1. In normal unheated human serum, virulent pneumococci may be prepared for phagocytosis by two separate antibodies, acting in conjunction with complement. One of these is the type-specific anticarbohydrate antibody reacting with the carbohydrate fraction of the pneumococcus. The other is probably also a type-specific antibody, but quite distinct from the former, and therefore must react with a different antigenic constituent of the bacterium. 2. In the normal human serum heated to 56°C., these two antibodies may, after prolonged contact with the organism, promote phagocytosis of the pneumococcus without the adjuvant action of complement. 3. Although these two antibodies are equally effective in the phagocytosis of 24 hour culture organisms by normal blood, the anticarbohydrate antibody tends to become the predominant factor as the pneumococci approach the state in which they exist in the animal body. 4. In so far as we have been able to show, the anticarbohydrate antibody is the only antibody in immune serum which can induce phagocytosis. This substance by itself is active in a phagocytic system, but just as in the normal serum, complement enhances its effect. The failure to demonstrate the presence in the immune serum of an antibody, distinct from the anticarbohydrate antibody, analogous to that found in the normal serum, may be due to the experimental difficulty of removing all the anticarbohydrate antibody from a concentrated immune serum. 5. Thus it is seen that a single well defined antibody (the anticarbohydrate antibody) may be responsible for the phagocytic action of normal unheated serum, normal heated serum, inactivated immune serum, and immune serum activated by complement. These facts appear to us to invalidate Neufeld's division of the phagocytic antibodies into (a) bacteriotropins (antibodies, the phagocytic titre of which is not raised by the addition of complement); (b) opsonic antibodies (antibodies, comparable to the lysins, which are only active in the presence of complement). 6. Complement alone is incapable of inducing phagocytosis of the pneumococcus. In the phagocytic process, it appears simply to increase the speed at which the reaction takes place. Its role may be compared to that of a catalyst in a chemical reaction. 7. On the basis of these findings, it is proposed that the term "tropin" be discarded as misleading and unnecessary, and that the term "opsonin" be retained to denote any heat-stable antibody which prepares bacteria for phagocytosis. Contrary to current usage, it would not suggest a combination of antibody with complement.
Lymph nodes have two obvious functions, the production of certain cells and the arrest of foreign material brought to them by the lymph. The second of these functions, that is, the filtering capacity of the nodes, has been the subject of a large amount of indirect experiment and speculation. It would be unprofitable and entirely repetitive to describe this work in view of the excellent reviews of Hellman (1) and Oeller (2).The nodes are held to provide two sorts of filtration, the first of simple mechanical type and the second biological--due particularly to the phagocytic activity of the reticulo-endothelial cells. Opinions as to the combined efficiency of these two types--normal nodes alone being under consideration--vary from assertions of complete effectiveness to very much the reverse.As a result of a great deal of experience with the lymphatics in the hind leg of the dog, it became relatively simple for us to perfuse the popliteal and iliac lymph nodes under conditions of pressure and flow normal for the animal and with the blood circulation completely intact. Prior to a description of typical experiments it will be well to review the architecture of a lymph gland, such as the popliteal node of the dog, together with what is known of the normal flow of lymph through it.Text- fig. 1 is a drawing of a popliteal node injected with a dilute solution of India ink. The injection mass has been delivered through a cannula in one of the large trunks along the saphena parva vein. The injection pressure was 20 mm. of mercury. This is less than the 393
It could be said with little fear of contradiction that the hemolytic streptococcus presents a more hazy picture to bacteriologists and immunologists than does an organism like the pneumococcus. Its study presents many difficulties. In the first place, many strains which are pathogenic for man may show little or no primary virulence for animals. In the second place, antisera cannot be produced readily and consistently against all pathogenic strains. In the third place, although it is certain that many different types exist, typing by agglutination is full of pitfalls, both in technique and in the interpretation of results.It seemed to us that the foundation for any work on the hemolytic streptococcus was a careful study of the characteristics of the organism on first isolation from the body, and the ways in which it changed on mouse passage or culture passage; and the results of this part of the work are recorded in this first paper. We were aided in this investigation by the studies of several workers in this field, although it was sometimes difficult to correlate their descriptions of the variants of the hemolytic streptococcus with our own observations. Cowan (1) was the first to correlate cultural characteristics with virulence. She described a virulent S colony and an avirulent R colony. These variants were apparently found in stock laboratory cultures.
1. The phagocytic titre of whole human blood against the three types of pneumococcus was determined in a number of individuals. The titre varied over a considerable range in different subjects. 2. Contrary to expectation, the titre in early cases of untreated pneumonia was quite high against the infecting organism, pointing to a local rather than a general lowering of resistance in infection with this organism. 3. Sia's work was confirmed, that the specific carbohydrate has a specific anti-phagocytic action on the blood. This action is more marked in the case of Type III than in Type I.
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