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Results for “Antigen-Antibody Complex”

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Nutritional deficiency, immunologic function, and disease.

Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed.

Anemia, Hemolytic

The binding of complement by complexes formed between a rabbit antibody and oligosaccharides of increasing size.

Immune complexes formed between a homogeneous rabbit antibody to type III pneumococcal polysaccharide and a series of oligosaccharides of varying size derived from it were prepared and tested for their ability to fix guinea pig hemolytic complement. Antibody and either tetra-, hexa-, or octasaccharide formed only monomeric antibody-hapten complexes and did not show any complement binding. A dodecasaccharide and a 16-sugar residues oligomer formed dimer and trimer immune complexes. These complexes were also unable to fix complement. However, as the size of the sugar oligomers was increased to about 21 sugar residues per oligosaccharide molecule or more, the resulting complexes exhibited substantial complement binding, concomitant with the formation of antigen-antibody aggregates higher than trimers. On the other hand, an independent study carried out with the same material suggested changes in the conformation of the Fc moiety in the antibody molecule upon addition of oligosaccharide ligands as small as a 16-residue unit. Since the resulting complexes hardly ehibited any complement binding, ligand-induced conformational changes in the Fc part of the antibody molecule appears to be an insufficient condition per se for triggering complement fixation.

Animals

Passive serum sickness in the mouse: the role of vasoactive amines in glomerular deposition of immune complexes.

This paper reports a study of the importance of vasoactive amines in glomerular localization of passively administered immune complexes in the mouse. Two strains of mice were investigated, one sensitive and the other relatively resistant to the anaphylactogenic effect of intravenously administered immune complexes. The effect on glomerular deposition immune complexes in animals of both strains treated with either vasoactive amine depletors or antagonists leads to the conclusion that in this experimental system vasoactive amines do not play a major part in the glomerular localization of immune complexes.

Anaphylaxis

Effect of altered lymphocyte function on immunologic disorders in NZB/NZW mice.

NZB/NZW F1 female mice were treated with the immunosuppresive enzyme L-asparaginar antibodies, diminished deposition of gamma-globulins in kidneys, significantly delayed the onset of proteinuria, and reduced deaths from nephritis. These effects were associated with reduction of cellular IgM antibody synthesis to both T-dependent and T-independent antigens, but the graft-versus-host reaction was not affected. After several weeks of therapy, antibodies against Asnase appeared in the circulation, the effect on antibody synthesis was lost, ANA and anti-DNA appeared, followed by proteinuria and deaths from nephritis. Therefore Asnase proved to be an effective therapy in NZB/NZW mice, but its usefulness was limited by the appearance of inactivating antibodies.

Animals

Inhibitory T cells.

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Agammaglobulinemia

Some properties of togavirus hemagglutinin studied with the aid of kaolin-adsorbed virus.

Acidification (at pH 5.75) of Semliki Forest virus and West Nile virus suspensions completely eliminated their hemagglutinating activity within several minutes, but did not affect their infectivity or change their ability to absorb homologous hemagglutination-inhibition antibodies. In order to assay antibody absorption it was necessary to remove all of the immune complex from the reaction mixture, because the immune complex inhibited additional hemagglutinin. Removal of the immune complex can be accomplished by the use of kaolin-absorbed virus. This procedure is simple and dependable and has been carried out with viruses from several groups--Toga-, Myxo-, Paramyxo- and Picornaviridae.

Adsorption

Insoluble human plasma protein immunoadsorbents. Large-scale production and storage.

Methods for producing and preserving large volumes of insoluble immunoadsorbents (for removing unwated antibodies to serum proteins) from surplus blood bank plasma by glutaraldehyde were evaluated by quantitative and qualitative means using radioactive 125I and immunoelectrophoresis, respectively. Some of the factors affecting the desired physical characteristics and antibody-absorbing properties of the imjunoadsorbent studied were: plasma acidification, varying concentrations of glutaraldehyde, addition of small amounts of formalin, storage under varying conditions of temperature, and exposure to preservatives in the wet and lyophilized state for periods up to 2.5 years. The best preservation of antibody-adsorbing properties (under storage conditions) was obtained in the washed state at 4 degrees C, but good preservation was also obtained at room temperature in the presence 10% formalin and in the unwashed state at room temperature in the presence of unreacted glutaraldehyde. Lyophilization destroyed about 70% of an adsorbent's activity.

Animals

Isolation of anti-haemagglutinin antibodies with an influenza A virus immunoadsorbent.

The X-31 strain of influenza A (H3N2) virus has been covalently bound to CNBr activated agarose for the separation of anti-haemagglutinin antibodies. The virus immunoadsorbent was used repeatedly under high ionic strength alkali buffer and acid conditions without altering appreciably its antibody binding capacity. Sequential elution of bound anti-haemagglutinin antibodies with increasing concentrations of sodium iodide has enabled the physical separation of antibody populations with low and high avidity for the virus immunoadsorbent. In haemagglutination inhibition (h1) assays, the less avid population reacted only with the homologous X-31 virus, wheras the more avid antibody population reacted both with the homologous and the related cross-reactive A/England/42/72 (H3N2) strains. Sequential elution under acid conditions did not completely remove the bound anti-haemagglutinin antibodies and those eluted retained little of their anti-haemagglutinin activity. From a practical point of view, given a specific antiserum, it is feasible to use whole virus as an immunoadsorbent for the purpose of isolating populations of antibodies of different avidities and cross-reactivities. Furthermore, sodium iodide as an eluting agent has proved most effective in recovery of active and stable antibodies from the agarosebound virus.

Agglutinins

In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus.

In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.

Animals

The polysaccharide capsule of Bacteroides fragilis subspecies fragilis: immunochemical and morphologic definition.

A large-molecular-weight capsular polysaccharide was isolated from strains of Bacteroides fragilis subspecies fragilis. By means of electron microscopy and staining with ruthenium red, the thick polysaccharide capsule was also visualized. With use of a radioactive antigen-binding assay, antibody to this capsular polysaccharide was demonstrated in antisera prepared in rabbits to each of eight strains of B. fragilis fragilis. Antibody of similar specificity was not found in antisera prepared to Bacteroides melaninogenicus or to strains of Bacteroides fragilis subspecies vulgatus and Bacteroides fragilis subspecies distasonis; such antibody was found in antisera to only one of two strains of Bacteroides fragilis subspecies thetaiotaomicron. The radioactive antigen-binding assay is a sensitive test for the detection of antibody to capsular polysaccharide. This polysaccharide antigen may form the basis of a serogrouping system for B. fragilis.

Antigen-Antibody Complex

Detection of serum-blocking factors by inhibition of allorosette formation in rats with long-surviving renal allografts following short-term postoperative ALS treatment.

Thirty-nine (LEW x BN)F1 kidneys were transplanted to LEW rats. Twenty-four untreated recipients survived for a mean time of 16.1 +/- 1.7 days (group 1). Fifteen recipients received 4 ml of antilymphocytic serum per rat (group 3). In the last group 10 recipients survived for more than 4 months. The spleen cells of these permanently surviving 10 rats were obtained by splenectomy and used in a graft-versus-host assay, and this assay showed that the reactivity of these cells was normal. Following splenectomy the animals were given an (LEW x BN)F1 skin allograft, followed 18 days by a second. After another 18 days (LEW x Buf)F1 "third party" skin allografts were transplanted to the same animals. Animals of group 2 rejected their first grafts with a mean survival time of 12.2 +/- 1.2 days, whereas the second grafts were rejected normally as were the third party grafts. Attempts were made to detect lymphocytotoxic antibodies and haemagglutinins before and after the transplantation of skin grafts and none could be found up to day 53. The sera of group 2 inhibited allorosette formation by 38%. This serum-blocking factor was donor specific. It is probable that the survival of the kidney transplants following antilymphocytic serum treatment was brought about by the development of blocking antibodies.

Animals

Pneumococcal type-associated variability in alternate complement pathway activation.

Opsonization of Streptococcus pneumoniae may be mediated by the alternate complement pathway. To study the importance of this interaction to human disease, complement consumption by pneumococci of various serotypes was measured in humwn serum chelated with ethyleneglycoltraacetic acid, a substance that blocks the classic but not the alternate complement pathwway. Serotype I, in contrast to all other types studied, lacked ability to consume complement in this system. The ability for serotypes III, IV, and VIII to activate the alternate pathway could be eliminated by prior serum absorption at O C with they type in question, a condition that would remove antibody but not complement. Types VII, XII, XIV, and XXV readily activated the alternate pathway in unabsorbed and absorbed sera. Differences could not be related to properties of the capsules. It was concluded that types I, III, IV, and VIII lack intrinsic ability to activate and thus be opsonized by the alternate complement pathway, although types III, IV, and VIII can do so in concert with specific antibody. The fact that these same types are especially prominent in human disease suggests that the ability to evade opsonization by the alternate complement pathway in pre-antibody phases of infection may be a virulence factor in pneumococci.

Antigen-Antibody Complex