Heat-killed Tubercle Bacilli Research Articles

Studies on the interaction between phagocytes and tubercle bacilli. I. Observations on the metabolism of guinea pig leucocytes and the influence of phagocytosis.

As a basis for studies on the interaction of phagocytes and tubercle bacilli experiments were carried out to obtain information on some biochemical characteristics of exudate leucocytes from guinea pigs. It was found that total cellular phosphorus was the most suitable measure of protoplasm. Cell counts were less reliable because of unavoidable clumping in the suspension, and dry weight measurements were less specific when contamination with erythrocytes occurred. The utility of phosphorus measurements in this connection depends upon the fact that an erythrocyte contains only 4 per cent of the phosphorus present in a leucocyte. From measurements on mixed suspensions consisting of varying known proportions of polymorphonuclear and mononuclear leucocytes as determined by differential counting, it was possible to compute true values for these two cell types with respect to oxygen consumption and lactic acid production. Thus it was found that monocytes consumed considerably more oxygen and produced more lactate than polymorphonuclear leucocytes. From the data obtained it is suggested that differences in metabolic activity found when comparing cell suspensions obtained by the use of different irritants are due to different proportions of the two cell types. In particular, the effects of oxygen tension and pH on the activities of the cells were studied. It was found that decreasing the proportion of oxygen in the atmosphere from that of air to 1 per cent reduced oxygen consumption by about 80 per cent, whereas lactic acid production was increased by about 45 per cent. It was also found that decreasing the pH of the medium below pH 7.5 caused a considerable reduction in the respiration, lactate production, and viability of polymorphonuclear leucocytes. The monocytes proved less sensitive to similar changes in pH, especially with regard to lactic acid production and viability. Observations were made of oxygen consumption and lactate production during phagocytosis. During the hour following the addition of heat-killed tubercle bacilli to the phagocytes, the oxygen consumption of suspensions rich in polymorphonuclear leucocytes rose by 60 per cent, and that of suspensions rich in monocytes rose by nearly 100 per cent. Lactic acid production was unchanged during phagocytosis.

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの冤疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの冤疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

結核加熱死菌免疫における流動パラフィンAdjuvantの免疫増強機序に関する実験的検討

The Influence of Cortisone on the Disposal of Heat-Killed Tubercle Bacilli by the Sensitised Guinea-Pig

The Influence of Cortisone on the Disposal of Heat-Killed Tubercle Bacilli by the Sensitised Guinea-Pig

Effect of adrenalectomy on tuberculin reaction in mice.

Summary1. Albino swiss mice immunized with heat-killed H37Rv tubercle bacilli in mineral oil of with active BCG infections are relatively anergic to PPD and O.T. used for skin tests. 2. Bilateral adrenalactomy does not reverse mouse tuberculin anergy.

Symposium

This review will describe certain developments which have appeared recently in the immunologic literature involving the transfer of viable cells from one animal to another. In 1940 Landsteiner and Chase showed that it was possible to remove cellular exudates from guinea pigs sensitized with simple chemical compounds, wash these cells and transfer them to fresh guinea pigs and then to demonstrate in the recipient guinea pigs dermal sensitivity to the original compound. More recently, Dr. Merrill Chase sensitized guinea pigs with o-chlorobenzoyl chloride: paraffin oil had been injected intraperitoneally into these animals 48 hours before, in order to induce the necessary cellular accumulation. These cells were collected, washed and injected into a recipient guinea pig, which thereupon developed a positive reaction to the allergen. Similar experiments were done with cells secured from lymph nodes of sensitized guinea pigs and in the case of heat-killed tubercle bacilli suspended in hydrocarbon as antigen. The same phenomenon has been demonstrated by Metaxas with intradermally injected cells, and by Lawrence in the human species with leucocytes collected from blood and injected intradermally. Tissue reactions of the immediate type of hypersensitivity have also been demonstrated by Chase as a function of transferred cells by the use of the Schultz-Dale technic, as well as by an adaptation of the PK type of reaction to the measurement of classical antibodies. It was felt in our laboratory that this type of approach might provide more direct information on the mechanism of antibody formation in the cells involved. Accordingly, a study of such cells was undertaken, using largely bacterial cells as antigens and measuring the agglutinins produced thereto.

The effect of adrenocorticotropic hormone on inflammation due to tuberculin hypersensitivity and turpentine and on circulating antibody levels.

The treatment with adrenocorticotropic hormone of guinea pigs sensitized with heat-killed tubercle bacilli caused suppression of their skin reactivity to tuberculin. Similar animals treated with saline did not show this change. Normal guinea pigs treated with adrenocorticotropic hormone showed suppression of inflammation, but not necrosis, produced by intracutaneous oil of turpentine. There was slight, but probably not significant, diminution of inflammation during saline administration. Tuberculin complement-fixing antibody titers were not altered by either adrenocorticotropic hormone or saline administration. Adrenocorticotropic hormone produced marked eosinopenia and lymphopenia in guinea pigs.

Increased in vitro tuberculin leucocyte cytolysis following a tuberculin skin test.

Guinea pigs which have been sensitized to tuberculin by the injection of heat-killed tubercle bacilli in paraffin oil show and increased in vitro tuberculin leucocyte cytolysis within 48 hours after a positive intracutaneous tuberculin reaction.

Tuberculin Reaction. III. Transfer of Systemic Tuberculin Sensitivity with Cells of Tuberculous Guinea Pigs.

SummaryThe results of the present investigations establish tlhat systemic tuberculin sensitivity can be passively transferred in the guinea pig with the cells of induced peritoneal exudates of tuberculous donors. The systemic shock produced in recipients passively sensitized in this manner is of the typical delayed tuberculin type. These findings supplement the observation of Chase1 that cutaneous tuberculin sensitivity can be passively transferred in the guinea pig with the cells of induced peritoneal exudates of donors sensitized with heat-killed tubercle bacilli by providing additional evidence that the sensitivity transferred is of the tuberculin type. In a limited number of trials it was also found that desensitization of tuberculous donors with tuberculin tends to abolish the capacity of their peritoneal cells to passively transfer tuberculin sensitivity. If this observation is confirmed it will provide strong evidence that desensitization results from the saturation of fixed cellular antibody with ...

Antibody formation in a lesion produced by tubercle bacilli suspended in paraffin oil. Excision of the antigenic depot: Westwater, J. O.: J. Immunol. 38: 267, 1940

Summary When heat-killed tubercle bacilli in paraffin oil are used as antigen, excision of the antigenic depot within 1 hour is not followed by antibody formation, but when excision is delayed 6 hours or longer it does not prevent the appearance of complement fixing antibody in the serum. The ultimate serum titer is lower when excision is performed before the thirtieth hour than in those animals in which excision is later, or in those from which the lesion is not excised. Complement fixing antibody appears earlier in the serum of the rabbits from which the lesions are excised than in those from which lesions are not excised.

Antibody Formation in a Lesion Produced by Tubercle Bacilli Suspended in Paraffin Oil: Excision of the Antigenic Depot

Summary When heat-killed tubercle bacilli in paraffin oil are used as antigen, excision of the antigenic depot within 1 hour is not followed by antibody formation, but when excision is delayed 6 hours or longer it does not prevent the appearance of complement fixing antibody in the serum. The ultimate serum titer is lower when excision is performed before the thirtieth hour than in those animals in which excision is later, or in those from which the lesion is not excised. Complement fixing antibody appears earlier in the serum of the rabbits from which the lesions are excised than in those from which lesions are not excised.

Sensitization to tuberculin produced in children by heat-killed tubercle bacilli: Flahiff, E. W.: Am. J. Hyg. 30: 65, 1939

Sensitization to tuberculin produced in children by heat-killed tubercle bacilli: Flahiff, E. W.: Am. J. Hyg. 30: 65, 1939

The Synergistic Effect of Paraffin-Oil Combined with Heat-Killed Tubercle-Bacilli

Abstract We have referred in a previous paper to the earlier literature on the synergistic effect of various antigenic and non-antigenic substances on immunization (1). Ramon, Lemetayer and Richou (2) had shown that lanolin and other substances added to diphtheric toxin promote the formation of antitoxin in the guinea-pig and rabbit. Coulaud (3) succeeded in producing intense and persistent sensitization of rabbits with heat-killed tubercle-bacilli incorporated in paraffin. Saenz (4) found that paraffin oil could be substituted for solid paraffin. Freund, Casals and Hosmer (1) observed that repeated injections of small numbers of killed tubercle-bacilli suspended in small amounts of paraffin-oil are followed not only by enhanced sensitization but also by heightened and persistent antibody-formation. The synergistic effect of paraffin-oil became evident strikingly when it was employed in Macacus rhesus monkeys. Burnet (5) and Fox (6) reported that the skin of this species of animal does not develop sensitivity to ordinary amounts of tuberculin even in the presence of extensive tuberculosis.

SENSITIZATION TO TUBERCULIN PRODUCED IN CHILDREN BY HEAT-KILLED TUBERCLE BACILLI1

Journal Article SENSITIZATION TO TUBERCULIN PRODUCED IN CHILDREN BY HEAT-KILLED TUBERCLE BACILLI Get access E. W. FLAHIFF E. W. FLAHIFF Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 30-SectionB, Issue 2, September 1939, Pages 65–68, https://doi.org/10.1093/oxfordjournals.aje.a118577 Published: 01 September 1939 Article history Received: 03 March 1939 Published: 01 September 1939

Caseation and Softening in Tuberculosis of Vaccinated and Unvaccinated Guinea Pigs

There is much evidence that vaccination with the BCG strain of the tubercle bacillus produces a certain degree of resistance to reinfection with virulent tubercle bacilli. The question has been raised, however, as to whether the allergy resulting from such vaccination might be a factor in producing a more extensive and more destructive type of tuberculosis. In an experiment to ascertain if any relationship exists between allergy and the character of the tuberculous lesions, one series of guinea pigs was injected subcutaneously in the left inguinal region with 5 mg. of the BCG culture, a second series was injected in a similar manner with 30 mg. of the virulent Ravenel strain of bovine tubercle bacillus killed by heating for 1 hour at 70°C., and a third group of unvaccinated guinea pigs were used as controls. Six weeks after vaccination the sensitivity of these animals to old tuberculin was determined by injecting into the skin of each animal, at widely separated points, 1, 5 and 10 mg. of old tuberculin, and reading the results 48 hours later. It was found that among the 14 guinea pigs of the first series, injected with BCG, 9 reacted to 1.0 mg. of tuberculin and 5 to 5.0 mg. Of the 15 guinea pigs of the second series, injected with the heat-killed tubercle bacilli, 3 reacted to 1.0 mg. of tuberculin, 6 to 5.0 mg., 5 to 10.0 mg., and one failed to react. The 11 untreated control guinea pigs did not react to the injection of tuberculin. The vaccinated as well as the unvaccinated control animals were then injected intratracheally while under ether anesthesia with approximately 100 tubercle bacilli of the virulent Ravenel bovine strain. Six weeks later all of the animals were killed and necropsied.

THE DEGREE OF DISPERSION OF THE BACILLUS AS A FACTOR IN INFECTION AND RESISTANCE IN EXPERIMENTAL TUBERCULOSIS

1. The skin lesions in rabbits and guinea pigs following intradermal injection of tubercle bacilli (5 strains) were greatly increased in size and severity when testicle extract was added to the inoculum. Such enhancement was followed by a more widespread and rapidly progressing disease only when virulent strains were employed. 2. Attempts to suppress the development of skin lesions resulting from the injection of either normal or tuberculous rabbits with very small quantities of tubercle bacilli mixed with testicle extract were unsuccessful. 3. The skin reactions of tuberculous guinea pigs to tuberculo-protein MA 100 were greatly increased in size and markedly reduced in intensity by the addition of testicle extract to the protein solution. The toxic effect of larger quantities of tuberculo-protein was not altered by the addition of testicle extract. 4. The dispersion of tubercle bacilli through the skin of tuberculous rabbits resulted in a marked enhancement of the Koch phenomenon but was not followed by any extension of the new infection to the viscera. Tuberculous rabbits infected on two occasions with dead tubercle bacilli suspended in testicle extract showed an increased resistance to the disease when compared with controls receiving dead bacilli suspended in saline solution. 5. The resistance conferred upon tuberculous guinea pigs by superinfection was greatly increased when the bacilli employed were dispersed through the skin with testicle extract. 6. The parenteral administration of large quantities of testicle extract to recently infected guinea pigs did not result in any increase in the extent of the visceral lesions. 7. The partial immunity conferred upon guinea pigs and rabbits by vaccination with heat-killed tubercle bacilli was increased as a result of dispersion of the vaccine through the skin with testicle extract.

FATE OF CHILDREN OF TUBERCULOUS FAMILIES. INCLUDING THOSE TREATED AND THOSE NOT TREATED WITH B C G

We started the study of the fate of children in tuberculous homes on Dec. 15, 1926. In 1927, we began to vaccinate some of the children with the attenuated living bovine strain of Calmette, called B C G. In 1931, at the request of Dr. E. R. Baldwin, we added to our procedure the use of heat-killed human tubercle bacilli for an additional small group of children. Up to the present we have administered B C G orally (to new-born children) and subcutaneously or intradermally (to children a few months of age). At first, to study the effects of the vaccine, we vaccinated a few older children by injection. The heat-killed vaccine was given subcutaneously or intramuscularly. The indications for vaccination were: 1. The child came from a home in which some one had tuberculosis. 2. The tuberculin test, roentgenograms of the chest and physical examination gave negative results before