Soluble Antigen-antibody Complexes Research Articles

CELLULAR DAMAGE BY SOLUBLE ANTIGEN-ANTIBODY COMPLEXES IN TISSUE CULTURE.

SummaryBy tissue culture method and with the use of phase contrast microscope, detailed morphology of cellular damage by soluble BSA-rabbit anti-BSA complexes was studied. Although the changes resembled those in the antigen-antibody reaction, they were characterized by early cellular excitation accompanied by increased pinocytosis. Injurious effects of the complexes seemed associated with the complement fixability of the complexes.

BRONCHOCONSTRICTOR EFFECTS OF SOLUBLE ANTIGEN-ANTIBODY COMPLEXES IN ISOLATED LUNG, AND THEIR INHIBITION BY NORMAL SERUM.

RECENT investigations in this laboratory with the perfused guinea pig lung have shown that a broncho-constriction, accompanied by histamine release, follows injection into the perfusate of soluble antigen–antibody (Ag–Ab) complexes prepared in antigen excess. It is known that soluble Ag–Ab complexes produce an increase in capillary permeability when injected subcutaneously in unsensitized animals1, and an anaphylactic syndrome when given intravenously2. They have also been shown to induce a contraction of guinea pig ileum in vitro3.

Inhibition of Complement Fixation by Human Serum

Summary Kinetic and static analyses of complement fixation (CF) reactions were carried out using EA, EA (human), solutions of human thyroglobulin-rabbit anti-thyroglobulin and latex particles coated with human γ-globulin (LPF II). Heated rheumatoid arthritis (RA) sera and N sera, rheumatoid factor (RF) and inhibitor (Ag-Ab)—a γ1M-globulin isolated from RA sera—were tested for their effect on CF reactions. Addition of RA serum and N serum to EA and gpC′ delayed immune hemolysis. Preabsorption of the sera with solid heat denatured γ-globulin did not affect their inhibitory activity. Inhibitor (Ag-Ab) was shown to delay lysis of EA by gpC′. The substance also inhibited CF by soluble antigen-antibody complexes, but CF reactions involving LPF II remained unaffected. RF did not interfere with the lysis of EA by gpC′. This substance was also inactive in CF reactions involving soluble antigen-antibody complexes. RF, however, inhibited CF by LPF II, especially when preincubated with LPF II for 90 min at 56°C. There was also a decrease in the latex fixation titer of RA sera when LPF II was preincubated with gp serum, suggesting some competition between RF and gpC′ for sites of attachment on the γ-globulin molecule.

STUDIES ON THE LOCALIZATION OF CIRCULATING ANTIGEN-ANTIBODY COMPLEXES AND OTHER MACROMOLECULES IN VESSELS. I. STRUCTURAL STUDIES.

A short term model in which circulating antigen-antibody complexes and host complement localized in vessel walls of guinea pigs was analyzed. Localization was accomplished by subjecting the animals to anaphylactic shock. The circulating macromolecules, such as antigen-antibody complexes, appeared to localize by being trapped in the vessel wall along the basement membrane that acted as a filter during a state of increased permeability of the vessel. It was suggested that this point of localization between the endothelial cell and the basement membrane may well represent the earliest focus of inflammation in diseases caused by the deposition of injurious macromolecules such as soluble antigen-antibody complexes from the blood stream. Complexes localized in the vessel walls did not provoke Arthus-type vasculonecrotic reactions even though in both these vessels and in cutaneous Arthus reactions antibody, antigen, and host complement (C'3c) were deposited in the vessel walls. The possibility was presented that since circulating macromolecules and probably complexes deposited in (a) relatively small amounts, and (b) in a position beneath endothelial cells, they were not strongly chemotactic toward circulating polymorphonuclear leukocytes. Vasculonecrotic reactions, therefore, were not observed. It was brought out that this may be similar to the situation in glomerulonephritis induced by localized immune complexes, in which severe necrosis is not observed. In the Arthus vascular reaction, host complement was found microscopically accumulated with the immune reactants in affected vessel walls.

Biologic Activities of Aggregated γ-Globulin

Summary Rabbit α-globulin, β1-globulin and subfractions of γ-globulin were aggregated by coupling with bis-diazotized benzidine and the aggregated products were studies for skin reactivity in normal guinea pigs and for C′-fixing properties. Induction of these biological activities upon nonspecific aggregation was characteristic of γ-globulin only. Aggregated products of neither α-globulin nor β1-globulin had either activity. Evidence was presented that only γ-globulin had affinity for guinea pig tissues to which antibody combines upon passive sensitization. All three of these properties, namely skin reactivity and C′-fixing activity upon aggregation, and affinity for guinea pig tissue were present approximately equally in all the chromatographic subfractions of γ-globulin. All γ-globulin subfractions of rabbit anti-ovalbumin sera contained antibody. Soluble antigen-antibody complexes prepared with these fractions gave skin reactions in normal guinea pigs and inactivated C′. On a weight basis, the soluble complexes and nonspecifically aggregated γ-globulin were comparable with respect to these biologic activities.

The Temporal Synthesis and Some Chromatographic and Ultracentrifugal Characteristics of Chicken Antibodies

Summary Chicken anti-bovine serum albumin antibodies formed following primary, secondary and tertiary antigenic stimulations were fractionated by diethylaminoethyl cellulose chromatography by elution with phosphate buffers of 0.1 M (A), 0.2 M (B), 0.3 M (C), 0.4 M (D), and 0.4 M + 2 M NaCl (E). As assayed by the passive hemagglutination method, early sera had three chromatographically-distinct macroglobulin antibodies (Fractions C, D and E). Fractions C, D and E each lost agglutinating activity following treatment with mercaptoethanol, and in zone ultracentrifugation each sedimented as macroglobulins. Secondary sera had HA antibody in all five chromatographic fractions, with greatly increased activity in fractions eluted with the lower salt concentrations (Fractions A and B), and lower activities in C, D and E. Fraction A was resistant to mercaptoethanol and sedimented as a 7 S antibody. Fraction B had a mixture of high and low molecular weight antibodies. The chromatographic heterogeneity of the macroglobulins was confirmed by ultracentrifugal analyses. The major faster-sedimenting components were in the 15 S, 19 S and 26 S classes. The relative concentrations of high and low molecular weight antibodies were followed during primary, secondary and tertiary responses, and the significance of these results is discussed. Soluble antigen-antibody complexes prepared from primary sera had sedimentation coefficients of 9.5 S and 21.5 S. The 19 S globulin contributed about 60% of protein to antigenprecipitated antibody.

ON BINDING OF SOLUBLE ANTIGEN-ANTIBODY COMPLEXES TO ERYTHROCYTES

Abstract : The surface of erythrocytes adsorbs soluble antigen-antibody complexes to a greater extent than it does either of the two components of the complex separately. Human albumin and rabbit antihuman-albumin antibody were investigated as a model of a soluble antigen-antibody complex. The specific concentration of the immune complex at the red cell surface suggests that these cells are actively involved in the removal of antigen-antibody complexes from the circulation.

Cutaneous allergy and vascular reactions in experimental streptococcal infections.

SummaryEarlier work with β-hemolytic streptococci has reproduced the pathological lesions of rheumatic fever and rheumatoid arthritis in experimental animals.Heart and joint disease appeared without any correlation to acute or delayed skin hypersensitivity.Intravenous streptococcal injections depress skin reactivity; intracutaneous injections enhance it. The injections by either route may result in specific heart and joint disease.Swelling of the capillary endothelium is slight, if any, in these repeatedly infected animals in contrast to the constant finding of swelling in acute streptococcal disease and in serum sickness.The experimental vascular lesions in serum disease and streptococcal granulomatosis appear to be identical, and as the former is caused by soluble antigen-antibody complexes in antigen excess this is also likely for the granulomatosis.Experimental and clinical experiences in acute and chronic rheumatism would seem to be explainable as antigen-antibody lesions in an immunoparalytic host.

Passive Acute Glomerulonephritis Induced by Antigen-Antibody Complexes Solubilized in Hapten Excess.

SummaryAcute glomerulonephritis has been produced passively in normal mice by soluble antigen-antibody complexes prepared from rabbit anti-DNP Bγg which was precipitated at equivalence with DNPBSA and dissolved in excess hapten, ∊NH2DNP lysine. The fate and distribution of the injected antigen-antibody complexes and of purified rabbit antibody, which was used as a control, were studied by the fluorescent antibody technic. The complexes were rapidly and efficiently phagocytosed by the cells of the reticuloendothelial system and had largely disappeared from these cells within 24 hours. In contrast, there was only slight localization of complexes within glomeruli following a single injection, but with 3 injections in 24 hours, which resulted in production of acute glomerulonephritis, marked accumulation of complexes occurred in glomeruli; this was apparent 24 hours after the last injection. Purified rabbit antibody did not localize in glomeruli and only in trace amounts in the cells of the reticuloendothelia...

Response of the Liver to Soluble Antigen-Antibody Complexes

Response of the Liver to Soluble Antigen-Antibody Complexes

The fate of fluorescein-labeled soluble antigen-antibody complex in the mouse.

Journal Article The Fate of Fluorescein-Labeled Soluble Antigen-Antibody Complex in the Mouse Get access Russell S. Weiser, Russell S. Weiser Department of Microbiology, University of Washington School of Medicine, Seattle 5, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol Laxson Carol Laxson Department of Microbiology, University of Washington School of Medicine, Seattle 5, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 111, Issue 1, July-August 1962, Pages 55–58, https://doi.org/10.1093/infdis/111.1.55 Published: 01 July 1962 Article history Received: 19 January 1962 Published: 01 July 1962

Experimental eosinophilia: III. Regional lymph node responses to reactions of tissue sensitization

1. 1. The administration of bovine serum albumin (BSA) and corresponding antiserum into the rabbit foot pad resulted in four-hour eosinophilic granular cell infiltrations into the sinuses of regional popliteal lymph nodes. 2. 2. Similar histologic alterations could not be reproduced by BSA or by antiserum to BSA alone, by noncorresponding antigen-antibody systems, histamine, or heparin. 3. 3. The development of lymph node eosinophilia through the action of specific immunologic reactants was not affected by agents with antihistaminic, antiheparin, or antiserotonin properties. 4. 4. The responsible eosinotactic mechanism of in vivo antigen-antibody union has not been determined but there is no evidence to indicate a role for antigen-antibody precipitate, soluble antigen-antibody complexes, or a product of antigen-antibody mixtures liberated in vitro.

Studies on the Role of Serotonin and Mast Cells in Anaphylaxis of the Mouse Produced with Soluble Antigen-Antibody Complexes

Summary The influence of various treatments on the anaphylactic response of the Swiss-Webster mouse to challenge with a soluble antigen-antibody complex composed of bovine serum albumin-antibovine serum albumin was studied. Protection against anaphylaxis was afforded by prechallenge treatment with either reserpine, epinephrine, norepinephrine, dopamine, histamine and sodium salicylate or with the “serotonin antagonists” lysergic acid diethylamide, its bromine analogue and chlorpromazine. The antihistamine agent, pyrilamine maleate, was without effect. The protective effect of reserpine can be abolished with 5-hydroxytryptophan but not with 3,4-dihydroxyphenylalanine. Histamine or sodium salicylate did not affect the response to intravenous challenge with serotonin or histamine. Prechallenge treatment with 5-hydroxytryptamine or 5-hydroxytryptophan increased the susceptibility of the animals to anaphylaxis. The highly sensitive pertussis-vaccinated mouse was protected against anaphylaxis by prechallenge treatment with epinephrine but not by prechallenge treatment with reserpine, the bromine analogue of lysergic acid diethylamide or dopamine. The refractory state induced by prior sublethal doses of antigen-antibody complex was not reversed by the administration of mouse complement or 5-hydroxytryptophan or a combination of both substances. Mice of the DBA/2 strain show only mild symptoms of anaphylaxis following doses of antigen-antibody complex three times those necessary to produce fatal anaphylaxis in a high percentage of Swiss-Webster mice. Examination of various tissues following anaphylactic death produced with the complex gave no indication that morphologic changes in mast cells accompany anaphylaxis.

Physical Chemical Studies of Soluble Antigen-Antibody Complexes. XII. The Free Energy Change in the Reaction between Bovine Ribonuclease and its Rabbit Antibodies

Physical Chemical Studies of Soluble Antigen-Antibody Complexes. XII. The Free Energy Change in the Reaction between Bovine Ribonuclease and its Rabbit Antibodies

Anaphylactogenic Properties of Soluble Antigen-Antibody Complexes in the Guinea Pig and Rabbit

Summary It has been confirmed that anaphylactic reactions can be produced in the guinea pig and rabbit by the intravenous injection of soluble antigen-antibody complexes. In the guinea pig, the symptoms, the emphysema produced in the lungs and the inhitition of symptoms by antihistamine were similar to those observed in the classical passive and active anaphylactic reactions. There was a preferential localization of the I131 activity in the lungs of guinea pigs during anaphylaxis induced by the injection of BSA-I131 anti-BSA complexes. A similar localization of I131 activity was observed in the lungs of guinea pigs passively sensitized with I131 anti-BSA and challenged 2 days later with BSA. A larger amount of activity was localized in the lungs of guinea pigs dying in anaphylaxis than in the lungs of guinea pigs having only mild reactions. A prior injection of antigen into guinea pigs increased the severity of the reactions produced by a subsequent injection of soluble antigen-antigody complexes. Considerable complement activity was removed from the blood of gunea pigs injected with soluble BSA-anti-BSA complexes, even when no or only mild anaphylactic symptoms occurred.

STUDIES ON THE EFFECT OF CERTAIN MACROMOLECULAR SUBSTANCES ON THE RESPIRATORY ACTIVITY OF THE LEUCOCYTES OF PERIPHERAL BLOOD

The oxygen, uptake of lightly heparinized human blood was found to increase markedly upon the addition of bacterial endotoxins, soluble antigen-antibody complexes, or polystyrene latex particles. The effect apparently reflects a transitory stimulation of respiratory activity of the blood leucocytes. The effect did not occur in the presence of anticoagulant amounts of citrate or ethylenediaminetetraacetate, was inhibited by iodoacetate and fluoride ions, and may be related to the energy-yielding processes involved in histamine release or phagocytosis.

Biologic Activity of Aggregated γ-Globulin

Summary Aggregated human and rabbit γ-globulin fixed complement and induced skin reactions in normal guinea pigs. The aggregated γ-globulin and soluble antigen-antibody complexes were comparable on a weight basis with respect to these biologic activities. The complement fixing properties of the aggregated γ-globulin were independent of the method for aggregation, i.e., heating, mercaptoethanol-urea or coupling by bis-diazotized benzidine, but were dependent on the species from which the γ-globulin was derived. Aggregated bovine or chicken γ-globulin did not fix complement. Horse γ-globulin showed a slight increase in its anticomplementary activity on aggregation with bis-diazotized benzidine. Combination of aggregated γ-globulin with tissue constituents of the guinea pig skin was probably one of the necessary processes in the skin reaction. The mechanism for the induction of the biologic activities by the formation of aggregated γ-globulin and of antigen-antibody complexes was discussed.

Production of acute glomerulonephritis in mice with soluble antigen-antibody complexes prepared from homologous antibody.

1) Passive serum sickness was produced in mice using homologous antibodies, obtained from immune ascitic fluid, in the form of soluble antigen-antibody complexes. Lesions were similar to those obtained with rabbit antibody-antigen complexes, but, in addition, amorphous eosinophilic material was seen in many glomerular capillary loops. Incidence and intensity of lesions using homologous antibody was greater than with equal amounts of heterologous rabbit antibody. 2) Homologous antibody was more effective in producing lethal anaphylaxis than rabbit antibody when both were given as soluble complexes.

Cx-Reactive Protein Response in Rabbits during Immunization with Foreign Proteins

Summary Primary immunization of rabbits with intravenous bovine serum albumin or human γ-globulin resulted in a biphasic Cx-protein response. The secondary response was attributed to the formation of antigen-antibody complexes in the vascular system, since Cx-protein responses could be elicited by intravenous injection of soluble antigen-antibody complexes, and by formation of complexes in vivo by passive transfer of homologous antibody followed by antigen. A secondary Cx-protein response did not occur following primary intravenous immunization with tobacco mosaic virus, an antigen which disappeared from the blood stream well ahead of the appearance of antibody.

The role of the reticuloendothelial system in mouse anaphylaxis as tested with homologous antibody-antigen complexes.

Blockade of the RES was accomplished by the intravenous injection of carbon particles, thorotrast, zymosan, or a suspension of Bordetella pertussis. The blockade resulted in a decrease in sensitivity to anaphylaxis produced by the intravenous injection of soluble antigen-antibody complexes consisting of an optimal shocking mixture of bovine plasma albumin and mouse antibody to this antigen. The decrease in sensitivity to anaphylaxis was dependent on the dose of blockading agent and on the time between blockade and challenge with complex. The loss of sensitivity to anaphylaxis could not be restored by the administration of fresh serum from normal mice nor by guinea pig complement. Antigen-antibody complexes were rapidly removed from the blood with an average half-time of 11.9 minutes in normal mice. Complexes were cleared at significantly more rapid rates in mice previously sensitized to antigen. Although not all the results can be explained on the basis of blockade the facts indicate that the RES does play an important but as yet undefined role in passive homologous anaphylaxis in the mouse.