Search PubMed⌕ Search

Biomedical subjects

R C Welliver

Publications and source records attributed to R C Welliver.

At least 73 records · Page 4Linked to original sources

Interaction of mucosal immune system and infections in infancy: implications in allergy.

The immune responses to viral antigens and other environmental agents to which the mucosal surfaces of the neonate are exposed during the perinatal period and early infancy are intimately related to the mechanism of innate immunologic reactivity of the mother-and, possibly, to the immunologic elements in the products of lactation for a breast-feeding infant-and the nutritional homeostasis of the neonate. The role of these factors in protecting against pathogenicity of viral infections in the respiratory and intestinal tract, and their impact on the development of allergic disease state in childhood will be reviewed.

Animals↗

The development of respiratory syncytial virus-specific immune complexes in nasopharyngeal secretions following natural infection.

Sequential samples of nasopharyngeal secretions (NPS) from 61 infants and children with respiratory syncytial virus (RSV) infection were examined for the presence of RSV-specific immune complexes in order to determine their possible role in recovery from or pathogenesis of RSV infection. Immune complexes in NPS were identified by the Raji cell assay using indirect immunofluorescence and RSV antigen in these complexes was also detected by indirect immunofluorescence. RSV-specific immune complexes were detected in 56% of subjects tested, being present as early as 3-6 days after the onset of illness and persisting for up to 36 days after the onset of illness. The appearance of immune complexes was temporally associated with the disappearance of RSV antigen from airway epithelial cells, suggesting a role for immune complexes in eradication of infection. RSV-specific immune complexes were identified with approximately equal frequency in patients with all forms of illness due to RSV, an observation which tends to rule out a role for immune complexes in the pathogenesis of RSV disease.

Age Factors↗

Appearance of complement components and immunoglobulins on nasopharyngeal epithelial cells following naturally acquired infection with respiratory syncytial virus.

Nasopharyngeal epithelial cells (NPEC) were collected from 144 infants and children with respiratory syncytial virus (RSV) infection, and were analyzed by fluorescent antibody techniques for the presence of cell-bound complement (C'3), IgA, IgG, and IgM class of immunoglobulins (Ig), and respiratory syncytial virus antigen. Viral antigen was present on the surface of NPEC in 100% of samples obtained in the first 3 days or illness. The percentage of patients positive for RSV antigen declined steadily, so that no patient still expressed viral antigen on NPEC by 57 days after the onset of illness. Cell-bound IgA, IgG, and IgM could be detected in most of the samples tested in the first 13 days after the onset of illness. Subsequently, the frequency of detection of cell-bound Ig gradually declined. Only 8-33% of patients tested 57 days after the onset of illness expressed IgA, IgG, or IgM on NPEC. About 45% of samples tested in the first 8 weeks after the onset of illness exhibited complement binding to NPEC. The percentage of subjects showing cell-bound C'3 reached a maximum at 8-13 says after the onset of illness, while cell-bound C'3 could not be detected in any of the samples collected 57-90 days after the onset of illness. Although cell-bound C'3 was generally present in association with cell-bound Ig on NPEC, in a small percentage (4.6%) of patients cell-bound C'3 could be detected in the absence of any cell-bound Ig. Cell-bound C'3 and IgA, IgG, and IgM were present with equal frequency in patients with all forms of clinical disease caused by RSV, and in patients less than or greater than 6 months of age at the onset of illness.

Antigens, Viral↗

Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection.

In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.

Antibodies, Viral↗

Development of antibody-dependent cell-mediated cytotoxicity in the respiratory tract after natural infection with respiratory syncytial virus.

Antibody-dependent cell-mediated cytotoxicity (ADCC) was measured in nasopharyngeal secretions collected from 42 infants and young children at various intervals after primary or secondary infection with respiratory syncytial virus. ADCC was determined by specific immune release of 51Cr from respiratory syncytial virus-infected HEp-2 cell culture monolayers, with lymphocytes from adult volunteers as effector cells. Specific ADCC responses in nasopharyngeal secretions after primary infection were observed as early as 3 days after the onset of clinical symptoms, and peak activity was observed 14 to 29 days after the onset of illness. ADCC responses after reinfection were significantly greater in both the acute and convalescent phases (P less than 0.05) than were ADCC responses after primary infection. ADCC in secretions was mediated primarily by the immunoglobulin G isotype of respiratory syncytial virus antibody.

Acute Disease↗

Rapid diagnosis of parainfluenza virus infection in children.

The indirect immunofluorescent-antibody (IFA) assay for detection of parainfluenza virus antigen was performed on samples of nasopharyngeal secretions obtained from infants and children with various respiratory illnesses to determine the usefulness of the IFA assay for rapid diagnosis of parainfluenza virus infection. Ninety-four samples of nasopharyngeal secretions were obtained from 78 children during a community outbreak of parainfluenza virus infection. Application of the IFA assay revealed the presence of parainfluenza antigen in 67 of the 94 samples. When these same specimens were inoculated into tissue culture, the presence of parainfluenza virus was confirmed in 62 (93%) of the 67 IFA-positive specimens by hemadsorption on tissue culture monolayers (31 cases), presence of parainfluenza hemagglutinin in infected tissue culture fluids (23 cases), or by other methods (8 cases). Only four IFA-negative specimens were subsequently shown to be positive for parainfluenza virus by tissue culture infectivity. The IFA assay provided a more rapid and more accurate method for diagnosis of parainfluenza infection in children than did routine tissue culture methods employed currently.

Adolescent↗

The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection.

We studied the development of respiratory syncytial virus (RSV)-specific IgE and the release of histamine in nasopharyngeal secretions from 79 infants with various forms of respiratory illness due to RSV. RSV-IgE was measured by an enzyme-linked immunosorbent assay; specificity was confirmed by appropriate blocking experiments. Histamine content in the secretions was determined by fluorimetric methods. RSV-IgE was detectable in only one of 19 patients with RSV infection without wheezing, but was detectable in the majority of 60 patients with wheezing (P less than 0.01). Titers of RSV-IgE were significantly higher in patients with wheezing (P less than 0.05). Histamine was detectable in secretions of some patients with all forms of illness but was detected significantly more often (P = 0.05) and in higher concentrations in patients with wheezing. Peak titers of RSV-IgE and concentrations of histamine correlated significantly with the degree of hypoxia (P less than 0.001). Formation of RSV-specific IgE and release of histamine may adversely affect the outcome of RSV infection.

Age Factors↗

Secretory antibody response to respiratory syncytial virus infection.

The secretory antibody response to primary and secondary infection with respiratory syncytial virus (RSV) in Igg, IgM and 11S IgA immunoglobulin classes was determined using an indirect immunofluorescence antibody technique. Nasopharyngeal secretions were collected after naturally acquired primary or secondary infection with RSV. Immunoglobulin A responses to RSV were significantly greater in infants older than 6 months of age at the time of infection than in younger infants. Reinfection with RSV resulted in enhanced antibody production in all three immunoglobulin classes, and virus-specific antibody persisted for longer periods after secondary infection. Repeated immunizations with live RSV vaccine may be necessary for the development of immunity to severe illness.

Age Factors↗

Comparison of fluorescent-antibody, neutralizing-antibody, and complement-enhanced neutralizing-antibody assays for detection of serum antibody to respiratory syncytial virus.

A comparison of three assays for the detection of serum antibody to respiratory syncytial virus (RSV) was carried out on 47 serum samples obtained sequentially from infants and young children with RSV infection. Neutralizing-antibody (NA) activity was determined by a semimicromethod of plaque reduction. Complement-enhanced NA activity was determined by the addition of guinea pig complement to NA assays. RSV antibody responses in immunoglobulin G, immunoglobulin M, and immunoglobulin A classes were determined by using indirect immunofluorescence techniques for fluorescent-antibody (FAb) assay. Antibody to RSV was detectable by all three techniques as early as 4 days after the onset of illness. At all phases of illness, titers obtained by complement-enhanced NA assays were significantly greater than those obtained by NA or FAb assays (P less than 0.01). RSV-FAb titers determined in the immunoglobulin G class correlated well with those determined by complement-enhanced NA or NA assays. The data suggest that the FAb assay for detection of RSV antibody in serum is somewhat less sensitive but also less laborious and more rapid than NA assays.

Animals↗

Clinical and laboratory diagnosis of respiratory syncytial virus infection.

Infection with RSV is one of the most common respiratory viral infections in childhood, particularly in infants under 1 year of age. The disease is characterized by epidemic proportions of infection which occur regularly in all parts of the world in the winter months. The spectrum of the clinical disease is quite variable, and the infection may present as bronchiolitis, pneumonia, croup, or exacerbation of pre-existing reactive airway disease. Recent evidence has suggested that RSV infection may be frequently associated with apnea in infancy and possibly sudden-infant-death syndrome. Although the laboratory diagnosis of this infection can be successfully accomplished by any well-known and conventional procedures, such as tissue culture infectivity and determination of serologic response, recently it has become possible to diagnose the infection very rapidly by application of such techiques as immunofluorescent staining and enzyme-linked immunonoabsorbent assay (ELISA).

Adolescent↗

The appearance of cell-bound IgE in respiratory-tract epithelium after respiratory-syncytial-virus infection.

We studied the appearance of IgE in the respiratory tract in 42 infants and young children with various forms of respiratory illness after infection by respiratory syncytial virus (RSV). IgE was bound to exfoliated nasopharyngeal epithelial cells in most patients with RSV infection during the acute phase of infection, regardless of the form of illness. However, the continued presence of cell-bound IgE was more common in patients with RSV-induced bronchiolitis or asthma than in patients with mild upper-respiratory-tract illness or pneumonia due to RSV. Persistence of IgE was also apparently related to the incidence of previous episodes of wheezing in patients or their families. The production of IgE and the subsequent release of chemical mediators of bronchospasm may contribute to the pathogenesis of acute illness due to RSV; persistence of IgE in the respiratory tract may explain the recurrent episodes of wheezing that occur in many patients after RSV-induced bronchiolitis.

Antigens, Viral↗

The antibody response to primary and secondary infection with respiratory syncytial virus: kinetics of class-specific responses.

Serum antibody responses to primary and secondary infections with respiratory syncytial virus were determined in 67 hospitalized infants. Responses in IgG, IgM, and IgA immunoglobulin fractions were assayed using an indirect immunofluorescent technique. Infection was confirmed by identification of RSV antigen in nasopharyngeal secretions using indirect immunofluorescence, and by recovery of the virus in tissue culture. IgM specific antibody response was commonly observed within a few days of onset of primary infection and persisted from two to ten weeks. Increases in titer of virus-specific IgG and IgA were observed in infants aged 6 months or more at the time of infection than in younger infants. At one year after primary infection, IgA and IgM specific antibody was undetectable, and IgG antibody was absent or present in low titer. Subsequent reinfection result ed in accelerated antibody response in all three classes of serum immunoglobulin. High titers of RSV-specific IgG, IgM, and IgA antibody were detectable at five and seven days after reinfection. These observations may explain the relatively mild nature of clinical illness associated with RSV reinfections in childhood.

Age Factors↗

Cell-mediated immune response to respiratory syncytial virus infection: relationship to the development of reactive airway disease.

The possibility that cell-mediated immunity might play a role in the pathogenesis of infection with respiratory syncytial virus was evaluated in a study of 39 infants. Infection with RSV was confirmed by identification of virus in nasopharyngeal secretions using immunofluorescence, and by tissue culture infectivity. CMI, as determined by a whole blood lymphocyte transformation technique, was evaluated in samples taken 0 to 10 and 20 to 60 days after the onset of illness. Patients diagnosed as having RSV-induced bronchiolitis or recurrence of asthma had evidence of significantly (P less than 0.01) higher degree of CMI in the 0 to 10-day period than patients with RSV pneumonia or upper respiratory illness. Higher CMI activity in the 20 to 60-day period was also seen in patients with more severe illness, with moderate-to-severe degree of hypoxia. A positive correlation was observed between the degree of LTF activity in samples taken 20 to 60 days after the onset of illness ard subsequent episodes of wheezing. Eleven patients had one or more episodes of wheezing in the first six months after RSV infection. LTF activity in samples taken during the 20 to 60-day period from these patients was significantly higher (P less than 0.02) than LTF activity in corresponding samples from six patients who were free of wheezing in the six months after RSV infection. The results suggest that alterations of RSV-specific cell-mediated immune mechanisms may result in an increased tendency toward airway reactivity on primary and subsequent exposure to RSV and possibly to other agents.

Bronchial Spasm↗