4. The Phagocyte Theory. This theory, which gained so many adherents when first promulgated by Metschnikoff, attributes to certain cells in the tissues the powers of "scavenging," overtaking germs of disease, and absorbing them into their own protoplasm. This, indeed, may be actually witnessed, and had been observed before the time of Metschnikoff. But it was he who applied it to disease. He came to the conclusion that the successful resistance which an animal offered to bacteria depended upon the activity of these scavenging cells, or phagocytes. These cells are derived from various cellular elements normally present in the body: leucocytes, endothelial cells, connective-tissue corpuscles, and any and all cells in the body which possess the power of ingesting bacteria. If they are present in large numbers and active, the animal is insusceptible to certain diseases; if they are few and inactive, the animal is susceptible.
It appears that the bacteria or other foreign bodies in the blood which are attacked by the phagocyte become assimilated until they are a part of the phagocyte itself. Metschnikoff explained also how it comes to pass that the phagocyte is able to encounter bacteria when both are circulating through the blood. It is guided in this attack upon the organisms by a power termed chemiotaxis. The bacteria elaborate a chemical substance which attracts the phagocyte, and this is termed "positive chemiotaxis."[80] But it may occur that the chemical substance produced by the bacteria may have an opposite, or repellent, effect upon the leucocytes, in which case we have "negative chemiotaxis."[81] It is not to be wondered at that such a theory of immunity based upon microscopical observations, should at first have been widely accepted, and there can be no doubt that Metschnikoff has collected a considerable mass of evidence in support of a theory of phagocytosis. But when it came to be known that blood serum, from which all leucocytes (phagocytes) had been removed, possessed the same immunising effect as before, it was clear that such effect was a property of the serum per se, and not only or wholly due to the scavenging power of certain cells in it. Even the phagocyte theory depends largely for its validity upon chemiotaxis, which latter was a property of the products of the bacteria contained in the blood serum.
5. The Antitoxin Theory. We have gathered, then, that whenever bacteria, introduced into the blood and tissues, fail to multiply or produce infection (as in saprophytic bacteria, or in immunity of a particular animal from a specific microbe), this inability to perform their rôle is brought about by some property in the living and normal blood serum which opposes their life and action; and further we have learned that this protective property is exhaustible according to the number of bacteria, and differs with various species of bacteria, and in different animals. Buchner designates these protective bodies, held in solution in the blood, alexines, and regards them as belonging to the albuminous bodies of the lymph and plasma. Where the blood and tissues do not possess this power, the animal is susceptible. Now, as we have already seen from the experiments of Ogata, Kitasato, and others, the blood of an animal dead of anthrax is protective against anthrax, from which and the foregoing it appears that microbes produce by their growth in the tissues poisonous substances we term toxins, which have the power of producing in the blood and body cells substances inimical to themselves, named antitoxins, and so long as these latter substances remain in the tissues the body remains insusceptible to further attacks of the same disease. Alexines are naturally produced antitoxins; antitoxins are acquired alexines. Hence we have the well-known terms "natural" and "acquired immunity." Of the former we have already spoken. Acquired immunity is a protection not belonging to the tissues of individuals naturally and as part of their constitution, but it is acquired during their lives as a further accomplishment, so to speak, of their tissues. This may happen in one or both of two ways. Either it may be an involuntary acquired immunity, or a voluntary acquired immunity. For example, the former is at once illustrated by an attack of the disease.
Small-pox, typhoid fever, even scarlet fever, are diseases which very rarely attack the same individual twice. That is because each of these diseases leaves behind it, on its first appearance, its antitoxic influence. Hence the individual has involuntarily acquired immunity against these diseases. An example of voluntary acquired immunity is also at hand in the old method of preventive inoculation for small-pox, or variolation. This was clearly an inoculation setting up an artificial and mild attack of small-pox, by which the antitoxins of that disease were produced, and protected the individual against further infection of small-pox; that is to say, it was a voluntary acquired immunity. This form of artificial production of protection is generally called artificial immunity. Let us now marshal together these various terms in a table as follows:
| Immunity in man = a condition of protection of insusceptibility to certaindiseases. | ||
| 1. Natural immunity = constitutional protection produced by alexines. | ||
| 2. Acquired immunity | ||
| = |  | Acquired naturally (involuntarily) produced by antitoxins formed byan attack of the disease. |
| Acquired artificially (voluntary)= | ||
(a) Active immunity, produced by direct inoculation of the weakenedbacteria or weakened toxins of the disease, e. g., vaccination,or Pasteur's treatment of rabies, or Haffkine'sinoculation for cholera. | ||
(b) Passive immunity, produced by inoculation, not of the diseaseof an animal suffering from the specific disease. | ||
It is hoped that previous remarks will have explained the meaning of the terms used in the above table, with the exception of the last two phrases of active and passive immunity. We propose now to consider in some detail the four illustrations quoted under these two headings, viz., vaccination, Pasteur's treatment of rabies, anti-cholera inoculation, and antitoxin inoculation. From all accounts, it is to be feared that these four phases of artificial immunity are hopelessly confused in the educated public mind. Nor is this to be wondered at when we reflect upon the rapid growth of the whole science of immunity, and upon the ever-varying forms of nomenclature through which it has passed.
Vaccination for Small-pox. In 1717 Lady Mary Wortley Montagu[82] described the inoculation of small-pox as she had seen it practised in Constantinople. So greatly was she impressed with the efficacy of this process that she had her own son inoculated there, and in 1721 Mr. Maitland, a surgeon, inoculated her daughter in London. This was the first time inoculation was openly practised in England.[83] For one hundred and twenty years small-pox inoculation (or variolation, as it is more correctly termed) was practised in England, until by Act of Parliament in 1840 it was prohibited.
There were different ways of performing variolation, but the most approved method was similar to the modern system of arm-to-arm vaccination, the arm being inoculated with a lancet in one or more places with small-pox lymph instead of, as now, with vaccine lymph. As a rule, only local results or a mild attack of small-pox followed, which prevented an attack of natural small-pox. Its disadvantage is apparent on the surface. It was a means of breeding small-pox, for the inoculated cases were liable to create fresh centres of infection. In 1796 Edward Jenner, who was a country practitioner in Gloucestershire, observed that those persons affected with cow-pox, contracted in the discharge of their duty as milkers, did not contract small-pox, even when placed in risk of infection. Hence he inferred that inoculation of this mild and non-infectious disease would be preferable to the process of variolation then so widely adopted in England. Jenner therefore suggested the substitution of cow-pox lymph (vaccine) in place of small-pox lymph, as in ordinary variolation.
It should not be forgotten that variolation was thus the first work done in this country in producing artificial immunity, and was followed by vaccination, which was only partly understood. Even to-day there is probably much to learn respecting it. Both variolation and vaccination may be described as active immunisation by means of an attenuated form of the specific virus causing the disease. The nature of the specific virus of both small-pox and cow-pox awaits discovery. Burdon Sanderson, Crookshank, Klein, and Copeman have all demonstrated bacteria in cow-pox or vaccine lymph, and in 1898 Copeman announced that he had isolated a specific bacillus and grown it upon artificial media.[84] Numerous statements have been made to the effect that a specific bacillus has been found in small-pox also. But neither in small-pox nor cow-pox is the nature of the contagion really known.[85]
These facts, however, do not remove the suspicion which has hitherto rested upon vaccine lymph as a vehicle for bacteria of other diseases which by its inoculation may thus be contracted. A few remarks are therefore called for at this juncture upon the recent work of Dr. Monckton Copeman and Dr. Frank Blaxall in respect to what is known as glycerinated calf lymph. Evidence has been forthcoming to substantiate in some measure the distrust which many of the public have from time to time felt in the vaccine commonly used in vaccination, hence the new form as above designated. This retains the toxic qualities required for immunity, but is so produced that it possesses in addition three very important advantages; namely, it is entirely free from extraneous organisms, it is available for a large number of vaccinations, and it retains full activity for eight months. It is prepared as follows: