The Fundamentals of Bacteriology

CHAPTER XXV.
IMMUNITY.

Immunity, as has already been stated, implies such a condition of the body that pathogenic organisms after they have been introduced are incapable of manifesting themselves, and are unable to cause disease. The word has come to have a more specific meaning than resistance in many instances, in other cases the terms are used synonymously. It is the opposite of susceptibility. The term must be understood always in a relative sense, since no animal is immune to all pathogenic organisms, and conceivably not entirely so to anyone, because there is no question that a sufficient number of bacteria of any kind might be injected into the circulation to kill an animal, even though it did it purely mechanically.

Immunity may be considered with reference to a single individual or to entire divisions of the organic world, with all grades between. Thus plants are immune to the diseases affecting animals; invertebrates to vertebrate diseases; cold-blooded animals to those of warm blood; man is immune to most of the diseases affecting other mammals; the rat to anthrax, which affects other rodents and most mammals; the well-known race of Algerian sheep is likewise immune to anthrax while other sheep are susceptible; the negro appears more resistant to yellow fever than the white; some few individuals in a herd of hogs always escape an epizoötic of hog cholera, etc.

Immunity within a given species is modified by a number of factors—age, state of nutrition, extremes of heat or cold, fatigue, excesses of any kind, in fact, anything which tends to lower the “normal healthy tone” of an animal also tends to lower its resistance. Children appear more susceptible to scarlet fever, measles, whooping-cough, etc., than adults; young cattle more frequently have black-leg than older ones (these apparently greater susceptibilities may be due in part to the fact that most of the older individuals have had the diseases when young and are immune for this reason). Animals weakened by hunger or thirst succumb to infection more readily. Frogs and chickens are immune to tetanus, but if the former be put in water and warmed up to and kept, at about 37°, and the latter be chilled for several hours in ice-water, then each may be infected. Pneumonia frequently follows exposure to cold. The immune rat may be given anthrax if first he is made to run in a “squirrel cage” until exhausted. Alcoholics are far less resistant to infection than temperate individuals. “Worry,” mental anguish, tend to predispose to infection.

The following outlines summarize the different, classifications of immunity so far as mammals are concerned for the purposes of discussion.

1. I. Natural
   1. A. Congenital
      1. 1. Inherited through the germ cell or cells.
      2. 2. Acquired in utero.
         1. (a) By having the disease in utero.
         2. (b) By absorption of immune substances from the mother.
   2. B. Acquired by having the disease.
2. II. Artificial—acquired through human agency by:
   1. 1. Introduction of the organism or its products.
   2. 2. Introduction of the blood serum of an immune animal.

1. I. Active—due to the introduction of the organism or due to the introduction of the products of the organism.
   1. A. Naturally by having the disease.
   2. B. Artificially.
      1. 1. By introducing the organism:
         1. (a) Alive and virulent.
         2. (b) Alive and virulence reduced by
            1. 1. Passage through another animal.
            2. 2. Drying.
            3. 3. Growing at a higher temperature.
            4. 4. Heating the cultures.
            5. 5. Treating with chemicals.
            6. 6. Sensitizing.
            7. 7. Cultivation on artificial media.
         3. (c) Dead.
      2. 2. By introducing the products of the organism.
2. II. Passive—due to the introduction of the blood serum of an actively immunized animal.

Immunity present in an animal and not due to human interference is to be regarded as natural immunity, while if brought about by man’s effort it is considered artificial. Those cases of natural immunity mentioned above which are common to divisions, classes, orders, families, species or races of organisms and to those few individuals where no special cause is discoverable, must be regarded as instances of true inheritance through the germ cell as other characteristics are. All other kinds of immunity are acquired. Occasionally young are born with every evidence that they have had a disease in utero and are thereafter as immune as though the attack had occurred after birth (“small-pox babies,” “hog-cholera pigs”). Experiment has shown that immune substances may pass from the blood of the mother to the fetus in utero and the young be immune for a time after birth (tetanus). This is of no practical value as yet. It is a familiar fact that with most infectious diseases recovery from one attack confers a more or less lasting immunity, though there are marked exceptions.

Active Immunity.—By active immunity is meant that which is due to the actual introduction of the organism, or in some cases of its products. The term active is used because the body cells of the animal immunized perform the real work of bringing about the immunity as will be discussed later. In passive immunity the blood serum of an actively immunized animal is introduced into a second animal, which thereupon becomes immune, though its cells are not concerned in the process. The animal is passive, just as a test-tube, in which a reaction takes place, plays no other part than that of a passive container for the reagents.

In active immunity the organism may be introduced in what is to be considered a natural manner, as when an animal becomes infected, has a disease, without human interference. Or the organism may be purposely introduced to bring about the immunity. For certain purposes the introduction of the products of the organism (toxins) is used to bring about active immunity (preparation of diphtheria and tetanus antitoxin from the horse). The method of producing active immunity by the artificial introduction of the organism is called vaccination, and a vaccine must therefore contain the organism. Vaccines for bacterial diseases are frequently called bacterins. The use of the blood serum of an immunized animal to confer passive immunity on a second animal is properly called serum therapy, and the serum so used is spoken of as an antiserum, though the latter word is also used to denote any serum containing any kind of an antibody (Chapters XXVII–XXXI). In a few instances both the organism and an antiserum are used to cause both active and passive immunity (serum-simultaneous method in immunizing against hog cholera).

In producing active immunity the organism may be introduced (a) alive and virulent, but in very small doses, or in combination with an immune serum, as just mentioned for hog cholera. The introduction of the live virulent organism alone is done only experimentally as yet, as it is obviously too dangerous to do in practice, except under the strictest control (introduction of a single tubercle bacillus, followed by gradually increasing numbers—Barber and Webb). More commonly the organisms are introduced (b) alive but with their virulence reduced (“attenuated”) in one of several ways: (1) By passing the organism through another animal as is the case with smallpox vaccine derived from a calf or heifer. This method was first introduced by Jenner in 1795 and was the first practical means of preventing disease by vaccination. This word was used because material was derived from a cow—Latin vacca. (2) By drying the organism, as is done in the preparation of the vaccine for the Pasteur treatment of rabies, where the spinal cords of rabbits are dried for varying lengths of time—one to four days, Russian method, one to three days, German method, longer in this country. (It is probable that the passage of the “fixed virus” through the rabbit is as important in this procedure as the drying, since it is doubtful if the “fixed virus” is pathogenic for man.) It would be more correct to speak of this as a preventive vaccination against rabies, since the latter is one of the few diseases which is not amenable to treatment. The patient always dies if the disease develops. (3) The organism may be attenuated by growing at a temperature above the normal. This is the method used in preparing anthrax vaccine as done by Pasteur originally. (4) Instead of growing at a higher temperature the culture may be heated in such a way that it is not killed but merely weakened. Black-leg vaccines are made by this method. (5) Chemicals are sometimes added to attenuate the organisms, as was formerly done in the preparation of black-leg vaccine by Kruse’s method in Germany. The use of toxin-antitoxin mixtures in immunizing against diphtheria and in the preparation of diphtheria antitoxin from horses is an application of the same principle, though here it is the product of the organism and not the organism whose action is weakened. (6) Within the past few years the workers in the Pasteur Institute in Paris have been experimenting with vaccines prepared by treating living virulent bacteria with antisera (“sensitizing them”) so that they are no longer capable of causing the disease when introduced, but do cause the production of an active immunity. The method has been used with typhoid fever bacilli in man and seems to be successful. It remains to be tried out further before its worth is demonstrated (the procedure is more complicated and the chance for infection apparently much greater than by the use of killed cultures). The term sero-bacterins is used by manufacturers in this country to designate such bacterial vaccines. (7) Growing on artificial culture media reduces the virulence of most organisms after a longer or shorter time. This method has been tried with many organisms in the laboratory, but is not now used in practice. The difficulties are that the attenuation is very uncertain and that the organisms tend to regain their virulence when introduced into the body.

In producing active immunity against many bacterial diseases the organisms are introduced (c) dead. They are killed by heat or by chemicals, or by using both methods (Chapter XXX).

When the products of an organism are introduced the resulting immunity is against the products only and not against the organism. If the organism itself is introduced there results an immunity against it and in some cases also against the products, though the latter does not necessarily follow. Hence the immunity may be antibacterial or antitoxic or both.

Investigation as to the causes of immunity and the various methods by which it is produced has not resulted in the discovery of specific methods of treatment for as many diseases as was hoped for at one time. Just at present progress in serum therapy appears to be at a standstill, though vaccines are giving good results in many instances not believed possible a few years ago. As a consequence workers in all parts of the world are giving more and more attention to the search for specific chemical substances, which will destroy invading parasites and not injure the host (chemotherapy). Nevertheless, in the study of immunity very much of value in the treatment and prevention of disease has been learned. Also much knowledge which is of the greatest use in other lines has been accumulated. Methods of diagnosis of great exactness have resulted, applicable in numerous diseases. Ways of detecting adulteration in foods, particularly foods from animal sources, and of differentiating proteins of varied origin, as well as means of establishing biological relationships and differences among groups of animals through “immunity reactions” of blood serums have followed from knowledge gained by application of the facts or the methods of immunity research. Hence the study of “immunity problems” has come to include much more than merely the study of those factors which prevent the development of disease in an animal or result in its spontaneous recovery. A proper understanding of the principles of immunity necessitates a study of these various features and they will be considered in the discussion to follow.