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Biomedical subjects

D W Knutson

Publications and source records attributed to D W Knutson.

27 records · Page 2Linked to original sources
PubMed1979

Clearance and glomerular localization of preformed DNP anti-DNP immune complexes.

The in vivo behaviour of well-defined immune complexes in rats was studied using complexes derived from DNP-conjugated bovine thyroglobulin (DNP-BTG) and purified specific goat anti-DNP IgG. Both clearance and glomerular localization were mainly dependent on the nature of the antigen. Soluble immune complexes formed with DNP17-BTG were cleared faster and showed a more marked localization in the glomerular mesangium than complexes formed with DNP3.4-BTG. A slight increase in the antibody to antigen ratio seemed to facilitate mesangial localization of soluble immune complexes. Insoluble immune complexes showed temporary localization as microemboli in the lumina of glomerular and peritubular capillaries. This study thus shows that not only the size and composition of the complexes but also the nature of the antigen within the complex can influence the clearance and organ localization of circulating immune complexes.

Animals↗
PubMed1979

Isolation of stable aggregates of IgG by zonal ultracentrifugation in sucrose gradients containing albumin.

Soluble heat aggregates of [125I]IgG (A-IgG) were prepared and separated by gel filtration or by zonal ultracentrifugation, and fractions containing different size aggregates were then analyzed by reultracentrifugation. A-IgG formed single narrow peaks with constant S rates when isolated, stored and analyzed in solution containing 0.5% serum albumin. Thus, stable homogeneous aggregates of IgG of known size can be simply prepared and should prove useful both as a model for immune complexes of specified sizes and as a standard for immune complex assays.

Animals↗
PubMed1979

Poststreptococcal acute glomerulonephritis: fact and controversy.

Poststreptococcal acute glomerulonephritis is prototypic of the immunologic glomerulonephritides. It most commonly follows streptococcal infection of the pharynx or skin. The diagnosis is usually not difficult when a nephritic clinical presentation (with such manifestations as hematuria, edema, and hypertension) is associated with serologic evidence of recent streptococcal infection and a depressed serum complement concentration. Currently, however, the nephritogenic antigen(s) has not been identified and has not been shown to be the same antigen for all nephritogenic streptococci; it may not even be a part of the infecting organism. The development of a vaccine to prevent this illness from occurring is therefore still not possible. Whether poststreptococcal acute glomerulonephritis progresses to chronic renal failure is still uncertain. Painstaking laboratory research together with careful, prospective long-term follow-up studies of patients with poststreptococcal acute glomerulonephritis may provide some of the answers to these critical questions.

Acute Disease↗
PubMed1979

Soluble oligovalent antigen-antibody complexes. I. The effect of antigen valence and combining ratio on the composition of fluorescein-carrier anti-fluorescein complexes.

Soluble oligovalent antigen--antibody complexes were prepared and analysed by ultracentrifugation in order to study the effect of the combining ratio, antigen valence and concentration upon the size and molecular composition of the composition of the complexes. Fluorescein (F) conjugates of rabbit serum albumin (RSA) and thyroglobulin (RTg) were combined with high affinity rabbit anti-F antibodies to form soluble complexes. The effect of the combining ratio paralleled findings in precipitating systems in that the largest soluble complexes were found at equimolarity and mild molar antibody excess. Tetravalent antigen formed precipitates at combining ratios near equimolarity, whereas trivalent antigens failed to precipitate at similar concentrations. Complexes prepared near equimolarity were most sensitive to changes in concentration, higher concentrations leading to larger complexes. The Ab/Ag ratios of different-size complexes in the same preparation were remarkably similar. This ratio was dependent on the antibody--antigen combining ratio, was limited by antigen valence and was not affected by concentration differences. The data support the hypothesis that soluble complexes are formed in two steps. First, antigen and antibody combine to form subunits whose Ab/Ag ratio is determined by the combining ratio and antigen valence. These subunits then combine to form larger complexes in a manner analogous to polymerization.

Antibodies↗
PubMed1979

Soluble oligovalent antigen--antibody complexes. II. The effect of various selective forces upon relative stability of isolated complexes.

Soluble oligovalent antigen--antibody complexes were isolated and analysed by ultracentrifugation to assess the effect of several forces upon the composition and stability of soluble complexes. Complexes were prepared with fluorescein (F) conjugates of rabbit serum albumin (RSA) or thyroglobulin (RTg) and high affinity rabbit anti-F antibodies. Isolated complexes containing two antigen molecules (Ag2 complexes) tended to dissociate and form an equilibrium with complexes containing one antigen molecule (Ag1 complexes). This equilibrium was thermolabile, concentration dependent and affected by the original combining ratio and the area in the gradient from which complexes were harvested. Small amounts of free antibody dissociated from soluble complexes also to form a dynamic equilibrium; this equilibrium was much less affected by the above parameters. The data support the concept that complexes grow in size by a process analogous to polymerization of simple subunits and that the driving forces for polymerization are of a lower order of magnitude and more affected by physical variables than the primary reaction between antibody and its antigen.

Antibody Affinity↗
PubMed1978

Estimation of relative glomerular capillary surface area in normal and hypertrophic rat kidneys.

The quantity of antiglomerular baSEMent membrane antibodies (antiGBM) binding to the glomeruli of rats 4 hr after i.v. injection of 660 microgram of antiGBM was used as a measure of relative glomerular capillary surface area (Sr). Intact immature and adult rats (N = 27) weighing 46 to 440 g were studied to assess the effect of normal growth on Sr. Young adult rats (N = 36) were studied at 0, 8, 15, and 22 days following uninephrectomy or sham operation to assess the effect of hypertrophic kidney growth on Sr. Bound antiGBM increased from 95 microgram to approximately 350 microgram as rats grew from 46 to 200 g; further growth was associated with no further growth was associated with no further increases in bound antiGBM. In contrast, there was no progressive increase in Sr following uninephrectomy or sham operation despite as 45% increase in kidney weight at 22 days over the comparable kidney in the sham-operated rats (1.32 +/- SEM 0.06 g vs. 0.91 +/- SEM 0.01 g, P less than 0.0001). Thus, increases in GFR during early normal kidney growth parallel anatomic increases in Sr, but increases in GFR with later growth or with compensatory hypertrophy in young adult rats are not accompanied by changes in Sr.

Animals↗
PubMed1977

Association and dissociation of aggregated IgG from rat peritoneal macrophages.

Stable aggregated IgG (A-IgG) of various sizes, having high biological activity, were incubated at 4 degree C with adhering peritoneal macrophages from normal rats and the kinetics of A-IgG binding to the cell surface were studied. Equilibrium constants were high (2.8-11.7 X 10(8) M-1) and varied as a function of aggregate size. The maximum number of A-IgG bound per cell varied from 230,000 for A-IgG9 to 90,000 for A-IgG74. Binding was 50% inhibited by near physiological concentrations of monomeric IgC. These data suggest that A-IgG are bound at multiple sites by attachment of Fc frgments to Fc receptors present on the macrophage surface with larger A-IgG being more avidly bound. Dissociation was slower for larger A-IgG while no clear trend was seen relating associating rates and aggregate size. Thus, differences in the avidity of binding of A-IgG are due primarily to slower dissociation of larger A-IgG. Dissociationissociation of A-IgG was slower from cells exposed initially to higher doses of A-IgG and dissociation did not follow simple first order kinetics. Thus, the avidity of binding appears to be heterogeneous in a population of similar sized A-IgG. As expected, association was dose-dependent, more rapid than dissociation, and followed pseudo first order kinetics. Based on all of the above data, it is proposed that binding of A-IgG proceeds in two steps. First, A-IgG are loosely bound to perhaps a single Fc receptor. Then, depending upon the availability and mobility of Fc receptors, additional Fc fragments are attached and the A-IgG becomes more firmly attached. Thus binding is slow, but once attached A-IgG are avidly held.

Animals↗
PubMed1977

Characteristics of soluble immune complexes prepared from oligovalent DNP conjugates and anti-DNP antibodies.

The stability of soluble immune complexes was investigated after isolation by gel filtration and sucrose gradient ultracentrifugation. Soluble immune complexes were formed between specific goat anti-dinitrophenol (DNP) antibodies and DNP conjugated to a large (19 S) carrier, namely bovine thyroglobulin. The composition and molecular weight of these complexes were determined by ultracentrifugation on calibrated sucrose density gradients and the use of different isotopic markers for antigen and antibody. A good separation of immune complexes containing one, two, or three antigen molecules per complex was obtained by ultracentrifugation while gel filtration was less effective. Ultracentrifugational analysis of fractions isolated by these two procedures showed that large immune complexes containing more than one antigen were relatively labile, whereas small immune complexes containing one antigen were stable. The stability of large immune complexes was dependent on dilution. Because dilution affects the size and composition of soluble immune complexes, it is important to emphasize that for the investigation of a causal relationship between the biological properties and the size and composition of immune complexes, analysis of the immune complexes should be performed in the same dilutions in which they will be used experimentally.

Animals↗