bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Mechanisms of Reversed Type Reaginic Hypersensitivity
Authors: Ishizaka Kimishige , Ishizaka Teruko
Published: December 2022

F(ab')2 fragments of anti-γE obtained by pepsin digestion and reduced-alkylated anti-γE induced reversed type erythema-wheal reactions in normal individuals and released histamine from leukocytes, whereas Fab′ fragments of the antibody failed to do so. The requirement of two antibody-combining sites in anti-γE for induction of the reversed type allergic reactions suggested that bridging of two cell-bound γE molecules by anti-γE is the initial step of the reactions. On a molar basis, the original antibody and F(ab')2 fragments were comparable in their ability to induce the reversed allergic reactions, but the C′-fixing activity of the fragments was only 0.4% that of the undigested antibody. The results strongly suggested that C′ is not essential for induction of the reversed type reactions.
7Sγ1, 7Sγ2 and IgM Immunoglobulins in the Deer Mouse (Peromyscus Maniculatus)
Authors: Coe John E.
Published: December 2022

7Sγ1, 7Sγ2 and IgM immunoglobulins (Ig) in the deer mouse (Peromyscus maniculatus artemisiae) were defined. Each Ig was isolated and specific antisera prepared. The electrophoretically faster 7S globulin (7Sγ1) and the larger sized globulin (IgM) had antigenic determinants in common with the Fab piece of the electrophoretically slower 7 S globulin (7Sγ2). Each Ig also had unique determinants, which in the case of the 7Sγ2 were located on the Fc piece. Because the genus Peromyscus has such a wide spectrum of related species and subspecies, the Peromysus mouse may be a useful rodent for studies on the evolution of Ig variation.
Ontogenesis of Immune Capability of Murine Bone Marrow Cells and Spleen Cells against Transplantation Antigens
Authors: Bortin Mortimer M. , Rimm Alfred A. , Saltzstein Edward C.
Published: December 2022

Bone marrow and spleen cell suspensions from C57BL/6 mice were tested for immune competence against transplantation antigens present in B6D2F1 hybrid mice. The test system was the Simonsen GVH spleen weight-gain assay. C57BL/6 mice, which ranged in age from newborns to adults, were the cell donors. Spleen cells first developed immune competence against transplantation antigens when the donor mice were between 6 and 8 days of age. Bone marrow cells failed to exhibit apparent immune competence at any age, with the cell dose employed, and as measured in this bioassay.
Induction of Delayed Hypersensitivity to Influenza and Mumps Viruses in Mice
Authors: Feinstone Stephen M. , Beachey Edwin H. , Rytel Michael W.
Published: December 2022

Delayed hypersensitivity was produced in mice to mumps and influenza virus antigens as a preliminary step to studies of the role of delayed hypersensitivity in resistance to viral infections. Since the footpad test was not found to be sufficiently quantitative or reliable, the in vitro technique of macrophage-migration-inhibition of George and Vaughan was adapted to the mouse model. Cells from sensitized mice were significantly inhibited from migrating when challenged with the homologous antigen. There was some inhibition of migration of sensitized cells with heterologous antigens, but this did not differ significantly from inhibition of non-sensitized cells so challenged, and could be largely circumvented by appropriate dilution of the challenge antigen. The migration of sensitized cells not challenged with either antigen was in the same range as that of the control, non-sensitized, unchallenged cells. It is concluded that macrophage-migration-inhibition provides an assay system for delayed hypersensitivity that is both sensitive and specific for the particular myxoviruses tested.
The Use of Concanavalin A for Distinguishing IgM from IgG Antibody-Producing Cells
Authors: Nordin Albert A. , Cosenza Humberto , Hopkins Walter
Published: December 2022

Harris and Robson (1) have reported the ability of concanavalin A to precipitate several classes of serum glycoproteins. This selective precipitation is probably due to the specificity of concanavalin A for non-reducing mannosyl and N-acetylglucosaminyl end groups (2). Among the serum glycoproteins precipitated, IgM has been identified by immunoelectrophoresis and by specific biologic activity (3). However, under identical conditions, less than 5% of the IgG of normal human serum was precipitated. These observations suggest the possibility of using concanavalin A to distinguish IgM from IgG antibody-producing cells. This paper illustrates that concanavalin A interferes with the ability of IgM to induce lysis of sheep erythrocytes (SRC) in the presence of complement (C′) without affecting IgG hemolysins.

Concanavalin A was prepared by the method of Agrawal and Goldstein (4). After the concanavalin A was eluted from a Sephadex G-50 column, the major peak was dialyzed against distilled water and lyophilized.
Chlorphenesin: A New Inhibitor of IgE-Mediated Histamine Release
Authors: Lichtenstein Lawrence M. , Adkinson N. Franklin
Published: December 2022

Several drugs have recently been shown to be active in inhibiting the antigenically induced in vitro release of compounds thought to be involved in anaphylactic reactions. These compounds offer interesting tools with which to study the mechanism of the reactions of immediate hypersensitivity as well as having the potential for therapeutic use in man. Of the drugs already in use in man diethylcarbamazine (Hetrazan), an antifilarial agent, inhibits the release of the slow reacting substance of anaphylaxis (SRS-A) from rat peritoneal leukocytes (1) while disodium chromoglycate (Intal) inhibits the release of histamine from rat mast cells in vivo (2). The latter, however, does not inhibit in vitro histamine release from human leukocytes (L. M. Lichtenstein, unpublished). Both of these drugs are currently being studied for their usefulness in the treatment of human asthma (3, 4). Recently, drugs of the catecholamine and methylxanthine series were shown to inhibit the release of histamine from human leukocytes: evidence was presented to suggest that they operated through the cyclic 3′5′ AMP system (5, 6).
An Immunofluorescence Study of the in Vitro Interaction between Lymphoid Cells and Target Cells
Authors: Clark Junius M. , Weiss Leon
Published: December 2022

The interaction between immunocompetent cells derived from the spleens of BALB/c mice and L-929 fibroblasts growing in vitro was examined. The percentage of globulin-containing mononuclear cells adherent to the allogenic fibroblasts increased as the time of exposure of the spleen cells to the L cells increased. Inasmuch as this increase in globulin-containing cells is closely associated with the destruction of the foreign monolayer, it is suggested that globulin produced by attached plasma cells or lymphocytes may be responsible for allogenic fibroblast destruction.
Distribution of Antigen-Binding Sites on Rabbit IgM Subunits
Authors: Coligan J. E. , Bauer D. C.
Published: December 2022

The distribution of antigen-binding sites on the reduced and alkylated subunits from IgM anti-BSA molecules was examined. When subunits prepared from specifically purified IgM antibody were allowed to react with a BSA-cellulose immunoadsorbent, over 90% of the subunits were specifically bound. This suggests that each subunit has a binding site, rather than there being an unequal distribution of sites among the subunits, which would have resulted in either 80% or 60% subunit binding.
Surface Antigens on Interspecies Hybrid Cells
Authors: Kano Kyoichi , Baranska Wanda , Knowles Barbara B. , Koprowski Hilary , Milgrom Felix
Published: December 2022

Interspecies hybrid cells were obtained by Sendai virus-mediated cell fusion followed by propagation of cells in media exerting proper biochemical pressures.

The mixed agglutination test with cell cultures was employed for the analysis of cell surface antigens. Rabbit immune sera were used to identify species-specific antigens. All man-mouse hybrid lines studied contained antigens characteristic for the mouse, and most but not all lines had antigens characteristic for man. Antigens of both parents were shown in man-hamster and man-rat hybrids.

Histocompatibility antigens of man-mouse hybrids were detected by human and murine antisera containing proper isoantibodies. Here again murine antigens were found in all lines, whereas human antigens were demonstrated in most but not in all lines.

Karyotypic analyses of man-mouse hybrid cells were carried out. From a comparison of the serologic and karyotypic studies, only a tentative conclusion could be drawn that human chromosomes of group C or D may be important for determining human antigens on the cell surface.
The Toxicity of Meningopneumonitis Organisms (Chlamydia Psittaci) at Different Stages of Development
Authors: Christoffersen George , Manire G. P.
Published: December 2022

Intact elementary bodies of Chlamydia psittaci are toxic for mice and will absorb antitoxin from hyperimmune serum. The intermediate reticulate form of the organism, however, is non-toxic and does not absorb antitoxin. It appears likely that soon after penetration of the susceptible cell, the organism loses the toxic antigen from its envelope, the antigen is missing during multiplication, and is resynthesized at maturation.
Detection of Anti-Phage Antibody by Passive Hemagglutination
Authors: Walker William S. , Liu Chi Tan , Adler Frank L.
Published: December 2022

A passive hemagglutination test for detecting and measuring antibody activity against phage T2 was developed. Phage treated with the detergent sodium dodecyl sulfate under specified conditions of concentration of reagents and pH effectively sensitized tanned sheep red cells to agglutination by antibodies specific for T2 phage. It was shown that several phage antigens, including those of the tail fibers that are implicated in neutralization tests, are absorbed to the tanned cells. The sensitivity of this test for detecting antibodies is shown to match or exceed that of the neutralization test, presumably because it is more comprehensive in its detection of the reactions between the several phage antigens and their respective antibodies.
The IgM Response of Children to Salmonella Typhosa Vaccine
Authors: Altemeier William A. , Bellanti Joseph A. , Buescher Edward L.
Published: December 2022

Eight children immunized with commercial typhoid vaccine had elevations of total IgM globulins that averaged 55% above pre-immunization levels within 10 days. Concentrations of IgM specific for the surface antigens of Salmonella typhosa were found by measuring the decrease in total IgM levels that followed absorption of six sera from four children with whole S. typhosa organisms. On the days when IgM globulins were highest, sera contained at least 22 to 32 mg/100 ml of anti-typhoid IgM. This antibody accounted for 18% to 32% of all IgM in these sera and, with one exception, most of the IgM globulin increase that had occurred since immunization.
Conversion of Non-Immune Spleen Cells by Ribonucleic Acid of Lymphoid Cells from an Immunized Rabbit to Produce γM Antibody of Foreign Light Chain Allotype
Authors: Bell Clara , Dray Sheldon
Published: December 2022

Spleen cells (SpC) from non-immunized rabbits were converted to antibody plaque-forming cells (PFC) by incubation with ribonucleic acid (RNA) extracts of peritoneal exudate cells (PEC) or lymph node cells (LNC) obtained from the immunized rabbits 5 days following one intravenous injection of 4 × 108 sheep red blood cells (SRBC). The RNA extract was inactivated by ribonuclease (RNase) but not by deoxyribonuclease (DNase) or trypsin, indicating that the conversion required intact RNA. Plaque formation was inhibited by 2-mercaptoethanol (2-ME) or goat anti-rabbit γM but not by goat anti-rabbit γG-Fc fragment indicating that the antibody produced by the PFC are of the γM immunoglobulin class. The conversion was specific for the SRBC antigen injected.

By use of antibodies to the b4 and b5 allotypic specificities of immunoglobulin light chains, the allotypic specificity of the γM antibody produced by the PFC was identified by direct precipitation of the γM in the plaque or by inhibition of plaque formation. The γM antibody produced by converted SpC invariably possessed the allotypic specificity characteristic for immunoglobulins of the donor of the “immune” RNA extract and not of the donor of SpC. These results could not be explained by contamination of the RNA extracts with anti-SRBC, thus implying that a component of the RNA extract, presumably RNA itself, is providing a code for the synthesis of at least a part of the γM immunoglobulin molecule.
Studies on Japanese B Encephalitis Virus Vaccines from Tissue Culture
Authors: French George R. , Hammon William McD.
Published: December 2022

The virulence spectrum of isolates from the 49th HK passage of OCT-541 (JBE) virus at 37°C was examined using an infectious center technique in singly infected HK cells. Thirty per cent of that portion of the virus population that could be examined in this manner were found to be less virulent for the weanling mouse than was the parent virus. Ten per cent of the isolates were of very low virulence and one isolate designated T-11 virus was sufficiently different to be studied in depth.

The T-11 virus infectivity titer for cell cultures exceeds the intracerebral LD50 for weanling mice 1 million-fold. Intracerebral inoculation of 250 TCID50 of virus produces a non-lethal immunizing infection in weanling mice. Peripheral inoculation of this host does not result in infection. T-11 virus retains complete neurovirulence for the suckling mouse when given intracerebrally. It will produce a non-lethal immunizing infection in 30% of weanling hamsters inoculated by peripheral routes.

Comparison of the attenuated virus with the virulent OCT-541 virus by several methods did not reveal the mechanism or defect by which this virus is different. Thus, T-11 virus has a half-life at 38°C and pH 7.1 similar or superior to that of OCT-541 virus. The two strains are equally sensitive to interferon and T-11 virus can not be demonstrated to induce more interferon than the parent virus. Single cycle growth curves in cell culture are identical for the two viruses. T-11 virus is inhibited in multicycle growth curves and is more sensitive to the saline-soluble fraction of unpurified commerical agars. It has several other plaque markers common to other tissue culture-passaged viruses.
Immunogenicity of Hemocyanins and their Subunits
Authors: Amkraut Alfred A. , Malley Arthur , Begley Donald
Published: December 2022

The primary, secondary and hyperimmune responses of rabbits to hemocyanin and hemocyanin subunits from three molluscan and three arthropod species were measured. The amount of antibody formed by hyperimmune animals was independent of molecular size when closely related molecular species were used. An apparent correlation of immunogenicity and phylogenetic origin of the material was found; mollusc hemocyanins induced higher antibody levels than arthropod hemocyanins. The primary response to closely related antigens increased with increasing molecular size. Primary responses were also found to be less dose dependent than were subsequent responses. The intrinsic difference between primary and secondary responses and the importance of physicochemical properties and hypothetical immunogenic determinants in immunogenicity are discussed.
Different Specificities in Antisera Prepared against Escherichia Coli Tryptophan Synthetase α Subunit
Authors: Murphy Terence M. , Mills Stanley E.
Published: December 2022

Four different antisera, prepared against purified Escherichia coli tryptophan synthetase α subunit using different adjuvants and schedules of injection, were examined in detail.

Each antiserum demonstrated specificity for A gene product by not reacting detectably with extracts of certain mutants which had deletions or nonsense mutations in their A genes.

Two of the antisera appeared in every way to react only with active α subunit enzyme. In contrast, the other two reacted at least partly with denatured molecules which could be produced by aging or by heating preparations containing α subunit.

In micro-complement fixation assays the latter two sera showed a variety of reactions against extracts of strains with missense A gene mutations. These reactions could be misinterpreted as cross-reactions between the sera and native, homogeneous mutant α subunit antigens.

The latter two sera also detected antigens in extracts of strains A109 and A229, strains in which A gene products had not before been demonstrated.
Requirement for Cellular Interaction in the Antibody Response to Bacteriophage T4 in Mice
Authors: Inchley Christopher J.
Published: December 2022

Pooled spleen cell suspensions were obtained from CBA mice immunized with 5 × 108 plaque-forming units (PFU) T4 bacteriophage at times up to 7 days previously, and were transferred into normal isogenic recipients. Analysis of the sera of recipient mice showed that little or no antibody was produced unless the transferred cells were isolated at times when the donors were already making high levels of anti-T4 antibody. It is considered that, for this antigen at least, there is a critical period during the early part of the response when the integrity of the spleen is essential, and when cell-to-cell interactions may occur.
Immune Response of Rabbits to Purified Papovavirus SV40
Authors: Tevethia Satvir S.
Published: December 2022

Rabbits inoculated intravenously with a single high dose of purified papovavirus SV40 synthesized antibodies to tumor or T antigen. The antibody activity against the T antigen was associated with 19S and 7S immunoglobulins. These rabbits also synthesized antibodies to viral structural antigens. However, the rabbits inoculated with a low dose of virus synthesized antibodies to viral structural antigen only. Restimulation of rabbits producing only antibody to viral antigens failed to induce the synthesis of T antibody.
Antibody Responses in Serum and Nasal Secretions According to Age of Recipient and Method of Administration of A2/Hong Kong/68 Inactivated Influenza Virus Vaccine
Authors: Fulk Robert V. , Fedson David S. , Huber Margret A. , Fitzpatrick James R. , Kasel Julius A.
Published: December 2022

Neutralizing antibody responses in serum and nasal secretions following vaccination with A2/Hong Kong/68 inactivated influenza virus vaccine were compared according to age and route of administration. Among all of the age groups receiving one dose of vaccine subcutaneously or intranasally, children developed the greatest frequency of antibody response and increase in mean antibody titer in both serum and nasal secretions. In adults, vaccination by either route induced less serum antibody and was ineffective in inducing nasal antibody. Neutralizing activity of nasal wash specimens was removed by absorption with antiserum directed against secretory piece. Vaccination also resulted in rises in antibody titer in serum and nasal secretions to A/Equi-2 virus, a type known to be antigenically related to A2/Hong Kong/68 influenza virus.
Quantitation of Staphylococcal Protein A: Determination of Equilibrium Constant and Number of Protein a Residues on Bacteria
Authors: Kronvall Göran , Quie Paul G. , Williams Ralph C.
Published: December 2022

For quantitation of cell wall associated staphylococcal protein A a method was developed using 125I-labeled myeloma globulins. The maximal sensitivity of the method could be varied according to the particular experimental questions. Using the same reagent the number of protein A residues on Staphylococcus aureus, Cowan I, was estimated to 80,000/organism. In comparison with the blood group antigen A the protein A residue is four times as densely located on this staphylococcal strain. The equilibrium constants for the reactions between two myeloma globulins and staphylococcal protein A were found to be 4.0 × 107 and 4.5 × 107 liters/mol, respectively.
The Capacity of Human Immunoglobulin E to Mediate the Release of Histamine and Slow Reacting Substance of Anaphylaxis (SRS-A) from Monkey Lung
Authors: Ishizaka Teruko , Ishizaka Kimishige , Orange Robert P. , Austen K. Frank
Published: December 2022

Monkey lung fragments passively sensitized in vitro with human serum rich in IgE antibody released both histamine and slow reacting substance of anaphylaxis (SRS-A) upon challenge with specific allergen or anti-IgE. The sensitizing activity of the atopic serum was heat labile and was removed by treatment with an anti-IgE immunosorbent. In the reversed-type reactions, 7S anti-IgE and its F(ab′)2 fragments had comparable activity in mediating the release of both histamine and SRS-A, and Fab′ fragments did not release either mediator suggesting that bridging of two cellbound IgE molecules may be the initial step of the reaction. Monospecific antiserum against human IgG, IgM, IgA or IgD failed to release either mediator from sensitized tissue. Isolated E myeloma protein also sensitized monkey lung fragments for the release of both histamine and SRS-A by anti-IgE. It thus appears that immunoglobulin E sensitizes monkey lung fragments for the direct (antigen-induced) or reversed (anti-IgE-induced) release of both histamine and SRS-A.
Distribution of γE-Forming Cells in Lymphoid Tissues of the Human and Monkey
Authors: Tada Tomio , Ishizaka Kimishige
Published: December 2022

The sites of synthesis of immunoglobulin E were studied by the fluorescent antibody technique. Frozen sections of human and monkey tissues were treated with guinea pig anti-γE and stained by fluorescent antibody against guinea pig immunoglobuins. The results showed that γE-forming plasma cells were predominant in the respiratory and gastrointestinal mucosa and in the regional lymph nodes. In addition to the plasma cells, the tonsils, adenoids, and broncheal and mesenteric lymph nodes contained germinal centers stained by anti-γE. In contrast, γE plasma cells were scarce in the spleen and subcutaneous lymph nodes. A possible role of locally synthesized γE immunoglobulin in respiratory allergy was discussed.
Synthesis of Secretory IgA in the Rabbit
Authors: Lawton Alexander R. , Asofsky Richard , Mage Rose G.
Published: December 2022

A fragment (γAt) of rabbit colostral IgA which differs from the parent molecule primarily in that it lacks most of the original T chain has been prepared by chromatography of IgA on Sephadex G-200 in 5 M guanidine. This fragment is capable of combining specifically with free T chain in vitro. When mammary tissue from homozygous b4 rabbits is incubated in the presence of 14C amino acids and varying concentrations of b5γAt, the latter competes with an endogenous b4γA subunit for newly synthesized T chain, suggesting that the γA and T chain molecules are synthesized in different cells. Furthermore, γAt stimulates the synthesis of T chain, whereas intact IgA does not. On the basis of these and other data we have proposed a model for the synthesis and secretion of colostral IgA in the rabbit which agrees in most respects with the model developed by Tourville and co-workers from immunofluorescence studies in human tissues.
Antibody Formation in Zwoegerziekte, a Slow Infection in Sheep
Authors: De Boer G. F.
Published: December 2022

Zwoegerziekte, a slow infection in Dutch sheep, appears to be similar to maedi and visna in Iceland. The disease is induced by a persistent virus infection. The sera of experimentally infected sheep were examined using the neutralization test in tissue culture, the complement fixation test and the indirect immunofluorescence technique. Antibodies were detected within a few weeks using the technique of indirect immunofluorescent staining or the complement-fixation test, whereas neutralizing antibodies appeared much later after experimental infection. From that time on the sera were positive with all three serologic techniques for an experimental period of three years.
Correlation Between Ocular Inflammation and Antibody Production
Authors: Hall J. M. , O'Connor G. R.
Published: December 2022

Rabbits were immunized by the intravitreal injection of BGG in the right eye and were killed 12 days later. Cell suspensions were made from uveal tract tissue and assayed for plaque production by a modification of the Jerne technique. Cells from the injected right eyes produced from 300 to 800 plaques/million cells. Cells from the left eyes, which had received only buffer, failed to produce plaques. In other experiments, rabbits were reinjected intravitreally in the opposite (left) eye at various times after primary immunization. The left eye cells produced more than 800 plaques/million cells. Cells from the right eyes were still capable of producing smaller numbers of plaques even though no inflammation had recurred. Examination of sections of uveal tract tissue revealed pyroninophilic cells in eyes that formed antibody.

These observations confirm the hypothesis that ocular tissue can actually be involved in antibody formation, and that under certain conditions the eye can act as an “accessory lymph node.”
C5 Chemotactic Fragments Produced by an Enzyme in Lysosomal Granules of Neutrophils
Authors: Ward Peter A. , Hill Jeffrey H.
Published: December 2022

Lysosomal granules from rabbit neutrophilic leukocytes contain an enzyme that cleaves the fifth component of human complement (C5) into chemotactically active fragments. The enzyme cleaves C5, but not the third component of complement, into chemotactically active fragments of variable molecular weights, depending upon conditions of incubation. One fragment consistently behaves in ultracentrifugation and gel filtration similar to the reference standard cytochrome c. The amount of chemotactic activity generated by interaction of the lysosomal granule lysate and C5 is a function of concentrations of C5 and lysate, as well as duration of incubation.

The C5-cleaving enzyme of neutrophil lysosomal granules has a neutral pH optimum for activity. Based upon gel filtration, it has an estimated molecular weight of 35,000, is inhibited by esters bearing basic amino acids, is susceptible to inhibition by ε-amino caproic acid and in varying degree is susceptible to action of soybean trypsin inhibitor and EDTA.

The presence in the neutrophil of an enzyme capable of cleaving C5 into chemotactically active fragments may reflect the potential for the neutrophil to exacerbate in a non-immunologic manner the acute inflammatory process once it is underway.
Interaction of Plasma Kallikrein with the C1̄ Inhibitor
Authors: Gigli Irma , Mason John W. , Colman Robert W. , Austen K. Frank
Published: December 2022

The development of a hemolytic assay for the measurement of the inhibitor of the activated first component of complement (C1̄INH) and the isolation of a functionally pure preparation of plasma kallikrein have permitted the following observations: The C1̄INH inhibits the enzymatic activity of purified human plasma kallikrein on TAMe and on its natural substrate kininogen. The interaction of C1̄INH and kallikrein proceeds in a fashion similar to the interaction of this inhibitor and the first component of complement. The reaction follows a second order kinetics, resulting in the formation of an inactive stoichiometric complex of C1̄INH and kallikrein.

The finding that C1̄INH acts effectively against both the activated first component of complement and plasma kallikre in is consistent with the view that the absence of this control step may be responsible for the episodic activation of C1 as well as the elaboration of the pathogenic peptide in patients with hereditary angioedema (HAE).
Complement-Requiring Neutralizing Antibodies in Herpesvirus Hominis Encephalitis
Authors: Lerner A. Martin , Bailey Elizabeth J. , Nolan David C.
Published: December 2022

Attempts at diagnosis of Herpesvirus hominis encephalitis by isolation of virus and a histologic search for type A intranuclear inclusion bodies from biopsies of the brain were made in eight patients who later were shown to have this disease. By these means a diagnosis was established in two of the eight patients.

In four of seven patients with herpesvirus encephalitis the initial serum showed titers of complement-requiring neutralizing antibodies to Herpesvirus hominis that were significantly greater (4 or more) than the titers of non-complement-requiring neutralizing antibodies. In another patient the CRN/N was 4 on the 15th day in the hospital. Complement dependence generally disappeared in later sera. The CRN/N was 4 or more during two of four episodes of recurrent mucocutaneous herpes simplex and in five of 17 persons without current recognized herpetic infection. Disparities in times of rise and fall in complement-fixing, complement-requiring and non-complement-requiring neutralizing antibodies indicate that the molecular species of the three immunoglobulins are distinct.
Studies on Brain Antigens
Authors: Hatcher Victor B. , MacPherson Catherine F. C.
Published: December 2022

A water-soluble bovine antigen specific for nervous tissue, α-BASNT, has been purified by a series of steps involving ammonium sulfate precipitation, DEAE-cellulose chromatography and preparative electrophoresis. The antigen also occurs in rat and human brain and in bovine spinal cord, but not in other bovine organs or in rat peripheral nerve. It is formed early in the development of the brain, as it was present in the brain of a 3-month-old human fetus. The cytoplasm of glial cells is rich in α-BASNT.

α-BASNT has a molecular weight of about 84,000, formed one band when analyzed at pH 8.9 or 7.2 in gels containing different concentrations of polyacrylamide, and in agar gel immunoelectrophoresis α-BASNT had the electrophoretic mobility of an α globulin. It contained 2% carbohydrate, and, although only slightly acidic, glutamic and aspartic acids composed 23% of its total amino acid content.

Differences between α-BASNT and other brain proteins that have been identified within the last decade are discussed.
Distribution of Allotypic Specificities A1, A2, A14, and A15 Among Immunoglobulin G Molecules
Authors: Tosi S. Landucci , Mage R. G. , Dubiski S.
Published: December 2022

The distribution of specificities A1, A2 (Fd-associated allotypes of rabbit heavy chains), A14 and A15 (Fc-associated allotypes of rabbit γ chains) was studied using 125I-labeled IgG from homozygous and heterozygous rabbits of known pedigree. The IgG of an A1, 14/A2, 15 rabbit whose pedigree showed that A1 was genetically associated with A14 had closely similar proportions of these two specificities (80%), whereas IgG of an A1, 15/A2, 14 rabbit with A2 in coupling with A14 had equal proportions of these two specificities (20%). A rabbit with suppressed phenotypic expression of the A1 allotype was also suppressed for the A14 to which it was coupled. The quantitative expression of the Fc allotype (A14 or A15) is influenced by the Fd allotype with which it is genetically associated. The binding experiments indicated that the genetic association between Fd and Fc allotypes was faithfully reproduced in at least 90% to 95% of γ chains and a search for “recombinant” molecules (A1 with A14 and A15 in an A1, 14/A2, 15 heterozygote) was negative within the limits of the method (5% to 10%). Although a preliminary report (1) suggested that such molecules did occur, these low figures seem to indicate that the formation of “recombinant” molecules which utilize the genetic information for the Fd region from one homologous chromosome and for the Fc region from the other cannot play a major role in generating the diversity of antibody heavy chains.
The Role of Immune and Natural Specific Antibodies in Immunologic Paralysis and Immunity of Mice to Pneumococcal Polysaccharide Type III
Authors: Kerman Ronald , Segre Diego , Myers W. L.
Published: December 2022

Young offspring of immunologically paralyzed mice were more susceptible to the induction of both paralysis and immunity to SIII than were normal mice of the same age. This difference decreased gradually with age. We attributed the difference in immunologic responsiveness between the two types of mice to a lesser concentration of natural antibody specific for the SIII in the offspring of paralyzed mice as compared to normal mice of the same age. Administration of either specifically purified anti-SIII or normal IgG restored the offspring of paralyzed mice to the same level of susceptibility to the induction of both paralysis and immunity as that exhibited by normal mice. The biologic activity of normal IgG was removed by a specific immunosorbent, thereby confirming that the effect of normal IgG was also due to specific anti-SIII antibody. We therefore concluded that a relative deficiency of natural anti-SIII antibodies was indeed responsible for the altered immunologic behavior of offspring of paralyzed mice, and that the results obtained are compatible with, and explained by, a role of preformed antibody in the regulation of antibody formation.
Sandwich Solid Phase Radioimmunoassays for the Characterization of Human Immunoglobulins Synthesized In Vitro
Authors: Salmon Sydney E. , Smith Beth A.
Published: December 2022

This report describes a sensitive, simple and rapid direct-binding solid phase sandwich radioimmunoassay for measurement of intrinsically labeled immunoglobulins synthesized in vitro. With the direct technique, small volumes of labeled tissue culture supernatants or cell sonicates can be placed directly in the sandwich assay tubes and, after a short incubation and washing, the bound specific antigen can be counted. This new direct assay complements the previously described sandwich inhibition radioimmunoassay for immunoglobulin quantitation. With the use of both techniques on the same samples, detailed quantitative characterization of cellular synthesis, assembly and secretion of immunoglobulins can be obtained under a variety of circumstances. The quantity, absolute specific activity and antigenic composition of immunoglobulins synthesized in vitro can be determined routinely with the application of the two sandwich techniques. A series of experiments on plasma cells that synthesize monoclonal IgG illustrate applications of the methods. The sandwich techniques are applicable to the detection of unlabeled or labeled immunoglobulins in the nanogram to microgram range and are suited to studies of in vitro immunoglobulin synthesis where such sensitivity and specificity are required.
Metal Cation Requirements for Phytohemagglutinin-Induced Transformation of Human Peripheral Blood Lymphocytes
Authors: Alford Robert H.
Published: December 2022

Citrate and disodium EDTA were effective inhibitors of PHA-induced lymphocyte transformation. A high concentration of citrate (24 mM) was required. Citrate inhibition was totally reversible by calcium and half as effectively by magnesium. In experiments in calcium-magnesium-free medium, calcium was determined to be five times as effective as magnesium in promoting transformation. EDTA was effective in low concentrations (1.6 mM) in blocking transformation. This effect was not entirely reversible by calcium, and was not detectably affected by magnesium. Several other metal cations were effective in reversing EDTA inhibition of PHA-induced transformation. Zinc and iron appear likely to be essential for PHA-induced lymphocyte transformation in vitro.
The Biologic Half-Life of Brain-Localized Antisynapse Radioantibodies
Authors: Day Eugene D. , Appel Stanley H.
Published: December 2022

Synaptic membranes of rat brain cortex were isolated and used as immunogen with complete Freund's adjuvant to produce antisera in four rabbits. Pseudoglobulin fractions of IgG that were free of C1 were isolated, radioiodinated, and shown to fix complement after reaction with antigens.

All four antisynapse radioglobulins contained antibodies that would localize in liver, kidney and spleen. One contained antibodies that would also localize in significantly large amounts in brain. None of the four contained antibodies that would localize in lung, heart, testes or thymus.

The biologic half-lives of tissue-localized antibodies were calculated from data collected between the 3rd and the 27th day after intravenous administration of radioglobulins. The biologic half-life of brain-localized antibody was 7.4 days and that of spleen-localized antibody, 5.8 days. The biologic half-lives of antibody in kidney and liver were 9.2 and 12.0 days, respectively, while the biologic half-lives of localized portions of normal globulin in brain, spleen, kidney, liver, thymus, heart, testes, lung and blood were all very uniformly 13.3 to 14.2 days.

The heightened disappearance rate of brain-localized antibody indicated that an active mechanism was operative in brain for the removal of antibody once it was localized.
Deficiency of the Fourth Component of Complement in Man
Authors: Torisu Motomichi , Sonozaki Hidekichi , Inai Shinya , Arata Makoto
Published: December 2022

A new type of complement deficiency was found in the course of mass medical examinations. The following findings were obtained in three persons with this deficiency. a) The sera showed a selective decrease in C4 hemolytic activity. b) Serum complement activity was largely restored by the addition of highly purified C4. c) On immunoelectrophoresis, a β1E precipitin line developed with the sera of all three cases and was not noticeably weaker than that observed with control serum. d) C1 inactivator activity in these sera was not reduced as compared with that in normal serum. e) The sera were shown to have potent C4 inactivating activity.
Communications
Authors: Oroszlan Stephen , Stanley Thomas B. , Gilden Raymond V.
Published: December 2022

On the basis of their tumorigenic properties in hamsters, human adenoviruses have been divided into subgroup A, highly oncogenic, and subgroup B, weakly oncogenic, adenoviruses (1). Recent studies (2–5) have established a third subgroup, C, which consists of types 1, 2, 5 and 6. These types under appropriate conditions transform rat embryo cells, and like the viruses of subgroups A and B they produce a subgroup specific mRNA and a common T antigen.

The nonvirion nature of the T antigen of subgroups A and B has been amply documented by immunologic and biophysical methods employing purified antigens (1, 6–9). This report presents similar results on the relationship between T and structural antigens of adenovirus 2, a member of subgroup C.

Soluble viral antigens were produced in KB cell monolayers, which were harvested 48 hr after infection with adenovirus 2 (prototype strain).
Reduced Complement Activity in Sera of Patients with Waldenström's Macroglobulinemia
Authors: Glovsky M. , Fudenberg H. H.
Published: December 2022

Whole serum complement activity and complement activity of C1, C2 and C3 were determined in the sera of 11 patients with Waldenström's macroglobulinemia. C1 and C3 levels were low in approximately 50% of the sera studied. Whole complement and C2 levels were low in three of the patients.

Microzone electrophoresis revealed that in four of the 11 patients the paraprotein had relatively rapid γ or β mobility. Three of these patients had low whole serum C activity and low C2.

No correlation between whole serum complement activity, immunoglobulin quantitative levels, cold agglutinins, cryoglobulins, anti-nuclear or anti-γ globulin antibodies could be made.
Complement Dependent Killing of Mycoplasma Pneumoniae by Antibody: Kinetics of the Reaction
Authors: Gale James L. , Kenny George E.
Published: December 2022

The neutralization or killing of Mycoplasma pneumoniae by either rabbit or human antiserum required a heat-labile factor from non-immune serum. Killing was rapid, but could be stopped by dilution, thus permitting study of the reaction. The absolute number of organisms killed in a constant time interval was independent of the initial number of organisms present, making this reaction analogous to complement-mediated lysis of sensitized red blood cells. Although the rate of killing was influenced by antibody content, the level of normal serum factor appeared to have a much larger influence on the rate of the reaction. This heat-labile factor is apparently complement or some components of complement: it can be blocked by a chelating agent, is sensitive to salt concentration, and can be removed by prior absorption with a non-related complement-fixing antigen-antibody complex. Killing did not take place at 4°C, suggesting that the reaction is enzymatically controlled. The relative rates of killing appear to parallel lipid CF titers, but the measurement of antibody is 10 times as sensitive.
Immunoglobulins of the Hamster
Authors: Bienenstock John , Bloch Kurt J.
Published: December 2022

Hamster γ1, γ2, γA and γM globulins have been identified by immunoelectrophoresis developed with antisera from rabbits injected with antigen-hamster antibody complexes. Binding of labeled antigen to hamster γ1 and γ2 antibodies was observed in sera obtained 1 to 8 weeks following injection of hapten-protein conjugates emulsified in complete Freund's adjuvant. Binding to γM antibodies was limited to weeks 1 and 2 and binding to γA antibodies was demonstrable only at week 3. Indirect evidence for the existence of a reagin-like homocytotropic antibody was presented.
Species Comparison of Antigenic Determinants of the Variable Region of Light Chains of Immunoglobulins
Authors: Ruffilli A. , Baglioni C.
Published: December 2022

The distribution of five antigenic determinants of human Bence Jones proteins in the light chains of several other species is described. It is shown that three of these antigenic determinants identify in several species a small group of cross-reacting light chains. These observations are discussed in view of the possible theories concerning the genetic control of these proteins.
Immunogenicity of Human γ Globulin Bound to Macrophages after Inhibition of Rna Synthesis
Authors: Cruchaud A. , Despont J. P. , Girard J. P. , Mach B.
Published: December 2022

Macrophages obtained from the peritoneal cavity of mice were incubated in vitro with human γ globulin (HGG), and then transferred to allogeneic recipients that were boosted 30 days later with soluble antigen. Recipients made better primary and secondary responses to HGG bound to macrophages than did animals immunized with soluble HGG.

The immunogenicity of HGG in macrophages was moderately decreased by treatment of the cells with concentrations of actinomycin-D that inhibited RNA synthesis.

These results are discussed in the light of the possible importance of informational RNA and of increased immunogenicity of macrophage-bound antigen in the immunologic response.
The Effect of Fumaropimaric Acid on Delayed Hypersensitivity and Cutaneous Forssman Reactions in the Guinea Pig
Authors: Feinman Lawrence , Cohen Stanley , Becker Elmer L.
Published: December 2022

Fumaropimaric acid, when injected into guinea pigs by the intraperitoneal route, is effective in suppressing the cutaneous reaction to intradermally administered hemolysin (Forssman reaction) and the cutaneous contact reaction to a skin-sensitizing compound, o-chlorobenzoylchloride (delayed hypersensitivity). Guinea pigs did not respond to fumaropimaric acid in a parallel manner with respect to these two kinds of reactions, suggesting that the mechanism of inhibition was different for each. Although a suggestive relationship between degree of anticoagulation and delayed hypersensitivity response was observed in these experiments, there was no correlation between anticoagulation and reactivity to the hemolysin. Similarly, a conventional anticoagulant, heparin, had no demonstrable effect on the Forssman reaction. These results support previous studies which relate the anti-Forssman activity of fumaropimaric acid entirely to its ability to interfere with the complement system. It is suggested that the effect of fumaropimaric acid on delayed hypersensitivity reactions may be due to its ability to inhibit an underlying chemical reaction which is related to some stage of the clotting sequence.
Dissociation of Antibody Production from Disease Suppression in the Inhibition of Allergic Encephalomyelitis by Myelin Basic Protein
Authors: Lisak Robert P. , Falk George A. , Heinze Robert G. , Kies Marian W. , Alvord Ellsworth C.
Published: December 2022

Normal guinea pigs challenged with a single injection of homologous myelin basic protein (BP) in Freund's complete adjuvant develop experimental allergic encephalomyelitis (EAE) and delayed hypersensitivity to BP but only rarely develop detectable circulating anti-BP antibodies. Treatment of guinea pigs with methotrexate before and during disease induction completely blocks EAE and suppresses delayed hypersensitivity to the homologous encephalitogenic BP. In contrast, animals treated with methotrexate for 19 days and sensitized after a 2-day time lapse develop the same intensity of EAE and delayed hypersensitivity to BP as those sensitized without prior methotrexate treatment.

Treatment of guinea pigs with BP in incomplete adjuvant prior to encephalitogenic challenge suppresses development of both EAE and delayed hypersensitivity and simultaneously evokes anti-BP antibodies. Combined treatment of guinea pigs with methotrexate and BP prior to challenge almost completely suppresses the induction of anti-BP antibodies but does not interfere with the protective effect of the BP injections. Thus, the EAE-resistant state induced in guinea pigs by repeated injections of BP in incomplete adjuvant is apparently not dependent on induction of anti-BP antibodies. A more reasonable explanation for the resistance to EAE is that antigen accumulation prevents development or survival of a clone of BP-sensitized cells. These observations suggest that production or prevention of disease is correlated with induction or suppression of delayed hypersensitivity to BP and not with the presence or absence of circulating antibodies to BP. Antibodies to BP appear to be a coincidental phenomenon not involved in the pathogenesis of EAE.
Homocytotropic Antibody in Primary Responder and Hyperimmune Rabbits
Authors: Kindt Thomas J. , Todd Charles W.
Published: December 2022

Homocytotropic antibody against ovalbumin was found in both the primary and secondary responses in the rabbit. A comparison was made between HCA from the primary response and that from the hyperimmune response. No significant difference was found between the two using these criteria of comparison: percentage of animals responding, molecular size, electrophoretic mobility, heat and mercaptoethanol sensitivity, latent period required and maternal transfer of the activity. It appears that the same IgE-like antibody which elicits homologous passive cutaneous anaphylaxis reactions can be present in rabbits after one injection of ovalbumin or after a series of injections.
The Effect of X-Irradiation on Delayed Hypersensitivity and Circulating Antibody in the Rat
Authors: Bowser Robert T. , Spence Denise B. , Exum Eurmal D.
Published: December 2022

Rats exposed to x-radiation 24 hr before antigen administration exhibited detectable skin reactions to tuberculin 2 days later than nonirradiated sensitized controls. Reaction sizes illustrate that the irradiated rat experienced a decreased sensitivity to tuberculin which persisted through day 14.

The radiation dose (475 rads) responsible for the observed depression of the delayed skin reactions produced a greater depression of the circulating antibody response.

The results obtained suggest that the cellular and humoral immune responses in the rat are radiosensitive.