INTERSTITIAL IMMUNE COMPLEX THYROIDITIS IN MICE

Mice immunized with soluble heterologous thyroglobulins developed autoantibody that cross-reacted with autologous thyroglobulin. There was a direct correlation between the temporal appearance and quantity of serum autoantibody and the presumed in situ formation of immune complexes in the interstitium of the thyroid glands. Immediately after the formation of interstitial immune complexes containing antibody of the IgG complement-fixing type, the thyroids were invaded by a transient but intense neutrophil infiltrate which within 1 wk was replaced by chronic mononuclear elements. By the combination of fluorescence microscopy and autoradiography, thyroglobulin was demonstrated to be one, if not the sole, antigen in the interstitial immune complexes. The interstitial immune complexes were granular to lumpy in appearance and formed at the basal area of the follicular cells in intimate association with the follicular basement membrane. Electron microscopy revealed electron dense deposits, presumably immune complexes, between the follicular basement membrane and the plasma membrane. The presumed in situ formation of immune complexes in this model is similar to that which occurs in the Arthus reaction and is a different mechanism of immune complex injury than that caused by tissue deposition of circulating immune complexes as occurs in serum sickness.

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Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis.

Journal of Experimental Medicine ◽

10.1084/jem.157.6.1885 ◽

1983 ◽

Vol 157 (6) ◽

pp. 1885-1905 ◽

Cited By ~ 33

Author(s):

D Koffler ◽

G Biesecker ◽

B Noble ◽

G A Andres ◽

A Martinez-Hernandez

Keyword(s):

Basement Membrane ◽

Immune Complex ◽

Immune Complexes ◽

Tissue Injury ◽

Membrane Attack Complex ◽

Intense Staining ◽

Immune Complex Glomerulonephritis ◽

Filtration Barrier ◽

Dense Deposits ◽

Foot Process

The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral epithelium, and the TBM. Further experiments designed to selectively enhance or inhibit the deposition of MAC and assess consequent renal dysfunction are required to substantiate hypotheses concerning the in vivo membranolytic potential of the MAC in experimental immune complex glomerulonephritis.

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Localization of Immune Complexes in the Basement Membrane of the Ductuli Efferentes of the Rhesus Monkey

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600001963 ◽

1980 ◽

Vol 38 ◽

pp. 456-457

Author(s):

D. Marsh

Keyword(s):

Basement Membrane ◽

Fluorescence Microscopy ◽

Rhesus Monkey ◽

Immune Complex ◽

Immune Complexes ◽

Vas Deferens ◽

Frozen Sections ◽

Efferent Ducts ◽

Complex Deposition ◽

Sperm Antibodies

As a result of vasectomy, spermatozoa are confined to the epididymis and vas deferens, where they degenerate, releasing antigens that enter the circulation or are engulfed by macrophages. Multiple antigens of the sperm can elicit production of autoantibodies; circulating anti-sperm antibodies are found in a large percentage of vasectomized men, indicating the immunogenicity of the sperm. The increased prevalence of macrophages in the liomen of the rhesus monkey testicular efferent ducts after vasectomy led to further study of this region. Frozen sections were used for evaluation of immunopathological status by fluorescence microscopy with fluorescein-conjugated antibody. Subsequent granular deposits of immune complexes were revealed by positive immunofluorescence staining for complement. The immune complex deposition in the basement membrane surrounding the efferent ducts implies that this region is involved in antigen leakage (Fig. 1).

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In situ formation of subepithelial glomerular immune complexes in passive serum sickness

Kidney International ◽

10.1038/ki.1980.74 ◽

1980 ◽

Vol 17 (5) ◽

pp. 631-637 ◽

Cited By ~ 49

Author(s):

Gertjan Fleuren ◽

Joris Grond ◽

Philip J. Hoedemaeker

Keyword(s):

Immune Complexes ◽

Serum Sickness ◽

In Situ Formation

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Covalent attachment of soluble proteins by nonenzymatically glycosylated collagen. Role in the in situ formation of immune complexes.

Journal of Experimental Medicine ◽

10.1084/jem.158.5.1739 ◽

1983 ◽

Vol 158 (5) ◽

pp. 1739-1744 ◽

Cited By ~ 103

Author(s):

M Brownlee ◽

S Pongor ◽

A Cerami

Keyword(s):

Immune Complexes ◽

Structural Proteins ◽

Covalent Attachment ◽

Nonenzymatic Glycosylation ◽

Collagen Binding ◽

Free Antibody ◽

In Situ Formation ◽

Immune Complex Formation

The chronic tissue damage associated with long-term diabetes mellitus may arise in part from in situ immune complex formation by accumulated immunoglobulins and/or antigens bound to long-lived structural proteins that have undergone excessive nonenzymatic glycosylation. In this report, we have tested this hypothesis using nonenzymatically glycosylated collagen. Binding of both albumin and IgG averaged four times the amount bound to unmodified collagen. Both albumin and IgG (anti-BSA) bound to nonenzymatically glycosylated collagen retained their ability to form immune complexes in situ with free antibody and antigen.

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In situ Formation of Subepithelial Immune Complexes in the Rabbit Glomerulus: Requirement of a Cationic Antigen

Nephron ◽

10.1159/000183165 ◽

1984 ◽

Vol 36 (4) ◽

pp. 257-264 ◽

Cited By ~ 11

Author(s):

Harry J. Ward ◽

Arthur H. Cohen ◽

Wayne A. Border

Keyword(s):

Immune Complexes ◽

In Situ Formation ◽

Cationic Antigen

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Quantitative studies of in situ immune complex glomerulonephritis in the rat induced by planted, cationized antigen

Journal of Experimental Medicine ◽

10.1084/jem.155.2.460 ◽

1982 ◽

Vol 155 (2) ◽

pp. 460-474 ◽

Cited By ~ 104

Author(s):

T Oite ◽

SR Batsford ◽

MJ Mihatsch ◽

H Takamiya ◽

A Vogt

Keyword(s):

Immune Complex ◽

Renal Perfusion ◽

Left Renal Artery ◽

Igg Antibody ◽

Human Igg ◽

Preferential Localization ◽

Dense Deposits ◽

Slit Pores ◽

Perfused Kidney

Cationized human IgG can bind to the rat glomerular basement membrane (GBM), act as planted antigen, and induce in situ immune complex formation accompanied by severe glomerulonephritis. Perfusion of highly cationized human IgG (isoelectric point {more than} 9.5) via the left renal artery resulted in preferential localization within the perfused kidney (up to 56 percent of dose injected); after intravenous administration, only 4 percent was bound to the kidneys. The planted antigen was localized along the glomerular capillary walls and was accessible for antibody administered intravenously 1 h after perfusion, when virtually no antigen remained in the circulation. Persistence of cationized human IgG in the perfused kidney was markedly prolonged when complexed with antibody; one-half the cationized human IgG was still present after 12 d. There was a difference in the disappearance rates of antigen and antibody, as cationized human IgG was removed faster from the kidney than the antibody, the binding of which remained almost unchanged during the first week. Renal perfusion of a minimum of 20 μg of cationized human IgG, followed by intravenous injection of antibody, regularly induced severe glomerulonephritis with a proteinuria of at least 100 mg/24 h. The degree and the persistence of proteinuria induced depended on the dose of cationized human IgG perfused. Experiments using radiolabeled antigen and antibody showed that after renal perfusion of 20 μg cationized human IgG, 11.1 μg was kidney bound at the time of antibody injection. At the onset of proteinuria, 4.0 μg of antigen and 31.9 μg of anti-human IgG antibody were present in the perfused kidney. Immunofluorescence revealed immune deposits consisting of cationized human IgG and rabbit IgG (anti-human IgG) along the GBM. The staining pattern was linear (confluent) during the first 2 d and became granular during the course of the disease. Electronmicroscopically, a prominent finding was the accumulation of dense deposits, mainly in the subepithelial space and beneath the slit pores.

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