The development of all antagonistic substances which confer the special character on antimicrobic sera, as well as antitoxins, may be expressed as the formation of bodies with specific combining affinity for the organic substance introduced into the system - toxin, bacterium, red corpuscle, etc., as the case may be. The bacterium, being a complex organic substance, may thus give rise to more than one antagonistic or combining substance.

By opsonic action is meant the effect which a serum has on (c) Opsonic action. bacteria in making them more susceptible to phagocytosis by the white corpuscles of the blood (q.v.). Such an effect may be demonstrated outside the body by making a suitable mixture of (a) a suspension of the particular bacterium, (b) the serum to be tested, and (c) leucocytes of a normal animal or person. The mixture is placed in a thin capillary tube and incubated at 37° C. for half an hour; a film preparation is then made from it on a glass slide, stained by a suitable method and then examined microscopically. The number of bacteria contained within a number of, say fifty, leucocytes can be counted and the average taken. In estimating the opsonic power of the serum in cases of disease a control with normal serum is made at the same time and under precisely the same conditions. The average number of bacteria contained within leucocytes in the case tested, divided by the number given by the normal serum, is called the phagocytic index.

Wright and Douglas showed that under these conditions phagocytosis might occur when a small quantity of normal serum was present, whereas it was absent when normal salt solution was substituted for the serum; the latter thus contained substances which made the organisms susceptible to the action of the phagocytosis. They further showed that this substance acted by combining with the organisms and apparently producing some alteration in them; on the other hand it had no direct action on the leucocytes. This opsonin of normal serum is very labile, being rapidly destroyed at 55° C.; that is, a serum heated at this temperature has practically no greater effect in aiding phagocytosis than normal salt solution has. Various observers had previously found that the serum of an animal immunized against a particular bacterium had a special action in bringing about phagocytosis of that organism, and it had been found that this property was retained when the serum was heated at 55° C. It is now generally admitted that at least two distinct classes of substances are concerned in opsonic action, that thermostable immune opsonins are developed as a result of active immunization and these possess the specific properties of anti-substances in general, that is, act only on the corresponding bacterium.

On the contrary the labile opsonins of normal serum have a comparatively general action on different organisms. It is quite evident that the specific immune-opsonins may play a very important part in the phenomena of immunity, as by their means the organisms are taken up more actively by the phagocytic cells, and thereafter may undergo rapid disintegration.

The opsonic action of the serum has been employed by Sir A. Wright and his co-workers to control the treatment of bacterial infections by vaccines; that is, by injections of varying amounts of a dead culture of the corresponding bacterium. The object in such treatment is to raise the opsonic index of the serum, this being taken as an indication of increased immunity. The effect of the injection of a small quantity of vaccine is usually to produce an increase in the opsonic index within a few days. If then an additional quantity of vaccine be injected there occurs a fall in the opsonic index (negative phase) which, however, is followed later by a rise to a higher level than before. If the amounts of vaccine used and the times of the injection are suitably chosen, there may thus be produced by a series of steps a rise of the opsonic index to a high level. One of the chief objects in registering the opsonic power in such cases is to avoid the introduction of additional vaccine when the opsonic index is low, that is, during the negative phase, as if this were done a further diminution of the opsonic action might result.

The principle in such treatment by means of vaccines is to stimulate the general production of anti-substances throughout the body, so that these may be carried to the sites of bacterial growth, and aid the destruction of the organisms by means of the cells of the tissues. A large number of favourable results obtained by such treatment controlled by the observation of the opsonic index have already been published, but it would be unwise at present to offer a decided opinion as to the ultimate value of the method.

Active immunity has thus been shown to be associated with the presence of certain anti-substances in the serum. After these substances have disappeared, however, as they always do in the course of time, the animal still possesses immunity for a varying period. This apparently depends upon some alteration in the cells of the body, but its exact nature is not known.

The destruction of bacteria by direct cellular agency both Phagocytosis. in natural and acquired immunity must not be overlooked. The behaviour of certain cells, especially leucocytes, in infective conditions led Metchnikoff to place great importance on phagocytosis. In this process there are two factors concerned, viz. the ingestion of bacteria by the cells, and the subsequent intracellular digestion. If either of these is wanting or interfered with, phagocytosis will necessarily fail as a means of defence. As regards the former, leucocytes are guided chiefly by chemiotaxis, i.e. by sensitiveness to chemical substances in their surroundings - a property which is not peculiar to them but is possessed by various unicellular organisms, including motile bacteria. When the cell moves from a less to a greater degree of concentration, i.e. towards the focus of production, the chemiotaxis is termed positive; when the converse obtains, negative. This apparently purposive movement has been pointed out by M. Verworn to depend upon stimulation to contraction or the reverse. Metchnikoff showed that in animals immune to a given organism phagocytosis is present, whereas in susceptible animals it is deficient or absent.