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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chimpanzee secretory immunoglobulin A (SIgA) was separated into two fractions by chromatography using the terminal galactose-binding lectin Jacalin. The SIgA fraction bound by Jacalin was cleaved by Haemophilus influenzae IgA1 protease, whereas the SIgA nonbinding fraction was not cleaved. It is proposed that these fractions represent IgA1 and IgA2 subclasses because the presence or absence of galactose-terminal oligosaccharides (Jacalin binding) and susceptibility or resistance to IgA1 protease are properties that define human IgA1 and IgA2 subclasses.
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PMID:Identification of two subclasses of IgA in the chimpanzee (Pan troglodytes). 140 36

Immunoglobulin-producing cells in mucosal tissues, quantitatively the body's most important humoral immune system, synthesize mainly dimers and larger polymers of IgA (poly-IgA) with incorporated J (joining) chain. Poly-IgA is actively transported to exocrine secretions by a transmembrane epithelial glycoprotein called secretory component. Enhancing secretory immunity by oral vaccination is an interesting possibility, but mucosal antigen uptake and local immune regulation are complex and only partly understood. Immunoglobulin isotype response patterns in the upper respiratory mucosa and distal gut are strikingly different. The preferential production of IgA1 in nasal and bronchial mucosae is intriguing in view of the frequent synthesis of IgA1-specific proteases by Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. A relationship of proneness to produce invasive disease and enzymatically induced deterioration of secretory immunity has been proposed. Differences in mucosal immune response patterns among patients with selective IgA deficiency or IgG subclass deficiencies also suggest that local humoral immunity is an important variable in resistance to infections.
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PMID:Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections. 158 57

The nonencapsulated, IgA protease-positive Haemophilus influenzae strain Rd and serogroup b clinical isolates were found to proliferate in human milk. Growth did not require supplemental X and V factors. In milk, strain Rd synthesized IgA protease, but it was completely inhibited by antibody, so secretory IgA in milk cultures remained intact. Inhibition was largely attributable to IgA1 antibodies. Rd cells also aggregated during growth in milk and showed colony size variation, whereas a protease-negative mutant of Rd (Rd225DK) aggregated less and had uniform colony size. Like differences in protease inhibition, these differences in growth pattern were mediated by secretory IgA1. Thus, milk antibody not only inhibited the extracellular protease but also interacted directly with the enzyme precursor or related antigens on growing bacterial cells. This self-protective property of milk secretory IgA may be an important immunologic attribute for the upper respiratory mucosa of the infant.
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PMID:Growth of Haemophilus influenzae in human milk: synthesis, distribution, and activity of IgA protease as determined by study of iga+ and mutant iga- cells. 160 7

Immunoglobulin (Ig)A proteases synthesized by human mucosal pathogens have a unique specificity for human IgA and will not cleave IgA from other species. In contrast, animal pathogens have not reliably been shown to cleave IgA of the animals they infect. This lack of an animal model has prevented an understanding of the importance of IgA1 proteases as virulence factors. One strategy to develop an animal model would be to identify a species capable of infection by a human IgA-producing pathogen whose IgA was susceptible to cleavage by IgA1 protease of that bacterium. The chimpanzee can be infected with Haemophilus influenzae and is closely related immunologically to man. For these reasons it was sought to determine whether chimpanzee secretory IgA (SIgA) is susceptible to cleavage by IgA1 protease of H. influenzae. This report shows that chimpanzee SIgA can indeed be cleaved at the hinge region by H. influenzae IgA1 protease into Fab alpha and (Fc alpha)2.SC fragments. The susceptibility of chimpanzee SIgA to IgA1 protease of a human pathogen could serve as the basis of an animal model to determine the importance of IgA1 protease in pathogenesis.
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PMID:Cleavage of chimpanzee secretory immunoglobulin A by Haemophilus influenzae IgA1 protease. 179 27

Ig class- and IgA subclass-specific immune responses to protein and polysaccharide Ag were studied in serum, external secretions, and at the single cell level in peripheral blood of systemically immunized adults. Immunization with tetanus toxoid induced predominantly IgG antibody responses in serum and in the PBMC. The IgA antibody response was low, and was mostly of the IgA1 subclass. In contrast, immunization with polysaccharide Ag (Haemophilus influenzae type b, Neisseria meningitidis serogroup A, C, Y, W-135, and Streptococcus pneumoniae capsular polysaccharides) elicited a major IgA response predominantly of the IgA2 isotype. Analysis of the molecular forms of secreted IgA antibodies indicated that polymers were produced early after immunization, irrespective of the nature of the Ag. When compared with serum antibody and to PBMC cell responses, systemic immunization with polysaccharides induced a minor salivary response dominated by IgG and IgM antibodies. In contrast, the presence of antipolysaccharide antibodies in bile, irrespective of their isotype, paralleled the serum response 14 days after the immunization with polysaccharide Ag. These results suggest that biliary Ig were mostly derived from serum. Different patterns of the expression of MHC class II Ag on T cells, B cells, and monocytes during the course of immunization with protein or polysaccharide Ag were observed: whereas protein Ag induced a high frequency of HLA-DP- and HLA-DR-expressing cells early in the course of immunization, polysaccharide vaccines elicited low and protracted increases of HLA-DP+ T cells. Polysaccharide vaccine covalently coupled to a protein carrier induced a higher frequency of antipolysaccharide antibody-secreting cells in peripheral blood and increased the IgG to IgA ratio among polysaccharide-specific antibody-secreting cells.
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PMID:Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses. 211 Feb 13

The distribution of total and antigen-specific IgA1 and IgA2 antibodies in human colostrum was determined by ELISA using subclass-specific monoclonal reagents. In 18 samples of colostrum the mean ratio of total IgA1 to IgA2 was found to be 53:47, respectively, but significant individual variations were observed. In two samples we found unusually low levels of IgA1, while IgA2 was in the normal range. IgA1 and IgA2 antibody activities were determined against the following antigens: bovine gamma-globulin and beta-lactoglobulin, tetanus toxoid, protein antigen I/II of Streptococcus mutans, influenza virus vaccine, polysaccharides of pneumococcal, meningococcal and Haemophilus influenzae type b origin, and lipopolysaccharide (LPS) from Escherichia coli K235. The IgA antibody activity directed against the polysaccharides was almost equally distributed between the two subclasses. However, antibody activity specific for protein antigens was found predominantly in the IgA1 subclass while anti-LPS activity was mostly of the IgA2 subclass.
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PMID:IgA subclasses of human colostral antibodies specific for microbial and food antigens. 247 28

The interaction of human IgA antibodies with the classical pathway of complement activation was investigated in a homologous human system, by means of two IgA1 and three IgG1 myeloma proteins having antibody activity against a defined antigen, staphylococcal alpha-toxin. In a solid-phase antigen-dependent C3b-binding ELISA system, the monoclonal IgG antibodies were previously shown to activate the classical complement pathway synergistically, resembling polyclonal IgG antibodies, whereas IgA antibodies were unable to activate complement by either pathway. In the present study, IgA antibodies were found to inhibit significantly the activation of complement initiated by antigen-bound polyclonal or mixed monoclonal IgG antibodies, in relation to the amount of IgA antibodies applied and bound to antigen. IgA1 myeloma proteins devoid of antigen-binding activity were without effect. Inhibition was independent of the ability of the IgA antibodies to compete against the IgG antibodies in binding to antigen, and was demonstrable with physiological concentrations of antibodies. Similar results were obtained with polyclonal serum IgA having antigen-binding activity. However, the binding of C1q to antigen-complexed IgG was inhibited only by a monoclonal IgA antibody that could compete against one of the three monoclonal IgG antibodies that bound C1q synergistically. This observation implied that at least two mechanisms were involved in the inhibition of C3b fixation. Fab alpha fragments of monoclonal IgA antibodies, obtained by cleavage with IgA1 protease from Haemophilus influenzae type b, were found to have a similar inhibitory effect on C3b fixation to the intact IgA1 antibodies. This observation supports the hypothesis that IgA1 proteases contribute to the invasive pathogenicity of certain mucosal bacteria, by cleaving secretory IgA1 antibodies to antigen-binding Fab alpha fragments, which are not only defective in mucosal defense properties, but which also protect the organisms from other immune effector systems, such as complement activation.
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PMID:Anti-inflammatory activity of human IgA antibodies and their Fab alpha fragments: inhibition of IgG-mediated complement activation. 260 39

Many bacteria which establish infections after invasion at human mucosal surfaces produce enzymes which cleave immunoglobulin A (IgA), the primary immunoglobulin involved with protection at these sites. Bacterial species such as Haemophilus influenzae which produce IgA1 proteases secrete this enzyme into their environment. However, when the gene encoding this protein was isolated from H. influenzae serotype d and introduced into Escherichia coli, the activity was not secreted into the medium but was localized in the periplasmic space. In this study, the IgA1 protease gene (iga) from an H. influenzae serotype c strain was isolated and the gene from the serotype d strain was reisolated. The IgA1 proteases produced in E. coli from these genes were secreted into the growth medium. A sequence linked to the carboxyl terminus of the iga gene but not present in the original clone was shown to be necessary to achieve normal secretion. Tn5 mutagenesis of the additional carboxyl-terminal region was used to define a 75- to 100-kilodalton coding region required for complete secretion of IgA1 protease but nonessential for protease activity. The iga genes were isolated by a plasmid integration-excision procedure. In this method a derivative of plasmid pBR322 containing a portion of the protease gene and the kanamycin resistance determinant of Tn5 was introduced into H. influenzae by transformation. The kanamycin resistance gene was expressed in H. influenzae, but since pBR322 derivatives are unable to replicate in this organism, kanamycin-resistant transformants arose by integration of the plasmid into the Haemophilus chromosome by homologous recombination. The plasmid, together with the adjoining DNA encoding IgA1 protease, was then excised from the chromosome with DNA restriction enzymes, religated, and reintroduced into E. coli. Comparisons between the H. influenzae protease genes were initiated which are useful in locating functional domains of these enzymes.
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PMID:Haemophilus influenzae immunoglobulin A1 protease genes: cloning by plasmid integration-excision, comparative analyses, and localization of secretion determinants. 282 Sep 26

It has previously been shown that secretory immunoglobulin A (S-IgA) influences the sorption of oral streptococci to hydroxyapatite as well as to cell surfaces. The present experiments demonstrate that bacterial IgA proteases, which cleave S-IgA in the hinge region, are capable of interfering with this mechanism. This result was obtained with an IgA1 specific protease from Haemophilus influenzae and with a protease from Clostridium ramosum that cleaves IgA1 as well as IgA2 of A2m(1) allotype. The modulation of S-IgA-mediated effects by IgA proteases were studied by means of an in vitro method which permits quantitative determination of the sorption of radiolabeled oral bacteria to hydroxyapatite beads. Other authors have suggested that IgA protease-mediated effects may be explained by a strongly reduced antigen-binding capacity of released Fab alpha fragments. Here we present evidence that streptococci, after exposure to specific S-IgA and IgA protease, are coated with Fab alpha fragments.
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PMID:Interference of IgA protease with the effect of secretory IgA on adherence of oral streptococci to saliva-coated hydroxyapatite. 304 Aug 26

Normal serum IgA and secretory IgA (sIgA) of subclass IgA1 were isolated from pooled human serum and milk, respectively. They were tested for their susceptibility to bacterial IgA proteases from Haemophilus influenzae, Streptococcus pneumoniae, Neisseria gonorrhoeae, and Neisseria meningitidis that cleave IgA of only the IgA1 subclass. They were also tested for susceptibility to a novel IgA-protease from Clostridium ramosum that cleaves IgA of the IgA1 as well as the IgA2 subclass of the A2m(1) allotype. Both normal serum IgA1 and sIgA1 exhibited resistance to most IgA proteases. The one exception was the IgA protease from C. ramosum which readily cleaved both the serum IgA1 and sIgA1 into Fab and Fc fragments. Secretory component (SC) had nothing to do with the resistance of these IgAs. The resistance of these IgAs to most of the IgA proteases was found to be due to their enzyme-neutralizing antibody activity, since the Fab but not the Fc fragment of sIgA1 showed enzyme-inhibitory activity against these IgA proteases. Similar enzyme-neutralizing antibody activity was found in the pepsin-digested normal serum IgG-(Fab')2 fragment. These results indicate that the induction of the enzyme-neutralizing antibodies against the bacterial IgA proteases took place not only in mucosal sIgA but also in serum IgA and IgG. No enzyme-neutralizing antibody activity against the novel IgA-protease of C. ramosum was detected in any immunoglobulin preparations used in the present study or in the serum of a patient who carries the IgA protease-producing strain of C. ramosum in his feces.
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PMID:Resistance of normal serum IgA and secretory IgA to bacterial IgA proteases: evidence for the presence of enzyme-neutralizing antibodies in both serum and secretory IgA, and also in serum IgG. 312 62


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