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Rh ACCINE THERAPY. Since the discoveries of Pasteur it has become recognized that a very large number of the diseases from which human beings suffer are due to infec- tion of the tissues by living micro-organisms, most of which belong to the simpler forms of plant life.

Immunity from such infections may be natural or may be acquired. By natural immunity we understand a natural re- sistance to infection by certain micro-organisms which are known to have pathogenic properties for other species of animals. It is known, for instance, that microbes which produce a rapidly fatal disease in one kind of animal are quite innocuous when introduced even in enormous numbers into another kind.

As an example of an acquired immunity may be taken the immunity conferred as a rule for a lifetime by an attack of measles or chicken-pox. The individual who has once overcome such an infection is usually immune from a further attack, even though exposed to infection.

It is this fact which led Jenner to try to confer immunity against smallpox by producing a modified mild " attack " by vaccination with calf lymph. It is now admitted that such vaccination does confer immunity, and that even should in- fection occur the disease runs a mild course.

Since the discovery of bacteria as causative agents of disease, much study has been devoted to the part played by the cells and fluids of the tissues in recovering from bacterial infections. Evidence has been sought for response on the part of the body to the bacterial invasion. It is to Metchnikoff that we owe the knowledge that the white blood corpuscles and other cells of the body react to the introduction of bacteria into the tissues.' Enormous numbers of these cells congregate at the site of inva- sion and engulf the microbes (phagocytosis). As Sir John Burdon Sanderson aptly put it, the white blood corpuscles act as the policemen of the body.

It was soon learnt, however, that this is not the only way in which the body reacts to microbic infection. Buchner was able to show that the tissue fluids and the blood serum in particular acquire new properties as a result of bacterial infection, properties which render them highly injurious to the invading microbes. It was shown, for instance, that if actively mobile typhoid bacilli are brought into contact with the blood serum of a normal individual the bacilli are but little affected by the serum. On the contrary, if the bacilli are brought into contact with the serum of an individual convalescent from typhoid fever their mobility ceases, they are massed into clumps (agglutination) and finally killed (bactericidal action) and dissolved (bacteriolytic action). Sir Almroth Wright was able to demonstrate that a further property is acquired by the serum, namely an increased power to render the bacteria more readily ingestible by the phagocytic cells (opsonic action). Exactly how and where these new proper- ties are acquired is not yet known, but one of the most striking facts emerging from the study of these reactions is that they are directed against the particular micro-organism which has in- vaded the tissues; the reactions are said to be specific. Thus the ! blood serum of a patient convalescent from typhoid fever, which is strongly bactericidal for the typhoid bacillus, behaves like a normal serum when brought into contact with any other kind of bacteria. Similarly, while an attack of typhoid fever confers i immunity against a second infection by the typhoid bacillus, it confers no immunity from infection by other bacteria, even those so closely related as the para-typhoid bacilli.

It must be admitted that recent work goes to confirm the

opinion that there is a concomitant non-specific response common

to the reaction against all microbic infections, but this does not

detract from the importance of recognizing the highly specific


 * nature of these immunity reactions.

A very important step forward was taken when it was demon-

' strated that the body responds to the introduction into the

tissues of dead bacteria in the same way as it does when living

bacteria invade the tissues, for this made possible artificial immunization. To attempt to confer immunity against any microbic disease by the introduction of very small numbers of even attenuated living bacteria is fraught with manifest dangers, for the bacteria are capable of multiplication in the tissues and are no longer under control. To attempt to confer immunity against disease by the introduction of dead microbes into the tissues is a different matter, for the dosage can be regulated and the bacteria cannot multiply in the tissues.

Thus it was that Sir Almroth Wright proposed to confer im- munity from typhoid infection by inoculation into the healthy tissues of a standardized suspension of dead typhoid bacilli in physiological salt solution (typhoid vaccine). The immense benefit derived from such inoculations was fully demonstrated during the World War 1914-8. Wright's studies in immunization had demonstrated that it was possible to confer immunity against microbic infections by the inoculation of bacterial vac- cines into healthy individuals. It seemed at first that nothing but harm could result from the inoculation of such vaccines once the tissues had become infected. It appeared, indeed, as if to do so were merely to add more poison to a system already being poisoned. Such, however, is not the case. Pasteur was the first to show, in connexion with rabies, that beneficial results could be obtained by inoculating vaccine during the incubation period of the disease. But it was the discovery by Wright that the rapidity with which a specific response to the inoculation of a vaccine occurs depends on the dose of vaccine given, and that this response occurs very rapidly if the dose is an appropriate one, which opened up the whole field of vaccine therapy. Wright showed that the inoculation of too large a dose of vaccine can lead to a state of lessened resistance to infection and that no immunizing response follows. But this so-called negative phase can be modified as regards severity and duration by the adjust- ment of the dose, even to the point of its virtual disappearance, and nevertheless a good immunizing response follows. And such a satisfactory response occurs when vaccines are inoculated into an already infected individual. This means that, if the gravest generalized infections be excepted, there is not in microbic diseases a wholesale poisoning of the tissues of the body. There is infection of certain tissues and others remain healthy or, at all events, capable of an immunizing response. And it is to the power of these healthy tissues to respond that we turn in vaccine therapy. Just as the tissues of a healthy individual inoculated with an appropriate vaccine respond by elaborating protective substances against the microbe or microbes contained in that vaccine, and such response confers immunity on the individual, so do the healthy tissues of an infected individual respond to a vaccine containing the infecting microbe, and such a response raises the resisting power of the individual to the infection.

Now infections by microbes can broadly be divided into two classes: (a) generalized, and (6) localized. By a generalized infection we mean that the microbes and their products have ready access to the blood and lymph stream, and thus exert their baneful influence not only locally but at a distance on various tissues of the body. In a localized infection, on the other hand, the microbes affect a particular region of the body only and the remaining regions are not at all or only quite secondarily affected. From what has been said before, it is obvious that in the first class vaccine therapy has but a limited sphere of application; in the second class it has a very wide one. For it is on the satisfactory response of the tissues that the success of vaccine therapy depends and this will bear definite relationship to the healthiness of the tissues; further, the gravity of the infection must necessarily enter into account, just as a small war calls for but a small effort, whilst a great war, in which the life of a nation is at stake, calls for a maximal and sustained effort.

When it is borne in mind that the substances elaborated in response to the inoculation of a vaccine are largely carried to the