bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Immunoglobulin E Levels in Patients with Neoplastic Disease
Authors: Waldmann Thomas A. , Bull Joan M. , Bruce Robert M. , Broder Samuel , Jost Margaret C. , Balestra Suellen T. , Suer Mary E.
Published: December 2022

The serum immunoglobulin E (IgE) concentrations of groups of patients with neoplastic disease were determined with a double antibody radioimmunoassay technique. The IgE levels were normal in patients with most of the types of neoplastic disease studied. However, the serum levels of IgE were reduced in patients with neoplasms affecting the B cell (thymic independent) system of lymphocytes and plasma cells. Thus, the geometric mean serum IgE concentrations of patients with chronic lymphocyte leukemia (18 ng/ml), multiple myeloma with an IgG paraprotein (27 ng/ml), and multiple myeloma with an IgA paraprotein (36 ng/ml) were significantly reduced (p < 0.05) below the geometric mean of normal controls (96 ng/ml). The reduction in IgE levels is a feature of a more generalized pattern observed in these patients of reduced polyclonal immunoglobulin synthesis and reduced numbers of B lymphocytes bearing normal polyclonal surface immunoglobulins. This reduction in the number of normal B lymphocytes and in the concentration of polyclonal immunoglobulins may be due to the production, by the malignant plasma cells and lymphocytes, of humoral regulators of B cell proliferation and immunoglobulin synthesis.

In contrast to these findings in patients with malignancies of the B cell system there was a 9-fold elevation of the geometric mean serum IgE concentration to 945 ng/ml in patients with Hodgkin's disease, a disease associated with abnormalities of cellular immunity and disorders of T cell function. It is suggested that a reduction of thymic dependent, T cell, regulators of IgE synthesis may occur in such patients and that this reduction in T cell regulatory function may be the cause of the high IgE levels seen in patients with Hodgkin's disease.
The Adjuvant Activity of a Mycobacterial Water Soluble Adjuvant (WSA) in vitro
Authors: Modolell Manuel , Luckenbach Gerd A. , Parant Monique , Munder Paul G.
Published: December 2022

Water soluble adjuvant (WSA), a cell wall fraction from mycobacteria, proved to be a adjuvant in vitro. WSA increased the immune response of mouse lymphoid cells against SRBC, DNP-dextran, and DNP-edestin. WSA seems to act in vitro primarily on macrophages. A direct B cell-stimulating activity of WSA could not be demonstrated. The adjuvant activity of WSA in vitro is apparently not mediated by T cells. WSA is much more effective when used in cultures that contain mouse peritoneal exudate fluid than in those which contain fetal calf serum.
In Vitro Stimulation of Human Lymphocytes with Heterologous Anti-Lymphocyte Sera: Evidence for a Specific Antigenic Receptor Mechanism
Authors: Zimmerman Barry , Baumal Reuben , Gelfand Erwin W.
Published: December 2022

Heterologous antiserum prepared against human lymphocytes (ALS)2 has been shown to stimulate lymphocyte proliferation in vitro, as measured by 3H-thymidine incorporation into DNA (1). This reaction is assumed to follow binding of the ALS to the lymphocyte plasma membrane, an event which triggers cell division (2). We have observed that ALS prepared against human thymus or thymus-derived (T) lymphocytes stimulated proliferation of lymphocytes in vitro, whereas ALS prepared against human cultured lymphoid cell lines which originated from bone marrow-derived (B) lymphocytes did not or did so poorly in spite of the fact that both ALS bound equally well to lymphocyte plasma membranes. This observation suggests that binding of ALS to lymphocytes per se is not a sufficient stimulus to induce proliferation.
Induction of Anti-DNP Antibodies: Suppressive Effect of Circulating Anti-Iodiotypic Antibodies to Mouse Myeloma Protein MOPC 315
Authors: Granato Dominique , Braun Dietmar G. , Vassalli Pierre
Published: December 2022

Immunization of BALB/c mice with MOPC 315, and α λ mouse myeloma protein with anti-DNP activity, induces the formation of anti-315 idiotypic antibodies. The idiotypic-anti-idiotypic reaction is partially inhibited by BALB/c serum containing anti-DNP antibodies, indicating an idiotypic similarity between 315 and at least some of the anti-DNP antibodies. Hemagglutination data indicate that a high proportion of induced BALB/c anti-DNP antibodies contain L chains of λ type. Mice with circulating anti-315 idiotypic antibodies show, after immunization with DNP-KLH, a depressed anti-DNP antibody response.
Prevention of Myeloma Growth in BALB/c Mice by Injection of Anti-Immunoglobulin Antisera
Authors: Manning Dean D. , Jutila John W.
Published: December 2022

Data presented here establish that neonatally initiated anti-Ig (anti-α or anti-µ) treatment of BALB/c mice provides them with complete, class-specific protection against subsequent challenge with the corresponding transplantable myeloma. The class-specific nature of protection indicates that the effect is due to anti-Ig antibodies per se and not to any possible contaminants of anti-plasmacyte antibodies.

In addition to protection from IgM myeloma growth, the rigorous schedule of anti-µ suppression used in these studies effected complete and stable loss of both serum IgM and serum IgA. A similar schedule of anti-α suppression resulted in complete protection from the IgA myeloma but did allow serum IgA, the only Ig affected by this antiserum, to recover to normal levels. The significance of these observations is discussed.
Interaction of C-Reactive Protein Complexes with the Complement System
Authors: Volanakis John E. , Kaplan Melvin H.
Published: December 2022

The reaction of C-reactive protein (CRP) with C-polysaccharide and the choline phosphatides, lecithin and sphingomyelin, previously shown to induce consumption of human complement, failed to effect consumption of guinea pig complement except in the presence of a thermolabile human serum factor. The amount of guinea pig complement consumed by CRP complexes was dependent on optimal proportions of CRP, C-polysaccharide, or phosphatide, and human serum cofactor in the reaction mixture.

In subsequent experiments, the serum factor was found associated with human Clq: On DEAE-cellulose chromatography of euglobulin, cofactor activity was associated with the first protein peak and was further enhanced by supplementation with two other chromatographic fractions, consistent with a trimolecular complex of Clq, r, and s. On gradient ultracentrifugation, cofactor activity corresponded to a value of 16.9S in the presence of Ca++ and 12.9S in the presence of EDTA. On filtration through Sephadex G-200 in the presence of Ca++, cofactor and C1 activities were concentrated in the excluded peak. In the presence of EDTA, cofactor activity was also demonstrable in the excluded peak although at lower levels. Fractions with cofactor activity consistently gave precipitin reaction for Clq.

Depletion of fresh human serum of Clq by treatment with washed immune precipitate or with aggregated human γ-globulin resulted in complete loss of cofactor activity. Alternatively, addition of purified human Clq provided the cofactor activity for consumption of guinea pig complement.

These combined data indicated that the consumption of guinea pig complement by CRP complexes required participation of human Clq, and that these complexes presumably do not interact with guinea pig Clq.
Immunologic Reactivity in Canine Marrow Graft Recipients
Authors: Ochs Hans D. , Storb Rainer , Thomas E. Donnal , Kolb Hans-Jochem , Graham Theodore C. , Mickelson Eric , Parr Marlen , Rudolph Robert H.
Published: December 2022

Immune reactivity was studied in 55 dogs between 20 days and 8 years after lethal total body irradiation (TBI) or cyclophosphamide (CY) and grafting of autologous or allogeneic marrow. This was compared to findings in 50 normal dogs. Cytogenetic and other blood genetic markers showed that the hemopoietic and lymphoid systems in allogeneic chimeras conditioned by TBI were repopulated only by cells of donor type. In contrast CY chimeras showed persisting mixtures of host and donor cells. Recovery of granulocyte counts and return of granulocyte function as determined by iodination tests were complete by day 25 after grafting. Blood lymphocyte counts did not reach the normal range until day 200. Lymph node histology showed lymphoid hypoplasia for 100 to 200 days and returned to normal thereafter. Short-term chimeras (<200 days postgrafting) had slightly lower and long-term chimeras (τ;200 days postgrafting) had significantly higher serum IgG level than did normal dogs. Antibody formation to chicken red blood cells and sheep red blood cells and bacteriophage φX174 (phage) was lower than normal in the first 200 days and within the normal range thereafter. The class of antibody after repeated immunization was predominantly IgM in short-term and predominantly IgG in long-term chimeras and in normal dogs. Phage clearance was normal in all chimeras. Transfer of immunity to distemper and phage was studied with equivocal results. Cellular immunity (first and second set skin grafts, stimulation of lymphocytes in mixed leukocyte culture and by phytohemagglutinin) was impaired in short-term chimeras and normal in long-term chimeras. An exception was the tuberculin conversion after Bacille Calmette-Guerin immunization which occurred as early as day 29. As a clinical correlate to these studies on immune function, long-term chimeras regained their health and are able to live in an unprotected environment without increased susceptibility to infections or other diseases.
Importance of Age of Host in Detecting Tumor-Associated Transplantation Antigens
Authors: Rose William , Girardi Anthony J.
Published: December 2022

We report here the importance of the age of the host in the detection of immunogenic tumor-specific transplantation antigens (TSTA)3 in transplantation experiments in vivo. Demonstration of the presence of TSTA on the K-BALB cell line, a BALB/3T3 cell line transformed by the Kirsten strain of murine sarcoma virus (MSV) but not producing virus, was dependent on the age of the BALB/c mice immunized.

Stephenson and Aaronson (1) previously failed to detect tumor-associated transplantation antigens (TATA) on this same cell line when they performed transplantation immunity studies in 6- to 8-week-old BALB/c mice. Their negative conclusion was based, in part, upon observing comparable protection when using K-BALB and the parental BALB cell lines as vaccines. The authors admitted that the BALB/3T3 parental cell line may have undergone antigenic changes concomitant with prolonged passage in vitro Furthermore, we (unpublished observation) and others (2) have found that the putative normal BALB/3T3 cell line is, in fact, weakly tumorigenic.
Association Constant and Heterogeneity Index of Antibodies Specific for a Natural Determinant of a Bacterial Protein
Authors: Macario Alberto J. L. , de Macario Everly Conway
Published: December 2022

The evolution of the immune response to a bacterial antigen was studied in a closed in vitro system, whereby the physiologic architecture of the responding tissue is preserved and communications with central organs (thymus, bone marrow), circulating cell and antibody pools, and antigen depots are cut off. The time-course changes in binding properties of antibodies directed to a distinct determinant of native, wild type, Escherichia coli β-d-galactosidase were determined by measuring their association constant for a naturally occurring ligand, a defective point mutant enzyme (AMEF), at various intervals during the response of rabbit lymph node fragments, which had been challenged in vitro, washed, and placed in culture, individually or in groups of five. Early secondary antibodies were distributed over a wide range of affinities, although antibodies in the serum of the donor rabbit were restricted at the moment of sacrifice and initiation of cultures. Later on, a gradual increase in affinity with progressive restriction occurred more often in multifragment cultures and in cultures challenged with 50 µg/ml than in those challenged with 5 µg/ml of β-d-galactosidase. The magnitude of the affinity rise was inversely correlated with the association constant of early antibodies and the peak affinity reached in each culture did not go over the highest value recorded in the serum of the donor, with only few exceptions. This indicates that although there is a strong tendency to maturation, there is a certain ceiling which is rarely surpassed. In some cultures a late fall in K0 was observed together with increased antibody heterogeneity. The overall data indicate that during microevolution of the immune response in vitro against a natural determinant in its native molecular configuration, a progressive contraction of high-rate antibody-forming clones occurs toward high affinity. Expansion of the memory potential over a wide range of affinities takes place in parallel. The limits of these processes, top affinity reached, and width of memory spectrum seem to be mainly determined by a prefixed array of precursors or memory cells. However, generation of new affinities during the immune response also seems to be possible.
The Influence of Removing Lymphoid Tissue on the Persistence of Tolerance of Skin Allografts in Mice
Authors: Silvers Willys K.
Published: December 2022

To determine what influence removing lymphoid tissue had on the survival of foreign grafts on tolerant animals, we lymphnodectomized and/or splenectomized tolerant A-strain mice, bearing CBA skin grafts of long-standing. The results indicated that these procedures had no demonstrable effect on the survival of the tolerated graft unless the hosts were rechallenged with a second CBA graft—a procedure which was routinely carried out 60 days after the ablative operation. After regrafting, 24 of 42 animals (57%) devoid of their axillary and brachial nodes rejected their original grafts and 16 (38%) rejected both grafts as compared to only two of 25 (8%) which rejected their original graft, and none both, in the corresponding sham-operated groups. Unilateral lymphnodectomy had significantly less influence on graft survival than bilateral lymphnodectomy. Moreover, the detrimental influence of bilateral lymphnodectomy on graft survival could be partially reversed by inoculating a coarse cell suspension of some or all of the removed nodes back into the animals from which they were derived. Finally, splenectomy, even when combined with lymphnodectomy, had little influence on graft survival.
Potentiation of Helper T Cell Function in IgE Antibody Responses by Bacterial Lipolysaccharide (LPS)
Authors: Newburger Peter E. , Hamaoka Toshiyuki , Katz David H.
Published: December 2022

The effects of bacterial lipopolysaccharide (LPS) on hapten-specific IgG and IgE responses to DNP-protein conjugates has been analyzed in an adoptive transfer system in mice. Administration of LPS to irradiated recipients of DNP-Ascarisprimed spleen cells at the time of secondary challenge enhanced the responses in both antibody classes to the original immunizing antigen demonstrating clearly that the mechanisms controlling both IgE and IgG antibody production are subject to the adjuvant influence of LPS. Responses in the IgE class appear to be more sensitive to enhancing effects of lower doses of LPS than is true of IgG responses. That the adjuvant effect of LPS is exerted on helper T cell function in this system has been directly shown in these studies by the substantial enhancement of development of carrier-specific helper function obtained by administering LPS at the time of carrier immunization. Whether this adjuvant effect reflects direct activation of T cells by LPS or, rather, an indirect effect mediated by macrophages and/or biologically active factors remains to be solved.
The Frequency and Activity of Single Helper T Cells
Authors: Marrack Philippa (Hunter) , Kappler John W. , Kettman J. R.
Published: December 2022

We have investigated the activities of T cell populations able to cooperate in the humoral immune response to TNP coupled to the carriers SRBC or KLH. We used Poisson analyses in which small numbers of carrier-primed spleen cells were added to cultures containing an excess of B cells and antigen. We have demonstrated that we could a) detect the activity of a single helper T cell; b) calculate its frequency in a given spleen cell suspension; and c) calculate its relative activity in stimulating the humoral immune response.
Lectins from Abrus Precatorius and Ricinus Communis
Authors: Pappenheimer Alwin M. , Olsnes Sjur , Harper Annabel Avery
Published: December 2022

The quantitative precipitation reactions of rabbit anti-abrin and anti-ricin sera have been studied with the purified toxins, abrin, and ricin, their isolated A- and B-chains and with the corresponding nontoxic Abrus and Ricinus agglutinins. In the case of ricin, the results are consistent with a model in which the agglutinin contains two lactose-binding B-chains, immunologically indistinguishable from the single B-chain of ricin and two A-chains which lack certain antigenic determinants present on the ricin A-chain. The relation between abrin and its agglutinin appears basically similar, although somewhat more complex. Both Abrus and Ricinus lectins react with lactose and with glycoproteins containing terminal nonreducing galactose residues that are present on certain proteins in the normal serum of many animal species and on the membranes of animal cells. Therefore precipitation reactions must be carried out in the presence of lactose or galactose. Dose-response curves of the effect of abrin and ricin on protein synthesis in HeLa cells are shown in the absence and presence of lactose. A method for estimation of potency of ricin antitoxin using the HeLa cell system is described.
Enhancement of the Humoral Response of T Cell-Depleted Murine Spleens by a Factor Derived from Human Monocytes in Vitro
Authors: Wood D. D. , Gaul S. L.
Published: December 2022

The humoral response of thymus-derived (T) cell-depleted murine spleen cultures was stimulated by the addition of human leukocytes. The stimulatory human cell type was found to be adherent and phagocytic suggesting that it is the monocyte. The stimulation appears to be mediated by a factor released by the adherent cells into the culture medium.
Generation of Non-Complement-Fixing, Blocking Factors by Lysosomal Extract Treatment of Cytotoxic Anti-Tumor Antibodies
Authors: Dauphinee Michael J. , Talal Norman , Witz Isaac P.
Published: December 2022

Alloantibodies against EL-4 lymphoma and P-815 mastocytoma were raised by immunization of DBA/2 and C57BL/6 mice, respectively. Such antisera were capable of mediating complement-dependent cytotoxicity and of blocking specific killing by alloimmune lymphocytes. Treatment with lysosomal enzymes derived from the tumor decreased the ability of these alloantibodies to mediate complement-dependent cytotoxicity but left intact their blocking activity. Such degradation, if it were to occur, in vivo could contribute to enhanced tumor growth.
Studies of Complement Complex C5b,6 Eluted from—EAC-6: Reaction of C5b,6 with EAC4b,3b and Evidence on the Role of C2a and C3b in the Activation of C5
Authors: Goldlust Marvin B. , Shin Hyun S. , Hammer Carl H. , Mayer Manfred M.
Published: December 2022

A macromolecular complex containing guinea pig complement fragment C5b (activated C5) and component C6 has been obtained from ĒĀC̄1̄,4̄b̄,2̄ā,3̄b̄,5̄b̄,6̄ (sheep erythrocytes carrying antibody and complement components, or fragments, C1, C4b, C2a, C3b, C5b and C6) or from ĒĀC̄4̄b̄,2̄ā,3̄b̄,5̄b̄,6̄ by elution. This complex combines with EAC4b,3b to yield an intermediate termed pseudo-EAC-6, which can be lysed by C7, C8 and C9, like genuine EAC-6, but which differs from the latter since it lacks C2a. In contrast, native C5 and C6 will produce EAC-6 only on reaction with ĒĀC̄4̄b̄,2̄ā,3̄b̄. Thus, cell-bound C2a is required for the reaction with native C5 but is not needed when C5 is supplied in the activated and complexed state C5b,6. Further, anti-C3 blocks the reaction of EAC4b,3b with C5b,6. These results suggest that in the reaction with native C5 the cell-bound C2a mediates the enzymatic activation of C5, whereas the cell-bound C3b supplies a binding site. In addition, the present experiments show that the activated state of C5b is stabilized by complexing with C6.
Regulation of the Immune Response
Authors: Sinclair N. R. StC. , Lees R. K. , Abrahams S. , Chan P. L. , Fagan G. , Stiller C. R.
Published: December 2022

Spleen cells from nonimmune mice were exposed in vitro to immune complexes containing solubilized sheep erythrocyte antigen and anti-sheep erythrocyte antibody, and then washed thoroughly. These antigen-antibody treated spleen cells displayed a decreased ability to transfer an adoptive immune response against whole sheep erythrocytes into syngeneic lethally irradiated recipients. Treatment with solubilized antigen or antibody alone produced little or no immunosuppression. Antigen-antibody complex suppression of immune competence was demonstrated to be: 1) immunologically specific, 2) not a result of carryover and release of antigen-antibody complexes, 3) rapidly attained (1 hr), 4) dependent on the Fc portion of antibody at low concentrations of antigen-antibody complexes, 5) stable to incubation of the antigen-antibody treated and washed spleen cells in antigen-antibody complex-free environments (in vitro and in vivo), and 6) the result of inactivation of cell-type(s) other than or as well as macrophages. An in vivo counterpart of in vitro antigen-antibody inactivation is described.
Antibody-Dependent Cell-Mediated Cytotoxicity
Authors: Scornik Juan C. , Cosenza Humberto , Lee William , Köhler Heinz , Rowley Donald A.
Published: December 2022

Antibody-dependent cytotoxicity is mediated by lymphoid cells carrying receptors for immunoglobulin. These receptors are specific for IgG since a) IgG, but not IgM or IgA antibodies, either in their polymeric or monomeric forms, are capable of inducing cytotoxicity and b) nonspecific IgG, but not nonspecific IgM or IgA, can inhibit antibody-dependent cytotoxicity. These receptors on effector cells can interact with heterologous antibodies, but affinity for homologous IgG is higher than for heterologous IgG. Normal IgG is not inhibitory in reactions which are known to be antibody-independent, e.g., lysis of allogeneic target cells by immunized spleen cells or cytotoxicity nonspecifically induced by phytohemagglutinin.
Antibody-Dependent Cell-Mediated Cytotoxicity
Authors: Scornik Juan Carlos , Cosenza Humberto
Published: December 2022

Macrophages obtained from peritoneal exudate are effector cells for antibody-dependent cytotoxicity. This effector function is independent of phagocytosis, and it is not inhibited by EDTA or aminophylline. Cells functionally similar to those in peritoneal exudate can be obtained from the spleen, but a functionally different population is primarily responsible for cytotoxicity mediated by spleen cells. Effector function of these splenic cells is inhibited by EDTA and aminophylline. These splenic cells tend to adhere to plastic and their function is resistant to a high dose of x-irradiation.
Histamine Receptor-Bearing Leukocytes (HRL)
Authors: Kedar Eli , Bonavida Benjamin
Published: December 2022

A rosette technique is described for the enumeration and identification of histamine receptor-bearing leukocytes (HRL). Mouse leukocytes from a variety of lymphoid tissues form rosettes with sheep erythrocytes coated with histaminerabbit serum albumin (RSA) conjugate. Rosette formation was specifically inhibited by either histamine-RSA or by histamine, but not by RSA. The percentage of rosettes in lymphoid tissues of adult mice ranged from 8% in the thymus to 70% in the peritoneal exudate leukocytes. Spleen, bone marrow, peripheral blood, and lymph node cells produced intermediate numbers of rosettes (20 to 40%).

Spleen and peritoneal exudate leukocytes derived from mice and rats immunized against allogeneic and syngeneic tumors, respectively, demonstrated a significantly lower frequency of HRL as compared with unsensitized cells. The vast majority of immune lymphoblasts, however, exhibited a high degree of rosette formation and were coated heavily with the indicator erythrocytes. Of particular interest was the observation that a number of tumor cells (four leukemias, one mastocytoma, and one plasmacytoma) showed little or no rosette formation.
Loss with age in NZB/W Mice of Thymic Suppressor Cells in the Graft-vs-Host Reaction
Authors: Gerber N. Lynn , Hardin John A. , Chused Thomas M. , Steinberg Alfred D.
Published: December 2022

The ability of lymphoid cells from NZB/W female mice to induce graft versus host disease (GVH) was studied by injections into newborn C3H/HeJ mice followed 9 days later by the Simonsen spleen weight:body weight assay. Spleen cells, 5 × 106, led to increasing GVH with increasing age until about 5 months of age, after which a decline in GVH was observed. The heightened responsiveness of 4 ½-month or 6-month NZB/W spleen cells could be suppressed by syngeneic lymphoid cells from mice under 2 months of age but not from mice 12 months of age. This suppressive function of young thymocytes and spleen cells increased with increasing cell dose. The suppressive function gradually decreased in thymocyte populations between 1 and 4 months of age. Nevertheless, 4-month thymocytes that no longer demonstrated suppressor function were able to synergize with 12-month spleen cells. These studies suggest that suppressor cells are lost as NZB/W mice age and that suppressor function is lost before helper function.
Use of Genetically Defined Nude Mice in the Study of the Mixed Leukocyte Reaction
Authors: Croy B. Anne , Osoba David
Published: December 2022

The H-2 complex and M locus have been defined for two incipient inbred strains of mice carrying the nu mutation. The strains differ at both loci from each other and cells from nu/nu mice of these allogeneic strains have been used to examine the role of T cells in the one-way mixed leukocyte reaction (MLR). A positive MLR requires the presence of both an allogeneic difference, and T cells. Proliferation by T cells is not essential, however, the cultures must contain a cellular component allogeneic to the T cell containing population.
Immune Hemolysis and a Basic Peptide from Cobra Venom
Authors: Okada Hidechika , Campbell William
Published: December 2022

Sheep erythrocytes sensitized with antibody and the first seven components of complement (EAC1-7) undergo rapid hemolysis in the presence of the eighth component of complement (C8) and a basic polypeptide (direct lytic factor, DLF) isolated from cobra venom which synergistically reacts with phospholipase A in hemolysis. EAC1-7 cells are not lysed by either C8 or DLF alone. DLF reacts after the reaction of C8 on EAC1-7 and not before it. These results suggest possible phospholipase activity in activated C8 molecules.
Cellular Events in Tolerance
Authors: Sanfilippo Fred , Scott David W.
Published: December 2022

Lewis rats pretreated with 10 mg of the soluble supernatant of ultracentrifuged sheep γ-globulins (ShIgSo) and challenged with trinitrophenylated (TNP)-ShIg in adjuvant initially developed significantly fewer anti-TNP plaque-forming cells than untreated controls. The effect was specific because ShIgSo tolerant rats responded normally to TNP-rabbit γ-globulin. Carrier tolerance lasted at least 6 months and could be induced with as little as 100 µg ShIgSo. Adoptive transfer experiments to irradiated recipients demonstrated that thymocytes could reverse carrier unresponsiveness. “Suppressor” cells were not detectable in carrier tolerant spleen populations. The diminution of responsiveness to TNP on a tolerated carrier thus provides a model for the study of T cell unresponsiveness in vivo.
Allergens of Mammalian Origin
Authors: Ohman John L. , Lowell Francis C. , Bloch Kurt J.
Published: December 2022

A purified fraction of cat pelt extract was prepared and subjected to electrophoresis in 7% acrylamide gel. The bulk of the allergenic activity was recovered from the prealbumin portion of the gel that contained a single band of protein (band B). Antiserum to band B reacted with both band B and albumin; after absorption with albumin, only antibody against band B could be detected. Electrophoresis of band B protein in 10% acrylamide gel resolved four protein bands; one of these bands was associated with the bulk of allergenic activity and reacted with absorbed antiserum to band B. The absorbed antiserum (anti-allergen antiserum) reacted in gel diffusion with a single component of crude cat pelt extract; this component had the molecular size characteristics of allergen. Anti-allergen antiserum removed significant amounts of allergenic activity from both crude cat pelt extract and purified fractions of cat pelt extract. It is proposed that the allergen defined by this antiserum be designated cat allergen 1.

The radioallergosorbent test was modified so as to provide an assay for allergen. The modified test provided a useful supplement to the skin test as an assay for allergen and showed that, of various cat tissue extracts, pelt extract was the most abundant source of allergenic activity. Extract of cat brain also contained significant amounts of allergen.
Maintenance of Latent Herpetic Infection: An Apparent Role for Anti-Viral IgG
Authors: Stevens Jack G. , Cook Margery L.
Published: December 2022

The mechanism by which latent herpetic infections are maintained in the neurons of murine spinal ganglia was investigated. Initially, it was found that when latently infected ganglia were transplanted to latently infected syngeneic mice, some circulating factor prevented viral reactivation. A systematic analysis of the system led to the demonstration that this effect could be reproduced when anti-viral IgG was administered to noninfected mice receiving the ganglionic transplant. Thus, IgG inhibited intraneuronal viral DNA and antigen synthesis, therefore restricting the appearance of infectious virus. Although a role for cytotoxic antibody has not been completely ruled out, this result suggests that antiviral IgG plays an important role in maintenance of latent herpetic infections.
Requirement for Complement Components and Fibrinogen in the Zymosan-Induced Release Reaction of Human Blood Platelets
Authors: Zucker Marjorie B. , Grant R. A. , Alper C. A. , Goodkofsky I. , Lepow I. H.
Published: December 2022

As shown earlier, zymosan particles incubated with human citrated plasma develop the ability to induce a release reaction in platelets. Thus when incubated zymosan is shaken for 4 to 15 min with human citrated platelet-rich plasma, ADP, ATP, and 14C-serotonin are released and the ADP causes platelet aggregation. Plasma depleted in vitro of C3 or GBG failed to generate activity on zymosan unless at least 65 µg of C3 or 100 µg of glycine-rich β-glycoprotein (GBG) were added/ml plasma. Plasmas from individuals with congenital deficiency of C3 or C3 inactivator (and hence GBG) were also inactive unless either purified C3 or hydrazine-treated plasma was added. Afibrinogenemic plasma was inactive unless at least 80 µg of fibrinogen was added/milliliter, a requirement previously reported for serum. Zymosan particles washed after incubation with normal plasma bore more fibrinogen (determined immunologically) than particles incubated with afibrinogenemic or ethylenediaminetetraacetic acid plasma and washed. The amount of zymosan-associated fibrinogen was not necessarily less on particles incubated with C3- or GBG-deficient plasma than on those incubated with normal plasma but was greater when purified C3 or GBG was added to the appropriate deficient plasma before incubation. Properdin-depleted plasma could not generate release-promoting activity on zymosan; activity was not restored by purified active properdin. When plasma from two patients with C̄1 inhibitor deficiency was depleted of C4 by incubation, one sample generated activity on zymosan normally. Serum from a guinea pig with C4 deficiency generated activity on zymosan when fibrinogen was added. Inulin and endotoxin did not develop release-promoting activity when incubated with normal plasma although they caused as much conversion of C3 and GBG as zymosan. Plasma incubated with inulin and endotoxin generated activity when subsequently incubated with zymosan, whereas plasma incubated with zymosan lost its ability to generate activity when incubated with fresh zymosan. We conclude that the alternate pathway of complement activation and fibrinogen are involved in generating release-promoting, platelet-aggregating activity on zymosan, and that activity may develop only during activation of properdin.
Antibodies to Proteins Dissolved in Sodium Dodecyl Sulfate
Authors: Stumph William E. , Elgin Sarah C. R. , Hood Leroy
Published: December 2022

Rabbits were injected with Drosophila embryo total nonhistone chromosomal (NHC) proteins or with bovine serum albumin, both in 0.1% sodium dodecyl sulfate (SDS). Antibodies were produced which reacted specifically with the protein injected as antigen; the antibodies were not directed against a random denatured protein-SDS complex as shown by failure to cross-react with other proteins in SDS. Antibodies to nonhistone chromosomal proteins were also produced by injecting rabbits with native chromatin. These antibodies reacted with isolated NHC proteins in 0.1% SDS. The presence of low concentrations of SDS did not seem to affect either production of antibodies or their general specificity. The antibodies produced in response to immunization with total NHC proteins or chromatin were directed against at least several proteins as determined by a procedure involving indirect immunofluorescent staining of antibody-antigen complexes in SDS polyacrylamide gels.
The Response of Rabbit Lymphocytes to Mitogens and Alloantigens: Evidence for T Cell Heterogeneity
Authors: Ozer Howard , Waksman Byron H.
Published: December 2022

Soluble concanavalin A (Con A), phytohemagglutinin-P (PHA), and pokeweed mitogen (PWM) stimulate DNA synthesis in cells from a variety of normal rabbit lymphoid organs. In lethally irradiated rabbits injected with thymocytes, these responses are virtually normal or, in some instances, increased. In thymus-deprived animals (thymectomy, lethal irradiation, bone marrow shielding) they are virtually abolished. We conclude that the substances tested are specific T cell mitogens in the rabbit, as in other species.

The response to Con A is both of higher magnitude and wider distribution among various lymphoid organs than the response to either of the other two mitogens. Responses to PHA relative to Con A vary in different organs, being lowest in thymus and highest in popliteal lymph nodes and manually separated cells of the thymus-dependent area (TDA) of the appendix. PHA-responsive cells were found to have the same organ distribution as cells responding in the one-way mixed lymphocyte reaction (MLR). It is proposed that responsiveness to PHA develops only in differentiated, peripheral T cells and that the PHA/Con A response ratio provides a convenient index in the rabbit for estimating function in these cell populations.

The appendix TDA was enriched in cells responsive to T cell mitogens and in the MLR relative to whole appendix as well as to the dome and follicle components of this organ. This finding confirms other evidence that this morphologic element of the gut-associated lymphoid tissue (GALT) is thymus-dependent.

A small proportion of rabbit B lymphocytes, limited largely to peripheral lymph nodes, were shown to respond to endotoxic lipopolysaccharide. As is the case in other animals, PWM appears to be mitogenic for both T and B cells in the rabbit.
Cross-Idiotypic Specificity of Rat Antibodies to Group a Streptococcal Carbohydrate
Authors: Stankus Richard P. , Leslie Gerrie A.
Published: December 2022

Specifically purified antibodies to streptococcal A carbohydrate (SACHO) from both related and unrelated Sprague-Dawley rats were found to possess cross-specific idiotypic determinants (ID 1). Anti-SACHO antisera from a single animal possessed both antibodies with these common idiotypic determinants and a distinct population with unique idiotypic determinants (ID 2). Undetectable in preimmune sera, removed by absorption on specific immunoabsorbents and intimately involved in the antibody combining site, ID 1 reveals the similarity of certain variable region structural features shared by antibodies from both related and unrelated individuals.
Differentiation of Lymphoid Cells: The Use of Specific Antisera to Characterize the Cells Required for the Induction of Immunoglobulin M Production in Vitro
Authors: Zimmerman Daniel H. , Okumura Ko , Rabkin Charles , Kern Milton
Published: December 2022

Anti-immunoglobulin as well as anti-thymocyte sera prevented the induction of immunoglobulin M production by rabbit popliteal lymph node cells that ordinarily occurs when such cells are cultured in vitro, in the absence of added antigen. Antibodies specific for the light chains and µ-chains of rabbit immunoglobulins were inhibitory whereas sera specific for α- and γ-chains were without effect. Univalent anti-µ-chain antibody and univalent anti-thymocyte antibody preparations were also inhibitory. All inhibitory antisera were without effect when added to cultures after the induction process was completed. Thymidine incorporation studies showed a lack of correspondence between the inhibitory activity and mitogenicity of anti-immunoglobulins.
Mononuclear Cell Chemotactic Activity of Kallikrein and Plasminogen Activator and Its Inhibition by C̄1 Inhibitor and α2-Macroglobulin
Authors: Gallin John I. , Kaplan Allen P.
Published: December 2022

The Hageman factor substrates prekallikrein and plasminogen proactivator were found to generate chemotactic activity for human mononuclear cells upon interaction with Hageman factor fragments. This activity superimposed the elution profile of kallikrein and plasminogen activator after chromatography on SP Sephadex and Sephadex G-150 and was inhibited by incubation of both enzymes with the active-site serine-inhibitor diisopropyl fluorophosphate. The natural inhibitors of each active enzyme also functioned as chemotactic inactivators; thus α2-macroglobulin inhibited the chemotactic activity of kallikrein and plasminogen activator whereas C̄1 inhibitor inhibited only the chemotactic activity of kallikrein.
Expression of IgG Allotypes in Human Lymphoid Tumor Lines Serially Transplantable in the Neonatal Syrian Hamster
Authors: Pothier Lillian , Borel Halina , Adams Richard A.
Published: December 2022

The presence of Gm(a), Gm(z), Gm(f), Gm(b0) and Gm(g), genetic factors of IgG1 and IgG3 heavy (H) chains, were determined in sera from hamsters bearing 15 human lymphoid tumors by using the standard agglutination-inhibition test. Documentation of immunoglobulin synthesis had already been established, nine lines synthesizing γ H chain, three lines synthesizing µ H chain and three lines synthesizing no immunoglobulins. All γ H chain-synthesizing tumor lines expressed Gm allotypes, but only the IgG1 determinants were detected. Tumor lines were derived from two patients known to be heterozygous for Gm(a) and Gm(f). The line from one of these patients synthesized only Gm(a). In the other line, which initially synthesized both Gm factors, there was deletion of expression of of Gm(f) on serial passage in the hamster. One line intermittently expressed on serial passage an allotype not present in the donor phenotype.
Identification of Two Populations of Immunoglobulin-Bearing Lymphocytes in Man
Authors: Lobo Peter I. , Westervelt Frederic B. , Horwitz David A.
Published: December 2022

Human peripheral blood lymphocytes bearing easily detectable surface immunoglobulin were quantitated with routine immunofluorescence procedures. The mean value in 17 healthy adults was 18% (range 9 to 30%). When the cells were preincubated at 37°C and washed at the same temperature before staining, the mean value decreased to 9% (range 4.5 to 18%) (p < 0.001). The mean value increased to 32% (range 15 to 49%) when the cells were prepared and washed at 4°C, and this value was also significantly different from values at room temperature (p < 0.01).

These temperature-related effects were explained by IgG that remained bound to the cell membrane at 4°C, but eluted at 37°C in serum-free medium. The total number of Ig-bearing lymphocytes and T lymphocytes determined by rosette formation with sheep erythrocytes approached 100%. These studies indicate two populations of Ig-bearing lymphocytes in healthy subjects: one with surface-stable Ig determinants, and another that lacks these markers, but has receptors capable of binding IgG.
Ir-Associated Murine Alloantigens: Demonstration of Multiple Ia Specificities in H-2 Alloantisera After Selective Absorptions
Authors: Sachs David H. , Cone James L.
Published: December 2022

Quantitative absorptions of anti-H-2 alloantisera with increasing concentrations of T cell-derived tumor cells of donor H-2 type has been found to remove antibodies to H-2D and H-2K region antigens selectively. Similar results were obtained after absorptions with thymocytes of the donor strain. In each case residual antibodies reacting with Ir-associated B cell alloantigens (Ia antigens) were unmasked by this procedure. Antisera which initially contained comparable titers of Ia and H-2 activity were depleted of H-2 activity at absorbing cell concentrations which did not appreciably alter the Ia reactivities, indicating that Ia antigens, if expressed on these T cell populations, must have been present at very low concentrations relative to H-2D and H-2K region antigens. Further absorptions with spleen cells from cross-reactive strains demonstrated a multiplicity of shared and unique Ia specificities in these sera. The multiple Ia antigens detected appeared all to be codominantly expressed on the same subpopulation of lymphoid cells.
Effects of Human C1 Inhibitor on Complement-Mediated Human Leukocyte Chemotaxis
Authors: Smith C. Wayne , Hollers James C. , Bing David H. , Patrick Richard A.
Published: December 2022

Human C1 inhibitor (C1 INH) enhances the chemotactic responsiveness of human leukocytes to lipopolysaccharide (LPS), AgAb complex, and zymosan-activated plasma or serum when added to the compartment of the chemotaxis chamber containing the cells. It seems to affect cells directly and causes an increased number of leukocytes to respond to the chemotactic factors at early time intervals. Spontaneous motility does not appear to be affected. Results of studies employing anti-C3 and anti-C5 sera seem to indicate that the chemotactic factor derived from C5 is involved in the C1 INH induced enhancement of chemotaxis. In fact, preliminary experiments utilizing trypsinactivated C3 as a chemotactic source indicate that C1 INH causes inhibition of chemotactic response to C3a. C1 INH is the first naturally occurring plasma component reported to cause enhanced chemotactic responsiveness.
Immunosuppression by Leukemia Viruses
Authors: Ceglowski Walter S. , Campbell Barbara P. , Friedman Herman
Published: December 2022

Infection of genetically resistant C57BL/6 mice with Friend leukemia virus resulted in a marked but transient immunodepression of the humoral immune response to sheep erythrocytes. The primary immune response to sheep erythrocytes was depressed in mice infected 1 or 3 days before challenge immunization, but no suppression was observed when the interval was greater. The suppression coincided with the time of transient viremia in the mice. The secondary immune response to sheep erythrocytes was inhibited when virus was injected within a few days before booster immunization. Induction of immunologic “memory” to sheep erythrocytes was also blocked in C57BL/6 mice given virus before priming with the SRBC. The immunosuppressive activity appeared due to a marked but transient effect of the virus on antibody precursor cells, as ascertained by cell transfer experiments. These observations are pertinent to the general question to the cellular site of action of immunosuppressive tumor viruses and the relationship between immunosuppression and the neoplastic properties of the RNA viruses.
Characterization of Guinea Pig Mitogenic Factor
Authors: Mills John A.
Published: December 2022

Guinea pig mitogenic factor (M.F.) was identified in antigen-stimulated guinea pig lymph node lymphocyte cultures by the ability of supernatants to stimulate DNA synthesis in non-immune lymphocytes. Its activity is not augmented by the presence of antigen and it will stimulate lymphocytes made unresponsive to the eliciting antigen. M.F. production by lymphocytes is detectable within 6 hr after antigen stimulation and reaches a maximum at 24 hr. DNA synthesis produced by M.F. is maximal at 48 hr. M.F. is heat stable at 60°C. Its molecular weight is in the range of 20,000 to 30,000 daltons. M.F. activity appears to be relatively resistant to the action of proteolytic enzymes.
Equine Anti-Hapten Antibody
Authors: Chua Ming-Ming , Morgan Don O. , Karush Fred
Published: December 2022

The immune response to a bacterial vaccine of Streptococcus faecalis (strain N) was characterized in all of the seven horses studied by the sustained production of about 90% IgM anti-lactose antibody over a period of 44 weeks with maximum values of the total antibody ranging from 4 mg/ml of serum to 12 mg/ml of serum. With respect to the binding of a lactose-containing ligand the association constants of the antibodies purified from sera obtained between 5 and 44 weeks fell in the range of 1 × 105 M-1 to 2 × 105 M-1. Not only was there no significant indication of maturation of affinity in this period but there was a selective limitation of affinity compared to that of 7S antibodies. It was inferred that the synthesis of IgM antibody involves the selective utilization of VH and/or VL genes.
Macrophages Activated in Vitro with Lymphocyte Mediators Kill Neoplastic but not Normal Cells
Authors: Piessens Willy F. , Churchill W. Hallowell , David John R.
Published: December 2022

Normal guinea pig macrophages incubated for 3 days in vitro with mediator-rich lymphocyte supernatants become cytotoxic for the syngeneic tumors, Line 1 hepatoma and MCA-25 fibrosarcoma. Under identical experimental conditions the survival of two normal syngeneic cell types, fibroblasts and kidney cells, was not affected. The activating supernatants were prepared by stimulating sensitized lymphocyte cultures with an antigen unrelated to the target cells. Therefore, this type of macrophage-mediated cytotoxicity appears to be nonspecific but restricted to cells with malignant growth capacities.
Immunochemistry of an Acidic Antigen Isolated from a Staphylococcus Aureus
Authors: Karakawa W. W. , Kane J. A.
Published: December 2022

Staphylococcus aureus, strain 7007, was shown to possess an anti-phagocytic surface antigen. This surface antigen was separated from the species-specific teichoic acid by a combination of DEAE-cellulose chromatography and Bio-Gel filtration. Chemical analyses indicated that the 7007 surface antigen consisted of aminomannuronic acid and fucosamine. Immunochemical analyses suggested that this polymer, although consisting of the same components as the staphylococcal T antigen described by Wu and Park was, in fact, immunologically distinct from the T antigen.

Antibodies directed against the surface antigen were isolated from anti-7007 rabbit serum by affinity chromatography. These antibodies were shown to belong to the IgG class of immunoglobulins and were effective in enhancing in vitro phagocytosis of 7007 cells by polymorphonuclear leukocytes.