Further, it was found by numerous estimations of the strength of opsonins in the sera of individuals suffering from the various infections that, as a rule, the patient getting worse or no better showed a lower strength than he did when getting better, or another would when he was recovering. Carrying out this idea further, Wright considered that one way to assist nature to resist infection was to bring about a higher strength in the opsonins of that patient's serum. It is upon this theory that vaccine therapy is based - i. e., a low opsonic content of a patient's serum is raised and maintained at a higher level. This aids in the phagocytic power of the patient's white blood-cells, as explained above, and therefore works toward the destruction of the invading germ. After long months of experiment Wright has devised:

1. A method of estimating the opsonic strength of a given serum relative to a given germ.

2. A method of raising that strength, if low, and maintaining it at a high point.

In order to have some standard for comparison the opsonic content of a patient's serum is always contrasted with that of a "normal "person's serum, and the result is called the "opsonic index,nd if the patient is, for example, a tuberculous one, we speak of the patient's tuberculo-opsonic index as being so and so. The normal index is always (arbitrarily) considered as I. The patient's index may be 1 or above, or below 1.

In order to understand the method Wright devised for estimating the opsonic index we must consider the factors that enter into the actual mechanism of opsonification and phagocytosis in any given field of tissue. We have then:

(1) The opsonins in the patient's serum; (2) the white blood-cells, and (3) the invading germs; and then, for comparison, we must take a fourth factor - (4) the opsonins in a normal serum.

Opsonins so act upon the germs as to render them subject to phagocytosis. A serum strong in opsonins would cause more phagocytosis than one weak in opsonins. A definite amount of serum is, therefore, mixed with a definite amount of bacteria and to this mixture is added a definite amount of white cells. This mixture is all placed in a suitable receptacle and in an incubator for a certain length of time. During this incubation the opsonins have an opportunity of acting upon the bacteria, and then these satisfied bacteria are taken up by the leucocytes. To just what extent they are taken up depends the estimation of the phagocytic, and therefore the opsonic, power of the serum with which we are dealing. If we now take a drop of the incubated mixture and spreading it out on a slide, stain it with suitable stains, we can actually see and count the bacteria that have been ingested by the white blood-cells. If we count 50 or 100 cells, and the number of bacteria in each, we can estimate the average number in each cell. This is called the bacterial average of the patient's serum.

Now, if we go back and "run through" a similar experiment, using the same amount of the same leucocytes and the same amount of the same bacteria, with a similar amount of normal serum (obtained from the blood of a healthy individual), we can in like manner obtain a bacterial average of a normal serum under exactly the same conditions as we obtained the bacterial average of the patient's serum.

As has been explained above, we always consider the opsonic index of the normal as 1. Now, to obtain the opsonic index of the patient we use a simple proportion. The normal bacterial average is to the patient's bacterial average as the normal opsonic index (1) is to the patient's opsonic index (or x).

The white blood-cells are obtained for such experiments from any healthy blood. The same cells are, of course, used in both mixtures. The bacteria are collected into a salt solution in suitable amounts. (The exact technique followed in the many different steps is quite accessible in the literature.)

Having a method then of estimating the strength of opsonins in a given serum we are to consider the two statements already made - that (1) it has been found that a patient not improving has usually a low index, and (2) if we raise that index, we can materially assist the patient in the struggle against the specific infection.

Wright has also, as said above, devised a method by which thindex can be raised and maintained. It is this: At least two very important things happen when a pathogenic germ invades a tissue: (1) the number of white blood-cells is increased by what is known as chemotaxis; (2) the opsonins specific for the invading germ are increased in number. Just where the opsonins are manufactured and poured out into the serum is not definitely known. Some think the endothelial cells lining the blood-vessels are their progenitors; others that they come from the fixed connective-tissue cells, and others again believe that the opsonins are elaborated by the white blood-cells themselves. However that may be, when the pathogenic germ is introduced, we find that for a time at least the tissue-cells somewhere are stimulated to secrete more opsonins. If this "natural" increase in leucocytes and opsonic power proves strong enough, the invading germ is overcome and the patient's immunity strength or some part of it is raised sufficiently to cause recovery. If, on the other hand, this does not take place, the patient gets worse and the therapeutic effort now is to increase the amount of white cells and opsonins by artificial means. Arguing from the above, and appreciating that although we can raise the number of leucocytes by various means, "this does not avail much," Wright made the extremely important discovery that if we take a growth of the same bacteria that are doing the mischief, and sterilize it so that it cannot do any more harm, and then inject into the patient's tissues this sterilized bacterial suspension, the opsonic strength will, after a primary fall, be raised, and if proper inoculations of such suspension be given at proper intervals, it is possible to maintain the opsonic index at a high level. * This is the basis of vaccine therapy, and the vaccines given to-day are suspensions in salt solution of the same bacteria that are causing the patient's infection and that have been sterilized and accurately measured as to dose, etc. When we say that " we treat a patient according to the opsonic index," we mean that we make frequent examinations of the patient's blood, and when we find that this index is low, we inoculate him with a vaccine that will raise this index to the level of, or above that of, a normal index. This is in contrast to the clinical method of the treatment, where no estimations of the index are made, but the vaccines are given at stated intervals and with dosage that seems to be followed by the most clinical improvement.

This then is a mere outline of the question of opsonic index and vaccine therapy. There are, of course, very many theoretical, technical, and practical factors that must be carefully considered in each step of the procedure before we can fully explain the status of the question of opsonins and the therapy.

Since the above technique, offering a definite practical therapy, has been brought out by Wright, many men throughout the world.

* Of how much real value it is artificially to increase the number of white blood-cells, and wh t method (nucleinic acid, horse serum, etc.) is best, we do not yet know. There is a general tendency to-day toward attributing more and more importance to the phagocyte, and efforts are being energetically made to determine just how and when or under what conditions the greatest phagocytosis takes place in the body of the infected patient.

have been investigating the truth of his suggestions and claims. The great questions have been:

1. Of what importance are opsonins as a factor in immunity?

2. Can we truly estimate the exact content of a given serum in opsonins by this somewhat elaborate technique of Wright's?

3. To what extent should we base our therapy upon the opsonic index, and to what extent upon the clinical findings?

The following will probably cover pretty accurately the present status of our knowledge in attempting to answer the above questions:

1. It is generally admitted that there are in the blood-serum chem-ico-physical bodies which have been appropriately called opsonins.

2. These opsonins have some specific action on certain bacteria as to render them more subject to phagocytosis.

3. "Normal" sera have pretty definite amounts of opsonic content, which do not vary to any great extent in health.

4. The opsonic content of a serum taken from an infected individual is quite apt to be found without the limits - i, e., either above or below.

5. The value of a number of successive estimations of opsonic content is of distinct diagnostic value as to variety of bacterium causing the individual infection.

6. Administration of the so-called vaccines has a tendency to raise a low index if properly given as to time and interval.

7. Administration of vaccines at suitable intervals and with suitable dosage is very frequently followed by marked clinical improvement.

8. Just what part in the machinery of immunity opsonins play is not yet understood.

9. To exactly what extent we can rely upon the opsonic index (as estimated by our present technique) to be a true index of the opsonic factor in immunity we cannot yet say.

10. In spite of the wide-spread tendency to administer the vaccines according to clinical findings it is probably most accurate, in the majority of cases, to follow the index as a guide.

Vaccine therapy based upon opsonins applies, of course, to those bacterial diseases which are combated, mainly at least, by phagocytosis. These include what is known as surgical infections, and are represented, for example, by the streptococcus, staphylococcus, colon bacillus, gonococcus, tubercle bacillus. The blood has no bactericidal or antitoxic effect upon these organisms, and it is only by phagocytosis, as far as we know, that these bacteria are resisted.

The best clinical results so far reported have been in chronic localized infections, such as lupus, tuberculosis of bones, joints, and urinary tract. In chronic staphylococcus infections of skin and subcutaneous tissues, as sycosis, boils, carbuncles, and acne, quite marked improvement is often noted. In joints inflamed by the gonococcus and in chronic colon bacillus infections of bladder or kidney occasional cures are to be expected. Marked results are reported in individual cases of infections by streptococcus proteus, influenza bacillus, diplococcus intracellularis, etc.