PART VI

VACCINES AND SERUMS

IMMUNITY

Immunity is (1) natural or biologic, i.e., the normal ability of an organism to fight against other organisms that attempt to kill it or injure it; (2) or it is inherited; (3) or it is acquired.

1. Normally all individuals resist disease and fight off or neutralize the germs of disease and their toxins, and it is only when the individual has a lowered resistance or there is an exceedingly large number of disease germs that attack him at one time or gain entrance into his organism, that he actually becomes infected. In other words, the human being is constantly destroying pathogenic germs.

2. Heredity may make the individual immune to certain diseases, or at least to modify the intensity of certain diseases. Some individuals and some families seem to have inherited an ability to withstand certain infections, although they may be more susceptible to other kinds of infections.

3. An acquired immunity is where the individual has become infected by germs of a certain disease, has overcome it, and afterwards is immune to that particular disease, i.e., he cannot again become infected. This immunity may have become acquired without knowledge on his part; repeated slight infections with this particular germ may have raised an immunity against that germ, even although he has never been severely infected. In other instances he may have the same disease again, but in much modified form. The human being may also be inoculated with a certain disease, as cow pox, and be afterwards immune to its serious relative, small pox; or, at least, if he becomes infected with small pox he will have it in a modified form. Exhaustion, debility, or any disease that has depleted his reserve forces makes the individual more liable to acquire infections.

The diseases that generally render permanent immunity, having once been successfully combated, are small pox, scarlet

fever, measles, whooping cough, mumps, chicken pox, typhoid fever, and probably cholera. On the other hand, influenza, pneumonia, diphtheria, erysipelas and streptococcic infection seem to render the individual more susceptible to future attacks of the same disease.

In some diseases the germs of infection rapidly spread over the body; in others they remain more or less localized, as typically seen in diphtheria and tetanus. The germs of these two infections secrete poisonous toxins, termed endotoxins, which cause serious and dangerous toxemia. Infections, the germs or virus of which enter the blood and are thus disseminated, are rapid in their destructive processes. Those that are spread through the lymph channels are disseminated much more slowly, and they may be localized by the protection which the lymph glands offer.

The protections of the body against invasion are: intact skin and mucous membranes; normal stomach digestive fluids; normal blood and normal serum; and the absence of focal infections as they are termed, in the mouth, throat, nose, or other part of the body. A focal infection can cause such deterioration of the withstand power of the system as to allow other infections to occur. Death from infection is generally due to destruction of the blood corpuscles, or to the toxins secreted by the germs of infection so depressing the circulatory system as to cause cardiac failure.

It is not purposed to more than briefly discuss the protective powers of the blood against bacteria. The substances in the blood serum that have this protective power have been termed broadly alexines. The exact behavior of some of these protective bodies or substances has been more particularly termed agglutinines, precipitines and lysines. The power of the polymorpholeucocytes to swallow bacteria has been termed phagocytosis. These leucocytes thus protect from escape the toxins of the germs which might cause serious toxemia. On the other hand, what has been termed by Wright as opsonin is a substance that may stupify or otherwise make the germs of infection ready for the phagocytic activity of the leucocytes.

If an individual is not overwhelmed by the onslaught of a

large number of virulent germs, he begins immediately to manufacture antibodies which will produce an antitoxin against the toxins of the infecting germ. If he does not form these antibodies rapidly or has not these antibodies pre-formed from previous infection or from artificial protection, he may be helped, in certain diseases, by vaccinations with the dead germs of the disease with which he is attacked. These vaccinations stimu→ late to more rapid formation the antibodies which fight the original disease. Later in the disease he should produce antitoxins or protective substances to overcome the toxins produced by the dying bacteria. If he cannot elaborate sufficient antitoxin he may succumb to the disease. To help him to immediately combat these toxic substances early in the disease antitoxins are administered, and the antitoxin treatment has come to be the greatest protective measure that can be offered in certain forms of disease. As bacterial science advances, more of the infectious diseases will be combated by antitoxic serums, though for some of the germ diseases, such as tuberculosis, it probably never will be possible to produce antitoxins.

It has been shown in the laboratory that a certain number of antitoxin units will overcome a certain number of toxic units. This has been especially demonstrated in diphtheria, and it is now known exactly how many units of antitoxin will overcome a unit of toxin in a given animal.

In some diseases antibodies are produced called agglutinins which are specific for particular germs. After a patient has been ill a week or more with typhoid fever his blood will contain an agglutinin that will cause agglutination, or clumping, of live typhoid bacilli, when the test is made outside of the body. This is the Widal reaction for typhoid fever, and is diagnostic. These agglutinin tests are being utilized for diagnosis in other infections, as the paratyphoid infections, etc. Also the Abderhalden ferment tests are being used to demonstrate the presence or absence of many conditions. The Wassermann test for syphilis when positive shows that that disease is present; if it is negative it may not show that the disease is absent. The gonorrheal complement fixation test when positive demonstrates the presence of that infection.

ALLERGY

In the order of their intensity it may be stated that "hypersensibility" or "sensitization" is the term for the increased susceptibility of an individual to a poisonous substance; that von Pirquet's term "allergy" means an altered activity or altered reaction of the patient, an increased reaction; and that "anaphylaxis" is the term for the group of symptoms which occur from such a poisonous reaction. This anaphylactic reaction is often found as an idiosyncrasy of certain individuals to certain drugs or kinds of food, and in its mild form is evidenced by eruptions on the skin, slight increase in temperature, more or less gastrointestinal disturbances, often urticarial eruptions on the skin, occasionally asthmatic symptoms, and a concentrated and irritating urine.

Certain plant poisons, the pollens, and sometimes odors from certain animals and the dust or odors from certain substances cause hay fever and asthma in susceptible individuals. Hay fever patients, if possible, must go annually to a region where the plants that cause them disturbance do not grow; other susceptible individuals must be constantly careful that they do not inhale the odors from substances that cause their disturbance.

Bacteria, like other living cells, must prepare their food for absorption by the formation of ferments. According to Vaughan, for a bacterium to be poisonous to a human being it must have the ability to split up and feed on human proteins, otherwise it cannot grow, and cannot harm the individual. Also for bacteria to live and grow the ferments of the human body must not be immediately destructive to them, although later antibodies may be formed which will destroy them. Pathogenic bacteria, therefore, are for a time at least poisonous to the human body, unless a previous infection of the individual has produced permanent antibodies and therefore immunity.

If proteins taken into the gastrointestinal canal are properly digested and absorbed only in normal molecular forms, poisoning or anaphylactic reaction will not occur. If, however, the same proteins or partially digested portions of the proteins

are absorbed parenterally, i.e., outside of the intestine, poisoning may occur and sensitization and anaphylaxis result.

Novy and de Kruif1 state that anaphylatoxin is produced by the circulation of the matrix of the poison in the blood. This matrix circulating in the blood becomes a poison when any alien substance is added to the serum, and many of the simplest substances may cause this transformation of the matrix into a poison. The sudden development of this anaphylatoxin or "taraxin" as these investigators state may bring on the explosive symptoms seen in eclampsia and surgical shock, or may be the cause of some of the sudden symptoms in autointoxications, and many of the symptoms of infectious diseases are probably caused by the formation of anaphylatoxin. In other words, infection leads to "taraxy," as they term it. They urge the importance of the consideration that perfectly harmless substances in the blood may suddenly, under certain conditions, develop this anaphylatoxin and taraxy, and serious symptoms may immediately result.

It has been shown that surgical shock may be caused by absorption of muscle juices from the destruction of muscle tissue, and hence the condition is one of protein poisoning.

Typically anaphylaxis is a fever reaction, with rapid heart, with flushings of the skin, frequently eruptions on the skin of erythema, urticaria, or patches of angioneurotic edema, and possibly cerebral excitation. Sometimes in susceptible individuals very dangerous reactions occur from injections of serum, with swelling of the mucous membranes, especially of the bronchial tubes, with the development of asthma and dyspnea even to the point of suffocation. Such a reaction may be immediate, and has occurred when an antitoxin made of horse serum was injected into individuals who were susceptible to protein poisoning from emanations from the horse. Consequently, it is unjustifiable to inject a serum prepared from the horse into any individual without the knowledge that he is not subject to asthma or hay fever from contact with the horse. Also any asthmatic patient should be given protein injections only with the greatest of care. In such cases, at least, it is

Journal A. M. A., May 26, 1917, p. 1524.