bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of Reticuloendothelial System Blockade Produced by Antilymphocyte Serum
Authors: Sheagren John N. , Barth Rolf F. , Edelin Joseph B. , Malmgren Richard A.
Published: December 2022

Mice treated with antilymphocyte serum (ALS) were found to have impaired blood clearance of aggregated human serum albumin (AA) and colloidal carbon. The clearance of AA was found to be immediately slowed by ALS with return to a normal rate by 24 hr. Clearance of a very small blood-flow dependent dose of AA was similarly affected, suggesting that the blockade of the AA clearing system could be related to altered perfusion of reticuloendothelial system organs (primarily decreased hepatic blood flow). Carbon clearance, in contrast, was found to be accelerated for a few hours prior to the development of blockade. Clearance of a very small blood flow-dependent dose of carbon also showed transient, immediate impairment, but then became and remained normal at a time when clearance of the larger dose of carbon was blocked. Impairment of carbon clearance appears, therefore, to be due to altered phagocytosis at the cellular level.
Receptor Sites for Complement on Certain Human Peripheral Blood Lymphocytes
Authors: Michlmayr Gerhard , Huber Heinz
Published: December 2022

Receptor sites for complement (C) on human peripheral blood lymphocytes were assessed by their capacity to bind red cells coated with C. Rosette formation was observed around 20% (12 to 29%) of blood lymphocytes obtained from normal donors. The number of lymphocytes with rosettes was related to the amount of C bound to the red cells. Treatment of lymphocytes with trypsin or incubation with antilymphocyte globulin inhibited the receptor activity. In contrast to the inhibition of rosette formation resulting from adding EDTA to the incubation mixture of monocytes and C-coated red cells, there was no inhibitory effect by EDTA on lymphocytes and C-coated red cells. Rosettes were almost exclusively observed around small lymphocytes. When lymphocytes were separated in a discontinuous bovine serum albumin gradient, the highest percentage of lymphocytes with receptor activity was found in fractions of low density. In patients with chronic lymphocytic leukemia there was a significantly lower percentage of rosette-forming cells.
Differentiation of Rosette-Forming Cells from Myeloid Stem Cells
Authors: Edwards G. E. , Miller R. G. , Phillips R. A.
Published: December 2022

Evidence is presented that the myeloid and lymphoid systems of the adult mouse are derived from a common stem cell. Ionizing radiation was used to induce unique chromosome markers in individual stem cells of the myeloid system. This marked stem cell was injected into genetically anemic mice of genotype W/Wv and repopulated their myeloid systems with chromosomally marked cells. To determine whether or not cells of the lymphoid system also contained the chromosome marker, we purified rosette-forming cells from the spleens of mice bearing a marker.

Mice were immunized with sheep erythrocytes (SRBC), and at the peak of the secondary immune response a spleen cell suspension was prepared. Cells in this suspension were allowed to bind SRBC and form rosettes, and the rosette-forming cells (RFC) were purified by velocity sedimentation. The RFC population appears to include all antibody-producing cells, but the converse may not be true. Karyotype analysis of the purified rosettes showed a high frequency of chromosomally marked cells, indicating that some RFC can be derived from stem cells that can also differentiate into myeloid cells.

These stem cells are probably pluripotent and able to give rise to RFC of many specificities. RFC specific for SRBC were found among the progeny of all the clones examined. It is highly unlikely that stem cells with restricted specificity would give such a result. The simplest interpretation is that there exist in bone marrow of adult mice pluripotent stem cells able to differentiate into functional cells of both the myeloid and lymphoid systems.
Studies on the Cytotoxic Immune Reaction
Authors: Manski W. , Ehrlich G.
Published: December 2022

Rabbit corneal epithelium tissue culture kept at low temperature (6°C) or exposed to colchicine or puromycin (10 µg/ml) in the growth medium ceased to show cytotoxic effects in response to duck anti-rabbit corneal serum. The above loss of susceptibility to antibodies was found to be reversible. It was shown experimentally that the underlying mechanism involved primarily a loss of antibody binding by the inhibited tissue cultures.
Structural Studies of Immunoglobulin E. II. Amino Terminal Sequence of the Heavy Chain
Authors: Terry William D. , Ogawa Makio , Kochwa Shaul
Published: December 2022

Determination of the primary structure of immunoglobulin proteins provides information that can be used to extend our knowledge of the structural relationship between different classes of immunoglobulins, as well as their genetic and evolutionary characteristics. Primary structural information will also be important ultimately in attaining an understanding of the antibody and non-antibody functional properties of these molecules.

Immunoglobulin E (IgE) is the most recently discovered of the human immunoglobulins and is the one, therefore, about which we have the least structural information. IgE antibodies bind antigens, and also have the capacity to sensitize receptors in human tissue for immediate hypersensitivity reactions (reviewed in 1). Structural studies of IgE will provide data for comparison with the amino acid sequences already determined for other classes of human immunoglobulins, and also may be useful in investigating the nature of the interaction between IgE molecules and cellular receptors.
Appendix and γM Antibody Formation. IV. Synergism of Appendix and Bone Marrow Cells in Early Antibody Response to Sheep Erythrocytes
Authors: Ozer H. , Waksman B. H.
Published: December 2022

Earlier studies have shown that the γM antibody response in rabbits injected intravenously (i.v.) with low doses of heat-aggregated bovine γ globulin is abolished by lethal whole body irradiation but preserved in animals whose appendix and bone marrow are shielded (1). Antibody-forming cells, however, were not found in the appendix itself but in that part of the mesenteric lymph node draining the appendix and in the spleen (2). We show here that the early response of rabbits to sheep red blood cells (SRBC) also requires the presence of both appendix and bone marrow cells.

Materials and Methods. New Zealand albino rabbits received 2 × 109 SRBC i.v., and their spleen cells were assayed 5 days later for direct plaque-forming cells (PFC) by a modification of the technique of Jerne et al. (3). Appendectomy, whole body irradiation (900 rads, central axis dose), and shielding of femoral bone marrow (after prior excision of both popliteal lymph nodes) were carried out by techniques already described (1, 2).
Complement Fixation: The Effects of IgG and IgM Antibody Concentration on C1-Binding Affinity
Authors: Linscott William D.
Published: December 2022

When red cells were reacted with increasing amounts of IgG antibody, the number of sites capable of binding C1 increased in a non-linear manner with constantly decreasing rate. At low antibody multiplicities, all of these sites bound C1 with approximately the same affinity, as shown by nearly complete C1 transfer at an ionic strength (μ) close to 0.06. As the amount of antibody increased, a heterogeneity in C1-binding affinities appeared, such that increasing amounts of C1 failed to transfer at μ = 0.059 but did transfer at μ = 0.140. It is suggested that this heterogeneity in C1 binding to IgG may reflect different C1-binding affinities of antibody doublets, triplets, etc. When red cells were reacted with increasing amounts of IgM antibody, the number of C1-binding sites increased linearly. The slope of the plotted curves of these data was close to 1. These sites bound C1 with a range of affinities that was constant, providing all sites were saturated with C1, over a wide range of IgM concentrations. If the antibody:C1 ratio exceeded approximately 1.5:1, a selection in favor of more firmly bound C1 appeared, so that the proportion of cell-bound C1 which transferred at any ionic strength below 0.14 became inversely proportional to the antibody concentration. It is suggested that this heterogeneity in C1 binding to IgM may reflect differences in the number of antibody combining sites which are occupied by antigen.
Serologic Evidence That Infectious Canine Hepatitis Virus Commonly Infects Humans and Is Related to Human Adenovirus Type 8
Authors: Smith Kendall O. , Gehle Warren D. , Kniker William T.
Published: December 2022

We have been interested in the possibility that viruses commonly occurring in household pets and other domestic animals infect man. Human infection with infectious canine hepatitis virus, (ICHV) has been suspected in the past, but evidence for this has been meager. Studies on the relationship of ICHV to human disease have been largely limited to veterinary workers (1) or to determining whether ICHV causes human hepatitis (2). ICHV, a canine adenovirus, was of particular interest to us in regard to human infection because Sarma et al. showed it to be oncogenic for hamsters (3). We reported recently that ICHV can infect human cells in vitro and initiate the synthesis of small amounts of new virus, and that infected human cells produce tumor-specific antigens (4). We also found that ICHV can frequently be isolated from the kidneys of dogs (5). This is not surprising because most dogs periodically receive doses of live attenuated ICHV vaccine for the prevention of infectious hepatitis and probably harbor virus for extended periods of time.
Experience with a Mixed Lymphocyte-Tumor Reaction as a Method of Detecting Antigenic Differences Between Normal and Neoplastic Cells
Authors: Kanner Steven P. , Mardiney Michael R. , Mangi Richard J.
Published: December 2022

A one-way mixed lymphocyte-tumor reaction having kinetics of DNA synthesis similar to those of the standard mixed lymphocyte reaction is described. This reaction may prove to be effective in detecting both antigenic differences between normal and neoplastic cells and host reactivity to tumor.
Identification and Genetic Control of the Mt-3 and Mt-4 Allotypes of Rabbit Serum α2-Macroglobulin
Authors: Berne Bernard H. , Dray Sheldon , Knight Katherine L.
Published: December 2022

Two rabbit serum α2-macroglobulin (α2M) allotypes, Mt-3 and Mt-4, which are distinct from the previously described Mtz1 and Mtz2 allelic allotypes of α2M, were identified. The Mt-3 and Mt-4 allotypes are controlled by a pair of alleles at an autosomal locus that appears to be closely linked to the Mtz locus and not closely linked to the Aa, Ab, or Af immunoglobulin loci, or to the Lpq lipoprotein locus. Sera from Mt-3Mt-4 heterozygous rabbits do not precipitate in agar gel double diffusion plates with either anti-Mt-3 or anti-Mt-4 antisera, but do inhibit the precipitation of each antiserum with serum from the corresponding homozygous rabbits. Serum from a heterozygous rabbit precipitates with a mixture of the two antisera, indicating that both Mt-3 and Mt-4 determinants are present on the same α2M molecule and suggesting that Mt-3 and Mt-4 determinants are each present in a smaller number than that found on molecules from homozygous rabbits. Allelic exclusion does not occur at the molecular level in the Mt-3Mt-4 heterozygous rabbit; in this respect, the Mt-3/Mt-4 system resembles the Mtz1/Mtz2 system, but is dissimilar from all other known serum allotype systems. Individual α2M molecules possess allotypic specificities of both the Mtz1/Mtz2 and Mt-3/Mt-4 systems.
The Effect of Selective Modification of Tryptophan, Lysine and Arginine Residues of Basic Brain Protein on Encephalitogenic Activity
Authors: Swanborg Robert H.
Published: December 2022

Basic protein (BP), which caused experimental allergic encephalomyelitis in guinea pigs in a dose of 30 μg, was isolated from bovine brain. Studies were carried out to characterize the encephalitogenic determinant by means of selective and permanent modification of tryptophan, lysine and arginine residues of BP. When tryptophan residues of BP were altered by the addition of 0.045 μmol 2-hydroxy-5-nitrobenzyl bromide/mg BP, preparations exhibited a significant decrease in encephalitogenic activity. In contrast, acetylation of free amino groups of lysine with acetic anhydride, or modification of guanidinium groups of arginine with 2,3-butanedione, had no effect on the encephalitogenic activity of BP. These results suggest that tryptophan is an essential component of the encephalitogenic determinant, whereas lysine and arginine are probably not present in this site.
The Kinetics of in Vivo Tolerance Introduction in Mice
Authors: Das Saroj , Leskowitz Sidney
Published: December 2022

C57BL/6 mice were rendered immunologically tolerant by an intraperitoneal injection of 200 μg of bovine γ globulin (BGG). An intraperitoneal injection of 1 mg of polyornithine (poly-O) given from 24 hr before to 5 hr after the injection of BGG produced immunity rather than tolerance. After 8 hr the induction of tolerance by BGG was no longer reversible by the poly-O. In a further test of the induction period of tolerance, washed spleen cells were transferred to x-irradiated recipients which were then immunized. If spleen cells were removed from donor mice as little as 4 hr after they had been injected with 2 mg of BGG, significant loss of ability to produce immunity in recipients was seen.
The Effect of Aging on Human Serum Immunoglobulin Concentrations
Authors: Buckley C. E. , Dorsey F. C.
Published: December 2022

Single radial diffusion was used to measure the concentration of IgG, IgA and IgM in sera of 811 healthy individuals aged from birth to 92 years. Evaluation of age, race and sex differences was accomplished by multivariate analysis on loge transformed data using age as a linear covariate for each race-sex group within the 0 to 13, 14 to 27, 28 to 54 and 55 to 92 year age spans. Age contrasts between all groups were highly significant (p < 0.0001), while race and sex contrasts within all groups revealed only a significant difference in IgG related to race (p < 0.0133). Maximum serum immunoglobulin concentrations were reached in the third decade. Highly significant changes related to aging occur in older individuals as well as early in life. Average IgM concentrations decreased significantly by the sixth decade (p < 0.0005). Average IgG decreased significantly from the third through the sixth decade (p < 0.0027). Changes in serum IgA after maturity were small and not significant. These observations document the occurrence of a relative hypoglobulinemia in healthy older individuals.
Further Studies on Guinea Pig Skin Sensitizing Activities of Human Myeloma Proteins
Authors: Ovary Zoltan , Kunkel Henry G. , Joslin Fenneke G.
Published: December 2022

Guinea pigs may be sensitized for reverse passive cutaneous anaphylaxis (RPCA) by the following human γG subclasses: γG1, γG3 and γG4. Native or reduced and alkylated γG2 and γE are unable to do so. Sensitization is independent of the light chain type and also of Gm determinants. Incomplete molecules from heavy chain diseases of subclasses γG1, γG3 or γG4, but not of subclass γG2, may sensitize guinea pig skin. RPCA reactions may be obtained with anti-light chain antibodies with γG1, γG3 or γG4.
A Method for Preparing Specific Fluorescein-Conjugated Antibody Reagents Using Bentonite Immunoadsorbents
Authors: Reisberg Margaret A. , Rossen Roger D. , Butler William T.
Published: December 2022

A simple, rapid, and reproducible method is described for the preparation of fluorescein-conjugated specific antibody reagents. Bentonite clay was used to adsorb and insolubilize antigen. Release of antigen from bentonite particles was prevented by treating the adsorbed antigen with a water-soluble carbodiimide reagent. The resulting immunoadsorbent could be used both to isolate homologous antibody and to remove cross-reacting antibodies from heterologous antisera. These immunoadsorbents were reusable, well-adapted to batch techniques, and stable on storage at -70° to 4°C for periods in excess of 1 year. Prior isolation of antibody globulin is not required before fluorescein conjugation when antibody is to be isolated subsequently by immunoadsorbents. The quantity of fluorescein isothiocyanate (FITC) used for conjugation of the antiserum was rigorously controlled by adding 1-µ1 portions of dissolved FITC, so that subsequent fractionation to remove excessively labeled globulin is not required. With these methods highly specific antibody reagents can be prepared in a single working day when homologous antigen is already available. More than 95% of the protein in such conjugates has antibody activity as measured by the ability to bind to homologous antigen. When used to locate antigen in tissue, the antibody reagents exhibit virtually no background fluorescence.
Physical Separation of Hemopoietic Stem Cells from Cells Causing Graft-vs-Host Disease
Authors: Phillips R. A. , Miller R. G.
Published: December 2022

The goal in these experiments was to obtain a physical separation of the cells causing graft-vs-host disease (GVHD) from hemopoietic stem cells. Because these two types of cells were thought to differ in size, a cell separation method, velocity sedimentation, that separates cells primarily on the basis of cell volume was used. To test the effectiveness of this separation procedure, spleen and bone marrow from donor mice were fractionated and GVHD activity in the various fractions was assayed by injecting the cells into appropriate recipients. These experiments showed that for both tissues GVHD is caused by a homogeneous population of small cells having a sedimentation velocity at 4°C and unit gravity of 3 mm/hr. Because hemopoietic stem cells are known to sediment at 4.0 mm/hr under these conditions, it was concluded that hemopoietic stem cells in the mouse can be physically separated by velocity sedimentation from the cells that cause GVHD.
The Termination of Immunologic Unresponsiveness to BSA in Rabbits
Authors: Benjamin David C. , Weigle William O.
Published: December 2022

Rabbits made unresponsive to BSA at birth were given two courses of immunization with various cross-reacting albumins and a subsequent injection of BSA. The same fraction of unresponsive rabbits as control rabbits responded to this subsequent injection by producing antibody reactive with BSA. Normal control rabbits were found to produce higher levels of antibody than did the previously unresponsive rabbits. Assays for both antibody-producing cells in the spleens and serum antibody of the previously unresponsive rabbits showed that 1) the subsequent injection of BSA failed to recruit precursor cells specific for BSA, 2) those cells primed by the injections of the terminating antigens were exhausted by multiple injections of BSA, and 3) unresponsiveness appeared to be terminated to all determinants shared between BSA and the terminating antigen. Following immunization of either normal or BSA unresponsive rabbits with cross-reacting albumins, a subsequent injection of BSA resulted in the production of antibody specific for the cross-reacting albumin which could not be absorbed with BSA. The response in normal rabbits to the determinants on the BSA unrelated to the determinants on the cross-reacting antigen was secondary in nature.
In Vitro Induction of Sulfanilic Acid-Specific Antibodies by RNA Extracted from Rat Spleen
Authors: Juras D. S. , Abramoff P.
Published: December 2022

Rats were immunized with bovine serum albumin (BSA) or sulfanilic acid conjugated to BSA (sa-BSA) and RNA was extracted from spleens that were synthesizing antibody. The extracted RNA was used to induce sulfanilic acid-specific plaque forming cells (PFC) in a population of non-immune isologous cells in vitro. The induction was specific, since a significant number of PFC appeared in the presence of RNA from sa-BSA but not from either BSA-immunized or non-immunized rats. Sucrose gradient analysis of extracted RNA showed most of the immunogenic activity to be associated with light RNA (4 to 12S). The immunogenic activity of RNA was inhibited by RNase, partially inhibited by pronase, and not affected by DNase. Agglutination inhibition used to detect antigen associated with immunogenic RNA gave negative results. Analysis of RNA extracted from spleens of rats immunized with radioactive sulfanilic acid conjugated to BSA showed that radioactivity was not preferentially associated with immunogenic RNA.
Procarbazine As an Immunosuppressant in Animals
Authors: Stewart P. Brian , Bell Rosalind
Published: December 2022

Procarbazine, a methylhydrazine derivative, has been shown to be a potent immunosuppressant in mice, rats and rabbits. Procarbazine was much more effective if given continuously, starting 21 days before exposure to antigen or grafting and for 7 days after (procarbazine day -21 regimen) than if given 2 days before and continued for 13 days after (procarbazine day -2 regimen). Its action was best demonstrated in mice. Procarbazine prolonged the survival of skin grafts in strains incompatible and compatible at the H2 locus. It was also capable of prolonging second set skin grafts in the H2 compatible model, and is the only chemical immunosuppressant that can do this. It also suppressed completely circulating hemagglutinins to SRBC. In rabbits, the procarbazine day -21 regimen produced a prolongation of skin allograft survival and significantly depressed the level of humoral antibodies to bovine serum albumin, but less effectively than in the mouse. This could be due to the fact that rabbits could tolerate only one-twentieth of the procarbazine dosage on a weight basis, as the mouse.
Heterogeneity of Carbohydrate Content of Human IgA Myeloma Proteins
Authors: Wang An-Chuan , Fudenberg H. Hugh
Published: December 2022

Carbohydrate determinations were performed on seven human IgA myeloma proteins, four of them in both monomeric and polymeric form. The results showed that IgA molecules are hetero-geneons in carbohydrate content, that the carbohydrate portion probably does not contribute directly to the polymerization of IgA molecules, and that the IgA2 subclass does not appear to possess galactosamine.
Canine Secretory Immunoglobulins: Identification of Secretory Component
Authors: Ricks John , Roberts Mary , Patterson Roy
Published: December 2022

Immunoglobulin A was demonstrated in canine tracheal secretions, saliva, tears, nasal secretions and colostrum. Another molecular species, presumably canine secretory component, was demonstrated in colostrum, tracheal secretions and tears. The IgA in colostrum was purified by a combination of Sephadex G-200 and DEAE-cellulose chromatography, and an antiserum which reacts with IgA and secretory component was prepared against this purified IgA. Immunoglobulins G, A and M were measured semiquantitatively in colostrum and milk and compared to serum values. Immunoglobulin A has the highest colostrum to serum ratio, IgG has the next highest and IgM is usually found in higher concentration in serum than in colostrum. The actual concentrations of IgG, IgA and IgM in the colostrum, however, varied widely among the six dogs studied.
Thymus Dependency of the Immune Response to Hemocyanin: An Evaluation of the Role of Macrophages in Thymectomized Mice
Authors: Unanue Emil R.
Published: December 2022

The role of the thymus in the immune response to keyhole limpet hemocyanin (KLH) was studied in the mouse. Adult mice were thymectomized, lethally irradiated and reconstituted with bone marrow cells. The immune response to KLH was greatly impaired by thymectomy. Only some thymectomized mice could respond to large doses of KLH but in low amounts. The thymectomized mice did not respond to KLH bound to live macrophages nor to KLH administered simultaneously with an adjuvant like beryllium. Macrophages from both thymectomized and control mice handled KLH similarly.
Primary Rejection of Homologous Intraperitoneal Fibroblasts: An Electron Microscopic Study
Authors: Weiss Leon , Smyth Prudence
Published: December 2022

This is an electron microscopic study of the rejection of a simple graft. 2 × 106 L cells (a tissue culture culture strain of fibroblasts derived from C3H mice) are injected intraperitoneally into BALB/cJ mice. Following the injection intraperitoneal nodules 2 to 4 mm in diameter appear by day 2 and remain until days 5 to 7. The surface of the nodules is covered by histiocytes and L cells. These cells bear surface projections and are strikingly similar to mesothelium. Each nodule displays a central zone, and inner and outer shells. The outer shell is dominated by L cells; a few macrophages, plasma cells, lymphocytes and granulocytes are present. The inner shell contains many L cells, many macrophages, and lymphocytes, and relatively few plasma cells and mast cells. Host cells and L cells are in close touch, their contiguity increased by interdigitation of filiform cytoplasmic processes. Cytoplasmic continuity is seldom observed. Emperipolesis is occasionally noted. Especially toward the inner part of this shell both L cells and host cells are vacuolated and show other signs of damage. In certain nodules the L cell surface shows virus-like particles on stalk-like processes. The central zone is necrotic, often caseous. At the junction of the central zone and inner shell fluid necrotic material lies between vital cells and is taken into lysosomes of macrophages and, to a lesser extent, of other cell types. Some collagen is present throughout the nodule. Rarely are the nodules vascularized. During the rejection of the nodules, Peyer's patches, abdominal lymph nodes, and the spleen are enlarged by L cells. Changes similar to those present in the nodules are observed in these lymphatic structures.
An In Vitro Model of the Anamnestic Response of Rabbit Lymph Node Cell Suspensions to Keyhole Limpet Hemocyanin
Authors: Herscowitz Herbert B. , Stavitsky Abram B.
Published: December 2022

Suspensions of popliteal lymph node cells from rabbits primed with keyhole limpet hemocyanin (KLH) were stimulated in vitro with KLH to give an anamnestic response. Newly synthesized IgG antibody as determined by the incorporation of radioactive leucine was first detected in the culture medium on days 2 and 3, reached a peak on days 5 to 7 and declined thereafter. The antigen-stimulated cells also synthesized increased amounts of non-antibody proteins, including α, β and γ globulins, which accounted for over 90% of the incorporated radioactivity. Both antibody and protein syntheses were antigen dose-dependent and required contact of primed cells with KLH for several hours. The synthesis of DNA and RNA increased in antigen-stimulated cells and preceded the appearance of radioactive antibody.
Lymphocytotoxic Antibody Response to Cardiac Allotransplantation in Man
Authors: Johnson Armead H. , Butler William T. , Rossen Roger D. , Mittal Kamal K.
Published: December 2022

Sera of 4 of 7 patients who developed a strong lymphocytotoxic response after cardiac transplantation showed a possible association with known histocompatibility groups. In 3 of these 4 patients the antibodies appeared to have specificity for antigens known to be present in donor but not in recipient lymphocytes. Thirty sera from the 7 cardiac allograft recipients were fractionated by sucrose density gradient ultracentrifugation. In each sample lymphocytotoxic activity was detected exclusively in the 19S region. In contrast, 3 sera from 2 renal transplant patients showed detectable lymphocytotoxic activity only in the 7S region. Among possible explanations for these results are that 7S antibodies were preferentially absorbed by the cardiac allografts or that these sera contain substances which block the action of 7S lymphocytotoxins.
Mechanisms of Passive Sensitization
Authors: Ishizaka Kimishige , Tomioka Hisao , Ishizaka Teruko
Published: December 2022

Immunoglobulins E and G were detected on human leukocytes by autoradiography. Evidence was obtained that specifically purified anti-human γE antibody combined with basophilic leukocytes from both normal and atopic individuals, and that anti-γG antibody bound with neutrophils and monocytes. Upon passive sensitization, E myeloma protein bound with basophils and normal γG bound with neutrophils and monocytes. The results show that basophils have receptor sites for γE, and that both neutrophils and monocytes have receptor sites for γG. Binding of the Fc fragments, but not the F(ab′)2 fragments, of E myeloma protein with basophils indicated that γE combines with basophils through the Fc portion of the molecules. The binding of γE with basophils appears to be a process of passive sensitization for both antigen-induced and antibody-induced histamine release from leukocytes.
Precursor Cells in Density Fractions of Lymph Node Cells: Relation to Antibody-Producing Cells
Authors: Moav Neomi , Harris T. N.
Published: December 2022

Spleen cells of mice were transferred intravenously into x-irradiated syngeneic recipients which were also injected with sheep red blood cells (SRBC). The dose of irradiation was sufficient to prevent active immunization by the SRBC injected. At intervals thereafter, spleens of recipients were teased and the cells plated in agar against SRBC, to determine relative numbers of precursor cells for this immunologic response which had been transferred.

In normal mouse spleen cells fractionated by bovine plasma albumin (BPA) density gradient centrifugation, cells pooled from the higher or the lower density range of fractions yielded equal numbers of plaque-forming cells (PFC) in the recipients' spleens 6 to 8 days later. The same was found in cells obtained from spleens 30 days after primary injection of SRBC. In cells obtained 5 days after secondary injection of SRBC, however, the low density cells contained more precursor cells per million than cells in the high density fractions. In other portions of such spleen cell suspensions, which had been incubated for the production of anti-SRBC rosettes and then fractionated, the high density fraction again contained fewer precursor cells per million than the low density fraction. In this case, the high density fractions also contained the rosette-forming cells (RFC) because these were now included in rosettes. The latter, the high density, rosette-rich, fraction of the rosette preparation produced no more precursor cells than the similar fraction of the original suspension, indicating that the cells currently producing antibody were not a major source of precursor cells.
Immunoglobulin Elevations in the Serum of Patients with Chronic Bronchitis and Emphysema
Authors: Falk George A. , Siskind Gregory W. , Smith James P.
Published: December 2022

Serum concentrations of immunoglobulins G, A and M (IgG, IgA and IgM) were measured in 49 patients aged 41 to 80 with severe chronic obstructive pulmonary disease (chronic bronchitis and emphysema) and in 67 normal subjects of similar age and sex distribution. In the normal subjects, concentrations of IgA rose significantly with increasing age whereas concentrations of IgG and IgM remained constant. In contrast, concentrations of IgA and IgM remained constant in the patient group whereas concentrations of IgG rose significantly with increasing age. When patients were compared to normal subjects of comparable age, average serum concentrations of IgA were found to be elevated in the younger patients (ages 41 to 50) whereas average concentrations of IgG were elevated in the older patients (ages 61 to 80). Deficiency in IgG, IgA or IgM was not a feature of chronic bronchitis and emphysema at any age.
Temporal Dissociation of Experimental Allergic Encephalomyelitis Transfer Activity and γ Globulin Staining of Lymphoid Cells from Sensitized Lewis Rats
Authors: Richardson Walter P. , Paterson Philip Y.
Published: December 2022

Discussion and Summary

The occurrence of peak EAE transfer activity in LNC several days after time of maximum staining for γ globulin suggests that the factor(s) responsible for transfer of EAE lesions is distinct from conventional immunoglobulins. This finding provides a clear explanation for our earlier observation, viz., anti-rat γ globulin serum does not alter EAE transfer activity of D9 LNC (1).

We are aware that we have no evidence as to whether any of the γ globulin demonstrated in LNC represents antibody specifically reactive with nervous tissue. Our findings agree with that of Oldstone and Dixon (unpublished) that antibody reactive with brain is demonstrable in thoracic duct lymph of Lewis rats only between 5 and 7 days after sensitization. At no time could they find such antibody in blood serum.

Based on the results here reported (Table I), it is conceivable that two different immune responses, i.e., antibody production and delayed-type hypersensitivity, account for development of clinical neurologic signs and lesions, respectively—both being essential for occurrence of typical EAE. Under the conditions we employed for LNC transfer of EAE during the past 8 years, occurrence of paralytic signs has been a rare event in recipient Lewis rats receiving D9 LNC. This is true despite the fact that many animals develop severe lesions of EAE throughout the brain and spinal cord. Recent work has shown that phytohemagglutinin injected simultaneously with spinal cord-adjuvant markedly suppresses clinical signs of EAE in Lewis rats but has little, if any, effect on development of lesions of the disease (G. O. Westenfelter, P. Y. Paterson and D. G. Drobish, to be published). Bornstein and Crain (4) have reported a dissociation between serum factors causing synaptic blockade and those causing demyelination when acute phase EAE serum is added to myelinating and electrically active nervous tissue cultures. Pabst and Dupuy (5) have described production of paralytic, often lethal, disease without appreciable histologic changes in guinea pigs injected with plasma derived from donors sensitized to nervous tissue and given lethal doses of x-irradiation. Finally, Brown et al. (6) and Tung and Unanue (7) have secured strong evidence that in another well established experimental autoimmune disease, allergic orchitis, both antibody and sensitized lymphoid cells must act in concert in order for the full-blown disease to occur.
Immunoenzymology of Liver Alcohol Dehydrogenase
Authors: Fuller Thomas C. , Marucci Americo A.
Published: December 2022

The factors which govern the interaction and the inhibition of horse liver alcohol dehydrogenase (H-L-ADH) by specific antibody have been examined in detail. Both guinea pig and rabbit antisera inhibited the enzymic activity of H-L-ADH to varying degrees, with residual activity remaining even in the presence of a large excess of antibody. The inhibitory capacity of the antisera increased with prolonged immunization. The extent of enzymic inhibition was dependent on the molecular composition and the size of the immune complex, the order of addition of the reactants and the concentration of the substrate and the coenzyme. Inhibition of H-L-ADH was instantaneous and was not influenced by the presence of guinea pig complement.

A number of possible mechanisms which could account for the inhibition of H-L-ADH by antibody are discussed.
IgG Subclasses in the Baboon (Papio Cynocephalus)
Authors: Damian Raymond T. , Greene Nathan D. , Kalter S. S.
Published: December 2022

Heterogeneity of baboon (Papio cynocephalus) IgG, attributable to differences in the Fc regions of heavy chains, could be demonstrated by the use of specific antisera made in rabbits to isolated γ-chains. Four components of IgG were discernible in immunoelectrophoretic analysis. These antigenic determinants are not shared with man, as shown by absorption experiments with human globulin. The antigenic determinants are not polymorphic, but are a constant feature of the IgG of baboons from several distinct populations. Antibody activity to bovine serum albumin could be demonstrated in two or possibly all four of the components by radioimmunoelectrophoresis. These data support the conclusion that the baboon has four subclasses of IgG, which are delineated by antigenic determinants different from those delineating the human IgG subclasses. Preliminary evidence that these determinants are found in other monkey species is also presented.
Depressed Cellular and Humoral Hemolysin Responses of Rabbits Injected Intraperitoneally with Mineral Oil before Immunization
Authors: Huard Mary Ida-Jo , Siebeling R. J.
Published: December 2022

Intraperitoneal injection of rabbits with mineral oil 4 days before challenge immunization with sheep erythrocytes, by the same route, resulted in a delay in appearance of antibody and a significant depression of both the serum antibody response and the number of antibody plaque-forming cells. There was a 90% or greater suppression of the number of antibody-forming cells in the spleen and mesenteric lymph nodes of rabbits pretreated with oil as compared to control animals injected with red blood cells only.

Injection of oil on the same day as the red cells resulted in a marked increase in the serum titer, as well as a moderate increase in the number of plaque-forming cells in the spleen and lymph nodes. Some of the antibody detected 7 days after immunization was of the 7S class, as indicated by 2-mercaptoethanol resistance. Sera from normal animals and animals pretreated with oil contained mainly 19S hemolysins during the first 2 weeks after immunization.

Challenge immunization of rabbits by the intravenous route circumvented the immunosuppression induced by intraperitoneal injection of oil. Rabbits treated with oil either simultaneously or 4 days before intravenous immunization had as good or greater an antibody response than control animals. However, most of the plaque-forming cells appeared in the spleen, with very few in the mesenteric lymph nodes.

Four days after oil injection over 90% of the peritoneal exudate were macrophages. The role of such macrophages in the immune response, as well as the nature of the effect of oil on these cells, is discussed in relation to reticuloendothelial system blockade and antibody formation.
Specificity of Tolerance to Antigens the Immune Response to Which Is Controlled by the PLL Gene
Authors: Selawry Helena , Green Ira , Benacerraf Baruj
Published: December 2022

The ability of guinea pigs to respond immunologically to a group of structurally related, positively charged synthetic polypeptides is under the genetic control of a single dominant autosomal gene (1, 2). All inbred strain 2 guinea pigs and some of the outbred Hartley strain guinea pigs possess this gene, referred to as the poly-l-lysine (PLL) gene, and can respond to several synthetic polyamino acid antigens (poly-l-lysine, poly-l-arginine, a random copolymer of l-glutamic acid and l-lysine (GL), and protamine) and to the hapten conjugates of these materials. Despite the similarity of these antigens, the cellular immune responses elicited by each of these compounds are highly specific (3). All inbred strain 13 guinea pigs and some outbred Hartley's fail to make a strong antibody response and never develop cellular immunity when challenged with these polypeptides: they apparently lack the PLL gene (2).
Localization of b Markers, α-Chain and SC of SIgA in Epithclial Cells Lining Lieberkühn Crypts
Authors: O'Daly José A. , Craig Susan W. , Cebra John J.
Published: December 2022

Local synthesis of immunoglobulins (Igs) has been demonstrated in tissues surrounding epithelial cell layers engaged in secretion, such as in salivary glands, gastrointestinal tract, mammary glands and respiratory tract (1–4). Several theories have been put forth (4–6) to explain the passage of Igs, particularly secretory IgA (sIgA), from the plasma cells in the sub-epithelial spaces to the lumen of the various glands and organs. These have also been necessarily concerned with the assembly of the sIgA 11S dimer and its association with secretory component (SC), because the latter component can be localized in epithelial cells (1, 7) rather than in the plasma cells which synthesize the α and light chains of IgA. As yet, the route of the IgA molecule from the plasma cells to the lumen of various secretory glands has not been clearly delineated. However, the presence of IgA in between and/or at the apex both of the absorptive and glandular epithelial cells of the intestine has been described (4, 8, 9).
Studies of Antimuscle Factor in Myasthenia Gravis. II. Reactions of Fragments Produced by Enzymatic Digestion
Authors: McFarlin Dale E. , Johnson John S.
Published: December 2022

Antimuscle factor (AMF) is present in the sera of approximately 30% of patients with myasthenia gravis (MG) and 95% of patients with MG and thymoma (1); it also occurs in 24% of non-MG patients with thymomas (1). Sera from some normals and disease controls also bind to muscle in low titers (1, 2). In an earlier study the AMF in 12 sera from MG patients was found in IgG but not in IgA or IgM (2). However, it has not been established whether the binding of AMF to skeletal muscle represents an antigen-antibody reaction.

Sjöquist and Stålenheim have recently demonstrated that staphylococcal A protein specifically reacts with the IgG of several species to produce the biologic phenomena usually associated with antigen-antibody interactions. However, they have shown that staphylococcal A protein binds to the Fc rather than the Fab fragment of IgG and therefore does not represent a reaction of antigen with antibody (3).
Antigenic Variation of 7Sγ1, 7Sγ2 and γM Globulins Within the Genus Peromyscus
Authors: Coe J. E.
Published: December 2022

Three immunoglobulins were examined for their respective antigenic variation within the genus Peromyscus (white-footed mouse). Antigenic relationships among 7Sγ2, 7Sγ1 and γM globulins of 15 peromyscus species or subspecies were studied by using rabbit antisera specific for immunoglobulin from one of the species, Peromyscus maniculatus artemisiae (deer mouse). All peromyscus species tested contained antigenically similar 7Sγ2, 7Sγ1 and γM globulins. The γM globulins of all species or subspecies appeared identical to that of P. m. artemisiae. In contrast, 7Sγ2 globulins antigenically identical to those of P. m. artemisiae were found in only four peromyscus sera, which represented other subspecies of P. maniculatus. The 7Sγ1 globulins were antigenically identical in 12 of the peromycus, although the electrophoretic mobility of the 7Sγ1 globulin and its Fc piece differed from species to species. The results suggest that the structures of these immunoglobulins are evolving at dissimilar rates and 7Sγ2 globulin is undergoing more rapid evolutionary change than γM globulin.
Delayed Hypersensitivity to Catechols
Authors: Godfrey H. P. , Baer Harold , Watkins Roy C.
Published: December 2022

We have studied the fate of two chemicals related to poison ivy catechols after their administration to guinea pigs by the topical and oral routes. Tritiated pentadecylcatechol (PDC), a sensitizer and a tolerogen, and tritiated pentadecylveratrole (PDV), a nonsensitizer and nontolerogen, were rapidly absorbed into the serum after administration by either route and were also found in tissues in excess of their serum content. Although serum levels of PDC were higher than those of PDV after topical administration, the reverse was true after the oral route. Excretion of both chemicals was mainly via the feces but some was also found in urine. Because of the persistence of PDC (and to a lesser extent of PDV) in the bile (but not the serum and urine) an enterohepatic circulation of these materials was felt to exist and to be related to the induction of tolerance.

After topical administration of PDC a biphasic pattern of radioactive uptake was found in the draining but not the opposite inguinal lymph nodes. Radioactivity rapidly declined in the draining nodes after the onset of sensitivity. The draining lymph nodes of PDV-treated animals showed a saturation-like uptake of radioactivity with only slight decline over the month after administration. There was no difference between draining mesenteric and nondraining inguinal nodes after oral PDC or PDV; after oral PDC, however, a rapid uptake and loss of radioactivity occurred which was not due to serum entrapment by the nodes. This data suggests that the induction of tolerance is associated with the entry of free PDC or its metabolites into the lymph nodes via the blood stream whereas sensitization is associated with entry via the lymphatics.

PDC was rapidly cleared from the site of application after the onset of sensitivity; the rate of PDV skin clearance was constant. It is possible that delayed contact sensitivity is associated with a phenomenon similar to the immune clearance of soluble antigens.
Human Secretory Immunoglobulins
Authors: Brandtzaeg Per
Published: December 2022

A serum component with disulfide-linked secretory piece (SP) was detected. It was comparable to native secretory IgA in size and immunoelectrophoretic mobility, and also because its quaternary structure was highly stabilized, thus rendering an antigenic determinant of the bound SP inaccessible. Pools of normal human sera did not contain detectable amounts of this component; but single radial immunodiffusion revealed 59% positive sera in a control group (average concentration: 3.4 mg/100 ml), and 78% positive sera in an A-myeloma group (average concentration: 10.0 mg/100 ml). It was concluded that any condition that increases the permeability of glandular and mucosal tissues may raise the “spill-over” or absorption of secretory IgA into the circulation.
Prevention of Death from Endotoxin with Antisera
Authors: Brown Kenneth R. , Douglas Herndon , Braude Abraham I.
Published: December 2022

Fatal passive anaphylaxis to endotoxin was induced in mice given rat antiserum to endotoxin. In order to remove this dangerous property of antiserum, measures were taken to eliminate anaphylaxis and restore protection. Anaphylaxis to endotoxin was prevented by Isuprel, epinephrine and reserpine and by physicochemical alteration of the serum by dilution or UV irradiation. When anaphylaxis was avoided by any of these maneuvers, the antisera prevented death from endotoxin. Separation of immune globulin fractions on Sephadex columns also eliminated the anaphylactic property and the 19S and 7S fractions of immune serum prevented death from endotoxin. The observed anaphylaxis is thought to result from antigen-antibody complexes releasing vasoactive amines. Cytophilic antibody was not involved. This solution of the problem of passive anaphylaxis to endotoxin is an essential step in preparing a safe antiserum for preventing death from endotoxin in man.
Properties of the Combining Sites of Rabbit IgM Antibodies
Authors: Kishimoto Tadamitsu , Onoue Kaoru
Published: December 2022

Hapten-binding properties of the rabbit IgM antibodies obtained by immunizing rabbits with salmonella cells coupled with 1-azo-naphthalene-4-sulfonate group were determined. It was reconfirmed that the IgM antibodies had 10 detectable combining sites and that half of the total combining sites in the preparation were much higher in affinity for hapten than the other half. The antibodies were separated into two fractions by adsorption with an insoluble immunoadsorbent. The results of hapten-binding experiments with these antibody fractions by equilibrium dialysis showed that each fraction contained the high- and low-affinity sites in about equal numbers, and that equal numbers of high- and low-affinity sites appeared to be present on a single molecule of the antibody. The F(ab′)2 fragment prepared by peptic digestion of the IgM antibody showed similar hapten-binding properties to those of the native antibody, indicating that the observed difference in the affinity of the combining sites was not related to the state of assembly of the subunits in the native molecule. A significant decrease of the combining sites was observed with the peptic monomer fragment, Fab pep, and it seemed that the low-affinity sites were more affected than the high-affinity sites in the process of peptic digestion.