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Biomedical subjects

M W Steward

Publications and source records attributed to M W Steward.

At least 109 records · Page 6Linked to original sources
PubMed1982

Experimental antigen-antibody complex disease in mice. The role of antibody levels, antibody affinity and circulating antigen-antibody complexes.

Chronic antigen-antibody complex disease (A-ACD) was induced in mice by daily injections of HSA. The disease was characterized by death, intense glomerular basement membrane deposition of complexes in the kidneys, proteinuria and an impairment of the glomerular filtration rate. In mice that had been selectively bred to produce antibody of low affinity to protein antigens injected in saline, the incidence of chronic A-ACD was 61% compared to 21% in mice selectively bred to produce antibody of high affinity. Low affinity female mice produced approximately ten times as much free antibody to HSA as did low affinity males and high affinity males and females, but this did not result in an increase incidence of chronic A-ACD in low affinity female mice. Low affinity female mice also had the highest levels of circulating antigen-antibody complexes detected by conglutinin and Clq binding assays, but there was no correlation between the presence of high levels of complexes in serum and tissue damage. In both lines of mice the mean affinity of free antibody to HSA started low and increased with time and the number of injections of antigen. However, development of chronic A-ACD in individual low affinity mice appeared to be associated with a failure to produce this time-associated increase in antibody affinity. These results are discussed with reference to the relevance of the measurement of the amount of affinity of free antibody in serum and the levels of circulating antigen-antibody complexes to the production of tissue damage in this model of chronic A-ACD.

Animals↗
PubMed1982

Circulating antigen-antibody complexes in onchocerciasis.

The presence of circulating antigen-antibody complexes in the sera of patients with onchocerciasis was investigated using the Clq and conglutinin solid-phase binding assays. Only 50% of patients' sera had demonstrable complexes, levels of complexes were unrelated to microfilarial load and specific anti-onchocercal antibody titres and results with the two tests for complexes were not correlated. Both IgM- and IgG-containing complexes were commonly involved but there was no correlation between the levels of complexes containing these isotypes. Evidence for the presence of IgE in complexes of sera from a minority of individuals was also obtained.

Antibodies↗
PubMed1981

The effect of Trichinella spiralis on the rate of clearance of 51Cr-labelled sheep red blood cells and 125I-polyvinyl pyrrolidone from the bloodstream of mice.

Mice infected for one to eight weeks with Trichinella spiralis cleared either 51Cr-labelled sheep red blood cells (SRBC) or 125I-polyvinyl pyrrolidone (PVP) given intravenously. PVP was cleared more rapidly from the blood of mice infected for one week than from uninfected mice with older infections which behaved in a similar manner to the controls. SRBC were consistently cleared faster from the blood of mice infected for one week than from normal mice. If the infections were older than this a more rapid clearance was also demonstrated as long as the infections were reasonably heavy.

Animals↗
PubMed1981

Chronic antigen-antibody-complex glomerulonephritis in mice.

Daily injection of human serum albumin into mice genetically selected to produce low-affinity antibody to protein antigens resulted in a more severe antigen-antibody-complex-induced glomerulonephritis than in mice producing high-affinity antibody. The low-affinity mice had higher levels of circulating antigen-antibody complexes, greater impairment of renal function and reduced reticuloendothelial clearance of 125I-PVP compared to high-affinity mice. Electron microscopy of glomeruli revealed the presence of subepithelial electron-dense deposits in low-affinity mice and predominantly subendothelial-mesangial deposits in high-affinity mice which corresponded to the predominantly capillary staining in low-affinity mice and mesangial staining in high-affinity mice by immunofluorescence. Auto-radiography of electron-microscopy sections demonstrated the presence of antigen in the electron-dense deposits, indicating that these deposits indeed contained antigen-antigen complexes.

Animals↗
PubMed1981

The effect of protein deficiency on the development of chronic antigen-antibody complex disease in mice.

Mice genetically selected to produce antibodies of either high or low affinity to protein antigens injected in saline were fed either a normal protein diet or a protein-deficient diet and were given daily injections of HSA for up to 73 days to induce chronic antigen-antibody complex disease. In low-affinity mice fed the normal protein diet, this resulted in impairment of renal function, deposition of immunoglobulin, C3 and HSA in the glomeruli, high levels of circulating antigen-antibody complexes and death from apparent renal failure in 50% of the animals. High-affinity mice on either diet had no impairment of renal function, fewer deposits in the glomeruli, lower levels of circulating complexes and no deaths. Low-affinity mice fed the protein-deficient diet had less impairment of renal function and less glomerular deposition of complexes than did low-affinity mice fed the normal diet. In addition, none of these mice died from renal failure. These results demonstrate that the protein-deficient diet reduced the severity of the experimental chronic antigen-antibody complex disease in low affinity mice but did not increase the susceptibility of high-affinity mice to the disease.

Animals↗
PubMed1981

Detection of circulating antigens and immune complexes in feline and human lymphatic filariasis.

Circulating worm antigens were detected in 61% to 81% of sera from Brugia pahangi -infected cats and in 0-93% of sera from humans with malayan of bancroftian filariasis by counter immunoelectrophoresis and a double antibody sandwich enzyme-linked immunosorbent assay, using rabbit antisera to B. pahangi adult worms. In some situations, both antigen tests were as sensitive as antibody tests. However, ELISA was likely to be affected by the presence of antiglobulins, such as rheumatoid factor, in the test sera. Only 10% to 22% of B. pahangi-infected cats (treated with drugs or not) had circulating immune complexes by the conglutinin-binding assay and no sera were positive by C1q-BA. A significantly higher percentage (56%) of B. malayi clinical sera was positive for immune complexes by either C1q- or conglutinin- binding assays as compared to other groups of B. malayi and Wuchereria bancrofti sera (6% to 14%).

Animals↗
PubMed1980

Measurement of antigen-antibody complexes in mouse sera by conglutinin, C1q and rheumatoid factor solid phase binding assays.

The application of three solid phase tests for the detection of antigen-antibody complexes in the sera of inbred and selectively-bred mice with experimentally induced chronic antigen-antibody complex disease is described. Two of the tests used--the C1q binding assay (C1qBA) and the conglutinin binding assay (KBA)--were previously described methods which we have modified for the detection of murine complexes. The third test is a new solid phase polyclonal rheumatoid factor binding assay (RFBA). The results demonstrate that the correlation of positivity with the three methods varied during the course of a chronic disease but in general results with the KBA showed a better correlation with the RFBA than with the C1qBA. Furthermore, the KBA and RFBA preferentially bound complexes of lower molecular weight than did the C1qBA. It is suggested that the parallel use of these three tests during the study of murine antigen-antibody complex disease will provide valuable information concerning the nature of the complexes involved; since the three tests, when run in parallel, will detect large complement fixing complexes (C1q), small complement fixing complexes (KBA) and small non-complement fixing complexes (RFBA).

Animals↗
PubMed1980

The induction of chronic antigen-antibody complex disease in selectively bred mice producing either high or low affinity antibody to protein antigens.

Mice selectively bred to produce either high or low affinity antibody to protein antigens were injected daily with bovine serum albumin (BSA) and studied for the development of chronic antigen-antibody complex disease. After 41-44 injections of BSA, evidence of circulating antigen-antibody complexes and renal localization of complexes was obtained in both lines. However, low affinity mice had significantly higher levels of circulating complexes than high affinity mice. Impairment of renal function was seen in low affinity mice but not in high affinity mice and there was significantly more complex deposition in the glomeruli of low compared to high affinity mice. Furthermore, the pattern of localization of complexes was predominantly mesangial in high affinity mice but in low affinity mice the deposition was both mesangial and in the glomerular basement membrane. The role of antibody affinity in the induction of chronic antigen-antibody complex disease is discussed in the light of these results.

Animals↗
PubMed1979

Chronic immune complex disease in mice: the role of antibody affinity.

Two lines of mice selectively bred for producing high and low affinity antibody to protein antigens were repeatedly injected with human serum albumin and the severity and pattern of immune complex disease induced in this way was studied in the two lines. In low affinity mice, there was a greater intensity of deposits in the glomeruli shown by immunofluorescence, and more antibody was eluted from kidney homogenates compared to high affinity line mice. In the low affinity mice, complexes were mainly on the basement membrane whereas in high affinity mice, the localization of immune complexes was predominantly mesangial. However, no significant difference in glomerular filtration rates between the two lines was obtained. The immunopathological significance of antibody affinity is discussed in the light of these results.

Animals↗
PubMed1979

The genetic control of antibody affinity. Evidence from breeding studies with mice selectively bred for either high or low affinity antibody production.

The genetic control of antibody affinity has been studied in mice selectively bred on the basis of the affinity of antibody they produce to protein antigens injected in saline. Two lines of mice have been obtained, one producing predominantly high and the other predominantly low affinity antibody. Breeding experiments have been performed with these two lines after ten generations of selection and the level and affinity of antibody to protein measured in parents, F1 hybrids and backcross offspring. The results indicate that antibody affinity is a genetically controlled parameter of the immune response and that this control is exerted independently of that controlling antibody levels. Furthermore, high and low affinity line mice have been typed for major histocompatibility complex antigens and the results show that the two lines are not significantly different. This therefore suggests that genes controlling antibody affinity are not linked to the major histocompatibility locus.

Animals↗
PubMed1979

Antibody affinity and clearance function studies in high and low antibody affinity mice. The effect of protein deficiency.

The effect of dietary manipulation on the relationship between macrophage clearance function and antibody affinity has been investigated in genetically selected high and low affinity mice. The results confirm that protein deprivation reduces the clearance rate of polyvinylpyrrolidone (Kpvp) and the relative affinity (Kr) of antibody to human serum albumin in mice normally producing high affinity antibody. Although protein deprivation of mice of the low affinity line reduced Kpvp, the mean Kr was not altered. Furthermore, although the two lines had significant differences in Kr values there were no demonstrable differences in macrophage clearance function as assessed by clearance of PVP, radiolabelled aggregated IgG and preformed antigen-antibody complexes. Analysis of values of Kr and Kpvp in individual animals indicated that these two parameters are not correlated. These experiments, provide further evidence for the profound effect of dietary manipulation on the immune response and suggest that in these genetically selected mice at least, the genetic control of antibody affinity is exerted at a level other than that measured by macrophage clearance function tests.

Animals↗
PubMed1977

Relationship of antibody affinity to onset of immune complex disease in New Zealand mice.

Affinity (KR) of antibody to human serum transferrin in New Zealand mice was measured by a globulin precipitation technique. KR was low in mice immunized early in life, increased with age of immunization up to 16-26 weeks, and then fell to low levels. KR in young and old NZB mice was increased by immunization with antigen in Freund's complete adjuvant. The correlation between low affinity antibody production and susceptibility to immune complex disease is discussed.

Age Factors↗
PubMed1977

The effect of immunological adjuvants on the relative affinity of anti-protein antibodies.

Inbred mice of a strain (B1OD2 new) known to produce either no detectable antibody or antibody of low affinity to two protein antigens administered in saline, were immunized with human serum transferrin (HST) in one of nine adjuvants. Such immunization increases the level and relative affinity of anti-HST antibody. The adjuvants used varied in the degree to which they augmented these parameters of the antibody response--that is, FCA and FIA were capable of inducing high levels of high affinity antibody, whereas other adjuvants elicited lower levels of high affinity antibody. The possibility is discussed that substances with adjuvant activity may effect antibody production at two stages: (1) at the stage of antigen selection of cells for proliferation and (2) at the stage or proliferation of antibody producing cell precursors.

Adjuvants, Immunologic↗