bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Immune Response to Penicillin and Cephalothin in Humans
Authors: Spath Peter , Garratty George , Petz Lawrence
Published: December 2022

The characteristics of immunohematologic reactions to cephalothin were investigated with emphasis on the incidence and mechanism of development of positive antiglobulin tests. Three hundred twenty direct antiglobulin tests were performed on 97 patients who received cephalothin at an average dose of 6.3 g/day and for an average of 5.5 days. Four of the 97 patients developed a positive antiglobulin test for an incidence of 4%. Studies were done concerning the mechanism of the positive direct antiglobulin tests. The data indicate that nonimmunologic binding of proteins occurs in vitro since multiple absorptions of a serum with cephalothin-sensitized erythrocytes revealed that the cephalothin-sensitized cells absorb IgG and other serum proteins, even after repeated absorptions sufficient to remove all cephalothin antibodies. Non-immunologic binding of proteins to cephalothin-sensitized red cells was further confirmed by demonstrating the absorption of complement (C3) from EDTA-plasma, and by the absorption of albumin. Such a mechanism may operate in vivo since cephalothin, when added to whole blood at a concentration of 500 µg/ml, causes protein absorption to the erythrocytes. An immune mechanism causes positive antiglobulin tests in vivo as evidenced by the fact that eluates from patients' erythrocytes react with cephalothin-and penicillin-sensitized erythrocytes but not with non-sensitized erythrocytes. Further, eluates from Rh sensitized erythrocytes did not react with cephalothin-sensitized red cells indicating that the concentration of antibody protein in such eluates is not high enough to produce positive indirect antiglobulin tests by the mechanism of non-immunologic absorption of proteins. Studies characterizing the serum cephalothin antibodies revealed IgM antibodies in 88% of 40 sera tested. Although IgG antibodies occurred in only 25% of these sera, the sera of four patients having a positive antiglobulin test all contained high titer IgG antibodies. Absorption of sera of patients with positive antiglobulin tests with penicillin-sensitized erythrocytes revealed varying degrees of cross-reactivity with such erythrocytes.
Characterization of Precipitating Antibody in Equine Infectious Anemia
Authors: Nakajima Hideo , Kono Yuji , Ushimi Chuzo
Published: December 2022

The characterization of precipitating antibody from horses experimentally infected with equine infectious anemia (EIA) virus is reported. Precipitation was demonstrated in an agar gel, using purified virus as antigen. Precipitating antibody was present in the γ globulin fractionated from infected serum with ammonium sulfate and by diethylaminoethyl cellulose chromatography. Antibody was also recovered in the 7S globulin fraction separated with Sephadex G-200 from sera collected both early and later in the disease. When 7S globulin was added to purified antigen, precipitation between the resulting antigen-globulin complex and a reference EIA antiserum was inhibited. Precipitating antibody was first detected shortly after the first febrile reaction. At that time no neutralizing antibody was found, but the appearance of precipitating antibody coincided fairly well with that of the complement fixing (CF) antibody. In contrast to CF antibody, which usually dropped below a detectable level shortly after onset of the disease, the precipitating antibody remained detectable for at least 150 days. The relationships of precipitating antibody to the CF and neutralizing antibodies are discussed. Listed are factors indicative of the value of the immunodiffusion reaction for diagnosis of EIA.
Cells Involved in the Immune Response. XXIV. The Demonstration of the Multiclonal Nature of the Antigen-Reactive Cell Population in the Bone Marrow of the Normal Adult Rabbit
Authors: Richter Maxwell , Abdou Nabih I.
Published: December 2022

The antigen-reactive cell (ARC) population in the bone marrow of the normal rabbit was investigated for its distribution in the various bone marrow compartments (right and left tibias and femurs). Irradiated immuno-incompetent rabbits were injected with lymphoid cells obtained from only one of the bone marrow compartments and challenged with sheep and horse erythrocytes. Recipients of cells of only one of the compartments were often capable of responding with antibody formation and more than one compartment was observed to contain ARCs. These results imply that more than one clone of ARCs exists with respect to any particular antigen.
Complement Utilization by Guinea Pig γ1 and γ2 Immunoglobulins through the C3 Activator System
Authors: Sandberg Ann L. , Götze Otto , Müller-Eberhard Hans J. , Osler Abraham G.
Published: December 2022

The recent demonstration of the C3 activator system in human serum (1) suggested a possible mechanism for the utilization of late complement components by guinea pig γ1 immunoglobulins which, as was previously shown, bypass interaction with C1, C4 and C2 (2–4). Antibodies with the γ2 mobility activate the C sequence at C1 and in addition may follow the same pathway of late component utilization described for the γ1 variety. Both of the guinea pig immunoglobulins possess a site on the F(ab′)2 fragments for activation of the C sequence at the C3 stage. The site for initiation of the classical C sequence, possessed only by the γ2 immunoglobulins, resides on the Fc fragment since it is destroyed by treatment of the molecule with pepsin.

The C3 activator system has also been shown to furnish an alternate pathway for the activation of the late complement components (C3–C9) (1).
Hyperlipidemic Myelomatosis
Authors: Mullinax F. , Himrod B. , Berry E. R.
Published: December 2022

An unusual patient with multiple myeloma and hyperlipidemia provided the basis for study of the chemistry of lipid binding by her myeloma protein. Lipid-free M protein prepared by ultracentrifugation and gel chromatography existed as IgA κ monomers and disulfide-linked dimers which were used for serologic, gel diffusion and proteolytic digestion studies. Native plasma, lipid-free plasma and purified M protein reacted in agar diffusion with α- and β-lipoprotein. The plasma also agglutinated RBC of sheep, but not those of man or other species. Inhibition of agglutination by the isolated M protein was strongest with choline, which at 0.0001 µg/ml reduced the titer from 1:2048 to 1:256. Less marked inhibition was noted with lysolecithin, phosphorylcholine and sphingomyelin. Pepsin digestion of the M protein produced serologically inactive fragments. Neither agglutination nor inhibition of agglutination was produced by H or L chains. Apparently the IgA protein binds free lipids, lipoproteins or sheep RBC through choline side chains.
Detection of Human Homogeneous Immunoglobulins with Antibody Activity for Synthetic Haptenes
Authors: Woods Roy , Terry William D.
Published: December 2022

In order to identify homogeneous immunoglobulin paraproteins with antibody activity, sera containing homogeneous proteins of the IgG, IgA, IgM, IgD, IgE and Bence Jones varieties were screened against a panel of radioactively labeled nitrophenyl and sugar derivatives. The screening procedure was a modification of the Farr technique which measures antigen binding by antibody. The radioactively labeled synthetic ligands used in the study included the following: 3H-DNP-lysine, 3H-DNP-ε amino caproate (DNP-cap), 125I-HOP, 125I-NIP, 125I-IM-5 and 125I-SLAC. In the DNP-lysine and DNP-cap systems, known proteins which bind these ligands were used as positive controls. If a test serum showed binding that approached or exceeded the extent of binding by the positive control, the paraprotein was precipitated with ammonium sulfate, resuspended in normal saline and retested. In the other systems, if the partially purified paraproteins bound a minimum of 10% of the counts when compared to negative controls, they were considered to be positive.
Studies on Human Myeloma Proteins with Antibody-Like Activity
Authors: Freedman M. H. , Pruzanski W.
Published: December 2022

More than 500 human sera containing one or more M-components were screened for antibody-like activity, using both double diffusion in agarose and modified Farr binding studies. Antibody activity was detected in two IgG myeloma proteins and two IgM macroglobulins using a number of negatively charged, positively charged, and neutral haptens. We have at least one of these M-components growing in cell culture producing two different cell lines, and we have obtained small crystals with two of the M-components. Equilibrium dialysis of the purified M-components yielded K0 values with low affinity. We have isolated, using liquid isoelectric focusing, a homogeneous IgG(γG1, K) protein from a leukemic patient 2 months after a bone marrow transplant operation. The IgG was not directed against the histocompatibility antigens. We detected significant binding with this protein and 3H-hydrocortisone. (Supported by MRC grant MA-3001 and the Ontario Treatment and Research Foundation).
An Electron Microscopic Study of Human γG1 Immunoglobulin Crystals
Authors: Labaw L. W. , Davies D. R.
Published: December 2022

Crystals of a human γG1 immunoglobulin molecule have been examined in an electron microscope. The micrograph exhibits periodicities in several directions corresponding to the repeating unit in the crystal lattice. A series of two optical integrations of the micrograph in two directions virtually eliminates the random noise and the repeating molecules become clearly visible. The overall appearance of the molecule is characterized by three globular units, presumably corresponding to one Fc and two Fab portions. These units are assembled to give a complete molecule having a form ranging from a Y to a T. This is in agreement with previous electron microscope studies and with the x-ray diffraction studies of these crystals.
A Monoclonal IgG Protein with a “Hinge” Region Deletion
Authors: Deutsch H. F. , Suzuki T.
Published: December 2022

A protein has been isolated in crystalline form from the serum of a patient with a γG1-hyper-globulinemia. It has a m.w. of 145,000 in low ionic strength media but dissociates into subunits of about 50,000 in 5 M guanidine solutions. This indicates that the molecule contains covalently linked L-chain dimers and free H-chains. The charge properties of these subunits were so similar as to prevent their separation by ion transport or by ion-exchange chromatographic techniques. Gel filtration in solutions containing 5 M guanidine of the reduced-alkylated γ globulin causes separation of H- and L-chains. Amino acid analysis of the H-chain shows the presence of only eight half-cystines and a relatively low content of proline. Preliminary amino acid sequence studies of cyanogen bromide, of papain and of pepsin cleavage products of the H-chain indicate that some of the constant regions of this subunit have the expected sequences.
Abnormal Human Globulins
Authors: Kunkel H. G. , Deutsch J. F.
Published: December 2022

The question whether myeloma proteins and other monoclonal γ globulins represent abnormal products of malignant cell lines has been under discussion for many years. Recently extensive evidence has accumulated for normal counter-parts for a wide variety of myeloma proteins; each unusual protein after detailed study has turned out to represent a new class, subclass or genetic variant of the immunoglobulin system. In fact the incidence of a given type of human myeloma protein closely parallels the concentration of a similar protein in the normal spectrum of immunoglobulins. The present report describes two exceptions to this rule. The first case involves the Deutsch protein described in the previous abstract which is known to have a deletion in the heavy chain. Subgroup typing clearly demonstrates that this was a γG1 protein which contained the “non a” antigen; however, it lacked the expected Gm(f) marker ordinarily found in the Fab portion of such proteins.
Influence of Genetic Factors on the Antibody Response to Streptococcal Carbohydrates
Authors: Eichmann Klaus
Published: December 2022

Two characters of anti-streptococcal antibodies have been investigated for inheritability: 1) the degree of antibody heterogeneity and 2) the individual antigenic specificity. Genetic influences on the degree of antibody heterogeneity were demonstrated by selective brother-sister mating of rabbits which had “heterogeneous,” “restricted” and “monoclonal” immune responses. The degree of antibody heterogeneity of the parental rabbits was reflected by that of their offspring. Antibodies from closely related rabbits may share their individual antigenic specificity. Each of three different individual specificities was shared by antibodies from two to seven of 42 related rabbits but not by antibodies from 48 unrelated rabbits. The identical individual specificity of two antibody components isolated from the sera of a pair of siblings was demonstrated by immunodiffusion and radioprecipitin experiments. Both antibody components had identical allotypes, but other antibodies with the same allotype did not share their individual specificity.
An Anti-Benzene-Arsonate Antibody of Restricted Heterogeneity with Light Chains of b5 Allotype: Amino Acid Sequences of Amino-Terminal Regions of Light Chains from Antibodies and Normal Immunoglobulins of Various Allotypes
Authors: Mage Rose G. , Appella Ettore , Winfield John B. , Pincus Jack , Chersi Alberto
Published: December 2022

A rabbit which lived for over 3.5 years produced anti-benzene-arsonate antibody at various times over a 33-month period. The animal was partially suppressed for expression of b5-κ-type light chains when it was first immunized with benzene-arsonate coupled to edestin (Ed-Ars). The purified antibodies from January, 1968, October, 1969 and May 1970 were S-sulfitolysed and an LII fraction of light chains prepared. In October, 1969, the L chains were of a single V-region subgroup and gave a unique sequence for the first 21 residues. Light chains of earlier and later anti-Ars were very similar at the first 21 positions but additional residues were detectable at several positions in lesser amounts. We found an unusual residue, Ala, at position 8 which has only been found in human λ-type L chains of subgroup II. The major sequence of the anti-Ars antibody L chains was of the KII-length (Hood) but some of the heterogeneity could be explained as due to a similar chain, of KI length.
A Method for Further Separation of Specifically purified Antibodies by Liquid Isoelectric Focusing
Authors: Freedman M. H. , Painter R. H.
Published: December 2022

Specifically purified anti-p-azophenyltrimethylammonium antibodies from individual rabbits have been separated by isoelectric focusing on a preparative scale over a pH range of 5 to 8 into as many as 30 components differing in isoelectric properties and demonstrating reduced heterogeneity. A number of these components have many of the properties characteristic of homogeneous antibodies. The isolated antibodies are electrophoretically discrete and show homogeneous binding properties towards the p125I-iodophenyltrimethylammonium hapten, giving two combining sites/mol protein with a heterogeneity index of 1.00 ± 0.05. On alkaline urea disc electrophoresis, the fully reduced and alkylated antibody light chain patterns were monodisperse. Several specifically purified rabbit and goat antibodies directed against neutral, positively charged and negatively charged haptens have been purified. This procedure appears to afford a general method for the further purification of antibodies to a state suitable for sequence studies and detailed structural studies on the nature of the combining sites.
The Molecular Restriction of Neonatal Anti-Hapten Antibody
Authors: Montgomery P. C. , Williamson A. R.
Published: December 2022

Neonatal New Zealand White rabbits were primed with DNP-BγG intraperitoneally within 11 hr of birth and boosted s.c. with the same antigen prior to day 16 of life. Sera obtained from serial bleedings were subjected to isoelectric focusing on thin layers of polyacrylamide gel. The specific antibody spectrum was visualized by interaction with labeled hapten, fixation and autoradiography. Binding studies were carried out by the modified Farr technique. Eighty-three per cent of the neonates were producing anti-DNP antibody after the first boost and of these 64% gave restricted isoelectric spectra. Eleven percent of the restricted responders displayed isoelectric spectra analogous to those seen with myeloma proteins and were classified as uniform responders. All uniform responders possessed α values of unity and there was a general correlation between the α values and the isoelectric spectra. The data demonstrated that neonates can frequently produce structurally restricted antibody directed against a complex antigenic stimulus.
Relationship of Amyloidosis to Bence Jones Proteins and Plasma Cell Dyscrasias
Authors: Osserman Elliott F.
Published: December 2022

Studies of 70 cases of amyloidosis (A) in the past 18 years have provided strong evidence of a significant association between this condition and underlying plasma cell dyscrasias (PCD), particularly with Bence Jones (BJ) proteins (New England J. Med., 261: 1008, 1959; Sem. Hemat., 1: 3, 1964). In all cases of A with the so-called “primary,” “atypical” distribution of infiltrates (i.e., tongue, heart, GI, skin), BJ proteinemia and/or proteinuria was demonstrable with a majority (⅔) of type L. This preponderance of type L over type K is significantly greater than that observed in our cases of myeloma (K:L, approx. 1:1) and indicates a particular association between type L BJ and A. As previously reported (Sem. Hemat., 1: 3, 1964), A-related BJ proteins were labeled with fluorescein (A-BJ-Fl) and compared with non-A-related BJ proteins (also Fl-labeled) for binding affinity to normal tissues (muscle, kidney, liver).
Auto-Immunity and the Origin of Plasma Cell Tumors
Authors: Warner Noel L.
Published: December 2022

Two general observations form the basis for considering the possible autoimmune etiology for plasma cell tumors in man and mouse. 1) Antibody specificity of myeloma proteins. Although the true percentage of such proteins with autoantibody activity is not clear, it is certainly apparent that a significant proportion of myeloma and Waldenström macroglobulins show autoantibody specificity. This particularly includes several types of antiglobulin specificity such as a true anti-antibody activity (Warner, McKenzie and Fudenberg), and several anti-DNP myelomas with cross-reaction to γ globulin (a mouse IgG2a globulin and a human Waldenström macroglobulin). 2) Genetic susceptibility to plasma cell tumor induction. Mice of different inbred strains and hybrids were treated with three injections of mineral oil early in life. A high incidence of plasma cell tumors subsequently developed in BALB/c, NZB and (BALB/c × NZB) F1 hybrid mice.
Genetically Determined Immune Deficiency As the Predisposing Cause of “Auto-Immunity” and Lymphoid Neoplasia
Authors: Fudenberg H. Hugh
Published: December 2022

Burnet has postulated that autoimmunity arises from emergence of “forbidden clones” which make auto-antibody. Our postulate, in contradistinction, is that auto-antibody-producing cells are always present, producing enough autoantibody to remove damaged or aged tissues. In normals, the number of such cells is kept in check by normal T-cells. When T-cell function is defective, the “governing system” controlling auto-antibody producing clones fails, and autoimmune disease, mediated in most diseases by cellular immunity, emerges. The governing mechanism in normals may be one analogous to that which limits the amount of antibody produced to a given antigen, and keeps the antibody (and Ig levels) from continuously rising in normal subjects. Experimental data for this concept are provided by several lines of evidence: 1) Normals have low levels of rheumatoid factor and other “auto-antibodies” in their serum.
Suppression of Antibody Synthesis
Authors: Fauci Anthony S. , Johnson John S.
Published: December 2022

Suppression of the hapten-specific response to a hapten-carrier conjugate was seen when the conjugate was injected either together with another hapten conjugated to an homologous carrier or together with the homologous unconjugated carrier. Simultaneous injection of non-immunogenic, unconjugated hapten did not suppress the anti-hapten response to a different hapten conjugated to a carrier. Preimmunization with unconjugated carrier, which augments the carrier-specific response, suppressed the hapten-specific primary response to a hapten-carrier conjugate and enhanced the degree of competition seen when two hapten-carrier conjugates were given simultaneously.
Immunity to Hemophilus Influenzae Type b
Authors: Rodrigues Louis P. , Schneerson Rachel , Robbins John B.
Published: December 2022

The capsular substance of H. influenzae type b was isolated in a highly purified form. Serologic identity was demonstrated among the polysaccharides of seven different strains of H. influenzae type b. The polysaccharide had a molecular weight greater than 200,000 estimated by gel filtration and 152,000 by analytic ultracentrifugation and was shown to be relatively non-toxic and non-pyrogenic for laboratory animals.
The Immediate Allergic Response: in Vitro Action of Cyclic Amp-Active and Other Drugs on the Two Stages of Histamine Release
Authors: Lichtenstein Lawrence M. , DeBernardo Robert
Published: December 2022

The catecholamine isoproterenol, which inhibits the in vitro allergic response, does so early in the reaction in the first or activation stage of IgE-mediated histamine release and then at concentrations 104 lower than in the whole reaction. This inhibition is markedly decreased by the beta blocker propranalol but not by the alpha blocker phentolamine. Prostaglandin E1, which like the catecholamines stimulates leukocytic adenylcyclase, similarly inhibits in the first stage. Theophylline and dibutyryl cyclic AMP also inhibit primarily in the first stage but have a small but significant inhibitory effect later in the reaction, in the second stage. The metabolic inhibitor 2-deoxyglucose, on the other hand, inhibits only in the second or histamine release stage. Diethylcarbamazine inhibits both stages equally but a concentration of 10-2 M is required for a maximal effect. The action of the cyclic AMP-active drugs early in the reaction sequence strengthens the hypothesis that this system operates as a “second messenger” in the allergic release of histamine.
The Carbohydrate Moieties of Mouse Immunoglobulins: Composition and Evidence against a Role in Transplacental Transport
Authors: Miller Frederick
Published: December 2022

The carbohydrate composition of several mouse myeloma proteins was determined. The basic IgG glycopeptide contained five residues of N-acetyl-glucosamine, two of fucose, one of galactose and six of mannose with only occasional units having neuraminic acid. Similarities in sugar content between human and mouse IgA and IgM are noted. Glycopeptides derived from immunoglobulins were not immunogenic in rabbits and antibodies prepared against heavy chains did not appear to react against oligosaccharide determinants. Sugar-depleted immunoglobulins, prepared by the use of specific glycosidases, behaved no differently from control material in transplacental transport suggesting no major role for the sugars in this function. Data pertaining to the location of the labile disulfide bonds, roughly analogous to that for man, is presented.
Comparison of the Effect of Elastase on Human Secretory IgA and Serum IgA
Authors: Tax Anne , Korngold Leonhard
Published: December 2022

During the last several years three papers were published on the effect of pancreatic elastase on immunoglobulins (1–3). De Vaux St. Cyr and Heremans (1) reported that digestion of human IgG with elastase yielded two fragments which they believed to be similar to the Fab and Fc produced by trypsin digestion of IgG, and Waller et al. (3) demonstrated that the two fragments resulting from elastase digestion of IgG gave a reaction of identity in gel diffusion studies with the Fab and Fc obtained by papain digestion.

To date there has been no report on the effect of elastase digestion on serum IgA or secretory IgA. Recent studies (4–7) have suggested that human secretory IgA is less susceptible to proteolytic degradation than serum IgA. The following investigation was undertaken in order to compare the effect of elastase digestion on these two immunoglobulins.

Materials and Methods. Secretory IgA was prepared from colostrum obtained 1 to 4 days postpartum.
Detection of Anti-Phage Antibody by Passive Hemagglutination
Authors: Walker W. S. , Fishman M. , Adler F. L.
Published: December 2022

A hemagglutination test capable of detecting 2.5 × 10-5 µg of antibody nitrogen was applied to the measurement of anti-T2 phage activity during early phases of the antibody response induced in vivo or in vitro. Using this test serum antibody was detected within 24 hr of immunization and rose rapidly, whereas conventional neutralization tests indicated a slow increase in activity. Neutralization tests in the presence of complement indicated a rise in activity with time that paralleled the increase in hemagglutination activity. Antibody induced in vitro was detected by the conventional neutralization test only with difficulty but was readily demonstrable by the hemagglutination test.
Spontaneous Thyroiditis in the Obese Strain of Chickens
Authors: Nilsson Lars-Å. , Rose Noel R. , Witebsky Ernest
Published: December 2022

By means of radioimmunoelectrophoresis and radioelectrophoresis, thyroxinebinding antibodies were demonstrated on one or several occasions in about 16% of obese strain (OS) chickens, but not in normal White Leghorn chickens. Thyroxine antibodies were generally demonstrated at a later time than hemagglutinating thyroglobulin antibodies. By means of absorption experiments, evidence was obtained that thyroxine is present as an antigenic determinant on the chicken thyroglobulin molecule. Thyroxine-binding antibodies occurred in greater frequency in sera with higher hemagglutinating antibody titers. Thyroxine-binding antibodies were present in 22% of chickens with moderate thyroid infiltration and residues of functioning thyroid tissue but only in 9% of chickens with total or almost total destruction of the thyroid tissue. Intravenous injection of OS sera with thyroxine-binding antibodies into normal chicken embryos caused an increase of the mean thyroid follicle diameter. This was explained as due to hypophyseal feedback after binding and inactivation of the thyroxine.
Herpesvirus Neutralization: the Role of Complement
Authors: Wallis Craig , Melnick Joseph L.
Published: December 2022

Complement functions in the neutralization of herpesvirus by causing immunoaggregation. Complement-requiring antibody (CRA) in early immune serum appears to behave like a monovalent antibody since it sensitizes virus to the action of complement, but immunoaggregates fail to develop until complement is added. It appears that each aggregate contains many virions and antibody molecules, but it functions only as a single infectious unit. The titer is reduced in proportion to the degree of immunoaggregation. Late immune serum is polyvalent since it is able to aggregate and neutralize virus in the absence of complement. However, complement may also enhance the neutralizing activity of such late immune serum. This enhancement can be detected only if monodispersed virus is used in the test system. Aggregates present in usual virus harvests resist neutralization (persistent fraction). Antibody can decrease virus titers only to the level of the number of virus aggregates present in the harvest.
Direct Observations on the Effect of “Proliferation Inhibitory Factor” on the Clonal Growth of Target Cells
Authors: Badger Alison M. , Cooperband Sidney R. , Green Jon A.
Published: December 2022

A colony assay system is described in which the division of target cells can be microscopically observed for several days in the presence of proliferation inhibitory factor (PIF). At dilutions of 1:20 and higher PIF suppresses cell division in HeLa target cell cultures without loss of viability. Dilutions of 1:10 and lower have some cytotoxic activity. Both unstimulated and PHA-stimulated leucocyte culture supernatants have PIF activity; however, unstimulated supernatants are not as potent, and dilutions of 1:10 suppress cell division by 50% in the absence of cytotoxicity. The cytotoxic effect can be abrogated by dilution or by adding the PIF to colonies of more than one cell. Loss of target cells from the glass surface measured by visual observation does not account for the inhibition of DNA synthesis. The PIF effect can be reversed by removal of the PIF-containing medium from the target cells and its replacement with fresh or conditioned medium. Although highly effective on HeLa cells, PIF has no effect on cell replication of mouse L cells.
Acute Viral Infection: Tissue Injury Mediated by Anti-Viral Antibody through a Complement Effector System
Authors: Oldstone Michael B. A. , Dixon Frank J.
Published: December 2022

Anti-viral antibody was able to injure virus-infected cells in the presence of a complement effector system. In lymphocytic choriomeningitis (LCM) and mumps infected culture cells, viral antigen was present on the surface of cells and accessible to interact with anti-viral antibody. Once complement had been activated, cellular injury ensued with the amount of damage directly related to the proportion of cells containing viral antigen. Mice treated with cobra factor were protected from the lethal effects of LCM challenge while showing no deficiency in either infectious viral replication or presence and activity of sensitized lymphoid cells. Such mice showed significant depletion of C3 and total complement levels. Once cobra factor treatment was ended, protection disappeared rapidly, and C3 and total complement levels returned to normal.
Characterization of a Soluble Nuclear Ribonucleoprotein Antigen Reactive with Sle Sera
Authors: Mattioli Martha , Reichlin Morris
Published: December 2022

A soluble nuclear ribonucleoprotein antigen reactive with SLE sera in precipitin and complement fixation reactions is described. The antigen was shown to be quite labile and was not recovered from human autopsy material (liver and spleen) but was easily demonstrated in extracts of surgically removed human thymoma and thymus, as well as in extracts of human chronic myeloid leukemia and normal bone marrow cells. It could also be extracted from calf thymus tissue and the thymus and spleen of the rabbit. It was characterized as ribonucleoprotein because the antigenic activity was destroyed by both ribonuclease and trypsin and the washed immune precipitate contained material which yielded an orcinol reaction product with an absorption spectrum indistinguishable from ribose. The antigen was found to be unstable at relatively moderate temperatures (40°C), at pH below 5.0 and above 9.0, and was destroyed by treatment with sodium metaperiodate. Antibodies to this antigen, designated Mo, were found in a high proportion of SLE sera and were absent from a variety of sera from patients with other connective tissue diseases as well as normal sera. The nuclear fluorescent pattern associated with this system was shown to be “speckled.”
Studies on Rabbit Lymphocytes in Vitro
Authors: Sell Stewart , An Teisa
Published: December 2022

Polyacrylamide beads 400 µ to 800 µ in diameter were covalently coated with antibody globulin and the coated beads were used to fractionate lymphocyte populations. Beads coated with anti-lymphocyte, anti-immunoglobulin and anti-allotypic globulins bound rabbit peripheral blood lymphocytes. Adherent cells were eluted from coated beads after non-adherent cells had been washed off. The eluted population of lymphocytes adherent to anti-immunoglobulin- or anti-allotypic globulincoated beads was enriched in cells that contain detectable immunoglobulin antigens. Although only partial separation was obtained, it was concluded that this method might be applied with more satisfactory results to cell mixtures of other types.
Effect of Blocking Cell Receptors on an Immune Response Resulting from in Vitro Cooperation between Thymocytes and Thymus-Independent Cells
Authors: Doria G. , Agarossi G. , Pietro S. Di
Published: December 2022

The immune capacity of spleen cells from neonatally thymectomized mice to produce antibodies to sheep RBC in vitro was restored by adding thymocytes to culture. This cell cooperation was prevented when the spleen cells but not thymus cells were treated with rabbit antibodies to mouse serum proteins prior to culture. Thymocytes appeared to lack demonstrable receptor molecules such as those detected on thymusindependent cells and present in normal serum.
Carrier Function in Anti-Hapten Antibody Responses
Authors: Katz David H. , Paul William E. , Benacerraf Baruj
Published: December 2022

The transfer of immunocompetent lymphoid cells from inbred guinea pigs to allogeneic recipients that had been primed with DNP-ovalbumin prepared such recipients for striking secondary anti-DNP antibody responses to an appropriately timed challenge with DNP-bovine γ globulin. This phenomenon (“allogeneic effect”) involved activation of host antibody-forming cell precursors (ACFP) as a result of the specific immunologic attack of donor cells. Thus, parental (strain 2) donor lymphoid cells elicited this phenomenon in (2 × 13)F1 recipients, whereas, as shown previously, F1 donor cells failed to elicit the response in parental recipients. The allogeneic effect can be elicited in recipients primed as early as 1 day or as long as 130 days prior to allogeneic cell transfer, although the effect was maximal at 21 days. Furthermore, the allogeneic effect appeared to cause expansion of the AFCP population of the recipient as well as differentiation of such cells into antibody-secreting cells.
Effect of Age upon Primary Alloantigen Recognition by Mouse Spleen Cells
Authors: Adler William H. , Takiguchi Tomoo , Smith Richard T.
Published: December 2022

The response of spleen cells from three mouse strains, C57BL/6 CBA and A/J, to alloantigenic stimulation in mixed cell cultures was studied throughout the first year of life. The degree of stimulation by alloantigen of spleen cells from each of the strains and the stimulation pattern in relation to the age of the animal were both variable. Spleen cells from the three strains had no reactivity to alloantigen at birth. Following a period of 1 to 4 weeks, the reactivity increased rapidly. Peak values for all strains occurred between 14 and 20 weeks of age. In the C57BL/6 and CBA mice the responsiveness of the spleen cells to alloantigen declined markedly and was minimal at a year of age. However, in the A/J mice the reactivity appeared to remain at near peak levels throughout the first year of life.
Isolation of H-2 Alloantigens Solubilized by the Detergent NP-40
Authors: Schwartz Benjamin D. , Nathenson Stanley G.
Published: December 2022

Murine tumor cells of two different H-2 genotypes (H-2b and H-2d) were radiolabeled in suspension culture with 3H-fucose, and intact, labeled cells were extracted with the non-ionic detergent NP-40. Solubilized native molecules bearing H-2 alloantigenic activity were isolated from other cell constituents by indirect immuno-precipitation. SDS-polyacrylamide gel electrophoretic analysis of specific precipitates of 3H-fucose-labeled H-2 alloantigens resulted in radiolabel patterns, that gave single peaks for each mouse strain examined. These peaks were proved to be H-2 alloantigens by competition experiments in which the alloantiserum used in the indirect precipitation was pretreated with a papain-solubilized, unlabeled, highly purified splenic H-2 alloantigen preparation of the same H-2 type. The efficiency of the NP-40 solubilization procedure was estimated to be nearly 100%.
Cytophilic Binding of Antigen-Conjugated Erythrocytes: A Sensitive Assay
Authors: Thrasher Susan G. , Doroszczak Nadia , Cohen Stanley
Published: December 2022

Certain antibodies may attach to the surface of macrophages by means of a receptor site located on the Fc portion of the molecule. This property, which is known as cytophilic binding, may be used as the basis of an assay procedure for the detection of antibody. If the antigen is conjugated to the surface of an erythrocyte, the cytophilic antibody can then act as a bridge linking the erythrocyte to the macrophage. This leads to the formation of rosettes which are readily visible in either stained or unstained preparations. When the reaction is performed with serial dilutions of antibody, reproducible end-points are obtained at low antibody concentrations. The sensitivity of the method compares favorably with that of several other immunologic procedures examined. Thus, cytophilic binding may be of use either for detecting antibody activity in an unknown preparation, or for the further characterization of a known antiserum in terms of its various Fc-dependent properties.
Immunosuppression by Leukemia Viruses
Authors: Hirano Shinji , Friedman Herman , Ceglowski Walter S.
Published: December 2022

The number of “background” antibody-forming cells to sheep erythrocytes and to E. coli was studied in mice infected with Friend leukemia virus (FLV). The number of “background” plaque-forming cells (PFC) to the sheep red blood cells (S-RBC) increased rapidly after infection, with a peak enhancement prior to maximal development of splenomegaly. The rate and magnitude of this enhancement were virus dosedependent, since the most rapid increase, and the largest numbers, occurred in spleens of mice infected with the most concentrated virus preparation. The number of “background” PFC to E. coli also increased in susceptible BALB/c mice infected with FLV, although the rate and the total number was much lower than for the S-RBC immunocytes. The maximal number of bacteriolytic plaque-forming cells (B-PFC) occurred after marked splenomegaly developed. Injection of FLV into leukemia-resistant C57BL/6 mice failed to stimulate a significant increase in the number of “background” PFC to either S-RBC or E. coli. Furthermore, heat- and formaldehyde-inactivated FLV had little effect on the number of “background” PFC to these antigens. It seemed probable that FLV infection stimulated the “background” increase in a manner analogous to the stimulation by adjuvants such as natural or synthetic nucleic acids. However, the possible presence of large amounts of nucleic acid in the virus preparations, as well as cellular debris, did not appear to account for the enhancing activity, since inactivated preparations had no effect. Furthermore, there was no serologic evidence for a cross-reacting antigen between the virus preparation and the S-RBC or E. coli. It seemed more likely that the virus infection per se, either directly or through intermediate steps, caused proliferation of a limited number of already committed antibody-forming cells (“background”) or their precursors.
Immunoglobulin Classes in Aquatic Mammals
Authors: Nash Donald R. , Mach Jean-Pierre
Published: December 2022

On the basis of serologic cross-reactivity, three immunoglobulin classes homologous to human IgG, IgM and IgA were identified in two species of acquatic mammal representing the orders Cetacea (dolphin) and Pinnipedea (sea lion). Molecular size was estimated by sucrose density gradient ultracentrifugation and Sephadex G-200 chromatography, indicating a 7S IgG, 19S IgM and heterogeneous serum IgA. Human secretory component was readily bound to the IgM of both species and to an apparently lesser extent to the larger molecular size populations of IgA. No binding was observed with IgG. Several antisera specific for human γ-chains gave a single precipitin line with the sea lion IgG but when made to react with dolphin serum produced two lines, suggesting the presence of two different subclasses of IgG in this species.
Release of Macrophage Migration Inhibitory Factor by Virus-Infected Spleen Cells
Authors: Tubergen David G. , Oldstone Michael B. A.
Published: December 2022

The capacity of viruses, as macromolecules, to initiate a specific immune response by the host and the ability of this response to influence the viral infection are well recognized. Less understood are the relative roles played by humoral antibody and cell-mediated, delayed-type hypersensitivity in this process. In passive transfer experiments humoral antibodies have been shown to initiate or intensify the injury of viral infections in animals (1, 2). The influence of cellular immunity upon viral infections has not been satisfactorily explored in vivo but its importance has been suggested by the enhanced susceptibility of individuals with defective cellular immunity to both natural viral infections and vaccinations (3). Recently, the macrophage migration inhibition test has been used as a measure of cellular immunity to a variety of antigens ranging from soluble proteins to bacterial and tumor antigens in several species, including man, guinea pig and mouse (4–7).
Common Structural and Antigenic Properties of Human γM Anti-γ Globulins
Authors: Franklin Edward C. , Frangione Blas
Published: December 2022

Chemical and immunologic studies of γM anti-γ globulins from five patients with mixed cryoglobulinemia and the inert γA myeloma protein from one of them demonstrated: 1) a peptide in the heavy chain detected on diagonal electrophoresis in three of the five γM rheumatoid factors (RF) and also in the inert γA myeloma protein from one of them; 2) PCA as the N-terminal residue in all the heavy chains; 3) the presence of certain antigenic determinants common to many anti-γ globulins; 4) the presence of the same determinants in the inert γA myeloma protein. These results confirm prior studies of similarities in the structure of two myeloma proteins produced by the same individual, and demonstrate yet another class of antibodies having certain common and unique structural features. The lack of anti-γG activity in the γA myeloma protein raises the possibility that in certain instances, the combinding site may be present but prevented from interacting with antigen because of other structural features in the molecule.
Immunoglobulin (Ig) Receptors on Human peripheral Leukocytes
Authors: Abdou Nabih I.
Published: December 2022

Immunoglobulin (Ig) molecules on human peripheral leukocytes were demonstrated by using the in vitro culture of leukocytes in the presence of class specific goat antihuman antisera or by observing the degree of binding of 125I-anti-Ig to cells. A γ globulin-free medium was found essential to elicit the responses. By passing leukocytes through columns filled with glass beads coated with class specific anti-Ig and then testing for Ig receptors on cells that were retained on the beads or cells that passed through the column, it was shown that retained cells and not passed cells carry receptors of the same Ig class used to coat the beads in the column. Excess anti-Ig in the column prevented the specific retention of cells. The data indicate that human leukocytes carry one Ig class, either IgG or IgM, but not both.
Leukemia Virus-Induced Immunosuppression
Authors: Friedman Herman , Ceglowski Walter S.
Published: December 2022

Spleen cells from mice infected with Friend leukemia virus lost their capacity to migrate in vitro as assessed by the capillary tube culture procedure used to demonstrate cellular immunity. Spleen, lymph node, thymus and bone marrow cells from normal non-infected mice readily migrated in vitro. A marked inhibition of spleen cell migration occurred when the donor mice were infected with FLV 5 to 7 days or more before culture. Less or no suppression occurred when mice had been infected for less than 5 days. Normal migration was evident with spleen cells from mice infected on the day of testing or one day earlier. Loss of lymphoid cell migration activity was directly related to the dose of virus used for infection: a smaller dose resulted in less pronounced inhibition. Furthermore, lymph node, thymus and bone marrow cells were less affected than were spleen cells. Superficial and deep lymph node cells and bone marrow cells lost migration activity 2 to 3 weeks after infection, whereas thymus cells were unaffected until the 4th week of infection. No migration-inhibitory factor could be detected in culture supernatants of spleen cells from FLV-infected animals sensitized with an allogeneic skin graft or tubercle bacilli and challenged in vitro with the appropriate antigen. In contrast, similar cultures of lymphoid cells from sensitized control mice released an inhibitory factor as assessed by inhibition of migration of normal spleen cells in vitro, when incubated with the appropriate antigen. These observations indicate that a normal functional capacity of lymphoid cells of mice, i.e., migration in vitro of macrophages and other motile cells, is rapidly inhibited by in vivo infection with a leukemia virus. The relationship between such inhibition and cellular immunity in leukemic mice was discussed.
The Complement-Fixation Reaction in Equine Infectious Anemia: Demonstration of Inhibition by IgG(T)
Authors: McGuire T. C. , Van Hoosier G. L. , Henson J. B.
Published: December 2022

The role of non-complement-fixing anti-equine infectious anemia (EIA) antibody in the conversion of complement fixation (CF) tests from positive to negative in EIA-infected horses was investigated. Complement-fixation inhibition (CFI) tests demonstrated antibodies in sera that were CF negative. These antibodies would bind to antigen, but would not fix complement. The inhibiting antibodies were isolated and shown to be IgG(T) by immunoelectrophoresis and immunodiffusion against monospecific anti-IgG(T) antisera. Separation of immunoglobulins from affected horse sera by DEAE cellulose chromatography revealed 11 of 13 had complement-fixing IgG and non-complement-fixing IgG(T) antibodies present simultaneously regardless of the reactivity of whole sera. The reactivity of whole sera in CF and CFI tests evidently depended upon the relative concentration and perhaps affinity of the Ig classes. The predominant class fluctuated in serial sera from four of six persistently infected horses.
Cellular Formation of Vibriolytic Antibody by Mouse Immunocytes: Cytokinetics and Specificity
Authors: McAlack Robert F. , Cerny Jan , Friedman Herman
Published: December 2022

A vibriolytic plaque assay in agar gel was developed which enumerates immunocytes secreting antibody to the common and type-specific antigens of Vibrio cholerae. No antibody-forming cells were found in the spleen of random bred or inbred mice prior to immunization with V. cholerae. Following immunization there was a consistent latent period of approximately 2 days before the first appearance of plaqueforming cells (PFC), followed by a rapid increase that reached a peak approximately 10 to 12 days after immunization. PFC directed against both the common and the type-specific antigen could be readily enumerated by testing individual spleen cell suspensions against both the homologous and heterologous vibrio strains, which are known to share a common antigen. A good correlation was evident between the appearance of PFC and circulating vibriolytic and agglutinating antibody, except for the long delay between the appearance of serum antibody and attainment of peak titer after 28 days. Anti-mouse globulin serum inhibited PFC, attesting to the immunoglobulin nature of the reaction, and inhibition tests with vibrio antigens, in the form of intact vibrios or lipopolysaccharide extracts, evinced the specificity of the PFC response.
Immunogenic Specificity of Bacillus Subtilis Phage Spo1-Dna
Authors: Braude N. A. , Zamchuk L. A.
Published: December 2022

Immunization of rabbits with the phage SPO1-DNA-MBSA complex results in the production of antibodies which react only with DNA containing 5-hydroxymethyluracil. These antibodies react predominantly with denatured DNA. Their ability to react with DNA containing 5-hydroxymethyluracil does not depend on the presence of glucose in DNA. Thus, it has been shown that 5-hydroxymethyluracil acts as a specific antigenic determinant.