Paul R. Cannon

The Relationship of Protein Metabolism to Antibody Production and Resistance to Infection

Publisher Summary This chapter focuses on the relationship of protein metabolism to antibody production and resistance to infection. The particular feature that differentiates acquired from natural resistance is the antibody mechanism. The protein nature of antibodies is now generally accepted because analytical, ultracentrifugal, and electrophoretic measurements all show highly purified antibodies to be typical proteins. If antibodies are specifically modified plasma globulins, a prolonged inadequacy of protein intake severe enough to cause a marked depletion of the protein reserves should also lessen the capacity of the antibody-producing tissues to synthesize specific antibody. A lessened antibody output is caused by severe protein deficiency and a depletion of the protein reserves; repletion of these reserves should restore the capacity of the antibody-producing tissues to form antibody. Protein repletion may affect both the protein reserves and the antibody-producing tissues whose structural and functional integrity may have been impaired by severe and prolonged starvation. Thus, the phagocytic cells of the liver, spleen, lymph nodes and lymphoid tissues, and bone marrow require a constant supply of amino acids and other nutrient materials.

Changing patterns of disease

0 F THE many unusual events which characterized the first half of the present century, especially in this country, one of particular significance to medicine was the development of marked changes in established patterns of disease. Tonight I wish to discuss a few of these changes from the standpoints of their nature and their underlying causes. The ones to be considered are the resultants of a series of medical discoveries which themselves were fitting accompaniments of a truly remarkable half-century. Over a period of but a few decades pathologic patterns originally established as a result of bacterial interactions with tissues merged into patterns of viral dominance and then into alterations produced by an increasing variety of metabolic, neoplastic, and retrogressive stimuli. In the course of these changes some of the older diseases tended to disappear, to be replaced by newer diseases and by newer problems. The disappearance of the older diseases is a fitting testimonial to the creative talents of the many gifted scientists who, through their discoveries, displayed some of the artistic and scholarly attributes which constitute the essential core of the humanities as we now conceive them.

Fatal agranulocytosis following sulfathiazoletherapy

Summary A case of acute and fatal agranulocytosis with toxic dermal lesionsproduced by therapeutic doses of sulfathiazole, occurring in an infant 8 weeks old, is reported. At the time of this writing, no other cases of agranulocytosis following sulfathiazole medication in infants have been recorded, although instances of extreme granulocytopenia in children due to other members of the sulfonamide group have been observed. An experience of this sort re-emphasizes the necessity of exercising the utmost care in the therapeutic use of sulfathiazole in infants and children and of making frequent blood examinations as well as of determining the concentration of the drug in the blood. Despite the fact that absolute proof of this sulfonamide being the sole cause of agranulocytosis is lacking, the circumstantial evidence in our case strongly suggests that both intoxication by and sensitization to this drug played significant roles in the production of the toxicodermatosis as well as of the agranulocytosis which resulted in the death of the patient.

Local Formation of Antibody by the Nasal Mucosa

The importance of the upper respiratory tract as a portal of entry for pathogenic micro-organisms amply justifies attempts to increase its resistance against their invasion. We have recently shown 1 that the local introduction of antigen into an area of mobilized histiocytes leads to the local formation of specific antibody. We have extended such studies to the nasal mucosa, assuming that a similar response might be obtained there following repeated applications of an antigen. This assumption was based on the probable mobilization of cells of inflammation in the mucosa, with consequent fixation of antigen among differentiated histiocytes. Rabbits were treated intranasally at daily intervals of 2 to 13 days with a formolized vaccine of Bact. paratyphosum B., either by insufflation (2), by instillation alone (12), or by instillation subsequent to earlier instillation of ox bile (1). The animals were then allowed to rest for 1 to 12 days, and were sacrificed. The nasal mucosa, lung, liver, spleen, and blood serum were mixed with 15 parts of a solution of equal parts of glycerol and 0.85% solution of sodium chloride. They were then ground in a mortar, with the exception of the serum, and extracted at 37°C. for 7 days. These extracts were titrated simultaneously against a living suspension of Bact. paratyphosum B. Six of the 19 animals were perfused with citrated salt solution immediately after death to remove the blood as far as possible from the organs to be extracted. Most of the blood was removed from all except the spleen. The content of agglutinin in the nasal mucosa in animals treated daily by insufflation or instillation for at least 11 days was always distinctly higher than that of either the spleen or liver.

Studies in Local Immunization of the Lungs of Rabbits with Pneumococcus Type I

Accumulating evidence indicates that an enhanced resistance to bacterial infection may be produced locally as well as generally. To gain further information as to the mechanism of this local immunity we have immunized rabbits intrapulmonically, subcutaneously and intravenously with a pneumococcal vaccine (Type I) and at a later period have tested the resistance of these animals to living pneumococci introduced intratracheally. We have also attempted to determine the fate of the pneumococci, both as to their retention within the lungs and their rates of appearance and disappearance in the blood stream. Adult male rabbits weighing from approximately 3000 to 4000 gm. were immunized daily for from 4 to 6 days by injections of one cc. of a formolized vaccine of pneumococci. The vaccine was prepared by growing the pneumococci in Kolle flasks and adding 0.2 cc. of formalin to each 100 cc. of the bacterial growth suspended in 0.85% solution of sodium chloride. The intratracheally treated animals were immunized by means of a curved metal tube introduced into the trachea through the mouth; the others were immunized by subcutaneous and intravenous injections of similar amounts of the vaccine. The turbidity of the vaccine was between that in tubes 1 and 2 of the McFarland nephelometer. From 5 to 15 days after the final treatment the animals were infected in groups of 4, consisting of one normal rabbit and an animal immunized by each of the 3 ways mentioned. The 24-hour growth from a blood agar slant of a living pneumococcus culture, Type 1, was suspended in 8 cc. of sterile broth, and 2 cc. was then introduced intratracheally into each of the 4 animals through the metal tube inserted into the trachea. Blood was obtained by cardiac puncture at 5, 10, 15, 30, 45, and 60 minute intervals after infection and cultures made by plating duplicate amounts of one cc. with veal infusion agar, pH 7.6.

Anemia following Splenectomy in White Rats.

Numerous European workers have observed that rats frequently develop a severe anemia following removal of the spleen. That this is not always the case, however, is shown by the fact that in certain laboratories splenectomy of rats has not been followed by anemia. Lauda 1 made an extensive study of this problem and found that in approximately 75% of his splenectomized rats, a very severe hemolytic type of anemia developed. He proved it to be of an infectious nature and transmissible to other splenectomized rats. Shortly afterward, Mayer, Borchardt and Kikuth, 2 in repeating Laudas work, observed within 24 to 48 hours after splenectomy, small rod-like or dumb-bell shaped inclusions in the erythrocytes. These later increased in numbers until at the height of the anemia there were 12 or more within each erythrocyte, appearing with the Giemsa stain as reddish coccobacillary forms. They concluded that these inclusions were identical with the ones observed by Mayer 3 in 1921 and named Bartonella muris ratti because of their similarity to the inclusions found in the erythrocytes of patients with Oroya fever. We have similar findings in white splenectomized rats. The effect depends primarily upon the source from which the rats were obtained. In 13 rats recently obtained from the Wistar Institute and the Albino Supply Company stock, we have found that no significant anemia follows removal of the spleen. In 2 Wistar rats, however, which had been in the animal room for several months, splenectomy was followed by a very severe anemia. We splenectomized 11 rats obtained from Chicago dealers and in every case, usually about the fifth day, a marked anemia has developed. This anemia appears to be identical with that described by Lauda as “the infectious anemia of rats.”