[Effect of levamisole on selected immunological indicators in patients with chronic post-traumatic osteitis].
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Two monoclonal antibodies (Mab), designated 60.3 and 60.1, markedly inhibited the phagocytosis of serum-opsonized zymosan by human polymorphonuclear leukocytes (PMN) as measured by the iodination reaction and by microscopic visualization. These antibodies also inhibited rosette formation with EC3bi without decreasing EC3b rosetting, suggesting that Mab 60.3 and 60.1 inhibit the phagocytosis of opsonized zymosan through reaction with the C3bi receptor (CR3) on the leukocyte surface. In support of this concept is the finding that the PMN of two patients with recurrent infections do not ingest opsonized zymosan, lack C3bi receptor function, and react weakly or not at all with Mab 60.3 and 60.1. At concentrations which completely inhibited ingestion of opsonized zymosan, both Mab partially inhibited iodination with Staphylococcus aureus 502A as the particle, and did not affect iodination when Staphylococcus epidermidis was used. This presumably reflects a variable need among the opsonized particles for CR3 for ingestion. Mab 60.3 also inhibited the phagocytosis of certain unopsonized particles as measured by iodination, indicating that the antigens recognized by the Mab do not influence phagocytosis solely by functioning as a C3bi receptor. Mab 60.3 increased the phagocytosis of unopsonized, heat-killed S. aureus by reaction with the PMN via its antibody-combining site, and with the staphylococcal protein A via its Fc region (reverse opsonization). This process required protein A-containing organisms (S. aureus 502A or Cowan 1 but not S. aureus Wood 46 or S. epidermidis), was inhibited by purified protein A, and was not seen either when the F(ab')2 or Fab fragments of the antibody, or when PMN which lack or have low levels of the antigen were employed. Thus, these studies, using iodination as a convenient method for the measurement of phagocytosis, demonstrated two effects of antibodies directed against PMN cell surface components: inhibition of phagocytosis by reaction with the C3bi receptor, and stimulation of phagocytosis by reverse opsonization.
Although it was once thought that bacterial infection was merely a function of the virulence of the microbe it is now known that other pathogens can alter host resistance. With respect to bacterial superinfection during viral pneumonias, three important factors must be considered; the role of the virus, the role of the bacterium, and the immune status of the host. The fact that no one bacterial species is responsible for all human cases of postinfluenzal bacterial pneumonia indicates that there is a general impairment of pulmonary antibacterial defenses brought about by the viral infection. The fact that the rate of intrapulmonary killing varies with different bacterial species indicates that the superinfecting organism can itself play a role in the dual disease process. Finally, it has been amply demonstrated that the resistance of the host is dependent on a variety of factors which include innate variables such as genetic endowment and a multitude of imponderable variables acquired through life experiences which can be considered under the general category of "host factors". All three factors interact and collectively impinge upon the resistance of the host. Lastly, as influenza virus infections occur most frequently in epidemic outbreaks, the relationship between influenza virus and secondary bacterial infections is the classic example. However, there is growing evidence that an association exists between other virus groups and bacterial pathogens in respiratory tract infections. Adenovirus, parainfluenza virus, and rhinovirus are among the agents that appear to pave the way for bacterial pneumonias. Mycoplasma pneumoniae, once considered to be a virus and the cause of primary atypical pneumonia, may also render the respiratory tract susceptible to bacterial invasion.
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Previous studies examined the ability of polymorphonuclear leukocytes (PMN) from patients and carriers of chronic granulomatous disease (CGD) to kill small numbers of bacteria in vitro. The purpose of the present study was to accurately measure the number of microorganisms killed by CGD PMN when the initial number of bacteria per neutrophil was increased. Bactericidal capacities of PMN from seven patients and five proven carriers of CGD were examined with five test ratios ranging from 1.25 to 100 bacteria/neutrophil. CGD PMN killed a limited number of catalase-positive S. aureus but the number of bacteria killed increased progressively as the initial test ratio was advanced. At the highest ratio (100:1) patient PMN killed a mean of nine S. aureus per cell (normal 48 +/- 13.2 SD). PMN from patients with CGD killed increasing numbers of catalase-negative S. faecalis with normal efficiency, reaching a mean of 14 S. faecalis killed per cell at 100:1. Individual variation in the ability of CGD PMN to kill S. Aureus was apparent but the degree of PMN bactericidal effectiveness did not correlate with the patient's clinical course. PMN from asymptomatic carriers of proven sex-linked CGD also had a wide spectrum of staphylocidal activity which ranged from normal to levels comparable to CGD patients.
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A study was made of the mechanisms of leucocyte phagocytic and bactericidal activity with relation to Staph, aureus and the NBT-test in simple and simulated variants in 71 patients with diabetes mellitus. A compensatory elevation of the phagocytic index and the phagocytic number was found in all the patients with a decrease in phagocytosis completion which testified to the internal defects of bactericidal activity which, according to the NBT-test results, consisted in insufficient activity of oxidation enzymes. The stimulated NBT-test showed a decrease in phagocytic potentialities in patients with diabetes mellitus. Phagocytosis defects in type I and type II diabetes mellitus were more noticeable in a severe and labile course of the disease.
The various "in vitro" tests for evaluating polymorphonuclear leucocyte function in children with recurrent infections are described and the different clinical conditions caused or accompanied by defects in polymorphonuclear function are summarized briefly. The necessity of correct interpretation of the results of the laboratory tests used in the diagnostic evaluation of patients with suspected immunodeficiency is stressed.
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