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Biomedical subjects

Z Moldoveanu

Publications and source records attributed to Z Moldoveanu.

At least 73 records · Page 4Linked to original sources
PubMed1989

Immune responses to influenza virus in orally and systemically immunized mice.

In our studies on the induction of an immune response by oral immunization, we have explored the potential of a novel approach for antigen delivery by microencapsulation. This procedure preserved the immunogenicity of the influenza virus introduced by either systemic or oral routes. Furthermore, the levels of specific antibodies in serum and in saliva were enhanced and lasted longer (up to 4 months) in animals immunized with of antigens in microencapsulated form than in animals immunized with equal doses of free suspension. Preliminary challenge experiments showed a correlation between levels of antibodies and protection. All mice systemically immunized were protected against the virus, while mice orally immunized with lower doses of microencapsulated antigen had better survival rates than those immunized with higher doses. Additional experiments suggested that low doses of immunogen were able to generate better protective immunity than high doses, which may instead be tolerogenic. Further experiments with a well characterized microencapsulated antigen (size of microcapsules, time of release of antigen, as well as its dose and form) will be necessary to establish conditions for optimal immunization protocols applicable for the oral or systemic routes.

Administration, Oral↗
PubMed1989

Biodegradable microspheres: vaccine delivery system for oral immunization.

The potential of biocompatible and biodegradable microspheres as a controlled release oral vaccine delivery system has been examined. Orally-administered 1-10 micron microspheres composed of poly (DL-lactide-co-glycolide) were specifically taken up into the Peyer's patch lymphoid tissue of the gut, where those greater than or equal to 5 micron remained for up to 35 days. Microspheres less than 5 micron disseminated within macrophages to the mesenteric lymph nodes and spleen. In contrast to soluble staphylococcal enterotoxin B toxoid, oral immunization with enterotoxoid in microspheres induced circulating toxin-specific antibodies and a concurrent secretory IgA anti-toxin response in saliva and gut fluid.

Administration, Oral↗
PubMed1989

Bacteroides-specific IgG and IgA subclass antibody-secreting cells isolated from chronically inflamed gingival tissues.

The emergence of cells that produce IgG and IgA subclass antibodies to Bacteroides gingivalis (Porphyromonas gingivalis) fimbriae and lipopolysaccharide (LPS) antigens was examined in mononuclear cells isolated from inflamed gingiva of different stages (slight, moderate or advanced) of adult periodontitis (AP). Antigen-specific IgM, IgG (including IgG1, IgG2, IgG3 and IgG4) and IgA (including IgA1 and IgA2) producing cells were enumerated by the ELISPOT assay and were compared with total Ig-producing cells of each isotype or subclass. In advanced AP, the B. gingivalis fimbriae-specific IgG- and IgA-secreting cells represented 5% of total IgG- or IgA-secreting cells, while those from the moderate stage comprised approximately 1% of these two isotypes. Cells producing antibody specific for B. gingivalis LPS were observed at frequencies of 0.1% and 0.4% for IgG and IgA cells, respectively in the advanced stage. When IgG subclasses were analysed in moderate AP, the anti-fimbriae subclass responses were largely IgG1 (60%), followed by IgG2 (20%), IgG3 (10%) and IgG4 (10%). Fimbriae-specific IgG subclass responses were elevated in the advanced stage of AP, and IgG4 (40%) and IgG1 (30%) were dominant, followed by IgG3 (20%) and IgG2 (10%). IgA1 cells predominated in both the moderate and advanced stages, however a relative increase in IgA2 cells occurred in advanced AP. Mononuclear cells isolated from gingiva of AP patients did not contain cells producing antibody to antigens such as Escherichia coli K235 LPS, cholera toxin or the hapten dinitrophenyl coupled to bovine serum albumin. These results show that local IgG and IgA subclass responses occur to a protein antigen of a major periodontal disease (PD)-associated pathogen, B. gingivalis, and the increase in IgG4 and IgA2 responses may be associated with host protection.

Antibodies, Bacterial↗
PubMed1988

A novel two colour ELISPOT assay. I. Simultaneous detection of distinct types of antibody-secreting cells.

A novel assay system has been developed which is based on the ELISPOT methodology and employs a combination of two immunoenzyme visualization systems yielding distinct colour products. This variation permits the simultaneous enumeration of two different types of cell secreting antigenically distinct products. Optimal conditions for the concurrent detection of human mononuclear cells secreting IgG or IgA antibodies are described.

Adult↗
PubMed1988

The sites of catabolism of murine monomeric IgA.

The tissue sites of monomeric IgA (mIgA) catabolism were determined in a BALB/c mouse model. Mouse mIgA myeloma proteins were labeled either by direct iodination or by coupling the residualizing label, dilactitol-125I-tyramine (125I-DLT) to the proteins; catabolites from protein labeled with 125I-DLT accumulate at the site of protein degradation, allowing identification of the tissue and cellular sites involved in catabolism of the protein. The circulating half-lives of 125I- and 125I-DLT-mIgA were the same. The distribution of radioactivity in tissues was measured at 1, 3, 24, and 96 h after iv. injection of 125I-DLT-labeled mIgA, dimeric IgA (dIgA), IgG, or mouse serum albumin. The greatest uptake of 125I-DLT-mIgA was attributable to the liver. This organ accounted for more internal catabolism of mIgA than all other tissues combined. In contrast, 125I-DLT-IgG was catabolized equally in skin, muscle, and liver. These data indicate that, in mice, the liver is the major site of mIgA catabolism. To determine the cell types involved, collagenase digestion was used to isolate parenchymal and non-parenchymal cells from perfused liver of animals injected with 125-DLT-mIgA. Most of the radioactivity was associated with the hepatocyte fraction, even though both cell types showed uptake of 125I-DLT-mIgA. Inhibition studies, with asialofetuin and mouse IgA demonstrated that the uptake of mIgA by liver cells was mediated primarily by the asialoglycoprotein receptor.

Animals↗
PubMed1988

Binding of IgA to erythrocytes from patients with IgA nephropathy.

Primate erythrocytes (RBCs) may be involved in the transport and processing of C3b-containing immune complexes (IC). Compared to RBCs from healthy controls, increased amounts of IgA were detectable on RBCs from 7 of 17 patients with IgA nephropathy (IgA NP). There was no difference in the amount of IgG or IgM. The highest amount of RBC-bound IgA corresponded to 6 ng IgA/10(8) cells. The mechanisms involved in the binding of IgA to RBCs were investigated in vitro. Isolated IgA1 or IgA2 did not bind to RCBs from a patient with IgA deficiency. In contrast, incubation of RBCs with a polyethyleneglycol (PEG) precipitate of serum from a patient with IgA NP which contained IgA-IC resulted in IgA1 binding. However, this binding was not inhibited by monoclonal anti-CR1 or by an excess of IgG or IgM. Factor I did not cause release of IgA from RBCs from patients with IgA NP. Heat-aggregated IgA1 also bound to RBCs and this binding was not affected by the presence of complement. We conclude that minute amounts of IgA-IC are bound to RBCs by a complement- and Fc receptor-independent mechanism. The quantity of IgA-IC associated with RBC is so small that it is unlikely to represent an important in vivo route of IgA-IC transport or processing.

Antigen-Antibody Complex↗
PubMed1988

Intranasal immunization of hamsters with envelope glycoproteins of human parainfluenza virus type 3.

Envelope glycoproteins of human parainfluenza virus type 3 (PIV-3) were selectively solubilized with n-octyl beta-D-glucopyranoside and reconstituted into lipid vesicles by dialysis of the detergent. The efficacy of the glycoprotein preparation as a subunit vaccine when administered to hamsters intranasally or subcutaneously was compared. Animals receiving four intranasal immunizations with 5 micrograms of the glycoprotein preparation were completely resistant to challenge infection. Only partial protection, however, was observed in animals immunized subcutaneously with the same dose of antigen. The local glycoprotein-specific IgA response was significantly higher in intranasally immunized animals and was implicated in resistance to challenge infection.

Administration, Intranasal↗
PubMed1987

Heterogeneity of binding of monoclonal IgA to staphylococcal protein A is related to the IgA polymerization state.

The human IgA2-lambda myeloma protein Fel consists of covalent dimers and monomers which are partially self-associated. Affinity chromatography of this protein on staphylococcal protein A-Sepharose revealed that approximately 8% of the protein was retained and eluted by acid buffer. Although retained protein Fel was highly aggregated, in the presence of dissociating agents mostly monomeric form was found. Affinity rechromatography and electrophoresis of both fractions from affinity chromatography revealed that the retained fraction possessed substantially higher affinity for SpA than did the nonretained one. This could be due to the multivalency of protein Fel aggregates.

Antibodies, Monoclonal↗
PubMed1987

Striking elevation of serum IgA, IgA-containing immune complexes, and IgA rheumatoid factor in clinically silent dermatitis herpetiformis.

We describe a patient with dermatitis herpetiformis with immunoglobulin A (IgA)-containing circulating immune complexes and IgA rheumatoid factor who presented with acute renal insufficiency; a renal biopsy specimen showed IgA nephropathy. The renal function and proteinuria spontaneously returned to normal despite markedly elevated levels of IgA-containing circulating immune complexes, IgA rheumatoid factor, and IgA antibodies to some environmental antigens. IgA1 was the predominant subclass. IgA2-containing immune complexes and IgM rheumatoid factor were not detected. Cultures of peripheral blood mononuclear cells produced increased quantities of IgA and IgA rheumatoid factor spontaneously and after pokeweed mitogen stimulation. These data indicate that renal function can improve and remain normal despite the presence of increased levels of IgA-containing circulating immune complexes and IgA rheumatoid factor.

Acute Kidney Injury↗
PubMed1987

IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans.

The finding that ingestion of antigens results in the selection induction of IgA antibodies in external secretions suggests that antigen sensitizes Peyer's patch lymphoid cells, which migrate to mucosal sites and generate local secretory IgA (S-IgA) antibody responses. Evidence for a common mucosal immune system in humans has been scanty because of the difficulty in demonstrating migratory behavior of Peyer's patch cells. In the present study, peripheral blood mononuclear cells (PBMC) from human volunteers who had ingested capsules containing killed Streptococcus mutans were assayed for spontaneous antibody-producing cells. Four of five volunteers exhibited circulating IgA-producing cells within 7 days and reached maximum responses by days 10-12. One IgA-deficient subject exhibited IgM responses with identical kinetics. Pokeweed-mitogen-stimulated PBMC produced anti-S. mutans antibodies predominantly of the IgA isotype. Significant S-IgA anti-S. mutans antibodies were detected in saliva and tears by day 14, and the antibodies reached maximum titers by 3 weeks. No changes in serum anti-S. mutans antibodies were noted. The IgA-deficient subject produced salivary secretory IgM antibodies. These results suggest that, after antigen ingestion, peripheral blood contains antigen-specific precursors of IgA plasma cells and that their presence precedes the appearance of S-IgA antibodies in external secretions. Therefore, these experiments provide further support for the existence of a common mucosal immune system in humans.

Adult↗
PubMed1987

Induction and molecular properties of secretory and serum IgA antibodies specific for environmental antigens.

A generalized secretory IgA response can be induced by ingestion of various antigens due to dissemination of sensitized precursors of IgA plasma cells from gut-associated lymphoid tissue to various secretory glands. Oral ingestion of a bacterial antigen by volunteers led to the parallel appearance of secretory IgA antibodies in several external secretions that was preceded by a transitory detection of IgA antibody-secreting cells in the peripheral blood. Naturally occurring secretory and serum IgA antibodies as well as secretory and serum antibodies induced by mucosal immunization belong predominantly to the IgA1 subclass; however, in external secretions IgA2 is the predominant subclass of natural antibodies to endotoxin and lipoteichoic acid. Although in external secretions specific IgA antibodies are of polymeric form, serum IgA antibodies to different antigens display considerable variability with respect to their distribution in polymeric and monomeric forms. However, after experimental infection, serum IgA antibodies to the influenza virus hemagglutinin are almost exclusively polymeric.

Administration, Oral↗
PubMed1987

IgA on the surface of erythrocytes from IgA nephropathy patients.

RBCs from one-third of IgA nephropathy patients examined had more IgA1 on their surface than cells from healthy volunteers. The amount of IgA1 on RBCs was estimated to be no more than 30 ng/4 x 10(8) RBCs. The level of IgG on the surface of RBCs from IgA nephropathy patients were the same as those from healthy volunteers. Free IgA1 myeloma protein binds poorly in vitro to RBCs from both an IgA deficient patient and healthy volunteers. Polyethylene glycol precipitate from the sera of IgA nephropathy patients bound to RBCs from an IgA deficient patient. Factor I did not release IgA1 bound to RBCs from IgA nephropathy patients. These results suggest that this binding is mediated through the interaction of IgA1 and RBCs, and that some alteration of the IgA1 molecule (complexes or aggregation) may account for this binding.

Erythrocytes↗
PubMed1986

Detection and specificity of antibodies secreted by spleen cells in mice immunized with Streptococcus mutans.

Immune responses of mice to Streptococcus mutans serotype c were analyzed by means of the enzyme-linked immunospot assay to determine the predominant specificities of the antibodies developed. In general, the numbers of splenic antibody-secreting cells correlated with serum antibody levels. A low dose (10(8) CFU) of killed whole cells injected twice intraperitoneally induced antibodies mainly against surface protein antigen I/II. A higher dose (10(9) CFU) given two to six times also resulted in a predominance of antigen I/II antibody-secreting cells and, in addition, antibody responses to surface protein antigen III and lipoteichoic acid occurred. Cells producing antibodies to serotype c polysaccharide were elicited only on repeated immunization. These results agreed with the development of antibodies in rabbits repeatedly immunized intravenously with killed whole cells of S. mutans, S. rattus, and S. sobrinus, which induced specific antibodies in accordance with the surface antigens that they express. Mice immunized twice with the same dose of purified antigens I/II and III developed greater numbers of antigen I/II splenic antibody-forming cells than antigen III splenic antibody-forming cells and higher serum antibody levels to antigen I/II than to antigen III. Furthermore, a single injection of antigen I/II but not of antigen III was sufficient to induce a strong specific-antibody response. Some evidence was also obtained for weak polyclonal stimulation of spleen cells by S. mutans cells and by antigen I/II, a result which could be relevant to the induction by S. mutans of antibodies reactive with mammalian tissues. It was concluded that for the antigens examined, S. mutans elicited the strongest antibody response against antigen I/II, which was also highly immunogenic in purified form.

Animals↗