they may become immune to the toxins of their hosts.
The hosts may become adapted to the presence of the bacteria whether they
ever attempt to repel them or not. Symbiosis or helotism may result.
The present metabolic conditions of our own bodies, as well as the metabolic
conditions of the organisms which may become parasites upon them, are the
results of this almost everlasting warfare between insistent guest and
unwilling host.
According to history, there have been many new forms of disease. It appears upon more careful search that the diseases recorded as new and intensely ferocious were really new only to certain nations or cities, and that their intense ferocity was due to great susceptibility of the people at that time. The ravages of the plague of the middle ages followed periods of want or of unusual climatic conditions. The damp weather facilitated the growth of various moulds upon the grains used as food; the poorer classes ate the diseased grains used as food; the poorer classes ate the diseased grain and became sick. They were thus subject to the attacks of bacterial diseases. Often they were half-starved during these years of poor crops, and were therefore more susceptible to disease. The bacteria which flourished among the very poor became thereby the more toxic and tenacious of life. Those whose lives were filled with luxury were rendered susceptible to bacterial invasion in part by their own ill habits, and in part by the increased virulence of the bacteria which were carried from the sick and starved of their poor neighbors. During the middle ages, the filthy habits of both rich and poor, in city and country, must have greatly increased the risk of infection, the susceptibility of all people, and the virulence of the infectious agent. The first appearance of any infectious disease finds almost any race extremely susceptible. On the other hand, infectious diseases are not likely to attain any great severity unless there is some factor which lessens the immunity of the race or the nation at that time. The history of plague among the Mongolians, of smallpox among the Indians, of leprosy in England and Scotland in the fifteenth and sixteenth centuries, of the times of plague in England in the seventeenth century, and of many bacterial diseases which savages of all races receive from their association with the civilized races, all seem to indicate the possibility of the development of racial immunity, or racial adaptation. At any rate, there is a form of racial and national immunity which is recognized by all writers on infectious diseases. (Note A.) Through all the ages of progressive development, the cells of all complex bodies have been adapting themselves to the propinquity of such pathogenic factors as are present in their environment. The manner in which this adaptation is brought about is not known, but there are some facts of biology, chemistry and history which give a little light upon the really difficult problem.
It is best first to consider the nature of the living molecule, which Verworn calls a “biogen.” In this discussion the terms of “Ehrlich’s Side-Chain Theory,” as modified by several more recent investigators into the subject will be employed. It seems that the living proteid molecule, or biogen, is composed of a nucleus, or ring, of comparatively simple structure, to which are attached almost innumerable radicals, or side chains, which are concerned in the various reactions characteristic of the living cell. These side chains are of very various chemical forms. They may be of almost inconceivable complexity, or they may be so simple that their molecular form is known even now. They all agree only in being attached to the central nucleus, and in being in some manner under the control of that center. It is known that these side-chains include one or more radicals of a carbohydrate nature, one or more of the fatty acid series, besides the innumerable nitrogenous chains whose degradation products are broken down, built up, and in many ways rearranged to form sources of energy, of foods for growth or the end products of katabolism which are ultimately excreted from the body. The reaction of proteids and albumens have indicated something of the complexity of the side-chains.
Proteids which give the “biuret reaction” are known to contain the group, (CO)2 (NH2)2. This is probably one of the common chains. The xantho-proteic reaction characterizes the presence in the proteid molecule of the phenyl grouping. This is also one of the chains commonly found. Miller’s reagent gives a positive reaction in the presence of those proteids which contain the groupings of which tyrosine is the most familiar example. Other chains are found almost universally present. Any discussion of the nature of these or of their cleavage products would require much more than the limits of this book. Many of these have been broken from the proteid molecule by the use of methods which display their molecular structure beyond doubt, and some of them have been synthesized in vitro. The nature of the relation of the side-chains to each other and the central “ring”—if it be a ring—is as yet only a matter of conjecture, for the most part. It appears that the chains containing iron or sulphur in certain combinations are able to hold oxygen in a very unstable union, and to give it up to the oxidizable chains under certain metabolic conditions, such as are to be found in the muscle cells when stimulated by nerve impulses, for example. In this case, too, it is well known that after all the free oxygen has been abstracted from the muscle cells, the appropriate stimulation is followed by muscular contraction accompanied by the evolution of carbon dioxid. Oxygen, then, must be united with some of the side-chains. The oxidizable substances or chains may be the carbohydrates or they may be other radicals. The form of the carbohydrate group (an aldehyde) and the character of the waste products resulting from muscle metabolism render it probably that in the case of muscles, at least, the oxidation of the carbohydrate chain forms the chief source of energy. There are some of these chains which serve the purpose of attaching food radicals, and others which serve other ends. Many of these have been studied more or less thoroughly, but none have attracted more interest than the ones hypothetically considered functional in protecting the body from the evil effects of poisons, and in destroying bacteria. These side chains are a normal part of the living proteid molecule, according to Ehrlich and others, and are probably concerned in attaching the normal food radical to the biogen. When the side chains of the biogen have absolutely no affinity for the molecules of any given poison, that cell enjoys absolute natural immunity from that poison. This happens, apparently, in the case of some arachnids, which are able to endure enormous doses of tetanus toxin without any perceptible injury. Their blood does not neutralize the poison for some weeks, at any rate, for extracts from their bodies, or a few drops of their blood will induce the death of rats with tetanus symptoms for weeks after the last injection of the poison into the body of the spider.
There are other conditions in which there is a form of immunity which is natural but not absolute. In these cases, the absence of appropriate receptors does not account for the phenomena observed. For example, Pfeffer’s bacillus of influenza grows with difficulty upon any culture medium. Its best food is made of agar-agar upon which a drop of pigeon’s blood has been spread. Now the pigeon is almost immune to influenza, yet its blood, in the slightly abnormal condition caused by being shed and brought into contact with the culture medium, offers the bacillus of influenza most excellent food. The pigeon owes its immunity to its phagocytes, according to Metchnikoff, and he bases his conclusion upon the facts just mentioned. It is not difficult to suppose that the changes occurring in blood under the abnormal conditions may affect its quality as a food for the bacillus. This is not remarkable, for in several instances compounds stereoisomeric with foods are of no value in the body, and other isomers of harmless substances are decidedly toxic. The rabbit is perfectly immune to bovine pleuro-pneumonia, yet the best culture medium known for a long time for the bacterium of this disease was made of rabbit’s blood and lymph. Rabbits cannot be infected with the disease at all.
In other instances, immunity is not perfect. This condition prevails among the human race and the higher animals in relation to many infectious diseases. Ernst made a special study of bacillus ranicida, which causes a sickness among frogs. The disease is nearly always fatal in cool weather, but occasions very little discomfort in the summer. Ernst found that frogs kept in a temperature of 25 degrees C. were almost or quite immune to the bacilli, while those kept at a temperature of 6 degrees to 10 degrees C. were always filled by the disease. The optimum temperature of the bacillus is 22 degrees C., hence the immunity of the frog during the summer months is due to the increase of the frog’s bacteriolytic powers during the warm weather. Chickens are immune to anthrax ordinarily. Wagner shows that the anthrax bacilli grow well upon chicken blood serum at its optimum temperature of 42 degrees C. If the temperature of chickens be reduced by making them stand in cold water, or if their resistance be lowered by the administration of chloral or antipyrin, their immunity fails and they fall victims to anthrax.
In all these cases, the immunity is natural, but is not absolute. Other forms of life, or these forms under other conditions, display immunity after infection, and this immunity is called “acquired.” The mechanism of this form of adaptation is probably somewhat as follows: When the toxin penetrates the body which is not immune, and comes in contact with its cells, it enters into chemical combination with the side chains whose affinities permit such combination. These are variously affected by the presence of the abnormal radical. The metabolism of the whole cell may be seriously affected, or the side chain may be thrown off, in which case the cell more quickly recovers. It is characteristic of the biogen that it resembles the crystal in its power to replace, or to cause to be replaced, all of its lost parts, so long as its functional integrity remains unimpaired. The mechanism of the one action we understand as fully as we do that of the other. When the biogen has been affected by a removal of certain of its side chains, or when these have been injured, the side chain is replaced from the food materials in its environment. But the biogen outdoes the crystal, for when the biogen loses a chain in such a manner, if the poisonous substance remain present, it replaces not only the lost portion but it also forms others of like structure. These chains which are formed in excess are thrown off into the general circulation, and there enter into chemical union with the poisons. The biogens themselves are thus protected. This is the condition in “acquired immunity.” In the investigations into this subject many laws have been recognized; the subject is not at all the simple matter that appears in this paragraph. There must be formed by the cell certain other chains, some of which are normal constituents of the cell while others are called into existence by the stimulation of the presence of the poisonous elements.
The chains of the cell which receive the poisonous elements are called by Ehrlich the “receptors.” When these are formed in excess, as Wiegert supposes, Ehrlich calls them “amboceptors.” These same bodies, the discarded chains which have an affinity for the poisonous groups, Metchnikoff calls “fixatives.” These may differ in some respects when described by their investigators, but they are practically identical from the functional standpoint. There are other bodies which still further antagonize the various poisons and toxins, and which destroy bacteria. Ehrlich and his associates have studied chiefly the bacterial toxins.
Wright and Mallory have studied the action of bodies which resemble Metchnikoff’s fixatives, if they are not actually identical. These substances Wright calls “opsonins” from their function of preparing the bacteria for digestion by the phagocytes. The “opsonic index” of blood of various degrees of bacteriolytic power has been determined with care, and this index is made a basis for prognosis and treatment in certain instances. The opsonic index is raised in the presence of the micro-organisms for which the estimate is made. It is proposed to raise the opsonic index of the patient who suffers from certain infections by injecting into his own veins some of a sterilized extract from cultures of the pus of his own body. Whether this procedure will result in raising the opsonic index in a manner more advantageous to the patient than the cells in their unmodified reactions to the toxin can do, remains to be determined by future investigations. The results already attained have filled bacteriologists with varying degrees of enthusiasm, as is usual in such cases. Absolute immunity cannot fail. Diseases to which the race is absolutely immune are of no consequence to us, save as the study of all life increases our knowledge of all other life. Partial immunity is a matter of very great moment. The human race is partially immune to all of the commonly recognized infectious diseases. This partial immunity is as good as absolute immunity under ordinarily normal conditions. Our own immunity fails, as does that of the animals and birds already mentioned, under conditions which render the metabolism of the body abnormal, or which injure the structural integrity of the body tissues. Immunity fails under the following conditions:
Injury of the epithelial cells may permit bacteria to gain entrance to the body cavities. Any decrease in the numbers or activity of the phagocytes may permit the bacteria to remain in the body unharmed. Abnormal katabolic products of abnormal cell metabolism may be harmless to bacteria, or they may even serve as food for them. The bacteriolytic power of the blood serum may be decreased by decreased alkalinity. Since this depends upon the oxygen-carrying power of the blood, this decrease in immunity is often due to a deficiency of erythrocytes or hemoglobin. The bacteriolytic powers of any of the living tissues may be decreased by the abnormal condition of metabolism. This occurs under the following conditions: Those cells are most subject to infection whose nutrition is decreased. This is the case when the blood itself is poor, or when the arterial supply is deficient, or when the pressure of the blood within the vessels is decreased below the normal limits. Those cells are subject to infection whose drainage is imperfect. This applies both to venous and lymphatic drainage. The accumulation of waste products in the neighborhood of the cell is one of the most potent causes of malfunction, and hence one of the most serious conditions in the presence of infection. Those cells are most subject to infection which are being subjected to irritating influences. The presence of dust in the lungs is a great aid to the bacillus of tuberculosis. Overwork of any cell group is also a cause of broken immunity. Those cells are subject to infection which lack proper nerve connections. This is true of all tissues, and the failure of normal metabolism under such circumstances is the cause of the broken immunity. Immunity seems to fail in the presence of great numbers of bacteria under conditions otherwise fairly normal. This statement is subject to much discussion. It is evident that clinical experience is not able to afford data sufficiently exact to settle this question, and experimental evidence of a satisfactory nature is wanting. Note A.—“In but few of the islands of the Pacific have the aborigines been displaced by conflict of arms or by industrial competition. The great cause of their disappearance, during the earlier periods of intercourse was their inability to cope with the microbes of measles, smallpox, leprosy and other diseases, unknown to them before the arrival of the Europeans and Chinese.”—Rev. John T. Gulick, in Publication 25, Carnegie Institution of Washington.
General Theories of Bio-Chemical Action, in Schryver’s Chemistry of the Albumens. Resume of the Theories of Metchnikoff and Ehrlich upon immunity, in any recent work on general pathology. |