bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro studies with “Transfer Factor”: Transfer of the Cell-Migration Inhibition Correlate of Delayed Hypersensitivity in Humans with Cell Lysates from Humans Sensitized to Histoplasmin, Coccidioidin, or PPD
Authors: Paque Ronald E. , Kniskern Peter J. , Dray Sheldon , Baram Peter
Published: December 2022

When “nonsensitive” cells from skin test negative donors were incubated with specific antigen and specific cell lysates obtained from strongly skin test-positive histoplasmin, coccidioidin, or tuberculin skin test donors, the “nonsensitive” cells were “sensitized” and liberated a substance which specifically inhibited the migration of guinea pig macrophages. Cell lysates, antigen, or nonspecific combinations of both, either in the presence or absence of “nonsensitive” cells, failed to inhibit the migration of guinea pig macrophages.
Comparison of Various Avian and Mammalian IgG Immunoglobulins for Salt-Induced Aggregation
Authors: Kubo Ralph T. , Benedict Albert A.
Published: December 2022

Salt-induced aggregation of chicken, pheasant and quail IgG has been demonstrated by ultracentrifugation and gel filtration. Avian IgG immunoglobulins had sedimentation coefficients of 11–14S in 1.5 M NaCl (high salt), and 7S in 0.15 M NaCl. The aggregation of chicken IgG was reversible. Rabbit, porcine, bovine, sheep and human IgG immunoglobulins did not form aggregates in high salt. The Fc fragments of chicken and pheasant IgG were precipitated by high salt, whereas the Fab fragments were not aggregated by high salt. The salt-induced aggregation of chicken IgG antibodies was suggested as an explanation for the enhanced precipitation of chicken IgG antibodies by antigen in high salt.
Evaluation of the Immunosuppressive Properties of Ribonuclease Complexes
Authors: Davis Robert C. , Cooperband Sidney R. , Mannick John A.
Published: December 2022

Complexes were prepared by bisdiazobenzidine coupling of bovine pancreatic ribonuclease (RNase) and human serum albumin (HSA). These preparations prolonged skin allograft survival in mice and inhibited phytohemagglutinin stimulation of human lymphocytes in vitro. The HSA-RNase complexes that were most active in inhibiting lymphocyte stimulation failed to interfere with immune specific macrophage immobilization. The immunosuppressive potency of HSA-RNase complexes did not correlate with their measurable RNase enzyme activities. Furthermore, HSA-RNase complexes of widely differing immunosuppressive potency could not be distinguished by differences in molecular size or charge.
The Antigenic Subunits of Influenza Viruses
Authors: de St. Groth S. Fazekas , Webster R. G. , Davenport F. M.
Published: December 2022

Antigenic subunits were prepared from nine strains of influenza virus by treatment with deoxycholate. The immunogenicity of these preparations for rabbits was compared with equivalent doses of whole virus vaccines. The primary response to the subunit vaccines was found to be delayed, with little or no production of macroglobulin antibodies. The total quantity of primary antibody at 21 days was about half of that produced by whole virus vaccines. The quality (average equilibrium constant) of the antibodies was the same after the two kinds of vaccine. Anamnestic responses to subunit and whole virus vaccines were indistinguishable both kinetically and in terms of the number or quality of antibody molecules produced.
Differentiation of Cross-Reacting Simian Cytomegalovirus Strains by Late 19S Rabbit Neutralizing Antibodies
Authors: Hampar Berge , Martos Lidia M. , Ablashi Dharam V. , Siguënza Robert F. , Wells Gladys A.
Published: December 2022

The results of studies reported previously (1–3) demonstrated heterogeneity in the neutralizing properties of early (7-day) and late (hyperimmune) 7S and 19S antibodies prepared in rabbits against human herpes simplex virus (HSV) and the simian herpesvirus SA8. In the case of the late antibodies, we showed reciprocal cross-neutralization with the 7S antibodies, whereas neutralization by the 19S antibodies was limited essentially to the immunizing virus (3). Recent studies in this laboratory have been concerned with determining antigenic relationships between cytomegalovirus (CMV) strains using late immune rabbit sera (4). Evidence is presented here that the properties of late 7S and 19S rabbit antibodies prepared against simian CMV strains are similar to those reported previously for late 7S and 19S anti-HSV and anti-SA8 antibodies with respect to their specificity for the immunizing virus.

Three simian CMV strains were employed. Strain SA6 was isolated from a naturally infected vervet monkey (5), and strains CV-207 and CV-209 were isolated from African green monkeys which had been inoculated with human CMV (6).
Immunoglobulin Responses in Serum and Nasal Secretions after Natural Adenovirus Infections
Authors: Bellanti Joseph A. , Artenstein Malcolm S. , Brandt Brenda L. , Klutinis Barbara S. , Buescher Edward L.
Published: December 2022

The serum antibody response of 23 individuals with adenovirus infection (types 4, 1, 6 and 7) was studied. Neutralizing antibody tests correlated well with radioimmunodiffusion; the latter technique, however, offered the advantages of simplicity and distinct separation of specific immunoglobulin antibodies. The antigen used in radioimmunodiffusion measured group—rather than type—specific adenovirus antibody.

Only four patients exhibited the early appearance of macroglobulin antibody in the serum followed by and then replaced by IgG. The majority of individuals showed a prolonged IgM response accompanied by high titered IgG antibody. IgA serum antibody developed in almost all the patients. Following type 4 adenovirus infection, nasal secretory antibodies, both IgA and IgG but not IgM, were detected at the same time or within a week of the detection of serum antibody, and were universally found in the 35 individuals who were studied.
The IgM Response of Children to Salmonella Typhosa Vaccine
Authors: Altemeier William A. , Bellanti Joseph A. , Buescher Edward L.
Published: December 2022

The amounts of IgM specific for the O somatic, H flagellar and Vi antigens of typhoid were compared in the sera of eight immunized children. The assay involved measuring the concentrations of IgM that various antigens absorbed from sera that were obtained near the height of the immune response. The concentrations specific for Vi were probably quite low, the amounts directed to the O antigen were measurable in two of eight children but constituted less than half of their anti-typhoid antibodies while IgM anti-H predominated in the response. The polymerized flagellin absorbent containing H and O antigens removed 22 to 76 mg IgM antibody/100 ml from sera taken within two weeks of immunization. This accounted for as much as 50% of all serum IgM globulins and in seven of the eight children for essentially all of the total IgM globulin increase that followed immunization.
Immunochemical Studies on the Poly-γ-D-Glutamyl Capsule of Bacillus Anthracis
Authors: Roelants Georges E. , Whitten Laura F. , Hobson Ann , Goodman Joel W.
Published: December 2022

The fate and distribution of tritiated poly-γ-d-glutamic acid in immunogenic and nonimmunogenic forms in rabbits with circulating anti-polypeptide antibody was compared with that in normal animals, in order to assess the role of antibody in the splenic retention of immunogens. The presence of circulating antibody did not appreciably modify the retention of either form of the polypeptide. The feature which was consistently associated with immunogenicity of the antigen was the retention in spleen of appreciably more labeled material, chemically identified as undegraded poly-γ-d-glutamic acid. In conjunction with other studies, these results suggest that the trapping in lymphoid organs of intact antigen molecules may be of crucial importance for immune induction.
Assay for the Immunosuppressive Capacity of Antilymphocyte Serum
Authors: Martin William John
Published: December 2022

51Cr-labeled thymus cells exposed in vitro to 1:1000 dilution of rabbit anti-mouse lymphocyte serum (RAMLS) and injected into mice localized in the livers of recipient mice to a greater extent than cells exposed to normal rabbit serum (NRS). The increased liver uptake was due to phagocytosis of a proportion of the injected cells. The percentage of thymus cells opsonized by RAMLS could be calculated from a knowledge of the relative liver-to-spleen localization ratios in mice injected with cells preincubated in NRS and in RAMLS. The percentage is given by

The percentage of cells opsonized by different preparations of RAMLS varied widely (5% to 90%). There was a good correlation between the ability to opsonize thymus cells and to depress the immune response to sheep erythrocytes.
Assay for the Immunosuppressive Capacity of Antilymphocyte Serum
Authors: Martin William John
Published: December 2022

The opsonizing antibody of both rabbit and horse anti-mouse lymphocyte sera was demonstrated to be predominantly IgG. The antilymphocyte opsonins in rabbit serum showed no strain specificity when tested against thymus cells of several mouse strains. Moreover, the percentage of thymus cells opsonized was similar to the percentages of thoracic duct lymphocytes and lymph node lymphocytes opsonized. Rabbit anti-mouse lymphocyte sera had variable cross-reactivity against rat thymus cells, with no correlation between the percentage of mouse and rat cells opsonized.
The Presence of Anti-Glomerular Basement Membrane Antibodies in Peripheral Blood
Authors: McPhaul J. J. , Dixon Frank J.
Published: December 2022

The use of immunofluorescent assay for circulating anti-glomerular basement membrane (anti GBM) antibodies is described. Groups of people studied for the presence of anti-GBM antibody included: a) normals; b) immune-complex glomerulonephritic patients; c) anti-GBM antibody-mediated nephritic patients; d) a hemodialysis-maintained group of kidney disease patients; and e) an allergy clinic group. Anti-GBM antibodies were found in the circulation only in patients with anti-GBM antibody-mediated nephritis. Paired-label isotopic studies to determine the percentage fixation of kidney-fixing antibodies, combined with serial dilution of the same anti-GBM antibody-containing sera, allowed estimation of the sensitivity of the assay to be in the range of 0.1 to 1.0 µg/ml antibody content. Despite the sensitivity of the technique and its specificity, two principal handicaps were encountered: a) only 40% of people known to have anti-GBM antibody-mediated glomerulonephritis were shown to have circulating anti-GBM antibodies, and b) several sera were encountered which fixed with wide anatomical definition to the target substrate and made it difficult to recognize the presence of anti-GBM antibodies in such sera.
Differences in Antigenicity of Human IgG Produced by Three Established Lymphocytoid Cell Lines from a Single Individual
Authors: Matsuoka Y. , Yagi Y. , Moore G. E. , Pressman D.
Published: December 2022

Three lymphocytoid cell lines established from peripheral leucocytes of a single individual were found to produce IgG of the kappa light chain type and of the G1-heavy chain subclass. These IgG globulins showed a limited electrophoretic mobility in slow γ2 region. Rabbit antisera against each IgG revealed the presence of idiotypic determinants in each IgG indicating the clonal nature of IgG-producing cells in these cell lines. The idiotypic determinants in one IgG were clearly distinguishable from those in the other two IgG globulins, while those in the latter two could not be distinguished one from the other. Thus, the two cell lines producing these mutually indistinguishable IgG globulins seem to have been derived from stem cells belonging to the identical or very closely related clones although they were established from different blood samples. The idiotypic determinants were found to be present in the Fab portion of the IgG molecules.
Mechanisms of Endotoxin Tolerance
Authors: Greisman Sheldon E. , Young Edward J. , Carozza Frank A.
Published: December 2022

By serial quantitation of tolerance following a single intravenous injection of a Boivin-prepared Escherichia coli endotoxin into rabbits, pyrogenic tolerance could be readily separated into two distinct phases, early (waning within 48 hr) and late (increasing after 48 hr). The early phase of tolerance a) exhibited no inter-endotoxin specificity, b) was not associated with detectable increments in circulating anti-“O” antibody and c) within the sensitive dose-response range was directly proportional to the intensity of the initial pyrogenic response. It was not, however, a generalized refractory state since full responsiveness persisted to an unrelated pyrogen, staphylococcal enterotoxin B. In contrast, the late phase of pyrogenic tolerance a) exhibited a high degree of inter-endotoxin specificity, b) coincided with the appearance of detectable increments in circulating anti-“O” antibody, and c) within the sensitive dose-response range bore no direct relationship to the initial pyrogenic response. This latter characteristic was also demonstrated in man. The specificity of late tolerance was not demonstrable if the initial immunizing endotoxin preparation possessed poor “O” antigenicity (highly purified Westphal preparations), or if the endotoxin preparation employed for testing tolerance was derived from mutant strains lacking “O” specific terminal polysaccharide side chains.

These findings support the concept that the pyrogenic tolerant state following intravenous endotoxin administration is mediated by two distinct mechanisms, an early transient cellular refractory state and a later production of antibody which assists the reticuloendothelial system with clearance and destruction of the molecule. “O” specific antibodies appear to play the major role in mediating the late phase of pyrogenic tolerance following a single intravenous injection of endotoxin.
Spontaneous Thyroiditis in an Obese Strain of Chickens
Authors: Kite Joseph H. , Wick Georg , Twarog Bettina , Witebsky Ernest
Published: December 2022

The development of spontaneous chronic thyroiditis in the Obese Strain (OS) of White Leghorn chickens was analyzed chronologically by serologic and histologic studies covering a period from 1 to 24 weeks of age. Histologic changes appear within 2 weeks after hatching, reaching a maximum after 4 to 5 weeks. The infiltration of the thyroid glands consists mainly of large mononuclear cells and many germinal centers are present. Circulating antibodies against thyroglobulin were demonstrated in the sera of OS chickens by passive hemagglutination and by agar gel diffusion. Antibody titers demonstrated by passive hemagglutination increased with age. There was some, but not absolute correlation between the presence of thyroglobulin antibodies and the severity of thyroid lesions. One chicken from a “normal” White Leghorn strain revealed a slight degree of thyroid infiltration, while animals from a pathogen-free “normal” strain were completely free of thyroid alterations. On the other hand, the parent Cornell C-strain of White Leghorn chickens occasionally showed weak degrees of thyroid infiltration. Neither sera of the Cornell C-strain nor of the two normal control strains contained antibodies against thyroglobulin.
The Reaction of Immunoglobulin-Coated Bentonite and Radioiodinated Antigen as a Basis for Antibody Detection and Antigen Binding
Authors: Cheng William C. , Talmage David W.
Published: December 2022

A colloidal suspension of bentonite particles prepared on the basis of differential sedimentation was found to adsorb irreversibly about its own weight of rabbit immunoglobulin G. The immunoglobulin-coated bentonite formed a colloidal suspension readily in normal rabbit serum and easily sedimented upon centrifugation. Thus, from a reaction mixture of adsorbed antibody and a radioactively-labeled antigen, the separation of free and bound antigen can be accomplished by centrifugation. When the adsorbed antibody to an albumin antigen was used, the antigen-binding characteristics of the adsorbed antibody were found to be essentially similar to those of the free or unadsorbed antibody as demonstrated by the Farr method; however, the Farr method was two to four times more sensitive in estimating antigen-binding. It is suggested that the present method of using inert particles coated with antibodies for detecting these antibodies may be extended to the detection of antibodies of other immunoglobulin classes or of antibodies in antiserum.
The Effect of Heterologous Antigenic Stimulation on Antibody Synthesis in Vitro
Authors: Krueger Robert G.
Published: December 2022

Spleen and lymph node cells from rabbits immunized with the RNA phages MS-2 and fr synthesized neutralizing and complement-fixing antibody after in vitro antigenic stimulation with related heterologous RNA phages. In the presence of more distantly related heterologous phages, a relatively small amount of 7S antibody specific for the phage used to immunize the intact rabbit was synthesized. However, in the presence of very closely related heterologous phages, relatively large amounts of 7S antibody highly cross-reactive for these heterologous phages was produced. Unrelated phages did not elicit any immune response at all. Possible explanations of this apparent alteration of the immunologic specificity of the in vitro secondary immune response are discussed.
Communications
Authors: Vaerman J. P. , Heremans J. F. , van Kerckhoven G.
Published: December 2022

The best criterion for establishing homologies between immunoglobulins from different animal species would certainly be the demonstration of similarities between their amino acid sequences. Such an investigation, although becoming less problematic with the advances in modern protein chemistry, can only be undertaken in a small number of specialized laboratories. It would, however, seem that a valuable substitute for such chemical information is available in the form of immunologic analysis. Serologic cross-reactions between related proteins are known to be due to structural similarities between the antigens and, by extension, to correspondence of their amino acid sequences. There is good justification, therefore, to regard the evidence of clear-cut serologic cross-reactions as a very strong criterion of homology between two polypeptide chains.

In the particular case of IgA, the serologic approach has previously been applied only to the identification of IgA in primates (1–7), dogs (8), rats (9) and the pig (Vaerman and Heremans, to be published).
Role of Serum Protective Factor (SPF) in Langat Virus Infection of Neonatally Thymectomized, Cyclophosphamide-Treated, or Antilymphocyte-Treated Mice
Authors: Thind Inderjit S. , Price Winston H.
Published: December 2022

The host response to viral infection may include stimulation of humoral and cellular immune mechanisms and interferon production. Whether these are causally related or are merely temporally associated with recovery from viral infection remains uncertain partly because of the nature of available evidence (1, 2). Recently we reported that a new specific viral resistance factor called serum protective factor (SPF) played the major role in recovery from primary Langat virus infection and cross-protection with arboviruses in mice in contrast to the insignificant roles of in vivo-produced neutralizing antibody and interferon (3–5). SPF can be distinguished from interferon (3, 4) by a) lability at pH 3.0 after 3 hr at 4°C, b) lability on dialysis against distilled water, c) specific activity in providing protection against very closely related viruses, d) persistence for at least 3 weeks following viral infection, and e) failure of in vivo production when mice are inoculated with inactivated viruses.
Cutaneous Basophilic Hypersensitivity: A New Interpretation of the Jones-Mote Reaction
Authors: Richerson Hal B. , Dvorak Harold F. , Leskowitz Sidney
Published: December 2022

A type of delayed skin reaction which occurs transiently after immunization with soluble protein antigens alone or in incomplete Freund's adjuvant is well known (1, 2); its relationship to classic delayed (tuberculin) hypersensitivity, however, has been controversial. Raffel and Newel (3) concluded that the two reactions are different and suggested for historical reasons that the former be termed “Jones-Mote” hypersensitivity to distinguish it from classic delayed hypersensitivity produced by antigens in complete Freund's adjuvant (i.e., containing tubercle bacilli). This distinction has in general not been observed, and a current tendency is to consider Jones-Mote reactivity simply a milder form of classic delayed hypersensitivity (4, 5).

Because of the apparent confusion associated with this reaction, we investigated Jones-Mote hypersensitivity with regard both to its antigenic requirements and its histologic features. We here present clear evidence that the Jones-Mote reaction is a distinct form of immunologic response, which is distinguishable on the one hand from delayed hypersensitivity and on the other from the classic antibody-mediated reactions such as anaphylaxis or the Arthus reaction.
The Comparative Immunosuppressive Effects of Heterologous Antisera to Various C3H Mouse Tissues
Authors: Sloboda A. E. , Landes Jane
Published: December 2022

Three different batches of rabbit anti-mouse thymocyte serum (RAMTS) were consistently more effective than simultaneously prepared antisera to mesenteric lymph nodes (RAMLS) in prolonging survival of ICR skin allografts on C3H mice. Antispleen sera (RAMSpS) were ineffective. It was concluded that cells from different lymphoid organs were not equally effective in evoking antisera capable of prolonging skin allograft survival.

Dose response experiments indicated that differences in the ability of RAMTS or RAMRS to prolong allograft survival were qualitative rather than quantitative.

Neither the time of antiserum collection nor apsorption with mouse erythrocytes affected the ability of RAMTS or RAMLS to prolong allograft survival.

Rabbit antisera to the following mouse tissues were ineffective in prolonging mouse skin allograft survival: liver (RAMLiS), kidney (RAMKiS), transplantable C3H mammary tumor (RAM72jS) and transplantable 6C3HED lymphosarcoma of thymic origin (RAM6C3HEDS).

All antisera showed high leukoagglutination titers against lymphocytes and thymocytes. Leukoagglutination did not, however, correlate with allograft survival.

Lymphopenia induced by either RAMTS or RAMLS treatment did not correlate with effects on allograft survival.

Administration of antisera produced an initial increase in nonlymphocytic leukocytes (monocytes and granulocytes) which seemed related to the length of allograft survival.
Detection of Hemopoietic Allografts by Localization of Radiolabeled Alloantibodies
Authors: Witz Isaac , Cudkowicz Gustavo , Pressman David
Published: December 2022

Radiolabeled alloantibodies have been used to show the presence of allogeneic cells in marrow chimeras. Alloantigens of grafted cells are available to circulating antibody since radiolabeled alloantibodies bind specifically to the cells after intravenous injection. Such antibodies localize in livers and spleens of untreated allogeneic mice and of irradiated mice bearing a bone marrow graft. The presence of allogeneic cells, as determined by localization of radioantibody, was shown 18 hr after injection of the radiolabeled antibodies. Maximum localization of the C57BL/6 anti-DBA/2 alloantibodies injected could be shown 2 days after transplantation of 2 × 107 DBA/2 marrow cells into irradiated C57BL/6 or C57BL/10 mice. Similar localization occurred also 9 days after transplantation of 5 × 106 cells. The results suggested that even smaller numbers of grafted marrow cells could be detectable at shorter intervals after transplantation by this sensitive method.
The Clonal Nature of Antibody Formation
Authors: Bosma M. , Weiler E.
Published: December 2022

With the aid of a cell transfer system using F1-hybrid spleen cells of syngeneic mice, poly-d-alanine (poly-ala) antigen and a modified antibody plaque assay, we were able to rigorously test and confirm the clonal nature of antibody formation.

Our results showed that when x-rayed mice were repopulated with relatively small numbers of spleen cells followed by two immunizations, only a few animals produced antibodies to poly-ala and in the spleens of most of these responder mice only one of two allelic gene regions determining 7S antibody phenotype (B or C allotype) was expressed. On the other hand, when relatively large numbers of spleen cells were transferred to x-rayed mice followed by two immunizations, all recipients responded to poly-ala and expressed both antibody-forming cells of B and C allotype. The all-or-none response characteristics at limiting spleen cell doses were amenable to Poisson statistics suggesting that some mice were repopulated by descendants of a single poly-ala-sensitive precursor unit, i.e., by an individual clone of antibody-forming cells. The application of Poisson statistics to mice expressing only one marker allotype confirmed this interpretation. The number of mice expected to be repopulated by a single poly-ala-sensitive precursor unit correlated very well with the number of responder mice expressing only one allotype. Thus antibody specificity and allotype must be transmitted together in cell lines and thereby characterize individual clones. The total number of prospective clones of poly-ala specificity was estimated to be about 150 per young adult mouse. The calculated size of a given individual clone was 20,000 to 50,000 synthesizing cells which represented about 14 to 16 cell divisions.
Further Purification of the Glycoprotein that Induces Nephrotoxic Antibody: Isolation of the Active Polysaccharide Fraction Mainly Composed of Glucose
Authors: Shibata Seiichi , Naruse Takuji , Miyakawa Yuzo , Nagasawa Toshihiko
Published: December 2022

Experiments that were done to determine the function of the protein and polysaccharide moieties of a highly purified renal glycoprotein revealed that the antigenic activity that induces nephrotoxic antibody relates more closely to the polysaccharide moiety.

By using the 90% phenol extraction method, the active polysaccharide fraction which possesses antigenic potency was extracted from renal glycoprotein that was shown to contain no nucleic acid. In this highly purified antigen (glycoprotein) the polysaccharide moiety was shown to consist mainly of glucose and the protein content was remarkably low, without any decrease in the antigenic activity that induces nephrotoxic antibody.
Adoptive Antibody Formation in the Syrian Hamster
Authors: Merritt K. , Little J. W.
Published: December 2022

Adoptive transfer of antibody formation was demonstrated in the Syrian hamster. Spleen cells from donors receiving a second injection of antigen were capable of producing detectable antibody in recipients whereas cells from donors receiving their first injection were not. Antibody formation could be transferred from donor to recipient when the donor-antigen contact was only 15 min and it occurred even when viability of the cells had been destroyed by freezing and thawing; it was therefore probably due to transfer of antigenic material. Within 60 min of donor-antigen contact, however, the ability to transfer antibody formation became dependent on the maintenance of viable cells in the spleen.
2,4-Dinitrophenyl-Hapten Specific Hemolytic Plaque-in-Gel Formation by Mouse Myeloma (MOPC-315) Cells
Authors: Yamada Hisashi , Yamada Atsuko , Hollander Vincent P.
Published: December 2022

A mouse myeloma (MOPC-315) producing immunoglobulin A, which specifically binds 2,4-dinitrophenyl-hapten, has been shown to form hapten-specific plaques by a hemolytic plaque-in-gel assay. Sheep erythrocytes coupled with dinitrophenylated bovine serum albumin and rabbit antibody directed to the heavy chain as enhancing serum were used. Virtually all of the tumor cells formed plaques. DNP-lysine sharply inhibited plaque formation at a concentration slightly in excess of the reciprocal of the binding constant of the myeloma protein.
Experimental Hemorrhagic Pneumonitis Produced by Heterologous Anti-Lung Antibody
Authors: Willoughby William F. , Dixon Frank J.
Published: December 2022

Rabbit antibody directed against basement membrane antigens of rat lung capillaries is capable of producing both pulmonary hemorrhages and glomerulonephritis in rats following intravenous injection. The injection of higher doses of antibody causes acute splenitis and focal liver necroses as well. Evidence for the immunologic pathogenesis of these lesions includes the following: a) in vivo localization of radiolabeled antibody can be demonstrated in lung, kidney, liver and spleen; b) fluorescent staining reveals that this antibody is bound in vivo to the vascular basement membranes of the pulmonary capillaries and renal glomeruli, as well as to the splenic reticulum and along the hepatic sinusoids; c) normal rabbit γ globulin and antibody that has been absorbed with lung antigen are both incapable of producing these lesions and neither shows specific organ localization as measured by the paired isotope technique.

Antigens derived from or related to vascular basement membrane can be demonstrated in the urine of normal rats, and in the serum of bilaterally nephrectomized rats. Apparently in the turnover of non-renal basement membranes, potentially antigenic fragments reach the circulation and are excreted by the kidneys.
Contribution of the b and c Light Chain Loci to the Composition of Rabbit γG-Immunoglobulins
Authors: Vice John L. , Hunt William L. , Dray Sheldon
Published: December 2022

The contribution of the b5, c7 and c21 genes to the formation of a single γG-immunoglobulin molecule has been analyzed in partially b5 suppressed b5b5 homozygous rabbits of phenotype c7c21. This was done by means of direct precipitation of 125I-labeled γG preparations with anti-b5, anti-c7 or anti-c21 as well as by indirect precipitation of these allotypes with anti-b4. No two of the allotypic specificities, b5, c7 or c21 were found on the same molecule. This indicates that neither the two unlinked light chain loci b and c, nor the allelic genes c7 and c21 contribute to the formation of the same molecule.

Two light polypeptide chain peaks were obtained after partial reduction and alkylation of the γG-immunoglobulins. Quantitative allotype analysis revealed that b5, c7 and c21 light chains accounted for all of the molecules in the first light chain peak, and only b5 light chains accounted for all of the molecules of the second peak. The c21 allotypic specificity is on the light chains as previously found for the b5 and c7 specificities.
Spontaneous Thyroiditis in the Obese Strain of Chickens
Authors: Wick Georg , Kite Joseph H. , Cole R. K. , Witebsky Ernest
Published: December 2022

The Obese Strain (OS) of White Leghorn chickens reveals spontaneous chronic thyroiditis which is characterized by infiltration with mainly large mononuclear cells, the occurrence of a great number of germinal centers in the thyroid glands, and the presence of circulating thyroglobulin autoantibodies.

Bursectomy on day of hatching resulted in a significant decrease in the incidence and severity of the disease when the chickens were examined 7 weeks after hatching. This decrease was paralleled by the absence of precipitating and hemagglutinating thyroglobulin antibodies in most cases. Bursectomy in ovo on day 19 of incubation had an even more pronounced suppressive effect on the development of the spontaneous, chronic thyroiditis and the presence of circulating thyroglobulin antibodies. Sham bursectomy had no effect. It is concluded that bursa-dependent lymphoid cells play a major role in the development of spontaneous, chronic thyroiditis in OS chickens.
Spontaneous Thyroiditis in the Obese Strain of Chickens
Authors: Wick Georg , Kite Joseph H. , Witebsky Ernest
Published: December 2022

White Leghorn chickens of the Obese Strain (OS) were thymectomized and thymobursectomized on the day of hatching. Histologic examination of the thyroid glands of the thymectomized group, 7 weeks after hatching, revealed a significant increase in the frequency and severity of spontaneous chronic autoimmune thyroiditis as compared to untreated OS controls. In the sera of both untreated and thymectomized OS chickens precipitating thyroglobulin antibodies were demonstrable in most cases. However, hemagglutinating thyroglobulin antibodies occurred in somewhat lower frequency and in lower titers in thymectomized animals than in untreated controls. Sham thymectomies had no effect. Thymo-bursectomy on the day of hatching had a slightly inhibiting effect on the development of spontaneous chronic thyroiditis in OS chickens when examined 7 weeks after hatching. This suppressive effect was less pronounced than the one found previously with bursectomy alone. Circulating thyroglobulin antibodies could be demonstrated only in a few sera of the thymobursectomized group. The results suggest a controlling function of the thymus on the self-recognition mechanism in chickens and support the earlier findings that bursa-dependent cells play the major role in the development of spontaneous chronic thyroiditis in OS chickens.
Evidence for Tolerance to SV40 Tumor Antigen in Hamsters Bearing Para-Adenovirus 12 Tumor Transplants
Authors: Lausch Robert N. , Tevethia Satvir S. , Rapp Fred
Published: December 2022

A study was carried out to determine why hamsters bearing PARA-12 tumor transplants made little or no humoral response to SV40 T antigen known to be present in the tumor cells. Experiments involving localized irradiation, partial surgery, or total excision of the tumor suggested that neither inadequate antigenic stimulation nor binding of antibody by tumor tissue was the explanation for the failure to detect T antibody. It was observed that tumor-bearing hamsters made a depressed antibody response to SV40 T antigen contained in another tumor line. Such animals, however, could make a normal antibody response to sheep red blood cells, indicating that there was no generalized immune depression. The administration of PARA-12 tumor tissue in Freund's complete adjuvant to normal hamsters led to the induction of antibody whereas the same immunization procedure in tumor-bearing animals yielded only a very weak or no response. The results indicate that the PARA-12 tumor-bearing hamsters did not make an immune response because they were tolerant to the SV40 T antigen. This tolerance was apparently dependent on the continued presence of the neoplasm because surgical removal of the tumor followed by appropriate immunization resulted in production of T antibody.
A Reaginic Type of Antibody Stimulated by Extracts of Bordetella Pertussis in Inbred Strains of Mice
Authors: Clausen C. R. , Munoz J. , Bergman R. K.
Published: December 2022

Strains of mice differed in their ability to produce reaginic type of homocytotropic antibody (72-hr passive cutaneous amaphylaxis (PCA) antibody) after a single injection of hen egg albumin (EA) and alkaline saline extract (SE) from Bordetella pertussis. The inbred strains NBL/n, C57BL/6J and C57BL/10J were superior to the AKR/n, STR/n and the random bred RML strains.

Further studies on the 72-hr PCA antibody in NBL/n and C57BL/6J mice have shown that in these strains the majority of the PCA-inducing antibody found in the serum after a single immunization of antigen and SE is of the reaginic type. The hemagglutinating titers correspond closely to the 2-hr PCA titers but not to the 72-hr PCA antibody concentration.

Reasonably high titers of reaginic type of antibody were found in ascitic fluid induced by repeated intraperitoneal injections of Freund's incomplete adjuvant and small doses of EA to mice that had received an initial i.p. dose of SE + EA. The reaginic antibody in whole serum was inactivated by heating at 56°C for 1/2 hr. However, when the serum was diluted in saline, this heating had only little effect on the antibody.

The reaginic type of homocytotropic antibody was not found in the 7S or 19S immunoglobulin, and was separated by DEAE cellulose as a distinct entity. It is probably an immunoglobulin similar to IgE of human serum.
Spontaneous Thyroiditis in the Obese Strain of Chickens
Authors: Wick Georg , Kite Joseph H. , Witebsky Ernest
Published: December 2022

The effect of neonatal sublethal total body x-irradiation on the development of chronic thyroiditis in chickens of the Obese strain (OS), the Cornell C strain and a “normal” strain of White Leghorns was studied histologically and serologically. At the time of death, 7 weeks after hatching and irradiation, a significant increase in severity and frequency of chronic thyroiditis was observed in both the OS and C strain chickens; thyroiditis was also found in more than half of the irradiated normal White Leghorn chickens. In all three strains under investigation the histologic findings correlated well with the presence of circulating antibodies to thyroglobulin (hemagglutinating and precipitating) in the sera of most of the diseased birds. Irradiation damage to the thyroid glands or to the immune system is discussed from the standpoint of single or combined factors that cause an increase in the severity and frequency of thyroiditis after neonatal x-irradiation of chickens.
Precipitation and Neutralization of Bacteriophage MS-2 by Rabbit Antibodies
Authors: Rohrmann G. F. , Krueger R. G.
Published: December 2022

The neutralizing and precipitating activities of 10 hyperimmune rabbit antisera to the RNA-containing coliphage MS-2 were compared. The neutralization constant, K, of these antisera was directly proportional to their concentration of precipitating antibodies. In the quantitative precipitin analysis, phage MS-2 has a minimal antigenic valence of 90 in extreme antibody excess. However, phage MS-2 did not behave as a typical large molecular weight antigen because it demonstrated a relatively narrow equivalence zone. The possible relationship between the precipitin data and the structure of the virus is discussed.
Studies of Thoracic Duct Lymphocytes of Mice
Authors: Cantor Harvey , Mandel Mark A. , Asofsky Richard
Published: December 2022

The activity of spleen, mesenteric lymph nodes, femoral lymph nodes, thymus, bone marrow, blood and thoracic duct lymphoid cells from Balb/c mice in producing graft-vs-host reactions when grafted to newborn C57BL/6 recipients was compared quantitatively using the Simonsen spleen assay. Blood and thoracic duct lymphocytes were more than four times as active as spleen cells. Spleen cells from mice drained of lymphocytes from the thoracic duct were less than 50% as active as normal spleen cells. Mesenteric lymph node cells were slightly less active than spleen cells. Femoral lymph node cells produced splenic enlargement intermediate between that produced by circulating lymphocytes and spleen cells. However, inocula of femoral node cells in excess of 2 × 106 produced early runting (by day 9 after grafting) in 100% of recipients. This capacity to produce wasting was found in no other cell population examined. Thymus cells were only 15% as active as spleen cells, and bone marrow cells produced no early splenic enlargement in recipients.

The results are interpreted as indicating (a) that the GVH activity of the spleen and probably of several other solid lymphoid tissues is accounted for by their content of lymphocytes from the circulating pool, and (b) that the femoral nodes contain a high proportion of cells qualitatively different in producing GVH reactions from those in other tissues.
Correlation Between Ocular Inflammation and Antibody Production
Authors: Hall J. M. , O'Connor G. R.
Published: December 2022

Rabbits were immunized intravitreally, intravenously, or intradermally with small amounts of protein antigen. Intravitreal immunization resulted in the development of uveitis associated with serum antibody production. Intravenous injection of the same amount of antigen was ineffective in this case, and intradermal injection was effective only if antigen was incorporated with Freund's complete adjuvant.

Intravitreally immunized animals were challenged at various times by a second intravitreal injection into the opposite eye. Even when antibody had fallen to undetectable levels, these rabbits showed a rapid onset of uveitis and an accelerated antibody response. Animals primarily immunized by the intravenous route or by the subcutaneous route also exhibited an accelerated response following intravitreal challenge into the eye. Intravenous challenge with small amounts of antigen caused a rapid rise in antibody titer in rabbits that had received a primary intravitreal injection in the right eye. However, contrary to the results obtained by others who have used higher challenge doses, uveitis did not recur in the right eyes of these animals.

The results of these investigations are discussed in relation to the X, Y, Z scheme of cell differentiation for immunologically competent cells.
Transglutaminase Levels during Development of Allergic Orghitis
Authors: Lee Johanna M. , Wajda Isabel J.
Published: December 2022

Injections of testicular tissue in complete Freund's adjuvant produced allergic orchitis in mice that are 100% susceptible to experimental allergic encephalomyelitis (EAE), but not in mice that are 100% resistant to EAE. In susceptible mice only, the levels of transglutaminase increased in the liver prior to the development of orchitis, and markedly increased in the testes during aspermatogenesis and the appearance of histologic damage.

The levels of transglutaminase were elevated in the brains of animals with experimental allergic orchitis and in the testes in animals with EAE, suggesting that these organs have an antigenic community.
Primary Rejection of Skin Allografts in the Anterior Chamber of the Rabbit Eye
Authors: Franklin R. M. , Prendergast R. A.
Published: December 2022

The survival of primary skin allografts placed within the anterior chamber of rabbits was examined in temporal sequence following transplantation to normal and x-irradiated recipients. Initial “take” was successful in all instances as judged by vascularization of graft stroma and hyperplasia of skin epithelium. Starting on day 6, and thereafter to an increasing degree, mononuclear cells infiltrated the graft and graft bed, eventually obscuring this border completely. Rejection of the irisimplanted tissue was complete by day 14, though graft epithelium which had extended to cover the undersurface of the cornea persisted for a few days longer before its ultimate rejection.

The present study offers direct evidence that primary full-thickness skin allografts placed within the anterior chamber succumb to a rejection process temporally and histologically similar to rejection of orthotopic skin grafts. The immunologic nature of this reaction is supported by the finding that whole body irradiation abrogates this response, and further that similarly transplanted autologous skin or lymph node fragments survive intact for at least 120 days. It is concluded that the anterior chamber is not a generally privileged site for allograft survival.
Release of Fab- and Fc-like Fragments from Human IgM by Reductive Cleavage
Authors: Albritton William L. , Schrohenloher Ralph E. , Bennett J. Claude
Published: December 2022

The three major classes of immunoglobulins which occur in human serum (IgM, IgG and IgA) exist either singly or as multimers of 7S subunits linked together by disulfide bonds. Reductive depolymerization of these immunoglobulins ultimately results in the production of the class specific heavy chains and either kappa or lambda light chains. Papain hydrolysis of IgG results in the formation of two Fab fragments consisting of a light chain and part of a heavy chain and an Fc fragment containing the remainder of the heavy chain (1). Essentially the same results have been reported for papain hydrolysis of IgM, but the yield of the Fc fragment is very low (2). Various other proteolytic enzymes have likewise been shown to produce rather characteristic fragments of immunoglobulins (3). Recently the production of Fab and Fc fragments by reductive cleavage of human IgM and IgA with sodium borohydride has been reported (4, 5).
Immunosuppressive Effects of Antilymphocyte Serum in Complement-Deficient Mice: Evidence that Immune Cytolysis Is Not Essential for ALS Activity
Authors: Barth Rolf F. , Carroll Gary F.
Published: December 2022

The suppressive effect of antilymphocyte serum (ALS) on the immune response to sheep erythrocytes has been studied in complement deficient mice which lack C5. ALS proved to be equally as potent in depressing splenic plaqueforming cells and serum hemagglutinin and hemolysin titers in deficient as compared to normal mice. These findings indicate that antibody mediated, complement dependent immune cytolysis of lymphocytes is not essential for ALS activity since C5 is required for this. They support the view that ALS may contain antibodies which facilitate the elimination of lymphocytes by phagoeytosis (23), rather than by immune cytolysis.
HL-A Antigens from a Continuous Lymphoid Cell Line Derived from a Normal Donor
Authors: Reisfeld R. A. , Pellegrino M. , Papermaster B. W. , Kahan B. D.
Published: December 2022

Water soluble HL-A antigens isolated from a cultured human lymphocyte cell line derived from the peripheral blood of a normal donor inhibited cytotoxic reactions of monospecific anti-HL-A antisera in a pattern identical to that found upon direct and absorption typing of the donor's peripheral lymphocytes. The possibility of obtaining large quantities of cells from mass cultures now makes the chemical and biologic characterization of HL-A antigens a reality.
Analysis of the Neutralizing Activity in Nasal Wash and Serum Following Intranasal Vaccination with Inactivated Type 13 Rhinovirus
Authors: Knopf Harry L. S. , Perkins John C. , Bertran Dinah M. , Kapikian Albert Z. , Chanock Robert M.
Published: December 2022

Nasal secretions and serum of volunteers were analyzed after intranasal vaccination with an inactivated type 13 rhinovirus. Methods for separating and characterizing immunoglobulins included sucrose gradient centrifugation, analytical ultracentrifugation and gel filtration. The major classes of immunoglobulins in secretions and sera were isolated by these techniques. Neutralizing activity in nasal secretions was concentrated in the 11S region of the sucrose gradient and was associated with IgA. Activity in serum was associated with 19S IgM or 7S IgG. These findings are in agreement with the results of similar studies in which live and inactivated viruses were introduced directly into the respiratory tract. They also suggest that the protective effect observed in earlier experiments with this vaccine was due to the development of 11S IgA in nasal secretions.
Suppression of Skin Hypersensitivity and Antibody Formation by L-Asparaginase
Authors: Khan Amanullah , Hill Joseph M.
Published: December 2022

Rabbits immunized with BSA in Freund's adjuvant were treated with different doses of L-asparaginase. The administration of this enzyme was started on the day of immunization and continued for 21 days. To measure the immunologic responses, weekly skin tests and quantitative antibody determinations were done. It was found that L-asparaginase in large doses (1000 IU/kg/day) suppressed both antibody formation and delayed hypersensitivity. With smaller doses, the suppression was partial and antibodies against L-asparaginase itself appeared in the serum, leading to a rapid elimination of the enzyme from the system by the end of the 3rd week. This rapid clearance of asparaginase in the latter part of its administration in small doses is probably due to the neutralizing effect of the antibodies, or rapid elimination of the antigen-antibody complexes, or a combination of the two. The possible mechanism and clinical significance of these findings was discussed.