bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical and Immunologic Properties of Rubella Antigens
Authors: Schmidt N. J. , Lennette E. H. , Gee P. S. , Dennis J.
Published: December 2022

The physical and immunologic relationships between infectious rubella virus, the hemagglutinin (HA) and the two complement-fixing (CF) antigens were investigated. The HA eluted from Sephadex G 200 together with the infectious virus and the large-particle CF antigen, and also equilibrated with these two antigens in sucrose gradients at densities of 1.21 to 1.19 g/ml. No HA activity was associated with the small-particle CF antigen. Both HA and infectivity were absorbed into chick erythrocytes, suggesting that the HA is a part of the infectious moiety, but a variable proportion of the large-particle CF antigen was not absorbed onto erythrocytes. Antisera produced by immunization of rabbits with large- or small-particle antigens showed reciprocal crossing in CF tests. Immunization of rabbits with the noninfectious small-particle antigen elicited the formation of neutralizing and HI antibodies as well as CF antibodies. Large- and small-particle CF antigens were also indistinguishable in tests with human sera from natural rubella infections.
Separation of New Skin Reactive Antigens from Dwarf Ragweed Pollens
Authors: Goldfarb A. R.
Published: December 2022

The fractionation of dwarf ragweed pollen extracts has been investigated extensively (1–4) and the results of these studies have been reviewed (5). The principal products, isolated previously, contained one common antigen which was described by King and Norman (3) and which they called antigen E (AgE). King's product, IV-C (3) and Robbins' most recent products, IVRBB and IVRCC (6), contained AgE exclusively as determined by quantitative immunodiffusion methods. On the other hand, Goldfarb's product, pool C, contained 80% AgE. These three sets of products showed significant chemical and physicochemical dissimilarities. The amino acid analyses of IV-C, IVRBB and IVRCC were different in respect to methionine, half-cysteine, proline and tryptophan content. Pool C contained 11% arabinose whereas the other two products were reported to contain 1% or less. On the assumption that arabinose was an impurity, we attempted to extract AgE from pool C by a variety of methods, including the procedure used by King to separate IV-C.
The Local Nature of Immunity in Tuberculosis, Illustrated Histochemically in Dermal BCG Lesions
Authors: Dannenberg Arthur M. , Meyer Olivia T. , Esterly John R. , Kambara Takeshi
Published: December 2022

Summary and Conclusions

Dermal BCG lesions and the subsequently developing cellular immunity and allergy were evaluated periodically in rabbits with the following procedures: a) measurements of the lesions during growth and regression, b) tuberculin tests, and c) biopsies of the lesions for histology, histochemistry and enumeration of acid fast bacilli. Certain sections were stained for both bacilli and β-galactosidase activity.

Macrophages were the most prominent cell type found in the lesions, although other cells especially PMN and lymphocytes were present in varying numbers. Macrophages developed into first immature epithelioid cells and then mature ones under the stimulus of tubercle bacilli and their products. This development was accompanied by a decrease in the number of bacilli present and a marked increase in certain enzymes, namely the lysosomal enzymes: β-galactosidase, acid phosphatase and β-glucuronidase, and the mitochondrial enzymes: succinic dehydrogenase and cytochrome oxidase.

Thus certain macrophages become highly activated in the local lesion. The association of such activation with an apparent destruction of intracellular bacilli suggests that cellular immunity involves both processes. In addition, the high degree of macrophage activation observed in the lesion suggests that cellular immunity is mainly a local (in contrast to a systemic) phenomenon.

In the BCG lesions, certain granulocytes (either eosinophils or toxic PMN) were found to contain considerably more RNase than the other cells present. In necrotic and liquefied areas RNase and DNase were especially active, and acid phosphatase and β-glucuronidase were somewhat active. It therefore seems likely that nucleases and other lysosomal enzymes contribute to cell autolysis and the liquefaction of the caseous focus. The latter process helps perpetuate tuberculosis in mankind.
Sedimentation Properties of Antibody Cytophilic for Macrophages
Authors: Berken Arthur , Benacerraf Baruj
Published: December 2022

7 S and 19 S fractions of rabbit and mouse antisera were tested for cytophilic properties for homologous macrophages. This activity was found only in the 7 S fractions.
An In Vitro Assay for Encephalitogenic Components of Central Nervous Tissue
Authors: Brockman J. A. , Stiffey A. V. , Tesar W. C.
Published: December 2022

It has been demonstrated that an encephalitogenic purified basic protein fraction from bovine spinal cord inhibited the migration in tissue culture of peritoneal exudate cells from sensitized guinea pigs and rats. A technique based on this observation has been developed for an assay of such encephalitogenic fractions. Where practical considerations required pooling, cells pooled from imbred animals were superior because cells pooled from random-bred animals appeared to give variable mutual inhibition.
Role of Thymus in Adoptive Tolerance
Authors: Argyris Bertie F.
Published: December 2022

Specific homograft tolerance was induced in neonatal C3H mice with CBA spleen cells. These mice were test-grafted with CBA skin. After bearing successful CBA skin grafts for 2 months or longer they served as donors for “tolerant” thymus and bone marrow transplants. Adult intact and thymectomized C3H mice were irradiated and injected with 10 million “tolerant” bone marrow cells. The thymectomized mice were, in addition, supplied with a subcutaneous “tolerant” thymus graft. The irradiated recipients of “tolerant” thymus and “tolerant” bone marrow accepted CBA skin, demonstrating adoptive tolerance. They also rejected C57B1/6 skin, demonstrating that “tolerant” thymus can reconstitute immune recovery of thymectomized, irradiated bone marrow treated mice. Nontolerant thymus grafts were unable to abolish the transfer of adoptive tolerance by “tolerant” bone marrow, both in intact and thymectomized irradiated recipients. “Tolerant” thymus was capable of imposing specific homograft tolerance on irradiated recipients of nontolerant bone marrow, especially if these recipients were thymectomized at the time of irradiation. These results support the evidence of others that thymus plays an important role in immunologic tolerance.
Mechanism of Cleavage of Rabbit IgG in Two Stages by Soluble Papain and Reducing Agent
Authors: Zappacosta Serafino , Nisonoff Alfred , Mandy William J.
Published: December 2022

The mechanism of an apparent two-stage cleavage of rabbit IgG by soluble papain and L-cysteine was investigated. In the absence of reducing agent papain had no detectable effect on the sedimentation velocity or precipitating activity of antibody. After treatment with iodoacetamide and gel filtration, in an effort to inactivate and remove papain, addition of reducing agent resulted in cleavage into univalent 3.5 S fragments. This was shown to be attributable to partial resistance of papain to alkylation, particularly in the presence of IgG, and to adherence of an appreciable quantity of the enzyme to IgG during gel filtration. The results are consistent with a mechanism in which papain acts through cleavage of the heavy chains, and in which the reducing agent activates the enzyme but does not necessarily act directly on the IgG molecule.
Vaccination Response in Rabbits Related to Quantity of Vaccinia Virus Particles and Passage Level
Authors: Dunlap Ruth C. , Galasso G. J. , Sharp D. G.
Published: December 2022

The antigenicity and immunizing potential of early and late L cell passage vaccinia virus were compared. Early passage virus produced a skin lesion in rabbits if as few as 200 VP were injected. Late passage virus produced no necrotic lesion in concentrations as high as 109 VP. Both early and late passage virus immunization gave skin immunity to challenge by early passage virus. Early passage virus stimulated high titers of neutralizing antibody; late passage virus produced lower antibody titers.
Phagocytosis and Intracellular Fate of Mycobacterium Tuberculosis: In Vitro Studies with Guinea Pig Peritoneal and Alveolar Mononuclear Phagocytes
Authors: Maxwell Kameron W. , Marcus Stanley
Published: December 2022

The role of cellular immunity in tuberculosis was studied by using in vitro techniques to observe cellular capacities for phagocytosis and bacterial inactivation. Peritoneal exudates were stimulated and collected and alveolar phagocytes were harvested using standard techniques.

Normal and BCG-immunized guinea pigs were used as phagocyte donors. Two strains (H37Rv, H37Ra) of Mycobacterium tuberculosis were used for infecting the phagocytes. Suspensions of these tubercle bacilli consisting of single cells were prepared by filtration.

Plate counts were used to indicate the amount of ingestion and cytopepsis by the phagocytes. It was shown using the H37Rv strain of tubercle bacilli that phagocytes from BCG-immunized animals had increased cytopeptic activity when compared to phagocytes from normal animals. Also, the alveolar phagocytes were more active in cytopepsis than were the peritoneal exudate cells.
Virulence of Skin Strains of Nephritogenic Group A Streptococci: New M Protein Serotypes
Authors: Johnson Jennifer C. , Baskin Reed C. , Beachey Edwin H. , Stollerman Gene H.
Published: December 2022

Studies of strains of group A streptococci from a population of patients with pyoderma and a high incidence of acute glomerulonephritis revealed the presence of many apparently virulent strains which could not be identified as belonging to known M protein serotypes. One of these, the Baker strain, has been identified so far as an apparently new M serotype which we suggest be designated provisional type 56.
Differences in the Amino Acid Compositions of Allogeneic Guinea Pig Transplantation Antigens
Authors: Kahan B. D. , Reisfeld R. A.
Published: December 2022

Amino acid analyses were performed on relatively homogeneous guinea pig transplantation antigens, which had been liberated by exposure to sound and purified by gel filtration and by discontinuous electrophoresis on polyacrylamide gel. Comparison of the amino acid compositions of the antigens extracted from two histoincompatible lines of guinea pigs revealed significant differences in their content of serine, alanine, leucine, isoleucine and valine. These data suggest that transplantation antigens have allotypic specificities related to protein structure.
Neonatal Thymectomy and Hemolysin Responses in Inbred Mice
Authors: Sinclair Nicholas R. St.C. , Elliott Edward V.
Published: December 2022

A time-course study of total, 19 S and 7 S hemolysins showed that inbred CBA/H and C3H/Jax mice were able to give fairly normal secondary responses to sheep erythrocytes at an age when the primary response was very much reduced or absent.
Immunologic Studies on Aspirin
Authors: Wicher Konrad , Schwartz Michael , Arbesman Carl E. , Milgrom Felix
Published: December 2022

Aspiryl-chloride was conjugated with bovine γ-globulin (BGG), rabbit γ-globulin (RGG) and crystallized egg albumin (CEA). Rabbit antisera were prepared by immunization with these conjugates incorporated in Freund's adjuvant. Antibodies to native carrier proteins were observed in antisera to conjugated BGG and CEA, but not RGG.

All antisera contained antibodies to aspiryl hapten and antibodies to antigenic sites which were created during the conjugation procedure and were apparently formed by both the hapten and the carrier. These sites had different antigenic structure in the three conjugates under investigation.
An Antigen-Binding Capacity Test for Human Immunoglobulin G (IgG) Fragments
Authors: Cerottini Jean-Charles
Published: December 2022

The ammonium sulfate method of Farr has been modified for the use of human immunoglobulin (IgG) Fab′ and Fc fragments. Precipitation of radiolabeled fragments bound to antibody was obtained by addition of 40% saturated ammonium sulfate (SAS). In the presence of normal serum more than 95% of both fragments were soluble in the same SAS concentration.

Antigen-binding capacities (ABC) for IgG fragments in antisera to IgG were measured simultaneously by using an antigen solution containing 131I labeled Fab′ and 125I labeled Fc. Specificity of the ABC test was evaluated by incubating the antigen mixture with antisera of various specificities. Addition of unlabeled Fab′ in excess to the paired labeled fragments specifically inhibited the binding of 131I Fab′ to antibody.

Comparison of binding capacities for Fab′ and Fc fragments in hyperimmune anti-IgG sera from various species showed some differences in the relative amount of antibodies against the antigenic determinants present on each fragment. However, these quantitative differences depended upon the period of immunization and the number of antigen injections. Rat antisera obtained after five injections of IgG showed similar ABC values for Fab′ and Fc, whereas 1 month after the first injection a much better response to Fc was found in that species. In comparison, ABC values for Fab′ and Fc were similar in rabbit antisera obtained at various time intervals during the course of immunization with IgG.
Experimental Pleural Effusion as a Manifestation of Delayed Hypersensitivity to Tuberculin PPD
Authors: Allen James C. , Apicella Michael A.
Published: December 2022

Evidence is presented that pleural effusions in guinea pigs may be induced by hypersensitivity to PPD in the absence of infection with tuberculous organisms. Transfer of this reaction with cells from immunized animals indicates a predominant role of the delayed type of hypersensitivity, and documents an additional physiologic effect of this form of hypersensitivity reaction in vivo. Differences found in the protein concentrations of these effusions are compatible with differences in control of macromolecular movement in effusions induced by this hypersensitivity reaction, when compared with effusions resulting from nonspecific chemical injury. Studies utilizing in vitro incubations of lungs from sensitized donors indicate a role of soluble mediators released during the hypersensitivity reaction in the induction of pleural effusions, and thus suggest the importance of such mediators in in vivo manifestations of delayed hypersensitivity.
Immunologic Tolerance Induced in the Adult Rabbit with Modified BSA
Authors: Frei P. C. , Cruchaud S. , Arnaudo L. , Vannotti A.
Published: December 2022

Previous experiments have shown that bovine serum albumin, cleared of its larger phagocytizable particles, is much less immunogenic than regular BSA and can sometimes induce tolerance.

These findings are confirmed in the present paper. It was also shown that 1 mg of BSA was the dose most likely to induce tolerance in the rabbit; a smaller proportion of tolerant animals was obtained with 7 mg, whereas no tolerance was obtained with 25 mg of the antigen. The 0.1-mg dose induced slightly less tolerance than 1 mg, but the difference was not significant.

In most experiments the antigen was screened by injection into a filter animal before injection into experimental animals. In some experiments this biologic filtration was replaced by gel filtration, which also allowed the separation of a “tolerigen” fraction from an immunogenic one. The immunogenic role of the larger component is probably related to its function of adjuvant, since screened BSA injected together with endotoxin is immunogenic and can no longer induce tolerance.

The specificity of this kind of tolerance was established by showing a normal immune response to HSA in rabbits tolerant to BSA. This state of tolerance may persist for several months—one animal has now been tolerant for more than 2 years.
Studies of Blood Group Substances
Authors: Marcus Donald M. , Cass Louise E.
Published: December 2022

A goat immunized with a human H substance without Leb activity produced IgM and IgG anti-H antibodies. The IgG anti-H contained two populations of antibodies with different specificities. The major population was inhibited by either type I or II difucosyl oligosaccharides, and the minor population was inhibited best by a type I monofucosyl H oligosaccharide. The IgM antibody was inhibited less readily by haptens than was the IgG antibody. The best inhibitor was a type I monofucosyl H oligosaccharide. It is proposed that anti-LebL antisera are directed against a type I difucosyl determinant, whereas anti-LebH antisera react well with either type I or II difucosyl determinants.
Catabolism of Human γG Immunoglobulins of Different Heavy Chain Subclasses
Authors: Spiegelberg Hans L. , Grey Howard M.
Published: December 2022

The rates of catabolism of human γG immunoglobulins of subclasses γG1, γG2, γG3 and γG4 were studied in heterologous species by determining the rates of elimination from the circulation of pairs of 131I- and 125I-labeled human γG myeloma proteins in mice, rabbits, guinea pigs and squirrel monkeys. In all species studied, γG1, γG2 and γG4 myeloma proteins were on the average catabolized at similar rates, whereas γG3 myeloma proteins were catabolized more rapidly. In contrast, individual myeloma proteins within a given subclass differed significantly in their catabolic rates in mice and monkeys, but except for γG3 myeloma proteins, did not differ in rabbits and guinea pigs. Also, individual myeloma proteins were catabolized differently depending on the species injected, in that certain myeloma proteins had a relatively long half-life in one species but a short half-life in another. These experiments indicate that the homologous species and heterologous species catabolize γG immunoglobulins of different heavy chain subclasses in grossly similar fashion, but that minor structural differences between individual proteins which might modulate the rate of catabolism are only recognized by certain heterologous species and not by others.
The Specificity of Antigen-Induced Thymidine-2-14C Incorporation into Lymph Node Cells from Sensitized Animals
Authors: Stulbarg Michael , Schlossman Stuart F.
Published: December 2022

Studies of the immunochemical specificity of antigen-induced thymidine-2-14C incorporation in lymph node cells obtained from animals sensitized to α,DNP(Lys)11–15 or α,DNP(Lys)9 have led to the following observations. 1) Only immunogenic members of the homologous series of α,DNP-L-lysines, equal to or larger in size than the heptamer, stimulate the incorporation of thymidine-2-14C into specifically sensitized cells. 2) Nonimmunogenic α,DNP-L-lysines neither stimulate these cells nor prevent stimulation by immunogenic peptides. 3) The specificity of the receptor for antigen on the sensitized lymphoid cell contrasts with the previously observed capacity of anti-α,DNP(Lys)n antibody to react with DNP-containing proteins and nonimmunogenic α,DNP-L-lysines, but parallels the specificity of the in vivo delayed or anamnestic response.

These results provide support for speculations concerning the existence of a still undefined molecule, different from antibody, which functions as the cellular-receptor for antigen and regulates the proliferative and biosynthetic response of the cell.
Suckling Mouse Cataract Agent (SMCA) in Mice
Authors: Clark H Fred , Karzon David T.
Published: December 2022

Lifelong infection is regularly produced in mice inoculated intracerebrally with SMCA at birth. However, the progeny of such infected mice do not develop cataracts and virus cannot be recovered from them. Furthermore, neither induction of cataracts nor transplacental passage of SMCA virus was demonstrated in the progeny of susceptible pregnant dams inoculated intravenously with high-titered preparations of SMCA at intervals throughout the gestation period.

SMCA-infected mother mice conferred solid protection against SMCA-induced cataracts on their progeny. Mice acquiring such maternal resistance and inoculated with SMCA were not able subsequently to protect their own progeny. Five consecutive generations of mice were inoculated intracerebrally with SMCA as newborn mice. The first, third and fifth generations were fully susceptible to cataracts, while the second and fourth generations were completely protected. Liver-spleen virus titers in protected generations were sharply reduced and eyes were nearly completely free of SMCA infection.

Protected second generation SMCA-inoculated mice were not immunologically tolerant. When re-inoculated with SMCA at 45 days of age, they subsequently conferred protection against SMCA-induced cataracts on their progeny. Despite the fact that neutralizing antibody is not readily demonstrated in SMCA-infected mice, transfer of maternal antibody provides the most reasonable explanation for the protection against SMCA-induced cataract conferred on suckling mice by SMCA-infected dams.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Nagaki K. , Stroud R. M.
Published: December 2022

Active C′1s was purified from human serum by euglobulin precipitation, CM-cellulose chromatography, DEAE-cellulose chromatography, and Pevikon electrophoresis. Molecular weight of active C′1s is between 110,000 and 120,000. Highly purified active C′1s contains no C′1q and gives a single precipitin line in the α-globulin region against anti-whole human serum. This line was correlated with hemolytic and esterase activities. Moreover, the hemolytic activity and esterase activity of C′1s were correlated with C′2 and C′4 destructive activities. Although active C′1s forms SAC′4,2a, it does not bind to EAC′4gp at low ionic strength as does C′1a. Furthermore, kinetics of formation of SAC′4,2a with active C′1s exhibit a different pattern from that with C′1a, suggesting that active C′1s transfers from site to site. A convenient spectrophotometric assay system for esterase activity of active C′1s has been developed for these studies using p-tosyl-l-arginine methyl ester (TAMe) as a substrate.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Linscott W. D.
Published: December 2022

Conditions for the optimal fixation of guinea pig C′1a to sheep erythrocytes sensitized with 7 S or low-avidity 19 S anti-Forssman antibodies were found to differ markedly from those giving optimal results with high-avidity 19 S antibodies. With 7 S antibody, best results were obtained by adding the C′1a at 0°, final µ = 0.065, and incubating in the cold for 10 min. Then the µ was reduced to 0.037 by adding low ionic strength sucrose-Veronal buffer and incubation at 0° was continued for another 10 min, followed by centrifugation and washing at 0°, µ = 0.037. Under these conditions, approximately 75% of the C′1a offered to the cells could be accounted for by transfer to EAC′4. In order to study the conditions affecting C′1a transfer, it was necessary to separate the transfer reaction from the following reaction with C′2. This was done by lysing washed EAC′1a with water, then restoring the isotonicity with cold five times concentrated sucrose-Veronal buffer, µ = 0.037.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Borsos T. , Rapp H. J. , Colten H. R.
Published: December 2022

Evidence has been obtained for the existence of functionally different C′4 molecules. Their existence was deduced from studies of the influence of temperature and immunoglobulin class on the generation of SAC′14 and of the interaction of attached C′4 with anti-C′4 antibodies. Four different kinds of sites have been identified: (1) Competent (hemolytic) sites generated with IgM or with IgG antibodies. The generation of these sites is favored by low temperature. (2) Incompetent (non-hemolytic) sites generated with IgM or with IgG antibodies that are capable of reaction with and activation of C′2. The generation of these sites is favored by elevated temperature. (3) Potentially competent hemolytic sites generated with IgG antibodies that can be converted to hemolytic sites by IgM antibodies. (4) Sites that are neither hemolytic nor capable of using up C′2 and cannot be converted to hemolytic sites. These sites were detected by their ability to react with anti-C′4 antibodies. Elevated temperature favors generation of these sites.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Polley M. J. , Müller-Eberhard H. J.
Published: December 2022

The injection of 20 µg of a highly purified preparation of human C′2 mixed with complete Freund's adjuvant into each popliteal lymph node of a rabbit, followed a month later by intramuscular injection of 40 µg of C′2 mixed with adjuvant, elicited a highly potent antiserum to C′2. The antibody inhibited the hemolytic activity of C′2, both in free solution and in cell-bound form, and produced a single precipitin line with whole human serum and with purified C′2 by Ouchterlony test. The two lines gave a reaction of identity. On immunoelectrophoresis, using agar as a supporting medium, purified C′2, which on Pevikon electrophoresis is a β globulin, was found to have an electrophoretic mobility almost equal to that of albumin. However, in the presence of purified C′4, and likewise in whole serum, its mobility was reduced to that of a β globulin, presumably due to C′2 to C′4 interaction.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Rosenberg L. T. , Tachibana D. K.
Published: December 2022

Titrations of hemolytic complement in mice of various inbred and non-inbred stocks show large differences. The following strains and strain pairs are of particular interest either because of the high levels or the hemolytic complement or because genetic evidence implies allelism at few genetic loci suffice to explain the phenotypic differences in total hemolytic complement. 1) A strain derived from a cross between a non-inbred CF-1 mouse and the B10.D2 old line breeds true for high levels of complement equivalent to the highest levels measured in the non-inbred population—averaging 400 C′CH50 units as determined by our test. 2) The strain pair C57BL10 averages 35 C′H50 units. 3) The strains pair C3H/SN and CBA, as well as C3H and new line hemolytic complement, in a manner suggesting simple Mendelian factors determining the differences. The chemical bases for the differences are as yet entirely unknown.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Muschel L. H.
Published: December 2022

External components of Gram-negative organisms such as Escherichia coli and Salmonella typhi possess barrier function that may be destrcyed by EDTA treatment. The effect of such treatment, which is not bactericidal, upon the resistance of cells to the immune bactericidal reaction mediated by C′ was therefore determined. When the amount of antibody was limiting, as with absorbed guinea pig serum, there was a marked difference in the susceptibility of EDTA-treated and control cells. There was only a relatively slight difference in sensitivity of EDTA-treated and control organisms to untreated normal serum, however, and in the presence of excess antibody, no detectable difference. Apparently, an excess of antibody tends to nullify the increased sensitivity to C′ resulting from EDTA treatment. It was previously postulated that the reason for the insusceptibility of Gram-positive bacteria compared with Gram-negative bacteria was the greater thickness of the cell wall of Grampositive species, 15 to 50 mµ, compared to Gramnegative species with walls to 7.5 to 10 mµ.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Müller-Eberhard H. J. , Perlmann P. , Perlmann H. , Manni J. A.
Published: December 2022

Target cells consisted of 51Cr-labeled chicken erythrocytes which were treated with rabbit antibody and purified human complement components to produce intermediate complement-cell complexes. They were incubated (in tissue culture medium containing 5% heat-inactivated fetal calf serum chromatographically depleted of C′8 and C′9) for maximally 15 hr with various preparations of human blood leukocytes at a leukocyte-target cell ratio of 50:1. Cell damage was measured by determining the proportion of 51Cr which was released into the medium. The following results were obtained: 1) Cell preparations consisting of 75% lymphoid cells and 25% polymorphonuclear leukocytes (PMN) damaged both C′3- and C′7-target cells, the latter more rapidly and extensively than the former. 2) Purified monocytes exhibited the same cytotoxic effect as the lymphoid cell-PMN mixture. 3) Purified lymphocytes damaged only C′7-target cells but not C′3-target cells. 4) None of the human cell preparations adversely affected target cells which had reacted only with C′1, C′2 and C′4.
An Examination of the Cross Reactivity of Human and Equine γG Globulins and Their Fragments by Immunodiffusion
Authors: Allen Peter Z. , Berger Barbara M. , Helms Charles M.
Published: December 2022

Rabbit antisera prepared against equine γG globulin, Fab, Fc, H and L chains were employed in immunodiffusion analysis to examine their cross reactivity with antigens related to various portions of the human IgG molecule. Antigenic similarities between the corresponding H and L polypeptide chains of both species were found and cross reactive groupings assigned to locations within chains. A collection of 23 Bence Jones proteins examined for cross reactivity with several rabbit anti-equine Fab and L chain reagents showed cross reactivity of human L chains to be associated principally with λ type proteins.

Immunodiffusion analysis of reciprocal cross reactions involving the ability of several rabbit anti-human IgG reagents to precipitate with antigens related to various portions of the equine IgG molecule showed cross reactivity to be associated with determinants on equine Fc and F′ fragments. Interspecies antigenic similarities between equine L chains and type λ human L chains was also demonstrated by the cross reaction shown by an anti-type λ Bence Jones protein reagent with equine L chains.
Communications
Authors: Davis William C. , Huber Heinz , Douglas Steven D. , Fudenberg H. Hugh
Published: December 2022

Defective intracellular killing of bacteria by purified circulating mononuclear phagocytes is demonstrated in chronic granulomatous disease of childhood. The relationship of this defect to the characteristic histopathologic finding of pigmentladen macrophages is considered. CGD is a genetic disease which is manifested by impaired bactericidal capacity of at least two circulating cell types, polymorphonuclear neutrophils and mononuclear phagocytes.
Communications
Authors: Dowling Peter C. , Kim Seung U. , Murray Margaret R. , Cook Stuart D.
Published: December 2022

Two complement-dependent demyelinating antibodies were isolated from the serum of acutely symptomatic multiple sclerosis patients. Demyelinating activity was associated with both the 19 S and 7 S fractions. Isolation procedures showed that the demyelinating factor associated with the 19 S fraction was IgM, while the demyelinating factor associated with the 7 S fraction belonged to the IgG class of immunoglobulins.
Recovery of Delayed-Type Hypersensitivity in Mice Following Suppressive Doses of X-Radiation
Authors: Volkman A. , Collins F. M.
Published: December 2022

A study was made of the effects of sub-lethal whole body x-radiation on an established state of delayed hypersensitivity induced by the intravenous infection of mice with M. bovis (BCG) or S. gallinarum. The level of delayed sensitivity was determined by measuring the foot-thickness 24 hr after the injection of a suitable eliciting antigen into the footpad. In appropriately sensitized mice the delayed reactivity to both PPD and the Salmonella antigen was largely suppressed by 400 rad of whole body x-radiation. No recovery of reactivity was detected in the 8 days following irradiation of tuberculin sensitive mice. On the other hand, in mice sensitized to S. gallinarum there was a gradual recovery in footpad reactivity.

X-radiation resulted in an abrupt decline in the absolute numbers of circulating lymphocytes, monocytes but not granulocytes. Low white cell counts were sustained throughout the remainder of the experiment. Concurrent autoradiographic labeling studies showed a fall in the labeling index of mononuclear exudate cells at the reaction site coincident with minimal footpad reactivity. The subsequent return of a normal labeling index in the cells of the infiltrate was associated with the recovery of a significant degree of specific footpad reactivity. These results were interpreted to favor the concept that delayed hypersensitivity is mediated by two cell populations. The first is relatively radioresistant and endowed with the specific sensitivity necessary to initiate a delayed reaction. The second, which is necessary for its ultimate expression, is derived from radiosensitive precursors that are capable of rapid regeneration.
Isoantigens of Thyroglobulin and Their Significance in Experimental Autoimmune Thyroiditis
Authors: Nakamura Robert M. , Weigle William O.
Published: December 2022

Isoantibodies and isoantigens of bovine thyroglobulin were demonstrated in the present experiments. Isoantibodies to bovine thyroglobulin were easily detected in rabbits rendered unresponsive to bovine thyroglobulin obtained from a single gland and then injected with pooled arsanil-sulfanil bovine thyroglobulin prepared from glands obtained from numerous animals. Sera from such animals contained precipitating and hemagglutinating antibodies to both the tolerated bovine thyroglobulin and pooled (unaltered) bovine thyroglobulin. After absorption of the sera with the tolerated thyroglobulin, the sera no longer reacted with the tolerated thyroglobulin but still reacted with the pooled thyroglobulin. In contrast to rabbits made unresponsive to an individual thyroglobulin, rabbits unresponsive to pooled bovine thyroglobulin did not lose their unresponsive state following injections of pooled arsanil-sulfanil bovine thyroglobulin.

The role of isoantigens in experimental thyroiditis is discussed. It appears that isoantigens of thyroglobulin are involved in the termination of a natural unresponsiveness to autologous thyroglobulin with production of autoimmune thyroiditis following injections of altered homologous thyroglobulin.
The Allergic Response of Rabbit Platelets
Authors: Siraganian Reuben P. , Secchi Antonio G. , Osler Abraham G.
Published: December 2022

The allergic response of rabbit platelets as observed by increased membrane permeability to 86Rb and by histamine release is Mg++-dependent. There is competitive inhibition by Ca++ at optimal levels of Mg++ (1 to 3 × 10-4 M). Calcium can substitute for Mg++ at suboptimal levels of the latter, but is less effective. Calcium increases the range of Mg++ levels for an optimal response, possibly by stabilizing a reaction intermediate. The latent period for 86Rb efflux is brought to a minimum of about 1 min, by optimal Mg++ concentrations. The minimal latent period for histamine release is about 5 min. The initial rate is inhibited by excess Mg++. The latent period is far less responsive in this respect.

The data suggest that increased membrane permeability and histamine release are successive steps in the allergic response of platelets, in which only a Mg++ requirement has been identified.
Immunochemical Studies of Foot-and-Mouth Disease
Authors: Cowan K. M.
Published: December 2022

Guinea pig antisera for foot-and-mouth disease virus (140 S), virus protein subunit (12 S) and the virus infection-associated (VIA) antigen were prepared by immunization with the isolated antigenic components or by infection, and made specific by absorption procedures. Guinea pigs immunized with purified inactivated 140 S antigen also produced antibody to the 12 S antigen which necessitated absorption with 12 S antigen. Similarly, guinea pigs immunized with purified 12 S antigen developed antibody to 140 S antigen which was removed by absorption with 140 S antigen. Antiserum specific for VIA antigen was prepared by absorbing serum from infected guinea pigs with both 140 S and 12 S antigens. Quantitative precipitin analyses were performed with the 12 S and 140 S antigens. However, interpretation of the results was complicated by the finding that 12 S antigen precipitated some of the antibody reactive with 140 S antigen, and that 140 S antigen removed a portion of the antibody reactive with the 12 S antigen. Evaluation of the immunization and precipitin analyses indicated that some antigenic relationship exists between the 140 S and 12 S components, the nature of which has yet to be resolved.
Delayed Contact Sensitivity to Catechols
Authors: Baer Harold , Dawson Charles R. , Kurtz A. Peter
Published: December 2022

Guinea pigs sensitized with catechols having cyclic and linear hydrocarbon side-chains did not exhibit reciprocal cross-reactivity. Those sensitized with catechols having cyclic hydrocarbon side-chains reacted to almost the same degree when tested with catechols having linear hydrocarbon side-chains with approximately the same number of carbon atoms. Guinea pigs sensitized with catechols having linear side-chains reacted poorly or not at all when tested with catechols having cyclic side-chains. This indicates the importance of the hydrocarbon side-chain in determining antigenic specificity and provides a chemical basis for non-reciprocal cross-reactivity. Specificity that could be attributed to a carrier molecule was minimal or absent. The data are compatible with a linear conformation of n-alkyl side-chains but indicate that, because of their flexibility, they can conform to other shapes. Aromatic character in the hydrocarbon side-chain did not markedly affect specificity, which seemed to be almost completely determined by size and shape.
Cluster Formation in Vitro by Mouse Spleen Cells and Sheep Erythrocytes
Authors: Shearer G. M. , Cudkowicz G.
Published: December 2022

The primary injection of sheep erythrocytes into young adult mice was followed by the appearance in the spleen of distinct populations of immunocytes secreting specific antibody. Different types of immunocytes were recognized by the properties of the antibody produced, i.e., the ability to lyse erythrocytes in agar gel directly and indirectly upon facilitation (plaque-forming cells), and the ability to agglutinate erythrocytes in liquid medium (cluster-forming cells). The optimal conditions for enumeration of cluster-forming cells were established. The number of cluster-forming cells in the spleens was much greater than that of plaque-forming cells, and the kinetics of appearance were different. Furthermore, previous cluster formation in liquid suspension did not influence the subsequent appearance of hemolytic plaques in agar gel by the same spleen cell preparation. The plaques developed around immunocytes other than the cluster-forming cells. It was concluded that cluster-forming cells and plaque-forming cells are engaged in the exclusive production of hemagglutinins and hemolysins, respectively.
Immune Lysis of Rabies Virus-Infected Cells
Authors: Wiktor T. J. , Kuwert E. , Koprowski H.
Published: December 2022

Cells of tissue cultures infected with rabies virus are lysed after exposure to antirabies antibody and complement, as shown either by counting of cells stained with trypan blue or by release of chromium 51 from labeled cells. Neither antirabies serum nor fresh guinea pig serum is active alone. The reaction is abolished by treatment of serum-complement mixture with EDTA, or treatment of complement by heat or hydrazine. Fluorescein-conjugated antibody without complement stained the surface of infected cells; with complement, intracytoplasmic staining was seen, indicating penetration of the cell membrane by antibody. Both lytic antibody and neutralizing antibody were found in the 7 S IgG immunoglobulin fraction of human and mouse antisera. Study of the sera of animals either immunized against rabies or in the incubation stage of the disease showed, however, that lytic and neutralizing antibody titers could vary independently. Lytic antibody was produced in man and animals infected with street virus, injected with inactivated vaccine, or infected with crude or purified live virus vaccine.
The X-Y-Z Scheme of Immunocyte Maturation
Authors: Dowden Stanley J. , Sercarz Eli E.
Published: December 2022

The first serum antibody detected in mice which spontaneously escaped from BSA paralysis was similar in three ways to that first detected in normal mice 8 days after a primary injection of AP-BSA. Each produced the 4-hr and 72-hr mouse PCA reactions, was similar in avidity, and had comparable low levels of antigen-binding capacity.

Antibody produced late after spontaneous escape and that produced late in the normal primary response effected only the 4-hr mouse PCA reaction. Such antibody was of avidity intermediate between the 8-day early anti-BSA and hyperimmune anti-BSA.

Only 7Sγl possessed anti-BSA activity by radioimmunoelectrophoresis, whether in mice which spontaneously escaped from BSA paralysis or in normal mice following primary or repeated immunization with either AP-BSA or S-BSA. 7Sγ2, γA, and γM were negative by this criterion. The absence of γM antibody to BSA was confirmed by passive hemagglutination and 2-mercaptoethanol studies on unfractionated antisera; and on antisera fractionated by micro-sucrose gradient ultracentrifugation or by ultracentrifugation of preformed 125I-BSA-anti-BSA complexes. The absence of 7Sγ2 anti-BSA was confirmed by the absence of guinea pig PCA reactions with positive mouse antisera to BSA.

The results support the notion that the anti-BSA response in mice newly escaped from paralysis is essentially similar to an early primary response.

The discussion has served to emphasize that the concept of reversibly paralyzed cells is in accord with many current models of paralysis involving short-term delays rather than extinction of specific immune responsiveness.
Prenatal Immunization of the Lamb to Brucella: Dissociation of Immunocompetence and Reactivity
Authors: Richardson Marvis , Beck Clifford C. , Clark David T.
Published: December 2022

Many animal species do not respond markedly to the somatic antigens of Brucella or Salmonella until several weeks of age (1). Smith (2) found that only 1 of 58 human infants receiving typhoid vaccine at 1 to 30 days of age produced agglutinins against somatic antigen, although 46 of the 58 responded to the less complex flagella antigen. Passive transfer of antibody has been shown to inhibit immunization (3, 4), and maternal antibody may negate immune response in the neonate. Other evidence suggests that late maturation of immunocompetence is responsible for the non-reactivity toward the somatic antigens of Gram-negative bacteria. Silverstein and coworkers (5) have found that although the fetal lamb responded fully to several types of antigen at various times during fetal life, it did not produce antibody to Salmonella typhosa at any time in utero or by 6 weeks of age.
The Effects of Single Low Antigen Doses on Immunologic Responsiveness in Adult Rabbits
Authors: Kraft Sumner C. , Rothberg Richard M. , Ford Harold E.
Published: December 2022

The effects of single low doses of bovine serum albumin (BSA) on immune responsiveness were studied by administering 0.1 or 1.0 mg of BSA intravenously (i.v.) to adult rabbits. Anti-BSA was detected in 50% of each group. The injection of 1.0 mg of BSA inhibited the antibody responses to challenging doses of 100 mg i.v. of BSA given 21 and 42 days later. This hyporesponsiveness was not due to the presence of circulating antigen. Following the first 100 mg BSA challenge, a transient decrease in the strength of the antibody-antigen bonds was observed. Rabbits receiving a 10-fold lower preliminary BSA dose did not exhibit immune suppression or a decrease in the strength of antibody-antigen bonds. The immunocompetent cells of these animals were affected by the 0.1-mg i.v. BSA injection, however, as demonstrated by slightly more antibody following the second 100-mg BSA challenge, a more rapid onset of immune elimination, and a higher mean effect of dilution following the second challenge. Since immunosuppression has not been observed using 10-fold lower or higher BSA doses, there appears to be something unique about a single 1.0-mg BSA injection. Although the cellular mechanisms involved remain unclear, 1.0 mg i.v. of BSA more efficiently suppressed the population of immunologically competent cells that form antibodies capable of stronger antigen binding.
Characterization of a Soluble Cytoplasmic Antigen Reactive with Sera from Patients with Systemic Lupus Erythmatosus
Authors: Clark Geoffrey , Reichlin Morris , Tomasi Thomas B.
Published: December 2022

A tissue antigen reactive with sera from SLE patients has been partially characterized. The antigen is a soluble cytoplasmic component which is present in a variety of human tissues and is distinct from known nuclear antigens. It is an acidic macromolecule which has the electrophoretic mobility of an α1 globulin and is resistant to most proteolytic enzymes including trypsin, pepsin and chymotrypsin. Antigenicity is destroyed by 0.02 M periodate and by 0.001 M parahydroxy mercuribenzoate. Antibodies to this antigen have been found in 40% of unselected LE sera and were absent from a large number of sera from normal persons and from the sera of patients with other connective tissue disorders.
Antiserum Neutralization of Bacteriophage Q β: A Mathematical Analysis
Authors: Hale Edward M. , Hirata A. A. , Brusenback R. A. , Overby L. R.
Published: December 2022

The inactivation of the bacteriophage, Q β, with specific antiserum was studied. The reaction exhibited a continual decrease in rate that was evident from the beginning. The same limiting value of the surviving fraction was reached by all concentrations of a serum. The deviation from first order kinetics was not attributable to dissociation or pre-existing phage heterogenity. The results support the idea of the development of resistant phages by interaction with antiserum components. The curve of neutralization could be approximated mathematically.
Effect of DEAE-Dextran on Interferon Production and Protective Effect in Mice Treated with the Double-Stranded Polynucleotide Complex Polyinosinic-Polycytidylic Acid
Authors: Dianzani F. , Rita G. , Cantagalli P. , Gagnoni S.
Published: December 2022

Interferon production by mice treated with the double-stranded polynucleotide complex I:C is increased up to 30 times by the presence of DEAE-dextran in injected I:C solutions. Consistent amounts of circulating IF could be detected only 90 min after treatment. The highest levels of circulating IF were produced within 3 hr after treatment with I:C (20 µg/mouse) and DEAE-dx (200 µg/mouse). The highest levels of circulating IF were maintained during a 10- to 12-hr period following a single stimulation. Repeated treatment of mice with I:C and DEAE-dx after the disappearence of previously induced IF were followed by new rises of IF production. If stimulation was repeated at the times when the previously induced level of circulating IF was still high, it was possible to maintain this level during the whole period of study (39 hr). Protection against challenge with Columbia SK virus was much higher in mice treated with repeated doses of inducer (90% survival) than in mice treated with a single dose of inducer (50% survival).