ovalbumin and Glomerulonephritis

ANCA-associated vasculitis (AAV) is an autoimmune disease characterized by small blood vessel inflammation, commonly affecting the kidneys and respiratory tract. It is unclear why the incidence of this condition increases with age. Previous studies in a passive antibody transfer system in aged mice have implicated innate effectors. To test the hypothesis that autoimmunity to myeloperoxidase (MPO), an autoantigen responsible for AAV, increases with age, anti-MPO autoimmunity was studied in murine models of active autoimmunity and disease induced by cellular immunity.. Young (8 weeks) and aged (either 15 or 22 months) mice were immunized with whole proteins or peptides from ovalbumin, as a model foreign antigen, or MPO protein or peptides. Mice were subjected to a model of active anti-MPO glomerulonephritis. Cellular and humoral immune responses, and tissue inflammation were assessed.. While cellular immunity to ovalbumin was diminished in aged mice, cellular autoimmunity to MPO and its immunodominant CD4+ and CD8+ T cell epitopes was increased after immunization with either MPO peptides or whole MPO protein, assessed by peptide and antigen-specific production of the pro-inflammatory cytokines IFN-γ and IL-17A. MPO-ANCA titres were not increased in aged mice compared with young mice. In experimental anti-MPO glomerulonephritis, cell-mediated injury was increased, likely due to CD4+ and CD8+ T cells, innate immunity and the increased vulnerability of aged kidneys.. Heightened cellular immunity to MPO develops with ageing in mice and may contribute to the increased incidence and severity of AAV in older people.

Topics: Aged; Aging; Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; CD4-Positive T-Lymphocytes; Female; Glomerulonephritis; Humans; Immunity, Cellular; Inflammation; Male; Mice; Ovalbumin; Peroxidase

Autoimmunity to the neutrophil enzyme myeloperoxidase (MPO) is an important cause of rapidly progressive glomerulonephritis, but the relative roles of MPO-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA) and autoreactive effector MPO-specific CD4(+) T cells are unclear. We confirmed that passive transfer of murine MPO-ANCA to agammaglobulinemic μMT mice immunized with OVA induces glomerular injury with capillary wall thickening, fibrinoid necrosis, mesangial cell proliferation, and periglomerular cell infiltration. Preimmunization of μMT mice with MPO induced MPO-specific CD4(+) T cells and significantly enhanced renal injury after MPO-ANCA transfer. CD4(+) T cell depletion prevented this augmentation of injury, confirming the importance of effector T cells in the development of MPO-ANCA associated glomerulonephritis. Therefore, MPO-ANCA can induce glomerulonephritis through both direct humoral mechanisms (recruitment of neutrophils and deposition of MPO) and indirectly by initiating MPO deposition in glomeruli, thereby directing effector CD4(+) T cell mediated injury. To confirm and support this data, we transferred T cells from MPO-immunized Mpo(-/-)μMT mice into Rag1(-/-) mice (control mice received ovalbumin specific T cells) and triggered injury by passive MPO-ANCA. Renal injury was significantly greater in mice transferred with T cells from MPO-immunized mice. These current studies demonstrate that MPO-ANCA induces injury via both humoral and cell mediated immune mechanisms.

Topics: Animals; Antibodies, Antineutrophil Cytoplasmic; CD4-Positive T-Lymphocytes; Female; Flow Cytometry; Glomerulonephritis; Immunization; Immunoglobulin M; Immunoglobulin mu-Chains; Kidney Glomerulus; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Ovalbumin; Peroxidase

We investigated the role of effector CD8 T cells in the pathogenesis of immune glomerular injury. BALB/c mice are not prone to autoimmune disease, but after 12 immunizations with OVA they developed a variety of autoantibodies and glomerulonephritis accompanied by immune complex (IC) deposition. In these mice, IFN-γ-producing effector CD8 T cells were significantly increased concomitantly with glomerulonephritis. In contrast, after 12 immunizations with keyhole limpet hemocyanin, although autoantibodies appeared, IFN-γ-producing effector CD8 T cells did not develop, and glomerular injury was not induced. In β2-microglobulin-deficient mice lacking CD8 T cells, glomerular injury was not induced after 12 immunizations with OVA, despite massive deposition of IC in the glomeruli. In mice containing a targeted disruption of the exon encoding the membrane-spanning region of the Ig μ-chain (μMT mice), 12 immunizations with OVA induced IFN-γ-producing effector CD8 T cells but not IC deposition or glomerular injury. When CD8 T cells from mice immunized 12 times with OVA were transferred into naive recipients, glomerular injury could be induced, but only when a single injection of OVA was also given simultaneously. Importantly, injection of OVA could be replaced by one injection of the sera from mice that had been fully immunized with OVA. This indicates that deposition of IC is required for effector CD8 T cells to cause immune tissue injury. Thus, in a mouse model of systemic lupus erythematosus, glomerular injury is caused by effector CD8 T cells that recognize Ag presented as IC on the target renal tissue.

Topics: Animals; Antigen Presentation; Antigen-Antibody Complex; beta 2-Microglobulin; CD8-Positive T-Lymphocytes; Female; Glomerulonephritis; Immunoglobulin mu-Chains; Interferon-gamma; Lupus Erythematosus, Systemic; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; T-Lymphocytes, Cytotoxic

The progression of kidney disease to renal failure correlates with infiltration of mononuclear immune cells into the tubulointerstitium. These infiltrates contain macrophages, DCs, and T cells, but the role of each cell type in disease progression is unclear. To investigate the underlying immune mechanisms, we generated transgenic mice that selectively expressed the model antigens ovalbumin and hen egg lysozyme in glomerular podocytes (NOH mice). Coinjection of ovalbumin-specific transgenic CD8+ CTLs and CD4+ Th cells into NOH mice resulted in periglomerular mononuclear infiltrates and inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. Repetitive T cell injections aggravated infiltration and caused progression to structural and functional kidney damage after 4 weeks. Mechanistic analysis revealed that DCs in renal lymph nodes constitutively cross-presented ovalbumin and activated CTLs. These CTLs released further ovalbumin for CTL activation in the lymph nodes and for simultaneous presentation to Th cells by distinct DC subsets residing in the kidney tubulointerstitium. Crosstalk between tubulointerstitial DCs and Th cells resulted in intrarenal cytokine and chemokine production and in recruitment of more CTLs, monocyte-derived DCs, and macrophages. The importance of DCs was established by the fact that DC depletion rapidly resolved established kidney immunopathology. These findings demonstrate that glomerular antigen-specific CTLs and Th cells can jointly induce renal immunopathology and identify kidney DCs as a mechanistic link between glomerular injury and the progression of kidney disease.

Topics: Animals; Antigen Presentation; Autoimmune Diseases; Cell Movement; Dendritic Cells; Disease Models, Animal; Glomerulonephritis; Kidney; Leukocytes, Mononuclear; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Muramidase; Ovalbumin; Podocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer

Little is known about the potential role of T cells in the inflammatory renal disease glomerulonephritis (GN). GN has been historically viewed as a product of immune complex-mediated complement activation, and the presence of autoantibodies made identifying T cell-specific effector contributions difficult to elucidate. In this issue of the JCI, Heymann et al. generate what they believe to be a novel, transgenic murine model of GN, demonstrating a direct role for CD8+ T cells, activated CD4+ T cells, and DCs in the pathogenesis of GN (see the related article beginning on page 1286).

Topics: Animals; Antigen Presentation; Autoimmune Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dendritic Cells; Disease Models, Animal; Glomerulonephritis; Kidney; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Transgenic; Ovalbumin; Podocytes; T-Lymphocytes

To investigate, whether T lymphocytes alone are sufficient to induce glomerulonephritis, a model in SCID mice was developed. Conditions for the generation and exclusive glomerular targeting of crosslinked ovalbumin (OVA) polymers and a series of OVA-specific T-cell clones and lines were established. Only a well-defined subfraction of OVA polymers exclusively targeted to the glomerular mesangium without causing local alteration in the absence of IgG. From numerous T-cell preparations spanning different Th-1/-2 profiles one T-helper cell clone characterized by ELISPOT assay as pure Th-1 (IFN-gamma and IL-2) induced nephritislike pathology. Histological examination at days 1, 2, 5, and 21 showed major infiltrates in proximal tubular regions (PTR) at day 5 accompanied by significant proteinuria. No injury was observed after deposition of irrelevant antigen or injection of other T-cell preparations. Detailed histological analysis revealed that Th-1 cell numbers peaked early in glomeruli (2.1 +/- 0.6 vs 0/gcs). Macrophages, however, were hardly detectable in glomeruli (0.5 +/- 0.3/gcs) at this time, while they formed the major constituent of the PTR infiltrates at day 5 (83 +/- 1). These data in a new SCID nephritis model indicate that memory Th-1 cells together with localized antigen presenting cells trigger nephritis.

Topics: Adoptive Transfer; Animals; Antigens; CD4-Positive T-Lymphocytes; Disease Models, Animal; Female; Glomerular Mesangium; Glomerulonephritis; Immunologic Memory; Kidney Glomerulus; Kidney Tubules, Proximal; Macrophages; Mice; Mice, Inbred BALB C; Mice, SCID; Ovalbumin; Proteinuria; Th1 Cells; Time Factors

The effects of hyperfiltration induced due to unilateral nephrectomy on immunologically induced glomerular injuries were studied. Glomerulonephritis was induced in rats by sensitizing them with egg albumin as an antigen. Unilateral nephrectomy did not affect the removal rate of the antigen from the glomeruli in the rats, but accelerated the rate of the glomerular injuries after cessation of the immunologically induced glomerular inflammation. The histopathological features were characterized by sclero-adhesive lesions with aneurysmal dilatation and hyalinosis of the glomerular capillaries. The parietal epithelial cells extended from the Bowman's capsule with matrices to cover the denuded basement membrane and formed adhesions. The neighboring capillaries collapsed, and the sclero-adhesive lesions progressed. These findings indicate that hyperfiltration at the capillary level did not accelerate the recovery from glomerulonephritis, but induced glomerular sclerosis with adhesions and deteriorated the trivial glomerular injuries to produce similar focal segmental lesions.

Topics: Animals; Complement C3; Glomerular Filtration Rate; Glomerulonephritis; Immunoglobulin G; Immunohistochemistry; Kidney Glomerulus; Male; Microscopy, Electron; Microscopy, Immunoelectron; Nephrectomy; Ovalbumin; Proteinuria; Rats; Serum Sickness

Topics: Administration, Oral; Animals; Antibody Formation; Antigens; Chronic Disease; Glomerulonephritis; Hypersensitivity, Delayed; Immune Complex Diseases; Immune Tolerance; Male; Mice; Ovalbumin

The participation of glomerular antigen presenting (Ia positive) cells in the development of glomerulonephritis was analyzed. Antigen-presentation by kidney cells was evident from the assay of ovalbumin-specific T cell proliferation responses by these cells. Experimental serum sickness nephritis was induced in preimmunized rats by the intraperitoneal sensitization of ovalbumin, and the participation of antigen presenting cells (APCs) in the peritoneal cavity and glomeruli was studied. APCs in the peritoneal cavity progressively increased in number following the antigen stimulation, while those in glomeruli were shown to increase in correlation with the development of glomerular hypercellularity. These results imply that the role of APCs in the sensitized area is superior in this model of immune complex nephritis.

Topics: Animals; Antigen-Antibody Complex; Antigen-Presenting Cells; Epitopes; Glomerulonephritis; Histocompatibility Antigens Class II; Kidney Glomerulus; Liver; Macrophages; Male; Microscopy, Electron; Monocytes; Ovalbumin; Peritoneal Cavity; Rats; Rats, Inbred Strains; Spleen; T-Lymphocytes

Several features suggest that IgA nephropathy is an immune complex (IC)-mediated disease. The source of antigen(s) is unknown but the predominant involvement of IgA suggest that it is associated in some way with the gut or respiratory tract. Taking into account the specific hepatobiliary transport by polymeric IgA of circulating antigens entering through the mucosal surfaces we examined the possible involvement of antibodies against food antigens in the circulating IC and the existence of a defect in their blood clearance in patients with IgA nephropathy. A rise in multimeric IgA-IC (Raji assay) occurred in three of seven control subjects with a peak at 2-4 h after food ingestion. The amount of multimeric IgA-IC present at fasting in four out of six patients, diminished 2-4 h after food challenge, reaching a new peak around 6 h. At fasting, three out of six patients had IC containing antibodies against diet antigens (e.g. ovalbumin). These IC paralleled, both in patients and controls, the levels of multimeric IgA-IC. In patients small multimeric IgA-IC predominated at fasting and 24 h after food ingestion, while larger IC were detected at 2-4 h of food challenge. The specific polymeric IgA-IC showed in controls a maximal peak with similar distribution to that of multimeric IgA-IC, but with a quicker disappearance from the circulation. By contrast, polymeric IgA-IC remained elevated 24 h after food ingestion in most patients. These results suggest that antibodies against common antigens are within circulating IC and that a defect in the hepatic clearance of circulating polymeric IgA-IC exists in patients with IgA nephropathy.

Topics: Antibodies; Antigen-Antibody Complex; Centrifugation, Density Gradient; Dietary Proteins; Food; Glomerulonephritis; Humans; Immunoglobulin A; Immunoglobulin G; Ovalbumin; Time Factors

To test the hypothesis that IgA nephropathy can result from a mucosal immune response, mice were orally immunized with one of three protein antigens for 14 wk. Such mice exhibited an essentially pure mucosal antibody response characterized by specific IgA-producing plasma cells in exocrine sites and specific IgA antibodies in serum. Furthermore, 73% of immunized mice had IgA and 88% had immunogen deposited in the glomerular mesangium, and 64% of immunized mice examined ultrastructurally had electron-dense mesangial deposits. All three were present concurrently in 57% of the immunized mice. No differences in regard to IgG or IgM were observed between immunized and control mice for any of these parameters. Mucosal immunization therefore can result in a specific immune response that leads to mesangial deposition of immune complexes containing IgA antibody. In its fundamental features the experimental renal lesion resembles that seen in the human disease IgA nephropathy.

Topics: Administration, Oral; Animals; Antibody-Producing Cells; Antigens; Bronchi; Female; Glomerulonephritis; Immunization; Immunoglobulin A; Intestines; Kidney Glomerulus; Mice; Mice, Inbred A; Mice, Inbred BALB C; Ovalbumin

A technique is described which allows the antibodies of circulating immune complexes to be isolated as their F(ab')2 fragments. The method is based on the precipitation of the complexes by the sequential addition of conglutinin and anti-conglutinin, and the subsequent digestion of these precipitates by pepsin. Using this technique it has been possible to show antibodies to Epstein-Barr (EB) virus antigens in the immune complexes of patients with Burkitt's lymphoma and to microbial antigens in two patients with nephritis. By substituting DNAase for pepsin it has also been possible to show antibodies to DNA-containing nuclear antigens in the serum of patients with systemic lupus erythematosus.

Topics: Antibodies, Viral; Antigen-Antibody Complex; Antigens, Bacterial; Burkitt Lymphoma; Collectins; Fluorescent Antibody Technique; Glomerulonephritis; Herpesvirus 4, Human; Humans; Immunodiffusion; Immunoglobulin Fab Fragments; Lupus Erythematosus, Systemic; Methods; Ovalbumin; Pepsin A; Serum Globulins

Experimental glomerulonephritis was produced in 16 rabbits by intravenous injections of ovalbumin in high doses (0.1 g/day during the first week, 0.2 g x 6/day during the second). The animals were killed on day 14. At that time all animals had 2--4+ proteinuria and a serum C3 level reduced to about 50% of the control level; 11 animals had a significantly raised blood urea level. In all rabbits the antigen had induced severe proliferative glomerulonephritis. Electron microscopy showed that many of the cells accounting for the hypercellularity were monocytes. Surprisingly, electron dense deposits were few and small, mainly on the subendothelial and subepithelial aspects of the glomerular basement membrane. In all the animals ultrastructural immunoperoxidase technique revealed deposits containing ovalbumin, rabbit IgG and C3. With immunofluorescence sparse deposits were occasionally seen. It is concluded that a severe experimental glomerulonephritis can be produced in a state of antigen excess, with the deposition of immune complexes being minimal. Immuno-electron microscopy is essential, however, in detecting even the smallest animals of deposited immune reactants.

Topics: Animals; Basement Membrane; Fluorescent Antibody Technique; Glomerulonephritis; Kidney Glomerulus; Male; Microscopy, Electron; Ovalbumin; Rabbits

Intravenous injection of mice with soluble complexes of highly avid rabbit antibody to egg albumin, prepared by dissolution of equivalence precipitates in large quantities of antigen, resulted in a purely mesangial localization of the complexes. When animals received three injections of complexes per day for 1 day it was noted that precipitates dissolved in 80 times the equivalence amount of antigen produced slight mesangial changes. When such complexes were injected for 2 or 3 days, outright mesangiopathic glomerulonephritis was observed in an increasing proportion of the animals. Equivalent amounts of antigen alone did not produce lesions.

Topics: Animals; Antigen-Antibody Complex; Antigens; Disease Models, Animal; Fluorescent Antibody Technique; Glomerulonephritis; Immune Complex Diseases; Kidney; Mice; Ovalbumin; Rabbits; Time Factors

Intravenous injections of mice three times a day for 3 days with soluble complexes of 3 mg. of moderately avid rabbit antibody to chicken egg albumin prepared by dissolution of equivalence precipitates in 80 times the equivalence amount of antigen resulted in a combined mesangial and loop localization of immune complexes. With complexes formed from antibody of low avidity, injected four times a day for 3 days, a predominately subepithelial loop deposition of complexes was observed. Complexes formed from moderately avid antibody gave rise to a mainly mesangiopathic glomerulonephritis, whereas low avidity complexes were associated with a diffuse glomerulonephritis. These results, in combination with those of the previous paper, successfully reproduce the basic form of the lesions seen in active immune complex disease by passive means and suggest that antibody avidity is a major determinant of the site of localization of immune complexes and therefore of the morphologic form of the resulting glomerulonephritis. The importance of these observations for our understanding of the pathogenesis of human immune complex disease is considered.

Topics: Animals; Antigen-Antibody Complex; Antigens; Disease Models, Animal; Fluorescent Antibody Technique; Glomerulonephritis; Immune Complex Diseases; Kidney; Mice; Mice, Inbred C57BL; Ovalbumin; Rabbits; Time Factors

Repeated intravenous injections of egg albumin in rabbits produced small antigen-excess complexes and severe glomerulonephritis. Immunoglobulins and complement in the glomeruli were not clearly demonstrated by immunofluorescence; deposits were found to be sparse by electron microscopy. This study demonstrates that soluble immune complexes are responsible for the glomerular reaction. The apparent absence of deposits is thus not sufficient to exclude an immune complex pathogenesis.

Topics: Animals; Antigen-Antibody Complex; Blood Urea Nitrogen; Complement C3; Disease Models, Animal; Fluorescent Antibody Technique; Glomerulonephritis; Goats; Immune Complex Diseases; Immune Sera; Immunoglobulins; Kidney Glomerulus; Male; Microscopy, Electron; Ovalbumin; Rabbits

Topics: Animals; Antibodies; Antigen-Antibody Complex; Antigen-Antibody Reactions; Antigens; Centrifugation, Density Gradient; Chickens; Chromatography, DEAE-Cellulose; Female; Fluorescent Antibody Technique; Freund's Adjuvant; Glomerulonephritis; Guinea Pigs; Immune Sera; Immunization; Immunodiffusion; Immunoelectrophoresis; Male; Microscopy, Electron; Ovalbumin

Topics: Animals; Antibodies, Antinuclear; Antigen-Antibody Complex; Electrophoresis; Female; Fluorescent Antibody Technique; Glomerulonephritis; Graft vs Host Disease; Immune Sera; Immunization; Immunoglobulin G; Kidney Glomerulus; Lupus Erythematosus, Systemic; Male; Mice; Microscopy, Electron; Nephritis; Ovalbumin; Rabbits

Topics: Animals; Antigen-Antibody Complex; Basement Membrane; Binding Sites, Antibody; Complement System Proteins; Female; Glomerulonephritis; Immunization; Immunoglobulin G; Iodine Isotopes; Kidney Glomerulus; Male; Microscopy, Electron; Ovalbumin; Proteinuria; Rabbits

Topics: Animals; Antigen-Antibody Complex; Blood Coagulation; Blood Platelets; Disseminated Intravascular Coagulation; Fibrinogen; Fibrinolysis; Glomerulonephritis; Immunization; Kidney Glomerulus; Liver; Lung; Ovalbumin; Plasminogen; Rabbits

Topics: Antigen-Antibody Complex; Chromatography; Chromatography, Gel; Complement System Proteins; Edetic Acid; Glomerulonephritis; Humans; Immune Sera; Immunodiffusion; Lupus Erythematosus, Systemic; Molecular Weight; Nephritis; Ovalbumin; Radioimmunoassay

Topics: Animals; Antigen-Antibody Reactions; Glomerulonephritis; Injections, Intraperitoneal; Kidney Glomerulus; Mice; Microscopy, Electron; Microscopy, Fluorescence; Nephrosis; Ovalbumin

Topics: Animals; Antibody Formation; Antigen-Antibody Reactions; Autoantibodies; Autoimmune Diseases; Fluorescent Antibody Technique; Freund's Adjuvant; gamma-Globulins; Glomerulonephritis; Humans; Kidney Glomerulus; Lymph Nodes; Lymphocytes; Ovalbumin; Pathology; Plasma Cells; Rabbits; Research; Spleen; Urine

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.

Topics: Anaphylaxis; Animals; Antibodies; Antigen-Antibody Complex; Antigen-Antibody Reactions; Arthus Reaction; Blood Vessels; Cattle; Complement System Proteins; Electrons; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Guinea Pigs; Immune Sera; Immunoelectrophoresis; Inflammation; Microscopy; Microscopy, Electron; Necrosis; Neutrophils; Ovalbumin; Pathology; Rabbits; Research; Serum Albumin; Serum Albumin, Bovine; Vascular Diseases

Topics: Animals; Antigen-Antibody Reactions; Complement System Proteins; gamma-Globulins; Glomerulonephritis; Kidney; Metabolism; Nephritis; Ovalbumin; Pepsin A; Proteinuria; Rabbits; Rats; Research; Tissue Extracts

The intravenous administration to mice of soluble antigen-antibody complexes in antigen excess resulted in a high incidence of glomerulonephritis and less frequently in endocarditis or arteritis. These lesions are present within 48 hours of the first of 3 injections and disappear within 2 weeks. The same pathological changes were produced with complexes prepared from either rabbit or chicken antibody. In the case of rabbit antibody, the severity of the glomerulonephritis was greater with the ovalbumin antiovalbumin system than with the BSA system. Anaphylaxis regularly occurred in mice given complexes prepared from rabbit antibody, but was not seen following administration of complexes prepared from chicken antibody. Pretreatment with cortisone diminished the severity of the glomerulo-nephritis and resulted in accumulation of amorphous, eosinophilic material within glomerular capillaries in mice injected with antigen-antibody complexes. The rabbit antibody used in these experiments failed to sensitize guinea pig skin to passive cutaneous anaphylaxis when injected in the form of soluble complexes. This indicates that these complexes do not dissociate to a detectable extent in vivo and thus favors the interpretation that complexes localize as such in the sites where tissue damage occurs. Chicken anti-mouse erythrocyte antibody produced hemolysis of mouse red cells in the presence of mouse complement. In contrast to a similar rabbit anti-serum, the hemolytic activity of the chicken antibody with mouse complement was very slight. This suggests that complement does not play an important role in the pathogenesis of these experimental lesions.

Topics: Animals; Antibodies; Antigen-Antibody Complex; Capillaries; Complement System Proteins; Glomerulonephritis; Mice; Ovalbumin; Passive Cutaneous Anaphylaxis; Rabbits; Serum Sickness