Group B streptococcal supraglottitis in a 3-month-old infant.
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Epiglottitis↗
Biomedical subjects
E L Mills
Publications and source records attributed to E L Mills.
Mechanisms of virus-induced immune suppression.
The recent demonstration that the acquired immune deficiency syndrome (AIDS) is caused by a retrovirus that affects humans has given rise to widespread concern about the immunosuppressive properties of viruses in general. A wide variety of viruses have been shown to be able to compromise immune function. Sometimes immunosuppression results from the pathologic processes that viruses are able to induce. In other instances virus-induced immune derangements may themselves be responsible for the onset of pathologic change. In some cases a single infectious viral agent may be able to modulate several immunologic mechanisms simultaneously. This review discusses some of the various complex mechanisms through which viral infections can alter the function of the immune system.
Acquired Immunodeficiency Syndrome↗
Syndrome of inappropriate secretion of antidiuretic hormone in enteroviral meningitis.
In nine of 102 children admitted to the Montreal Children's Hospital with a diagnosis of aseptic meningitis, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) developed. Patients with and without SIADH were similar with respect to clinical symptoms, duration of illness, and CSF inflammatory response. The SIADH group differed in that the largest age group was 1 to 5 years.
Child↗
Viral infections predisposing to bacterial infections.
Epidemiological and experimental evidence support the hypothesis that primary viral infection increases host susceptibility to secondary microbial invasion. The evidence is most compelling for a correlation between upper respiratory tract viruses and bacterial sinopulmonary disease; and cytomegalovirus and opportunistic fungal, bacterial and protozoal pathogens invading multiple sites. While a number of virus-induced alterations in host defenses have been described, the determinants of virus pathogenicity are still poorly understood.
Animals↗
Characterization of the effect of influenza virus on polymorphonuclear leukocyte membrane responses.
Depressed chemotactic activity of polymorphonuclear leukocytes (PMNL) infected with influenza virus could be due to changes occurring at the plasma membrane. The present study examined the effect of unopsonized influenza virus on chemotaxis, adherence, receptor binding, shape change, membrane fluidity, and release of specific granules from PMNL. Chemotactic activity of PMNL under-agarose to the chemoattractants, zymosan-activated serum ( ZAS ) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), and adherence of PMNL to a plastic surface were markedly decreased in virus-treated cells as compared to control cells. The binding of fMLP to the PMNL was increased in virus-treated cells compared with control cells. Exposure of cells to virus, ZAS , or fMLP caused 35%-50% of the cells to become bipolar in shape, whereas less than 5% of the cells exposed to buffer became bipolar. Influenza virus did not alter membrane fluidity as measured by electron spin resonance spectroscopy with the probe 5-doxyl stearate. Virus-treated PMNL stimulated with FMLP or Staphylococcus aureus exhibited a marked decrease in the amount of lactoferrin released into phagosomes, onto the cells' outer membrane, and into the extracellular medium as compared to control cells. The possible relationship between inhibition of lysosomal enzyme degranulation and decreased chemotactic activity and adherence of PMNL is discussed.
Cell Adhesion↗
Growth in patients with chronic granulomatous disease.
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Adolescent↗
Mononuclear phagocytes in the newborn: their relation to the state of relative immunodeficiency.
The neonatal period is a state of relative immunodeficiency during which newborns are particularly vulnerable to bacterial, protozoal, and viral infections. In addition, they localize infection poorly, mount a sluggish antibody response to injected antigens and are relatively anergic. Both in vivo and in vitro studies suggest that functional immaturity of neonatal macrophages may contribute to this immunologic hyporesponsiveness. Resistance to viral and bacterial infection and production of antibody can be enhanced in neonates by injection of adult macrophages. Specific functional defeats in newborns' monocytes have been demonstrated in their capacity to chemotax, to resist intracellular multiplication of virus and to effect antibody-dependent cell-mediated cytotoxicity towards virus-infected target cells. Monocytes from newborns also appear to present antigen poorly, and to co-operate with T-lymphocytes in the suppression of IgG-production by B cells.
Antibody Formation↗
The effect of influenza virus on oxygen-dependent metabolism of human neutrophils.
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Free Radicals↗
Effect of influenza virus on phagocytic cells.
Many viral infections predispose to bacterial superinfection, and it has been suggested that the increased susceptibility to bacterial infections is at least in part due to the effect of virus on the phagocytic cell function. Since the mechanisms by which the viruses affect neutrophil function are not well understood, we studied the function of polymorphonuclear leukocytes (PMNs) after incubation with influenza virus. Phagocytosis was assayed by incubating influenza virus (strain type A-Texas-77 [H2N2] ) treated leukocytes with 3H-thymidine-labelled staphylococci. The oxidative metabolism of the PMNs was studied by measuring the chemiluminescence generated by virus-treated PMNs after incubation with zymosan. Chemotaxis was measured under agarose. After incubation with 10(7) EID50 units of influenza virus, PMNs ingested only 35% of the bacteria, whereas control leukocytes ingested over 80%. Influenza virus also reduced the mobility of the PMNs and markedly suppressed the generation of chemiluminiscence. UV-killed virus with intact neuraminidase produced similar effects but virus with heat-inactivated neuraminidase did not. Virus envelope-neuraminidase may be responsible for some of the effects of the virus on the PMNs.
Blood Bactericidal Activity↗
Depression of monocyte and polymorphonuclear leukocyte oxidative metabolism and bactericidal capacity by influenza A virus.
Decreased host defense against bacterial disease associated with influenza infection may be related to virus-induced changes in phagocytic cell function. Influenza A virus initiates the respiratory burst in peripheral blood monocytes and polymorphonuclear leukocytes, with a peak chemiluminescent response approximately 3 min after virus is added to the cells in vitro. Electron micrographs of phagocytic cells incubated with influenza virus demonstrated virus attached to the cell membrane and within phagocytic vacuoles. After 20 min of incubation of the virus with phagocytic cells, the chemiluminescent response to opsonized zymosan or phorbol myristate acetate was decreased by 30 to 90%. Phagocytic activity of monocytes and polymorphonuclear leukocytes incubate with influenza virus was normal, but the bactericidal activity was significantly depressed. Influenza A virus therefore stimulates an oxidative burst in monocytes as well as polymorphonuclear leukocytes, leading to a subsequent depression of the oxidative metabolic response and bactericidal capacity of the phagocytic cells.
Blood Bactericidal Activity↗
Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity.
The present study examined the effect of various unopsonized strains of influenza A virus on release of myeloperoxidase (MPO) and acid phosphatase in polymorphonuclear leukocytes (PMNL). These results were correlated with the effect that these same viruses had on bactericidal activity in PMNL. Several strains of virus inhibited the fusion of azurophil granules with phagosomes containing Staphylococcus aureus. These same strains inhibited the extracellular release of MPO from PMNL (39-59%) and caused depressed killing (42-77%). In contrast, one of the influenza viruses (X-47a) did not inhibit PMNL MPO release or killing. The data indicate a close relationship between the ability of influenza virus to ablate normal intracellular lysosome-phagosome fusion with subsequent depression of bactericidal functions of PMNL.
Blood Bactericidal Activity↗
Recurrent infections and delayed separation of the umbilical cord in an infant with abnormal phagocytic cell locomotion and oxidative response during particle phagocytosis.
An 18-month-old infant with delayed separation of the umbilical cord and severe recurrent bacterial infections since the newborn period was found to have depressed polymorphonuclear leukocyte locomotion and oxidative metabolic response to particulate stimuli. Both her polymorphonuclear leukocytes and monocytes demonstrated a markedly delayed chemiluminescence response to zymosan, but there was a normal chemiluminescence response to soluble stimuli, phorbol myristate acetate and calcium ionophore A23187. The patient also had a marked delay in uptake of Staphylococcus aureus and Escherichia coli. The patient's polymorphonuclear leukocytes were normal morphologically, and myeloperoxidase was present in histochemical stains. The dichotomy between normal oxidative response to soluble stimuli and abnormal response to opsonized particulate stimuli, plus abnormal cell locomotion and phagocytosis, suggest an abnormality of cell membrane fluidity or contractility.
Bacterial Infections↗
Polymorphonuclear leukocyte dysfunction during influenza virus infection in chinchillas.
The increased susceptibility of chinchillas after intranasal inoculation of Streptococcus pneumoniae and influenza A virus to pneumococcal otitis media prompted a study to determine whether infection with influenza virus adversely affects polymorphonuclear leukocyte (PMNL) function and thereby impairs host defense. Thirty-four chinchillas were inoculated intranasally with either influenza A virus or sterile saline. The chemotactic, chemiluminescent, and bactericidal activities of the PMNLs were depressed four to eight days after inoculation of the virus compared with the values obtained before inoculation; these activities remained normal in animals inoculated with sterile saline. The maximum reduction in chemotaxis (37%), peak chemiluminescence (53%), and peak bactericidal activity (26%) of the PMNLs was observed on day 6. Phagocytosis remained normal throughout the period after inoculation. Thus, the susceptibility of chinchillas to pneumococcal disease after inoculation with influenza A virus may be due to the impaired chemotactic and oxidative microbicidal activities of PMNLs.
Animals↗
Role of myeloperoxidase and bacterial metabolism in chemiluminescence of granulocytes from patients with chronic granulomatous disease.
Phagocytosis of catalase-positive microbes by normal polymorphonuclear neutrophils results in increased metabolism as required for microbicidal action. Chemiluminescence is a product of the associated oxygenation reactions. Neutrophils from patients with chronic granulomatous disease are capable of phagocytizing catalase-positive microbes, but there is no associated respiratory burst, microbicidal action is greatly decreased, and chemiluminescence is not detected. However, these defective neutrophils can kill catalase-negative, H2O2-generating bacteria. In the present study, chemiluminescence by neutrophils from patients with chronic granulomatous disease after phagocytosis of H2O2-generating streptococci was detected. Acid extracts of myeloperoxidase from either control or patient neutrophils also yielded chemiluminescence in the presence of streptococci, but not in the presence of catalase-positive microbes.
Female↗
Initiation of the respiratory burst of human neutrophils by influenza virus.
The role of the oxygen-dependent microbicidal systems of polymorphonuclear neutrophils in virus inactivation is not known. We found that isolated neutrophils responded to incubation with purified influenza virus A particles by consumption of oxygen, generation of chemiluminescence, and production of superoxide; these reactions occurred in the absence of serum. Resting leukocyte oxygen consumption doubled in the presence of virus; the average rate of consumption 2 to 12 min after virus was added was 1.54 nmol/10(7) cells per min. Live virus also stimulated superoxide production in a dose-dependent manner at a rate up to 4.54 nmol/10(7) cells per min. Luminol-amplified chemiluminescence was a rapid dose-dependent reaction which peaked 2 to 4 min after live or ultraviolet light-inactivated virus was added. No light was emitted when heat-inactivated virus particles were used, suggesting that heat-labile factors on the virus envelope may be involved in oxidative stimulation. Virus-stimulated neutrophils from a patient with chronic granulomatous disease emitted no light. The evidence that virus initiated the respiratory burst of neutrophils provided a potential mechanism for virus destruction, either by direct intracellular inactivation or by neutrophil-mediated cellular cytotoxicity of virus-infected target cells.
Antiviral Agents↗
The effect of influenza virus on human polymorphonuclear leukocytes.
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Chemotaxis, Leukocyte↗
Luminol-amplified chemiluminescence: a sensitive method for detecting the carrier state in chronic granulomatous disease.
Patients with chronic granulomatous disease have a marked defect in neutrophil oxidative metabolism and microbicidal activity. Asymptomatic mothers of males with the disease can usually be identified as heterozygous carriers by intermediate leukocyte function. Most mothers of females with the disease, however, have normal leukocyte function, and the pattern of genetic transmission in these families has been difficult to establish. Of 14 mothers of males and females with chronic granulomatous disease, 10 had been found previously to have intermediate values for neutrophil bactericidal activity, oxygen consumption, hexose monophosphate shunt activity, and Nitro Blue Tetrazolium reduction, and 4 had normal in viro leukocyte function. In the present study, 4 of these 14 mothers had normal neutrophil bactericidal activity, 3 had normal zymosan-stimulated chemiluminescence, but none had normal luminol-amplified zymosan-stimulated chemiluminescence. The presence of luminol (5-amino-2,3-dehydro-1,4-phthalazinedione) in the phagocytic mixtures markedly increased the sensitivity of the assay, permitting detection of subtle defects in leukocyte oxidative metabolism in three previously unidentifiable carriers of the disease. Thus, luminol-amplified chemiluminescence appears to be one of the most sensitive methods available for detection of chronic granulomatous disease heterozygotes; the simplicity and reproducibility of the microtechnique permit evaluation of leukocyte function in infants and newborns.
Adult↗
X-linked inheritance in females with chronic granulomatous disease.
Chronic granulomatous disease in males is familial and its transmission is is usually clearly x-linked. The mode of inheritance in females with the syndrome is unknown and the carrier state difficult to identify. Defective polymorphonuclear leukocyte bactericidal activity in this disease is associated with an absence of the respiratory burst generated in stimulated phagocytes and may be detected by the chemiluminescence assay. Polymorphonuclear leukocytes from three of four females with chronic granulomatous disease had extremely low chemiluminescence production, their asymptomatic mothers had intermediate values, and their fathers were normal. Polymorphonuclear neutrophils of two affected males in these kinships generated no chemiluminescence, whereas two of seven female relatives had intermediate values, and all nonaffected males had normal values. In the three families in which leukocytes were studied by nitroblue tetrazolium reduction, two populations of neutrophils were demonstrated for the female patients and/or their mothers. The wide phenotypic variability for clinical disease, evidence of two leukocyte populations in the patients or their mothers, and low but detectable leukocyte chemiluminescence in the affected females is consistent with the Lyon hypothesis of x-chromosome inactivation in these families. The findings suggest an x-linked inheritance in these females with chronic granulomatous disease.
Female↗