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Biomedical subjects

J G Michael

Publications and source records attributed to J G Michael.

104 records · Page 6Linked to original sources

Contribution of humoral and cellular factors to the resistance to experimental infection by Pseudomonas aeruginosa in mice. I. Interaction between immunoglobulins, heat-labile serum factors, and phagocytic cells in the killing of bacteria.

Techniques have been described for the purification of mouse polymorphonuclear leukocytes (PMN) and macrophages and for determining their bactericidal activity against Pseudomonas aeruginosa in a rotating suspension. Requirements for human anti-Pseudomonas opsonins and heat-labile mouse serum factors have been determined. In the macrophage system, although heat-labile mouse serum factors had enhancing properties, both immunoglobulin G (IgG) and immunoglobulin M (IgM) opsonins alone sufficed to induce bactericidal activity. In contrast, both opsonins and heat-labile mouse serum factors were required for bactericidal activity by the mouse PMN. In the absence of heat-labile mouse serum factors, IgG and IgM opsonins contributed to the bactericidal activity of mouse macrophages to the same extent. However, in the presence of these factors, much less IgG than IgM antibody was required to achieve maximum bactericidal activity by these cells. Similarly, IgG opsonins were found to be more efficient than IgM opsonins in enhancing the killing of P. aeruginosa by mouse PMN.

Animals↗

Biological Activities of Rabbit Immunoglobulin M and Immunoglobulin G Antibodies to Pseudomonas aeruginosa.

Immunoglobulin (Ig)M and IgG antibodies, prepared in the rabbit against the protective antigen of Pseudomonas aeruginosa P4, were compared as to their biological activities in vitro and in vivo. In vitro biological activities of these antibodies were determined by passive hemagglutination, bactericidal, and opsonophagocytic tests. Increased effectiveness of IgM over IgG on a molar basis was demonstrated in all of these tests. However, in mouse protection tests, in which the purified globulins were injected intraperitoneally 4 hr prior to challenge with P. aeruginosa suspended in hog gastric mucin, IgM anticapsular antibody was found to be less effective than IgG antibody. The exact mechanism whereby IgG antibody exerts more protective ability than IgM antibody is still unknown. We present evidence to suggest that the difference in activity between the two classes of antibody is due to the ability of the IgG antibody to enter the bloodstream more rapidly than the IgM antibody and also to the ability of IgG to diffuse rapidly through the tissues of the organs.

Journal Article↗

Apparent production of 2 types of antibdoies by a single cell.

Immunization of mice with bacterial, sheep red cells coated with antigen resulted in apparent production of antibody-forming plaques with specificities for both hemolysis and bactericidal activity. The secondary response for production of these bifunctional types of plaques could be induced by red blood cells or bacteria alone. A significant mutual suppression of immune response between the two immunizing agents was observed.

Animals↗

Secondary and apparent primary antibody responses after group A streptococcal vaccination of 21 children.

A partially purified M protein, extracted from a mouse-virulent strain of type 3, group A streptococcus, was administered subcutaneously in gradually increasing amounts at weekly intervals to 21 children in a Family Program. Seven children with type 3 bactericidal antibody in prevaccination sera showed a secondary response. Of 14 children with no detectable type 3 bactericidal antibody prior to vaccination, 13 developed definite type 3 antibody during or soon after vaccination. This response appeared to be of the primary variety in at least some of the 13 children because (i) the total incidence of antibody response (20 of 21) was greater than can be accounted for by the documented incidence of clinical and subclinical type 3 infections among children of our Family Program during a period of 14 years, (ii) the response in the 13 children with no detectable antibody prior to vaccination was more delayed than in those showing a definite secondary response, and (iii) on the average, the amount of vaccine needed for a response in these 13 children was 15 to 28 times greater than that required for the secondary response. Local skin reactions were variable among the vaccinated children. Systemic reactions were infrequent and not severe. The giving of multiple injections of partially purified M protein did not seem to cause cutaneous hypersensitivity.

Adolescent↗

Dynamics in development of experimental streptococcal immunity in mice.

The interrelation between the humoral and cellular factors in the development of immunity to experimental streptococcal infection was investigated. Early resistance to infection was caused by stimulating the phagocytic cells to function efficiently in the absence of opsonins. Subsequently, the appearance of cytophilic antibodies provided further means for elimination of streptococci. Thus, in the early stages of specific antistreptococcal immunity, resistance was observed in the absence of circulating anti-M antibodies. The type-specific antibodies that appeared in the later stage did not seem to improve clearance of streptococci in the splanchnic tissues. After an intravenous lethal challenge of mice with virulent streptococci, these antibodies did not provide increased protection. The circulating anti-M antibodies were shown to play a beneficial, indeed, a crucial, role when the infection occurred in a region in which the phagocytic cells were present in a rather limited number.

Animals↗

Preferential inhibition of penicillinase induction by oxytetracycline and its effect on the penicillin susceptibility of staphylococci.

Exposure of penicillinase-producing staphylococci to a combination of penicillin and oxytetracycline resulted in a synergistic inhibitory activity of the antibiotics on the bacteria. Oxytetracycline was employed in concentrations having little or no effect on bacterial growth. It was found that the synergistic antibacterial effect was caused by the preferential inhibition of penicillinase induction by oxytetracycline, rendering the staphylococci more susceptible to penicillin.

Drug Synergism↗

The release of specific bactericidal antibodies by endotoxin.

Studies presented in this report are concerned with the effect of endotoxin upon the release of bactericidal antibodies as determined by the agar plaque technique. We found that shortly after the injection of mice with small amounts of endotoxin the number of plaque-forming cells in the spleen was substantially reduced and remained low for about 12 hr. At the same time the titer of specific bactericidal antibodies in the circulation was increased, 6-mercaptopurine was shown to be an effective suppressor of the immune response by inhibiting the multiplication of bactericidin-forming cells. However, administration of this drug did not modify the initial responses of antibodies and plaque-forming cells to endotoxin. Thus, we postulate that endotoxin does not induce destruction and subsequent reconstitution of bactericidin-forming cells, but that the observed changes represent a release of preformed antibodies from competent cells. For a limited time, thereafter, these cells become inactive, but soon resume their normal function of releasing bactericidal antibodies.

Animals↗

Analysis of sequential stages in serum bactericidal reactions.

Michael, J. Gabriel (House of the Good Samaritan, Children's Hospital Medical Center, Boston, Mass.), and Werner Braun. Analysis of sequential stages in serum bactericidal reaction. J. Bacteriol. 87:1067-1072. 1964.-The bactericidal reaction of "normal" human serum against Escherichia coli was found to be separable into two distinctive stages. The early (first) stage of the reaction lasts for a relatively short period of time, and involves factors that are present in sufficient amounts only in slightly diluted serum. The later (second) stage needs more time and requires factors present in highly diluted serum. The first stage depends on the presence of Ca(++) and Mg(++) and on the activity of all components of complement; the second stage does not require divalent cations and C'1, C'2, and C'4, but requires factors that can be removed by zymosan. Under our conditions, removal of lysozyme did not influence either stage of the reaction. Bacteria exposed to concentrated serum for a short time, during the first stage, are essentially unaffected as far as their potential for subsequent multiplication is concerned; the actual damage to cellular integrity occurs only during the second stage of the reaction. In the absence of cell division, the "sensitization" produced during the first stage can be preserved for prolonged periods, and the bactericidal reaction can be completed later by exposure to antibody-free, highly diluted serum (second stage). Cell multiplication abolishes the sensitizing effects of the first stage.

Blood↗

The role of digestive enzymes in orally induced immune tolerance.

The influence of digestive enzymes on the tolerogenic properties of an orally administered protein antigen, Bovine Serum Albumin (BSA), in the mouse has been investigated. A non-immunogenic peptic digest of BSA was found to be immunosuppressive when administered orally or directly injected into the mouse ileum. In contrast, untreated BSA was tolerogenic when administered orally but immunogenic following ileal administration. As determined by precipitin analysis of the proteins recovered from mouse feces, orally administered BSA was thoroughly degraded by the digestive system while the degradation in the ileum was quite limited. We conclude that to acquire tolerogenic properties, an orally administered protein must be first degraded by the proteolytic enzymes of the gastrointestinal digestive system.

Administration, Oral↗