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Biomedical subjects

R B Colvin

Publications and source records attributed to R B Colvin.

At least 235 records · Page 13Linked to original sources
PubMed1977

Passive transfer of autoimmune disease with isologous IgG1 and IgG2 antibodies to the tubular basement membrane in strain XIII guinea pigs: loss of self-tolerance induced by autoantibodies.

Initiation of an autoimmune tubulointerstitial disease was achieved in strain XIII guinea pigs by passive transfer of functionally pure IgG1 or IgG2 fractions of isologous anti-tubular basement membrane (TBM) serum. IgG2 appeared to be somewhat more effective than IgG1. The immunopathologic features in the IgG1 and IgG2 recipients were similar at the time of sacrifice, 14 days after transfer. The recipients that developed disease had higher than expected anti-TBM titers at 14 days. Furthermore, anti-TBM antibodies were of both IgG isotypes. In contrast, simultaneously administered IgG1 or IgG2 anti-BGG antibodies declined in titer in the recipients and were never found in the isotype fraction that had not been transferred. These findings indicate that the recipients of anti-TBM antibodies of either IgG1 or IgG2 isotype were stimulated to produce anti-TBM autoantibodies, which participated in the pathogenesis of the renal disease. The model demonstrates that autoantibodies may provide a mechanism (autoimmune amplification) for the intensification and perpetuation of antibody-mediated autoimmune diseases.

Animals↗
PubMed1977

Systemic expression of cutaneous basophil hypersensitivity.

Guinea pigs primed for cutaneous basophil hypersensitivity (CBH) with several soluble proteins or with sheep erythrocytes developed a systemic, delayed-onset, maculopapular rash when challenged parenterally with specific antigen. The rash was most readily induced 5 to 7 days after immunization, at a time when local CBH skin test reactivity was also optimal. Miscroscopically, the rash resembled local CBH skin test reactions, being comprised of a papillary dermal infiltrate of basophils and lymphocytes and a striking dilatation and compaction of superficial venules. In addition to the systemic rash, animals expressing systemic CBH (SCBH) exhibited a striking eosinophilia at 24 hr which gave way to basophilia at 48 hr. Focal collections of eosinophils, and of smaller numbers of basophils, were found in the lungs and spleen; both eosinophils and basophils infiltrated the medulla of the thymus. Thus, basophil-rich infiltrations are favored in the skin even after systemic challenge with antigen and occur only to a much smaller extent in other organs where eosinophils may predominate. These differences in the response of various organs to challenge with parenteral antigen suggest that as yet unidentified local factors play a determinative role in regulating the inflammatory response. The pathogenesis of SCBH is not yet established, but it shares many of the properties of local CBH: histology, carrier specificity, development early after sensitization in the absence of detectable antibodies. Passive transfer has not been accomplished with serum alone but has been achieved irregularly with cells plus serum. SCBH may serve as a useful model for several disease states in man characterized by a systemic rash and eosinophilia, including certain types of drug reaction.

Animals↗
PubMed1976

Immunopathogenesis of autoimmune tubulointerstitial nephritis. I. Demonstration of differential susceptibility in strain II and strain XIII guinea pigs.

Autoimmune tubulointerstitial nephritis (TN) was induced in strain XIII and Hartley but not strain II guinea pigs after immunization with rabbit tubular basement membranes (TBM) in CFA. Strain XIII guinea pigs developed extensive autoimmune TN associated with high anti-TBM (aTBM) antibody titers and linear deposits of IgG along renal cortical TBM after immunization with 10 mug to 10 mg of TBM. In addition, autoimmune TN was passively transferred to strain XIII animals by the i.p. injection of aTBM sera obtained from actively immunized Hartley guinea pigs. In contrast, strain II guinea pigs did not develop autoimmune TN after active immunization (10 mug to 10 mg) with rabbit TBM in CFA, and only produced high aTBM antibody titers with the highest immunnizing antigen dose. At this dose (10 mg) the strain II animals demonstrated linear deposits of IgG along renal cortical TBM but did not develop autoimmune TN. Further, recipient strain II guines pigs did not develop autoimmune TN after passive transfer of aTBM antisera despite renal cortical tubular deposition of aTBM antibodies. Both inbred guinea pig strains produced antibodies reactive with rabbit and rat renal basement membranes. No evidence for differences in nephritogenic TBM antigens could be demonstrated betweed strain XIII and strain II TBM. These observations indicate that 1) genetic factor(s) influence the production of antibodies reactive to autologous TBM, 2) after the deposition of antibodies on the TBM, additional or related genetic factor(s) determine the full expression of this autoimmune renal disease, and 3) aTBM antibody deposition on renal TBM is not sufficient to elicit autoimmune TN.

Animals↗
PubMed1976

Immunopathogenesis of autoimmune tubulointerstitial nephritis. II. Role of an immune response gene linked to the major histocompatibility complex.

Immunization of strain XIII guinea pigs with rabbit renal tubular basement membranes (TBM) in CFA consistently results in severe autoimmune tubulointerstitial nephritis (TN). Strain II guinea pigs similarly immunized do not develop this disease. F1 guinea pigs were found to be intermediate between inbred strain II and XIII animals with regard to extent of autoimmune TN and anti-TBM antibody production. The F1 X II backcrosses segregated into two groups with regard to antibody production and disease extent. Those backcrosses tissue typed as II+, XIII+ were similar to the F1 guinea pigs. Those backcrosses typed as II+,II+ demonstrated little disease and low anti-TBM titers similar to the inbred strain II animals. F1 X XIII backcrossed guinea pigs segregated into II+,XIII+ or XIII+,XIII+ subgroups on the basis of lymph node typing. The II+, XIII+ backcross animals resembled F1 guinea pigs with respect to anti-TBM response and disease extent; whereas the XIII+, XIII+ backcrosses developed severe disease and high anti-TBM titers as observed in the inbred strain XIII animals. These experiments suggest that susceptibility to autoimmune TN in the guinea pig is linked to the strain XIII major histocompatibility complex and that an immune response gene governing this susceptibility may be inherited as a single dominant or co-dominant trait.

Animals↗
PubMed1975

Fibrinogen/fibrin on the surface of macrophages: detection, distribution, binding requirements, and possible role in macrophage adherence phenomena.

The peritoneal cavity of guinea pigs proved to be a rich source of mononuclear cells (34-52%) with fibrinogen or fibrin (Fib) on their surface. The Fib was readily detected on the surface of viable cells in suspension by fluorescence microscopy using antisera to guinea pig fibrinogen. The fluorescent staining occurred either in a speckled distribution, similar to that of cytophilic IgG, or in a distinctive net-like pattern that probably represented fibrin formation on the cell surface. The binding of Fib to the cell surface required calcium, but not magnesium, in the medium and could occur in vitro during incubation in heparinized plasma that contained fibrinogen concentrations comparable to that in normal peritoneal fluid (0.58 mg/ml). Cell surface Fib was more susceptible to plasmin and trypsin digestion than surface cytophilic IgG. By morphologic and physiologic criteria, cells exhibiting surface Fib were chiefly, if not exclusively, macrophages. Granulocytes, erythrocytes, and lymphocytes from lymph node and thymus had no sppreciable Fib. Cells with surface Fib were rarely observed among mononuclear cells prepared by Ficoll-Hypaque sedimentation of guinea pig and human blood (1.4 and 4.6%, respectively). Pulmonary alveolar macrophages, functionally distinct from peritoneal macrophages, lacked surface Fib (0.8%). Polymerization of Fib on the surface of macrophages might participate in certain cell interactions, such as the adherence of peritoneal macrophages during the antigen-induced macrophage disappearance reactions. The unexpected finding of Fib binding to the surfaces of peritoneal macrophages raises the possibility of a biologically significant interaction between these cells and the clotting system.

Animals↗
PubMed1975

Role of the clotting system in cell-mediated hypersensitivity. II. Kinetics of fibrinogen/fibrin accumulation and vascular permeability changes in tuberculin and cutaneous basophil hypersensitivity reactions.

Radioactive tracers and immunofluorescence were employed to detect and quantitate fibrinogen/fibrin deposition in two types of cell-mediated hypersensitivity reactions in the guinea pig. Classic delayed hypersensitivity (DH) reactions to Old Tuberculin and to the azobenzenearsonate hapten were characterized by a progressive increase in the fibrinogen (125-I-HF) content which exceeded that of the albumin tracer (131-I-HSA) and paralleled the development of induration and erythema. Accumulation of 125-I-HF could be related both to increased vascular permeability to 125-I-HF and, more specifically, to retarded efflux of extra vascular 125-I-HF from tuberculin reaction sites. Warfarin inhibited 125-I-HF accumulation and the formation of urea-insoluble 125-I-HF (cross-linked fibrin) as well as induration in tuberculin reactions. Immunofluorescence studies revealed the site of Fib deposition to be extravascular, among the connective tissue fibers of the dermis, similar to that in DH reactions in man. In contrast, little 125-I-HF accumulated in cell-mediated reactions rich in basophils--cutaneous basophil hypersensitivity (CBH) reactions to keyhole limpet hemocyanin, ovalbumin, and dinitrochlorobenzene--due in part to less vascular leakage of macromolecules and to decreased formation of urea-insoluble fibrin. By immunofluorescence Fib deposits were found in CBH reactions in a pattern similar to that in DH reactions, but the intensity of staining was appreciably less. Thus, fibrin accumulation further distinguishes DH from CBH reactions and is very likely responsible for the induration characteristic of DH reactions.

Animals↗
PubMed1975

Specificity of basophils and lymphocytes in cutaneous basophil hypersensitivity.

Using a rosetting technique, it was found that the vast majority of basophils circulating in the blood or accumulating in the skin reactions of guinea pigs primed for cutaneous basophil hypersensitivity (CBH) lacked demonstrable specificity for sensitizing antigen, whether sheep erythrocytes, a soluble protein, or tumor cells. By contrast, one-third of cells teased from late skin reactions formed specific rosettes as did nearly 80% of circulating basophils in animals receiving repeated doses of whole sheep blood. Unreactive basophils teased from CBH reactions readily acquired rosetting capacity on exposure to immune serum. With regard to lymphocyte (and hence reaction) specificity, both CBH and classic delayed hypersensitivity (DH) reactions exhibited a high degree of carrier specificity when dinitrophenyl-conjugates were used. Thus, in the hapten-carrier combinations examined thus far, the antigen skin test requirements for both CBH and DH have been identical and are those required for inducing an active lymphocyte response. These findings indicate that control mechanisms other than homocytotropic antibodies must be sought to explain the accumulation and behavior of basophils in CBH reactions and, coupled with other data, suggest that lymphocytes and/or their products are likely candidates for this role.

Animals↗
PubMed1973

Role of the clotting system in cell-mediated hypersensitivity. I. Fibrin deposition in delayed skin reactions in man.

The expression of delayed-type hypersensitivity in animals has been inhibited by a variety of anticoagulants, but direct evidence for activation of clotting in the evolution of these reactions has been lacking. Using the fluorescent antibody technique we here demonstrate that fibrin deposition is a prominent and consistent feature of both allergic contact dermatitis and classic delayed hypersensitivity skin reactions in man. Fib was detected in 55 of 58 delayed reactions studied at the peak of their intensity. The characteristic distribution of Fib-principally in the intervascular portions of the reticular dermis with sparing of vessels and their associated cuffs of mononuclear cells-is unusual and quite different from that described in antibody-mediated lesions in animals or man. Fib was found in vessel walls in only 2 of 94 biopsies studied. With a single exception, deposition of immunoglobulins and complement was not observed. The pathogensis and significance of Fib deposition in these reactions are not yet clear. Fib is ultimately derived from circulating fibrinogen, and its accumulation provides additional evidence for locally increased vascular permeability in delayed hypersensitivity. Polymerization of extravascular fibrinogen could be triggered nonspecifically by dermal elements (e.g., collagen) or by a product of sensitized lymphocytes. The appearance of Fib early in the development of these reactions (4-8 h after epicutaneous test with DNCB) and inhibition studies with anticoagulants together suggest that clotting may have a role in their pathogenesis, possibly by the release of bioactive peptides from fibrinogen/fibrin or by contributing to the induration characteristic of delayed hypersensitivity.

Adolescent↗