bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Cellular Basis for Partial Tolerance: Antigen-Specific Suppression of Antigen-Induced Thymidine-2-14C Incorporation In Vitro
Authors: Borel Yves , Schlossman Stuart
Published: December 2022

The suppression of delayed hypersensitivity by induction of partial immunologic tolerance is antigen-specific both in vivo and in vitro. Lymph node cells from partially tolerant animals incorporate thymidine-2-14C either poorly or not at all in response to antigenic challenge in vitro. The latter response more closely parallels the diminution of delayed skin reactivity than the decrease in antibody production in partially tolerant animals.
Pyrimidine-Specific Antibodies: Reaction with DNA's of Differing Base Compositions
Authors: Garro Anthony J. , Erlanger Bernard F. , Beiser Sam M.
Published: December 2022

The reactivity of antinucleoside antibodies with DNA was found to depend on the base composition of the DNA. Anti-thymine antibodies reacted with denatured T2 phage DNA whereas anti-cytosive antibodies did not. This was attributed to the absence of cytosine in T2 phage DNA, and to the failure of anti-cytosine to react with glucosylated hydroxymethylcytosine. DNA preparations with different base ratios were tested for their reactivity with anti-cytosine and anti-thymine antibodies. Using DNA denatured in the presence of formaldehyde, which prevented reformation of base-paired structures, the reaction of Clostridium perfringens and Micrococcus lysodeikticus DNA's with anti-cytosine and anti-thymine antibodies could be correlated with the DNA base ratios. Calf thymus DNA reacted as expected from its base ratio with anti-thymine, but not as expected with anti-cytosine. The deviation observed in the anti-cytosine reaction pattern was related to an alteration in the antigenic identity of cytosine caused by formaldehyde during denaturation.
Cyclophosphamide Inhibition of Experimental Allergic Thyroiditis and Thyroid Antibody Production in Rats
Authors: Paterson Philip Y. , Drobish Diane G. , Biddick Audrey S.
Published: December 2022

Discussion and Summary

The data (Tables I and II) are remarkably similar to our previous findings in EAE (5, 6) in that injections of CY for 2 weeks after sensitization to thyroid in adjuvant inhibited development of EAT and the production of thyroid antibody. These findings also confirm those of Salvin and Liauw (4) concerning EAT in the guinea pig. The therapeutic effects of CY when the drug was given after the EAT lesions had developed also Table IIInhibition of production of hemagglutinating (HA) anti-thyroid antibody in rats sensitized and injected with cyclophosphamide (CY)Rat StrainCY TreatmentaProportion of Rats with HA Antibody at:b15 days21 daysLewis5 mg/k0/5c0/5None5/54/5CFN (Wistar)5 mg/k0/50/5None5/54/4aDaily intraperitoneal injections of CY in doses of 5 mg/kg beginning on day of sensitization and continued through the 15th day after sensitization.bNumerator, number of rats with HA antibody titers of 1:20 or greater; denominator, number of rats sensitized and tsted for HA antibody.cDays after sensitization. agree with the results we obtained with EAE in Lewis rats (7). It is noteworthy that the lesions of EAT did not recur after CY was stopped, in contrast to the relatively prompt recrudescence of EAE under similar therapeutic conditions (manuscript in preparation).

The inhibitory effect of CY on the production of anti-thyroid antibody (Table II) provides evidence that this alkylating drug has an immunosuppressive effect on the immune response to thyroid antigens and that CY-induced inhibition of the disease has an immunologic rather than an anti-inflammatory basis. We do not consider that the inhibitory effect of CY on HA antibodies is related causally to its inhibitory effect on EAT. There is no evidence that circulating antibodies against thyroid antigens play a role in EAT in rats. Actually, the available data favor a cell-mediated pathogenesis in this species and in guinea pigs (10–12). Reported serum transfers of EAT in guinea pigs (13) and rabbits (14, 15), however, suggest that thyroid antibodies may well be important in other animal species.

Whatever the nature of the primary immune factor responsible for EAT may be in rats, CY has a profound capacity to suppress or inhibit the immunologic response to thyroid antigen. As discussed in our previous work (5–7) and by Many and Schwartz (16), the inhibitory effect of CY probably is due to elimination of rapidly proliferating antigen-reactive cells. The basis for the therapeutic effect of CY is less clear, but is likely to be due to action of the drug on inflammatory cells entering the thyroid glands, which have been shown by Kosunen and Flax (17) to be of hematogenous origin.
Antigenic Analysis of Human Heart Tissue
Authors: Espinosa Enrique , Kaplan Melvin H.
Published: December 2022

A heart-specific protein antigen previously demonstrated in both acid and saline extracts of human myocardium by double immunodiffusion was further characterized. The antigen in both saline and acid extracts exhibited closely similar or identical immuno- and physicochemical properties. In immunoelectrophoresis it had an electrophoretic mobility between that of serum α-1 and β-2 globulins, was relatively thermostable to boiling temperature, and was precipitated at 30% to 70% saturated ammonium sulfate and 20% to 70% ethanol concentration. The sedimentation coefficient by sucrose gradient ultracentrifugation was 1.8S to 2.0S. The diffusion coefficient as measured by Sephadex gel filtration ranged between 7.3 and 7.7 × 10-7 cm2/sec and the molecular radius was 27.3 to 28.8 Å. Calculations based on these values permitted estimation of an approximate molecular weight of between 20,050 and 23,500 and a frictional ratio of about 1.5. Immunofluorescent staining of heart tissue with antisera specific for heart-specific antigen showed a staining reaction related to structures in sarcolemma-subsarcolemmal sites, and to a lesser degree the cross-striations of cardiac myofibers.
Murine Thyroiditis: Importance of Adjuvant and Mouse Strain for the Induction of Thyroid Lesions
Authors: Rose Noel R. , Twarog Frank J. , Crowle A. J.
Published: December 2022

For the production of experimental autoimmune thyroiditis in the mouse comparison of two preparations of complete Freund's adjuvant showed that one, using n-hexadecane and glycerol mono-oleate with freshly harvested tubercle bacilli, was more effective in eliciting both dermal hypersensitivity and thyroid lesions than a mixture of paraffin oil and mannide mono-oleate with dried tubercle bacilli. Both preparations were of comparable efficiency in eliciting thyroid-specific antibodies detected by passive hemagglutination. With either adjuvant, randomly bred CF-1 mice were consistently more susceptible to the induction of thyroid lesions than were inbred C3H mice. When the paraffin oil adjuvant was used, C3H mice developed no lesions despite high titers of circulating antibody.
Degranulation of Human Basophil Leukocytes by Anti-γE Antibody
Authors: Ishizaka Teruko , Tomioka Hisao , Ishizaka Kimishige
Published: December 2022

Leukocytes from normal individuals were incubated with 125I-labeled anti-γE for histamine release and the cells remaining after the reaction were examined by auto-radiography. The results showed that anti-γE degranulated basophil leukocytes. No serum component was essential for the degranulation of basophils. It was also found that ethylenediamine tetraacetate (EDTA), cyclic-AMP, theophylline and diethylcarbamazine, which suppressed anti-γE-induced histamine release from leukocytes, inhibited degranulation of basophils as well. The results indicated that the reaction between anti-γE and basophil-bound γE is responsible for both histamine release from the cells and their degranulation, and that mechanisms of these two reactions share common enzymatic pathways.
The Effect of Immunoregulatory α Globulin (IRA) on Antigen-Mediated Macrophage Immobilization in vitro
Authors: Davis Robert C. , Cooperband Sidney R. , Mannick John A.
Published: December 2022

Both human and guinea pig immunoregulatory α globulin (IRA) interfered with the in vitro immobilization of peritoneal macrophages from sensitized guinea pigs by specific antigen. When migration inhibitory factor (MIF) was induced in vitro by exposure of sensitized guinea pig lymphocytes to specific antigen and was then added to cultures of peritoneal macrophages from non-sensitized animals, IRA was unable to block the inhibition of macrophage migration caused by MIF. These results indicate that IRA interfered with antigen-specific immobilization of peritoneal macrophages by interaction with sensitized lymphocytes in the peritoneal cell population and did not block the response of macrophages to MIF.
Antibody Plaque-Forming Cells in Mice Immunized with Human γ Globulin (HGG)
Authors: Hege John S. , Epstein Wallace V.
Published: December 2022

Mouse spleen cells releasing antibody directed against human γ globulin (HGG) were enumerated using the carbodiimide modification of the Jerne antibody plaque technique. Intraperitoneal administration of mouse secondary response anti-HGG serum 1 day after primary HGG immunization resulted in an 86% decrease in numbers of anti-HGG plaque-forming cells (PFC) determined 6 days after immunization. Human anti-globulin preparations (rheumatoid factors) given intraperitoneally caused a 37% HGG-PFC decrease. In vitro plaque inhibition and serologic studies indicated that the mouse anti-HGG serum and the antibodies released by the plaque-forming cells were directed against antigenic determinants present on native HGG, whereas the rheumatoid factor preparations were directed against antigens characteristic of aggregated HGG. Thus HGG-PFC suppression by intraperitoneal rheumatoid factor may not be immunologically specific at the level of antigenic determinants.
Strain-Dependent Differences in the Specificity of Antibody Responses toward Lysozyme
Authors: Mozes Edna , Maron Elchanan , Arnon Ruth , Sela Michael
Published: December 2022

Most mouse strains responded well to immunization with lysozyme, but only certain strains produced antibodies against a conjugate consisting of the “loop” region (residues 60–83) of lysozyme attached to a synthetic polymer. The latter strains, which did not respond to the above synthetic conjugate, were also unable to produce antibodies specific for the “loop” region when injected with intact lysozyme. The F1 hybrid between low and high responders showed an intermediate response. It appears that the immune response to the natural determinants of proteins is genetically controlled.
Effect of Thymus-Derived Lymphocytes on Amount and Affinity of Anti-Hapten Antibody
Authors: Gershon Richard K. , Paul William E.
Published: December 2022

In recent years two classes of lymphocytes have been shown to participate in specific antibody responses in mice. One class of these cells, which has migrated through the thymus and is consequently referred to as “thymus-derived,” does not secrete detectable quantities of antibody but nevertheless interacts with antigen in a specific way. As a consequence of this interaction, the second class of specific cells, the bone marrow-derived lymphocytes, are more easily stimulated. The latter cells are the direct precursors of antibody-secreting cells (1–3).

Antibody affinity is a term used to describe the energy of interaction of antigen, usually hapten, and antibody. It is, of course, a character determined by the structure of the antibody (and that of the ligand); affinity should therefore be a marker of the bone marrow-derived cell population, which is directly responsible for the production of the antibody.
Regulation of Homocytotropic Antibody Formation in the Rat
Authors: Tada Tomio , Okumura Ko
Published: December 2022

Homocytotropic antibody formation against dinitrophenylated Ascaris extracts (DNP-As) was selectively suppressed by the passive administration of homologous antibody against the same antigen. Unrelated antiserum or cross-reacting antibodies against haptenic group or carrier determinants had no suppressing effect. The suppression was preferentially directed to the homocytotropic antibody response, while the hemagglutinating γM antibody formation was unaffected. The effect was most significant when the antibody was administered simultaneously with, or a few days after, the initial antigen injection, whereas previous administration was less effective. The synthesis of homocytotropic antibody was terminated by the passive administration of antibody at the time when the PCA titer was at the maximum. The suppressive activity was detected in the 7S γG fraction of hyperimmune antiserum, while the early 19S or intermediate fractions had little activity. Heterologous antibody to the same antigen showed a similar inhibitory effect, but about twice as much antibody was required for the same degree of suppression. The results indicate the presence of so-called “feed-back” regulation in the homocytotropic antibody response. The possible mechanisms and biologic significances of this regulation are discussed.
The Effect of Actinomycin D on the Lethality of Poly I:C
Authors: Pieroni Robert E. , Bundeally Amina E. , Levine Leo
Published: December 2022

Poly I:C, a synthetic double-stranded RNA composed of polyinosinic and polycytidylic acids, has become the subject of intense investigation because of its capacity to induce interferon formation and exert antineoplastic activity in experimental animals (1–4). It is currently being evaluated for possible antitumor activity in humans (4). A number of recent reports have shown that poly I:C simulates bacterial endotoxin in many of its activities (2–5), and shares several of the toxic properties of endotoxin (2, 6–9). For example, in addition to their capacity to stimulate interferon production (2), both poly I:C and endotoxin are pyrogenic (6) and embryotoxic (7), and provoke the Shwartzman phenomenon (8). It has been suggested that an inherent relationship exists between interferon induction and toxicity (2, 9).

A further similarity in the action of poly I:C and endotoxin is the observation that several agents, such as bacillus Calmette-Guérin (BCG) vaccine, lead acetate, and zymosan, which augment the lethality of endotoxin, exert a similar effect on poly I:C (2).
Immunochemical Analysis of a Galactosamine-Rich Teichoic Acid of Staphylococcus Aureus, Phage Type 187
Authors: Karakawa W. W. , Kane J. A.
Published: December 2022

A cell-wall carbohydrate consisting of ribitol, phosphorus, N-acetylgalactosamine and d-alanine was isolated from seven strains of Staphylococcus aureus, phage type 187. Immunochemical analysis indicated that N-acetylgalactosamine is the immunodominant determinant of this carbohydrate. Approximately 55% of the quantitative precipitin reaction between the carbohydrate and homologous antiserum was inhibited by 10 mg/ml of N-acetylgalactosamine, whereas N-acetylglucosamine was ineffective as an inhibitor at the same concentration. Evidence was presented that ester-linked d-alanine is also an antigenic determinant of the 187 carbohydrate.
Variable Effects of Anti-Lymphocyte Serum on Humoral Antibody Formation: Role of Thymus Dependency of Antigen
Authors: Kerbel R. S. , Eidinger D.
Published: December 2022

The immunosuppressive effects of anti-lymphocyte serum (ALS) administered alone, or in conjunction with adult thymectomy, were examined in mice subsequently immunized to one of six different antigens: sheep erythrocytes (SRBC), goose erythrocytes (GRBC), rat erythrocytes (RRBC), keyhole limpet hemocyanin (KLH), horse spleen ferritin (HSF), and polyvinyl pyrrolidone (PVP). The thymus-dependency of the immune responses to most of these antigens was known to vary considerably and the antigens were chosen for this reason. A striking range of differences manifested by ALS alone, or in conjunction with thymectomy, was observed, ranging from almost total suppression of immune responsiveness to some antigens (GRBC and SRBC), to moderate suppression of others (HSF and RRBC), to enhancement (PVP) or both initial 19S antibody enhancement and subsequent 7S antibody suppression (KLH). The results support the view that the immunosuppressive effects of ALS on humoral antibody formation are highly variable and inconsistent, that a major factor causing this variability is the thymus-dependency of antigen, and further, that the concept of thymus-dependency of antigens is entirely a relative one.
The Mechanism of Antibody-Induced Stimulation and Inhibition of the Immune Response
Authors: Dennert Gunther
Published: December 2022

The influence of passively administered specific IgG and IgM antibodies on the immune response of mice to sheep erythrocytes is described. The stimulation of the immune response to a given dose of antigen by partially purified IgM is proportional to the square root of the concentration of antibody injected. Labeling experiments show that this stimulation is caused by an enhanced concentration of antigen in the spleen. Low doses of IgG produce the same effects, namely antigen concentration in the spleen and stimulation of the number of plaque-forming cells. But in contrast to IgM, high doses of IgG do not concentrate the antigen in the spleen and severely inhibit the immune response. It is therefore suggested that antibody may have two effects: IgM and low doses of IgG stimulate an immune response by concentrating the antigen, whereas high doses of antibody inhibit by coating the antigen or by competing with the antigen receptor sites.
Specificity and Immunoglobulin Characteristics of Autoantibodies in Acquired Hemolytic Anemia
Authors: Vos Gerard H. , Petz Lawrence D. , Hugh Fudenberg H.
Published: December 2022

In a study of 55 red cell eluates obtained from patients with acquired hemolytic anemia of the warm type (AHA), it was established that antibodies of varying Rh specificities can be involved in the disease. Some were specifically reactive against well defined red cell antigens of the Rh system (anti-e, anti-C, and the like), some against all normal Rh red cells (anti-nl), some against partially deleted Rh red cells (anti-pdl), and some against fully deleted Rh red cells (anti-dl).

Antibodies against well defined Rh antigens (CDEce) were not often found in the red cell eluates. In contrast, anti-nl, anti-pdl and anti-dl autoantibodies were frequently present in the red cell eluates.

The demonstration of serum complement components on the red cells of patients seemed to be associated exclusively with autoantibodies of multiple immunoglobulin classes or multiple red cell specificities. The structural heterogeneity of immunoglobulin types (IgG, IgM and IgA) for the various varieties of autoantibodies (anti-nl, anti-pdl and anti-dl) can be pictured as arising from multiple antibody-forming cell lines.

The findings suggest that the initial site of action of autoantibody development in AHA results from a defect of the structural composition of the Rhesus genome, which is thereafter rejected by a normal immune mechanism. The subsequent development of a more generalized auto-immune abnormality involving the formation of multiple autoantibody-forming cell lines does not necessarily indicate the establishment of an aberrant immune apparatus.
Deposition of Immune Complexes in the Kidneys of Mice Infected with Lactic Dehydrogenase Virus
Authors: Porter David D. , Porter Helen G.
Published: December 2022

Mice showed renal glomerular deposition of immunoglobulin and complement as early as 7 days after infection with lactic dehydrogenase virus, concomitant with the appearance of circulating antibody. Immunoglobulin eluted from the kidneys contained virus-specific antibody. A minimal histologic alteration of glomeruli was observed despite the immune complex deposition.
Pharmacologic Inhibition of the Antigen-Induced Release of Histamine and Slow Reacting Substance of Anaphylaxis (SRS-A) from Monkey Lung Tissues Mediated by Human IgE
Authors: Ishizaka Teruko , Ishizaka Kimishige , Orange Robert P. , Frank Austen K.
Published: December 2022

Evidence was presented that agents capable of increasing intracellular levels of cyclic adenosine 3′,5′-monophosphate (AMP) also inhibit the direct, antigen-induced and reversed-type release of histamine and slow reacting substance of anaphylaxis (SRS-A) from monkey lung fragments sensitized in vitro with human atopic serum and E myeloma protein, respectively. Beta-adrenergic agents such as isoproterenol and epinephrine, which interact with β-receptors in tissues and thus activate adenyl cyclase, inhibited the release of both chemical mediators, and this inhibition was prevented by the β-adrenergic blocking agent, propranolol. The methylxanthine, theophylline, which acts as a competitive inhibitor of cyclic AMP phosphodiesterase, also inhibited the release of both histamine and SRS-A. A marked synergism was observed when β-adrenergic agents and theophylline were used together. Finally, an alkylated derivative of cyclic AMP, dibutyryl cyclic AMP, also inhibited the release of both mediators in a dose-response fashion. Agents that increase cellular levels of cyclic AMP appeared to inhibit the release of histamine and SRS-A at some point subsequent to antigen-antibody interaction and prior to the release of the mediator and in acting at such a site permitted desensitization of the sensitized tissues by specific antigen. Diethylcarbamazine was also found to inhibit the release of both histamine and SRS-A from sensitized monkey lung tissues. This agent demonstrated a remarkable synergism with the β-adrenergic agent isoproterenol, but the inhibitory activity of diethylcarbamazine was not prevented by the β-adrenergic blocking agent propranolol.
Variation in Immunosensitivity of SV40-Transformed Hamster Cells
Authors: Tevethia S. S. , McMillan V. L. , Kaplan P. M. , Bushong S. C.
Published: December 2022

Two cell lines were derived from a hamster tumor induced by SV40 which differ in their ability to form tumors in SV40-immunized animals. Both lines contained SV40 T and S antigens. The immunosensitive cell line (H-50 IS) was rejected by SV40-immunized animals, whereas the immunoresistant cell line (H-50 IR) produced tumors in SV40-immunized animals. H-50 IR cells contain SV40-specific transplantation antigens since they immunized hamsters against a challenge by the immunosensitive line; these cells were highly transplantable, and tumors appeared earlier than did those produced by the H-50 IS line. Both cell lines grew at similar rates in vitro, and were inhibited equally by SV40 immune sera in the colony inhibition test.
Distribution of 19S and 7S IgM Antibodies during the Immune Response in the Nurse Shark
Authors: Voss Edward W. , Michael Sigel M.
Published: December 2022

19S and 7S IgM nurse shark antibodies were purified by immunoadsorption specific for the 2,4-dinitrophenyl haptenic group. Purification of antibodies from bleedings at various times after immunization revealed that the two forms were present in varying proportions dependent on the time elapsed after the administration of antigen. Late bleedings showed elevated levels of 19S IgM, suggesting a final enrichment for the more efficient antibody molecule.
Immunosuppressive Effects of Incomplete Freund's Adjuvant on Hemolytic Antibody-Forming Cells in Spleens of Immunized Mice
Authors: Chakrabarty Asit K. , Friedman Herman
Published: December 2022

Intraperitoneal injection of mice with an emulsion of incomplete Freund's adjuvant before challenge immunization with sheep erythrocytes markedly inhibited the appearance of 19S and 7S hemolysin-forming cells. The time of administration of the oil adjuvant, relative to the day of immunization, was an important factor. Mice injected with 0.5 ml of oil emulsion 1 to 4 days before immunization had 85% to 95% fewer plaque-forming cells/spleen than did untreated controls. Injection of oil the same day or 5 to 6 days before immunization resulted in a slight to moderate immunologic depression. Imunologic suppression persisted in these animals throughout the time when antibody-forming cells were appearing in spleens of control animals. Both the magnitude of the response and the rate at which antibody-forming cells appeared were suppressed. Oil injection 7 days or more before immunization had no effect. The serum antibody response to the red blood cells was depressed during the 1st week after immunization, but generally increased to control titers by day 12. Most of the serum antibody in mice treated with oil was resistant to mercaptoethanol treatment, even late in the response. The results of these studies suggest that immunosuppression induced by incomplete Freund's adjuvant may be similar to that occurring in mice inoculated with classic RES blockading agents such as colloidal carbon or Thorotrast.
The Number of Antibody-Producing Cells in the Parathymic Lymph Nodes and the Spleen Following Intraperitoneal Injection of Antigen
Authors: Hirsh Dwight C. , Steward John P. , Amkraut Alfred A.
Published: December 2022

Following i.p. injection of antigen in the rat, the parathymic lymph nodes are α major, if not the major, site of antibody-producing cells. Though they contain only one-tenth the number of nucleated cells, these nodes have essentially as many antibody-forming cells as does the entire spleen. Technical limitations that occur when the spleen is employed for such studies are also minimized or absent when the PLN are used to determine the number of PFC by the modified Cunningham technique. Thus, the parathymic lymph nodes should receive increased attention in investigating the cellular kinetics of the immune response.
The Effect of Sensitized Lymphocytes on Peritoneal Exudate Macrophages in the Guinea Pig
Authors: Sonozaki Hidekichi , Cohen Stanley
Published: December 2022

The injection of antigen into the peritoneal cavity of delayed hypersensitive guinea pigs bearing peritoneal exudates leads to a marked reduction in the macrophage content of these exudates. Lymphocytes from immunized donors can confer this property on glycogen-induced exudates in non-immunized recipients. The reaction appears to represent an in vivo analog of the well-known migration inhibition reaction.
Cross-Reactions between 2,4-Dinitrophenyl and 5-Acetouracil Groups
Authors: Underdown Brian J. , Eisen Herman N.
Published: December 2022

Rabbit and guinea pig antibodies to the 2,4-dinitrophenyl (DNP) group were separated into two subsets, one of which (subset 1) precipitated with 5-acetouracil-human serum albumin (5AU-HSA). The two subsets had similar affinities for DNP ligands, but only the subset that precipitated with 5AU-HSA had measurable affinity for the 5AU determinant. The precipitation of anti-DNP antibodies by 5AU-HSA was observed only in sera containing antibodies with high average affinity for the homologous (DNP) determinant; these antibodies had much lower average affinity for the 5AU determinant (10,000- to 100,000-fold less). The affinity of anti-DNP antibodies for a number of pyrimidines, purines and related compounds was also very weak as compared with that for the DNP determinant. Cross-reactions of anti-5AU antibodies, induced by immunization with 5AU-proteins, corresponded roughly to those for anti-DNP antibodies, i.e., the affinity of anti-5AU antibodies was much greater for 5AU than for DNP. In spite of the ease with which these weak cross-reactions with “strange” (i.e., structurally unrelated) ligands were demonstrated, differences in affinity of antibody for homologous and strange ligands were pronounced. Thus, anti-DNP and anti-5AU antibodies had the high level of specificity expected of antibodies in general. The results are relevant to some of the difficulties in interpreting weak binding reactions displayed by many myeloma proteins.
Pathogenesis of Experimental Allergic Orchitis
Authors: Tung Kenneth S. K. , Unanue Emil R. , Dixon Frank J.
Published: December 2022

Experimental allergic orchitis (EAO) was passively transferred among histocompatible guinea pigs (strain 13) by lymph node cells from animals immunized with sperm in complete Freund's adjuvant. Systemic injection of sensitized lymph node cells inconsistently produced at best mild lesions in recipients. However, local transfer of cells into the interstitium of the testes initiated severe changes of EAO within 4 to 8 days. The lesion, identical to that observed in the primary disease, was characterized by an intratubular infiltration by monocytes that preceded degeneration of the germinal epithelium. The monocytes were of host origin and their precursors were radiosensitive. The lymph node cells had to be live and from a guinea pig immune to sperm for transfer of EAO.
Pathogenesis of Experimental Allergic Orchitis
Authors: Tung Kenneth S. K. , Unanue Emil R. , Dixon Frank J.
Published: December 2022

Guinea pigs with experimental allergic orchitis show an acute inflammation in the rete testis and epididymis. At these sites anti-sperm antibody is bound to sperm. The role of antibody in the production of disease was investigated. It was found that guinea pigs immunized to sperm antigens in complete Freund's adjuvant have autoantibodies in serum which bind in in vitro tests to the surface membrane of immature and mature sperm cells. The anti-sperm antibody when injected into normal guinea pigs, either systemically or in the interstitium of the testis, binds to sperm inside the rete testis and produces a mild acute inflammatory reaction at that site. Also, 125I-labeled IgG from normal guinea pigs when injected into the testis can cross the wall of the rete testis into the lumen. Anti-sperm antibody and normal Ig, on the other hand, do not appear to penetrate the seminiferous tubules. The main barrier for the crossing of Ig into the seminiferous tubules may be the layer of cells external to the basement membrane. Thus, antibodies to basement membrane injected locally do not bind to the tubular basement membranes. Hence, the results suggest that antibody, although not directly involved in the production of aspermatogenesis, can produce an acute inflammatory reaction by binding to the sperm in the sperm passage system.
Cross-Reacting and Monotypic T Antigens of Nephritogenic Pyoderma Streptococci: The Type 56 System
Authors: Bisno Alan L. , Svartman Mauri , Stollerman Gene H.
Published: December 2022

T antigens of “skin strains” of group A streptococci represent important epidemiologic markers for the study of acute glomerulonephritis. Although “skin strains” react with standard reference antisera to T-type antigens, agglutination reactions are in the form of “patterns,” indicating cross-reactivity with several reference antisera. “Skin strains” have been difficult to identify with available anti-M protein-typing sera because many of these strains appear to belong to M-types hitherto unrecognized. We isolated a new nephritogenic pyoderma type, M56, in which T antigens produced many confusing cross-reactions with standard reference sera. M56 strains cross-reacted characteristically with the common “skin” pattern, 3/13/B3264, but also with reference T28 antiserum. It was possible to remove selectively the cross-reactive type 56 antibody without affecting reactions of the reference sera with their homologous serotypes. We then set out to determine whether such “new” strains have their own unique T antigen by which they could readily be identified by properly prepared antiserum. After appropriate absorptions we prepared a T56 slide-agglutinating antiserum that identified M56 strains in various parts of the United States and in Israel. This widely distributed serotype would have been misidentified with currently available international reference sera. The monotypic system of M- and T-type 56, like the “Redlake” M49, T49, appeared to be at least potentially nephritogenic, to be widely distributed geographically and to contain unidentified cross-reacting T antigens.
Antigenic Competition Between Heterologous Erythrocytes
Authors: Gershon Richard K. , Kondo Kazunari
Published: December 2022

Passively administered anti-sheep red blood cell (SRBC) antibody inhibited the antibody response to an inoculation of 5 × 108 SRBC, although the antigenic competition that results from this immunization was unaffected. Reducing the immunizing dose to 5 × 106 SRBC, on the other hand, resulted in a vigorous antibody response but no antigenic competition. Thus, passive antibody is capable of blocking the antibody response by means other than simple neutralization of antigen. However, by increasing the amount of passive antibody both the antibody response and antigenic competition were eliminated, and therefore antigen neutralization may also occur. The differential effects of passive antibody administration and dose reduction were considered in the light of previously demonstrated thymic dependency of antigenic competition. It was concluded that passive antibody may allow antigen to interact with thymus-derived cells (T cells) while preventing interactions with bone marrow-derived cells (B cells), the precursors of the antibody forming cells.
The Enhancement of Rabbit Anti-BSA IgE, Homocytotropic Antibody Production by Corynebacterium Parvum Strain 10387
Authors: Pinckard R. Neal , Halonen Marilyn
Published: December 2022

The adjuvant properties of Corynebacterium parvum strains 10387, 10390 and 4781 were studied with respect to their ability to facilitate the induction of rabbit anti-bovine serum albumin (BSA) homocytotropic antibody. Ten milligrams dry weight of heat-killed suspensions of C. parvum were injected i.v. 6 days prior to i.v. injections of 5 mg BSA; booster i.v. injections of 5 mg BSA were given 28 and 56 days later. Every 7th day sera were tested for homologous passive cutaneous anaphylactic (PCA) activity. Nine of 12 rabbits that received C. parvum 10387 produced detectable anti-BSA homocytotropic antibody. In contrast only 2 of 12 rabbits given 10390 and none of 12 rabbits in either the group given 4781 or in the control group produced detectable anti-BSA homocytotropic antibody. Physicochemical studies indicated that the homocytotropic antibody was similar to the rabbit IgE class of immunoglobulin. Homologous PCA activity was found only in the 0.10 M NaCl fractions eluted from DEAE-cellulose and was not associated with rabbit IgG, IgA or IgM. The homologous PCA antibody was partially heat-inactivated at 56°C for 4 hr and was completely destroyed by reduction and alkylation; its average molecular weight was estimated to be 240,000. C. parvum strain 10387 appears to have unique adjuvant properties for facilitating the development of rabbit anti-BSA IgE, homocytotropic antibody.
Graft-vs-Host Reaction in a Xenogeneic Combination: Mechanism of the Reaction
Authors: Constantine Rodrique I. , Nakouz Joseph , Maclean Lloyd D. , Gordon Julius
Published: December 2022

The level of host immunosuppression that allowed development of a localized graft-vs-host (GVH) reaction in a xenogeneic combination was shown to be critical. Immunosuppression had to be sufficient to allow donor cell proliferation, yet permit survival of a low level of host mononuclear cells in the circulation. Furthermore, it had to be of short duration to allow recovery of the immunocompetence of the host in 4 to 6 days. These observations, using cyclophosphamide and anti-lymphocyte serum as immunosuppressive agents and normal and primed donor cells in allogeneic and xenogeneic GVH reactions, suggested that the localized xenogeneic GVH reaction is a composite of an initial GVH followed by a host-vs-graft (HvG) reaction.
Induction of Acquired Tolerance in Neonatal Opossums
Authors: Major Pervis C. , Burrell Robert
Published: December 2022

The extrauterine availability of what are essentially embryos makes neonatal opossums the animals of choice for studying acquired tolerance. Block (1) discussed the immunologic and hematopoietic characteristics of the opossum and described experiments concerned with the development of immunologic capacity in an embryonic stage which would have been impossible to perform in fetuses from eutherian mammals. La Plante et al. (2) were able to perform skin allografts in neonatal opossums. Such grafts were not rejected by neonates less than 12 days old. When five opossums with permanently surviving allografts were regrafted from the original donor and from a control third party donor, three of the animals retained the allograft from the original donor for over 90 days whereas all control grafts were rejected within 20 days. No change occurred in the original graft in any of the animals.

The present report is concerned with the induction of tolerance in such animals to “laboratory” antigens.
Antigenic Relationship Between Human IgE Immunoglobulin and Rat Homocytotropic Antibody
Authors: Liakopoulou Athanasia , Perelmutter Lewis
Published: December 2022

Homocytotropic antibody was produced in albino Wistar rats following immunization with bovine serum albumin (BSA) and killed Bordetella pertussis. Peritoneal mast cells from the sensitized animals obtained between the 13th and 15th days after primary injection underwent characteristic antigen-induced morphologic changes when they were brought into contact with BSA, anti-human IgE (anti-IgE), or antihuman Bence Jones (anti-BJ) sera. Similarly, lung preparations from the sensitized rats released histamine in vitro upon challenge with the same antigens. Neither the cells nor the lung tissue responded to anti-human IgG (anti-IgG) serum. In addition, cells and lung preparations from normal animals were not altered morphologically nor released histamine on incubation with either BSA or anti-human immunoglobulin sera. The percentage of morphologically altered cells and the amount of histamine released from the sliced lung suspensions by anti-IgE or anti-BJ (κ) sera were comparable to those induced by specific antigen toward which the animals were sensitized. These results indicated that rat homocytotropic antibody has antigenic determinants in common with the heavy chain of human IgE immungolobulin and the Bence Jones protein.
Augmentation of Pha Responsiveness in Mixed Thymus-Marrow Cultures
Authors: Winkelstein Alan
Published: December 2022

Only minimal increments of 3HTdr uptake were demonstrated in PHA-stimulated cultures of normal guinea pig thymocytes. Bone marrow cultures from both normal and erythroid suppressed animals failed to proliferate in response to this nonspecific stimulus. However, the combination of thymic and marrow cells resulted in significant augmentation of PHA responsiveness. Maximum synergistic activity occurred when thymus and marrow cells were cultured in equal amounts. The in vitro behavior of thymus and marrow cells alone and in combination is consistent with their immunologic activity in the intact animal.
Size and Density Analysis of Rodent Lymphoid Cells
Authors: Aisenberg Alan C. , Murray Caroline
Published: December 2022

Rat and mouse lymphoid cells have been fractionated on discontinuous bovine serum albumin gradients and analyzed for size with the Coulter counter. The thymocyte is smaller and denser than the small lymphocyte of thoracic duct lymph. If the major fraction of thoracic duct lymphocytes is derived from small thymocytes, then thymus cells must enlarge and become less dense either before or after their release into the circulation. Hemolysin-forming cells of the spleen are much less dense than either small lymphoid cell, but there is no apparent difference between 7S and 19S hemolysin-formers at any time during the 1st month after antigenic stimulation.
Precipitin Reactions of Clq with Various γ Globulins and Anionic Macromolecules
Authors: Agnello V. , Winchester R. J. , Kunkel H. G.
Published: December 2022

Recently a gel diffusion method has been established for demonstrating C1q precipitin reactions with aggregates or complexes of γ globulin. In this system the marked affinity of aggregated γG3 for C1q is very evident when compared to the reactions of γG1 and γG2 aggregates and is consistent with the known affinity of the monomeric proteins for C1q: γG3 > γG1 > γG2. In contrast, however, to the affinity studies with monomeric γG4 which show no combination of this protein with C1q, aggregates of some γG4 globulin do precipitate with C1q in gel diffusion. These aggregates are unusual in that they are not anticomplementary. This situation is not unique since certain anionic substances such as DNA precipitate strongly with C1q in gel diffusion but do not have a commensurate anticomplementarity in vitro or in vivo.

C1q precipitin reactions in gel diffusion have been found useful in detecting γ globulin complexes in pathologic fluids in certain immune complex diseases.
Leukocyte-Mobilizing Factor: A New Biologic Activity Derived from the Third Component of Complement
Authors: Rother K.
Published: December 2022

To recognize leukocyte-mobilizing activity, a simple test system was developed. It consisted of a rat or guinea pig femur perfused at a steady rate with medium 199. Leukocyte-mobilizing factor (LMF) was recognized by an increase in the number of cells in the effluent following addition of the test substance to the perfusate. LMF was found in the supernatants of the reactions of sensitized erythrocytes or other antigen-antibody complexes and the sera of either (1) rabbit, (2) guinea pig, (3) mouse, (4) rat or (5) the human. Similar results were obtained when C6-defective rabbit serum (Cdef) or C5-defective mouse serum was used instead of the reactants 1–5. LMF was also observed when purified rabbit β1C-globulin was incubated with functionally pure C1, C4 and C2, but not if any one of the four reactants was absent from the mixture. At pH 6.5 and 20°C, LMF was not precipitated from activated serum in 3.2 M ammonium sulfate.
Complement-Derived Leukotactic Factors in Human Synovial Fluids
Authors: Ward P. A. , Zvaifler N. J.
Published: December 2022

More than half the synovial fluids from humans with rheumatoid arthritis contain leukotactic activity for rabbit neutrophils. By ultracentrifugal analysis and antibody suppression techniques C and cleavage products of C5 have been identified as the responsible factors. Approximately half these fluids also contain an enzyme, possibly derived from lysosomal granules of neutrophils, capable of producing leukotactic cleavage products from C5 at neutral pH. Synovial fluids from patients with osteoarthritis or systemic lupus erythematosus are usually negative for leukotactic activity. Fluids were also studied from patients with inflammatory, non-rheumatoid arthritis, associated with spondylitis, Reiter's syndrome, ulcerative colitis, rheumatic fever and ill-defined arthritic states. Approximately half of these fluids were leukotactically positive, containing activity ascribable to cleavage products of C3, with sedimentation velocities of 4S or less. Many of these fluids also contain a C3-cleaving factor capable of producing additional leukotactic activity.
C5a: A Chemotactic Factor for Mononuclear Leukocytes
Authors: Snyderman R. , Shin H. S. , Hausman M. S.
Published: December 2022

Cleavage of guinea pig C5 results in the release of a biologically active fragmentation product (C5a) which enhances vascular permeability, contracts smooth muscle and is chemotactic for guinea pig and rabbit polymorphonuclear leukocytes (PMNs). Since C5a apparently affects a number of cell types involved in the acute inflammatory response, experiments were performed to determine if C5a was chemotactic for mononuclear leukocytes (MNL). Chemotactic activity was quantitated in modified Boyden chambers with glycogen-stimulated guinea pig peritoneal exudates as the source of MNL. Purified guinea pig C5 cleaved by trypsin, or by , as well as purified guinea pig C3 cleaved by trypsin, or by , were tested for chemotactic activity. Cleavage of C5, but not C3, resulted in the production of chemotactic activity for MNL, with activity detected in solutions containing as little as 3.5 µg of cleaved C5/ml.
Hemolytic Activity of the Reduction Products of Rabbit IgM Antibody
Authors: Kishimoto T. , Ikeda M. , Onoue K.
Published: December 2022

Our previous experiments on anti-hapten rabbit IgM antibody have shown that the 7S subunit and peptic dimer fragment of the antibody are divalent. These fragments agglutinated red cells coated with antigen and their hemagglutinating activity was comparable to that of IgG antibody on a weight basis. In the present experiment, hemolytic activity of the 7S subunit was studied. Specifically purified IgM antibody was subjected to mild reduction in 0.03 M cysteine followed by alkylation. The 7S subunit and its dimer were isolated by gel filtration. Both fragments maintained inter-µ-chain disulfide bond(s). Hemolytic activity of the 7S subunit was comparable to that of native IgG antibody. The dimer of the subunit had higher hemolytic activity than did the 7S subunit or IgG antibody on a weight basis. The results suggest that high hemolytic activity of the original IgM antibody is due to polyvalency of the antibodies.
Sites and Mechanisms of Complement Interaction with Guinea Pig Immunoglobulins
Authors: Sandberg A. L. , Osler A. G.
Published: December 2022

Guinea pig γ1 immunoglobulins incubated as preformed aggregates with undiluted guinea pig serum initiate their attack on the C sequence at C3, apparently bypassing C1, C4, and C2. This C interaction site is located on the F(ab′)2 fragment as demonstrated by the full retention of activity after digestion with pepsin. γ2 Immunoglobulins seem to possess two C interaction sites, one on the Fc fragment and the other on the F(ab′)2 fragment. Pepsin digestion of the γ2 antibodies reduced their C-fixing activity and also changed their mode of C interaction. Whereas the intact molecule utilized all nine C components, the F(ab′)2 fragment no longer reacted with C2 but diminished the activity of late components. Both types of immunoglobulins utilized C more efficiently at 37°C than at 4°C when incubated as preformed aggregates. However the soluble γ2 complexes exhibited enhanced C consumption at 4°C.
Specific Isolation of B Lymphocytes by Means of Their Receptor for Antigen-Antibody-Complement (Ag-Ab-C) Complexes
Authors: Eden A. , Bianco C. , Nussenzweig V.
Published: December 2022

A population of lymphocytes (CRL) from many mammalian species including man has a receptor for Ag-Ab-C complexes. CRL interact with sheep red blood cells (E) coated with antibody (A) and complement (C) forming rosettes (Bianco, C. and Nussenzweig, V., J. Exp. Med., 132: 702, 1970). In the mouse, CRL are part of the population of B lymphocytes (Dukor, P., Bianco, C. and Nussenzweig, V., in preparation). The interaction between CRL and EAC appears to be mediated by a receptor for modified C3 on the lymphocyte membrane. Papain fragments of rabbit γG anti-mouse C3 competitively inhibit and revert the binding of EAC to CRL. Based on this finding, a method has been devised to purify CRL, which consists of: 1) incubation of EAC with lymphocytes for rosette formation; 2) separation of rosettes by sedimentation in a linear bovine serum albumin (BSA) gradient (The purified clusters contain less than 5% free leukocyte contamination); 3) treatment of the clusters with papain fragments of anti-C3 antibodies in order to dissociate EAC from CRL; 4) separation of CRL from EAC by ultracentrifugation in a discontinuous BSA gradient.