bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Bordetella Pertussis on the Antibody Response in Mice to Type III Pneumococcal Polysaccharide
Authors: Kong Ah Swee , Morse Stephen I.
Published: December 2022

The effect of an i.p. injection of Bordetella pertussis on the primary humoral immune response in mice to the thymus-independent antigen SIII has been studied. Suppression of the antibody response occurred when pertussis cells were injected at the same time as an optimal immunizing dose of SIII. In contrast, the antibody response to high doses of SIII was enhanced by B. pertussis.

When SIII alone was injected, only 19S antibody was detected. However, when B. pertussis was administered with either optimal or high doses of SIII, 7S as well as 19S antibody against SIII was produced.
Infusion of Donor Lymphocytes into Stable Canine Radiation Chimeras: Implications for Mechanism of Transplantation Tolerance
Authors: Weiden Paul L. , Storb Rainer , Tsoi Mang-So , Graham Theodore C. , Lerner Kenneth G. , Thomas E. Donnall
Published: December 2022

Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. Chimeras were studed 7 to 46 months after 1200 R total body irradiation and transplantation of marrow from a littermate donor matched at the major histocompatibility complex. An attempt was made to perturb the stable chimeric state by infusion of large numbers (0.6 to 13.7 × 108/kg) of donor peripheral blood lymphocytes into each respective chimera. Two groups were studied: donors in Group A were normal; donors in Group B had been specifically sensitized against minor histocompatibility antigens of the chimera by repeated skin grafts. None of the nine chimeras in Group A developed significant clinical or histologic evidence of graft-vs-host disease (GVHD) after donor lymphocyte infusion. Eight of the 12 chimeras in Group B, however, developed GVHD which was transient in three and fatal in five. The results in Group A are not consistent with classical theories of tolerance, i.e., elimination or inactivation of potentially reactive cell clones, but suggest the presence of an active mechanism suppressing recognition of host antigens by the infused donor lymphocytes and development of GVHD. The results in Group B indicate that this mechanism can be overcome by infusion of sensitized donor cells.

In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanism suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD.
Effect of Lipopolysaccharide on the Induction of Tolerance to Polymerized Flagellin
Authors: Scott David W. , Diener Erwin
Published: December 2022

The effect of bacterial lipopolysaccharide (LPS) on the induction of tolerance to the T-independent polymerized flagellar protein (POL) of Salmonella adelaide strain SW1338 was studied in vitro. In contrast to published results with T-dependent antigens, LPS failed to prevent or reverse tolerance induction to POL under conditions in which tolerance was reversible by other means. Moreover, the addition of high doses of LPS to slightly supra-immunogenic concentrations of POL augmented-tolerance induction. These results suggest that the mitogenic properties of LPS are insufficient to convert a tolerogenic dose of POL into an immunogenic one and, therefore, that LPS may act only on T-dependent B cell responses. Since both POL (1338) and LPS are T-independent, mitogenic and so-called “polyclonal B cell activators,” these data have implications for signal discrimination in the immune response.
Effects of C-Reactive Protein on the Lymphoid System
Authors: Mortensen Richard F. , Gewurz Henry
Published: December 2022

C-reactive protein (CRP), an acute phase reactant which increases in concentration during inflammation, has been found to bind to human T cells and to inhibit certain of their functions. In the present study CRP was found to display a binding specificity for ϑ-bearing cells from mouse peripheral lymphoid tissue but not for thymus cells. CRP inhibited the proliferative response in a similar manner in both murine and human mixed lymphocyte reactions. This inhibition was prevented by the addition of the CRP substrate, pneumococcal C-polysaccharide (CPS), and was not a result of toxicity of CRP for lymphocytes. By contrast the response of spleen lymphocytes to mitogenic Con A concentrations was not altered by CRP. CRP also exerted an inhibitory effect on the in vitro generation of cytolytic T lymphocytes (CL) in mixed lymphocyte reactions of mouse spleen cells. The expression of the cytolytic process by T cells sensitized either in vivo or in mixed lymphocyte cultures was not altered in the presence of CRP. Therefore, CRP appears to influence the inductive phase of the allograft response and perhaps exerts a regulatory effect on cellular immune responsiveness during inflammatory reactions.
Studies on the Terminal Stages of Antibody-Complement-Mediated Killing of a Tumor Cell
Authors: Boyle Michael D. P. , Ohanian Sarkis H. , Borsos Tibor
Published: December 2022

The mechanism of the terminal steps in the lysis of antibody-sensitized tumor cells by complement (TAC) was studied. It was shown that once complement has reacted, lysis proceeded even in the absence of fluid-phase complement. Transformation of TAC to dead cells was found to be at least a two-step process: one of the steps was temperature dependent whereas the other was reversibly inhibited by EDTA. In analogy to the hemolytic system, TAC has been designated T*.
Trypsin Increases in Vitro Antibody Synthesis and Substitutes for Helper T Cells
Authors: Gisler Roland H. , Vischer Thomas L. , Dukor Peter
Published: December 2022

Trypsin, a neutral protease, enhanced the direct plaque response of T cell-sufficient mouse spleen cell cultures to sheep erythrocytes (SRBC) and significantly increased the number of spontaneous PFC against SRBC in cultures without antigen. Moreover, trypsin proved to be able to substitute for T cells in nu/nu spleen cell cultures stimulated with SRBC. Its restorative capacity in this type of response was comparable to the one of lipopolysaccharide. Restoration of antibody synthesis in T cell-deprived cultures could not be explained by enzymatic alteration of SRBC. The data are discussed in terms of a possible role of hydrolytic enzymes released by accessory cells during the induction of an antibody response.
Differentiation of Thymocytes: Evidence that Induction of the Surface Phenotype Requires Transcription and Translation
Authors: Storrie Brian , Goldstein Gideon , Boyse Edward A. , Hammerling Ulrich
Published: December 2022

Induction of thymocyte differentiation requires transcription of DNA and translation of RNA but not replication of DNA. This was determined in vitro by studying the effects of cytosine arabinoside, hydroxyurea, actinomycin D, camptothecin, cordycepin, cycloheximide, and puromycin on the induction by thymopoietin of thymocyte differentiation, measured by the acquisition of the differentiation allo-antigens TL and Thy-1 by an inducible fraction of mouse spleen cells.

This requirement for transcription does not establish whether the new mRNA represents transcripts of structural genes for the thymocyte allo-antigen markers; an answer to this question awaits the results of further experiments.
Generation of Cytotoxic Lymphocytes in Vitro: Response of Immune Rat Spleen Cells to a Syngeneic Gross Virus-Induced Lymphoma in Mixed Lymphocyte-Tumor Culture
Authors: Bernstein Irwin D. , Wright Peter W. , Cohen Edith
Published: December 2022

Spleen cells from W/Fu rats 4 to 6 weeks after immunization with syngeneic Gross virus-induced lymphoma (C58NT)D cells usually lack detectable activity in a short-term 51Cr release assay. The results presented here demonstrate that these spleen cells retain the capacity to generate significant proliferative and cytotoxic activity upon re-exposure to mitomycin C-treated (C58NT)D cells in vitro. Optimal conditions were defined in W/Fu rats for this secondary immune response in vitro to the (C58NT)D cells. The cytotoxic response was observed to be quantitative, reproducible, and specific. Optimal generation occurred 5 days after initiation of cultures with a 30:1 responding cell:stimulating cell ratio. In vitro generated cytotoxic cells inhibit tumor growth in vivo when administered as a mixture with tumor cells.
Antigen-Specific and Nonspecific Mediators of T Cell/B Cell Cooperation
Authors: Marrack Philippa , Kappler John W.
Published: December 2022

Further evidence is presented for two types of helper T cells in the mouse specific for the protein antigen, keyhole limpet hemocyanin (KLH). The first cell helps B cells respond to the trinitrophenyl hapten (TNP) coupled to KLH, is primed by relatively high doses of antigen in vivo, and yet the effector cell is stimulated by very low doses of antigen in vitro. The second cell helps B cells respond to a non-cross-reacting antigen, sheep red blood cells, presumably via production of a nonspecific factor. This cell is primed by relatively low doses of antigen in vivo, but the effector cell requires relatively high doses of antigen in vitro. Thus, the two T cell types are differently sensitive to antigen dose, both in priming and challenge. The properties of T cells responding to KLH by proliferation in vitro were also studied. These cells showed the same antigen-sensitivity in vitro, as cells producing nonspecific B cell-stimulating factors.
Antibody against the Antigen Receptor of a Plasmacytoma Prolongs Survival of Mice Bearing the Tumor
Authors: Beatty Patrick G. , Kim Byung S. , Rowley Donald A. , Coppleson Lionel W.
Published: December 2022

A transplantable plasmacytoma, TEPC-15 in BALB/c mice, induces a transient antibody response directed against the combining region of the myeloma protein produced by the tumor. Mice immunized with mitomycin-treated tumor cells produce similar antibody but do not develop tumor; mice so immunized survive longer than untreated mice when inoculated with viable TEPC-15 cells. This protection afforded by immunization can be transferred by serum alone; the protective effect of passively given serum is eliminated by absorbing out antibody directed against the myeloma protein.
Studies on Autoimmune Encephalomyelitis in the Guinea Pig
Authors: Lebar René , Boutry Jeanne-Marie , Vincent Christine , Robineaux Roger , Voisin Guy André
Published: December 2022

Complement-dependent demyelinating activity of whole brain homogenate (WBH)-induced experimental allergic encephalomyelitis (EAE) sera was tested on long term tissue cultures of in vitro myelinated fetal guinea pig cerebellum.

Complement-fixing (CF) auto-antibodies were shown to be the responsible agents, as demonstrated in experiments where all reagents belonged to the same species: guinea pigs of outbred (Hartley) and even of inbred (S2 or S13) strains. These antibodies were of the IgG2 class as shown by Sephadex G-200 and DEAE cellulose fractionation experiments.

The corresponding auto-antigen was present in the homogenate and myelin of the central nervous system (CNS) tissue. It was different from the encephalitogenic basic protein of CNS myelin (BP), as shown in experiments where the demyelinating auto-antibodies were induced, detected, and absorbed by WBH or by CNS myelin but not by BP. They were neither induced by nor cross-reacting with cerebroside and peripheral nervous system (PNS) tissue.
Association of Dane Particles with e Antigen in the Serum of Asymptomatic Carriers of Hepatitis B Surface Antigen
Authors: Takahashi Kazuaki , Imai Mitsunobu , Tsuda Fumio , Takahashi Takashi , Miyakawa Yuzo , Mayumi Makoto
Published: December 2022

Asymptomatic carriers of hepatitis B surface antigen (HBsAg) were surveyed for serum e antigen (e Ag) and antibody to e (anti-e) by immunodiffusion. Seventeen serum samples containing e Ag and 17 containing anti-e, but with similar HBsAg titers, were tested for the presence of hepatitis B core antigen (HBcAg) by means of immune adherence hemagglutination method. HBcAg activity was detected in all of the samples containing e Ag, and the titer of HBcAg paralleled that of HBsAg in each serum. In remarkable contrast, no HBcAg activity was found in any of the serum samples containing anti-e. Dane particles were demonstrated in 14 of 17 serum samples with e Ag by electron microscopy, but in none of 17 with anti-e. Although both e Ag and HBcAg were closely associated with each other, the non-identity of e Ag and HBcAg was clearly demonstrated by a two-dimensional immunodiffusion test.
Mouse Lymphotoxin
Authors: Trivers Glennwood , Braungart Dale , Leonard Edward J.
Published: December 2022

The addition of PHA to C3H mouse spleen cells in tissue culture led to the production of lymphotoxin (LT). Cytotoxicity was assayed by addition of the culture fluids to syngeneic target cells labeled with tritiated thymidine; after an incubation period of 72 hr the amount of radioactivity released into the supernatant was measured. The LT activity in unfractionated culture fluids survived lyophilization, remained unchanged for many weeks at 4°C, and progressively decreased on heating at 56°C for periods from 1 to 9 hr. Based on the G-200 Sephadex distribution coefficients for several preparations, the m.w. of mouse lymphotoxin was about 41,000 daltons. Lymphotoxin from three different spleen cell production runs was recovered from isoelectric focusing columns in sharply focused peaks, the pH of which ranged from 4.4 to 4.8.
Inflammatory Process in Murine Lymphocytic Choriomeningitis Is Maximal in H-2K or H-2D Compatible Interactions
Authors: Doherty Peter C. , Dunlop Malcolm B. C. , Parish Christopher R. , Zinkernagel Rolf M.
Published: December 2022

Capacity to transfer adoptively fatal lymphocytic choriomeningitis (LCM) to immunosuppressed, virus-infected recipients is a property of H-2 compatible, non-Ig-bearing virus-immune lymphocytes. Severe meningitis is recognized when donor and recipient share at least one allele at either H-2K or H-2D. Presence of unshared H-2 genes is not obviously inhibitory, and identity at the immune response (Ir) region of the H-2 gene complex is neither sufficient nor necessary. The same constraint applies to cytotoxic T cell activity in vitro; lymphocytes and virus-infected targets must be compatible for a minimum of one allele mapping at H-2K or H-2D. The present findings thus support the concept that populations of T cells, which are cytotoxic in vitro, also mediate inflammatory process in vivo and are a major, if not the only, effector population in murine LCM.
Eosinophil Chemotactic Factor (ECF)
Authors: König Wolfgang , Czarnetzki Beate M. , Lichtenstein Lawrence M.
Published: December 2022

Phagocytosis was found to stimulate ECF release from neutrophils (PMN). Human PMN (τ; 98%) were exposed to zymosan (Z), zymosan-coated with complement (Z(x)), or zymosan in the presence of serum (Z(s)). The release of ECF was shown to be time- and dose-dependent. Like ionophore-induced ECF, phagocytosis-derived ECF preferentially attracted and deactivated eosinophils. Chromatography on Sephadex G-25 revealed an elution pattern similar to the antigen-induced, basophil-derived and to the ionophore-induced PMN-derived ECF. The addition of complement either as Z(x) or Z(s) accelerated the release of ECF. With both stimuli, the initial kinetics of ECF paralleled the release of β-glucuronidase and NBT reduction. With Z alone, β-glucuronidase release and NBT reduction were negligible, whereas the amount of ECF released was similar to that induced by Z(x). In the presence of serum Z(s), decreased activity was noted. Supernatants of phagocytosis at late time periods showed less activity than early supernatants, suggesting that ECF might be inactivated. These data indicate that phagocytosis causes the release of an ECF, which appears to be similar to the IgE-induced ECF-A.
Appearance of IgG (Fc) Receptor(s) on Cultured Human Fibroblasts Infected with Human Cytomegalovirus
Authors: Rahman Adel A. , Teschner Marion , Sethi Krishan K. , Brandis Henning
Published: December 2022

Cultured human diploid fibroblasts (WI-38) after infection with human cytomegalovirus (CMV) but not when uninfected, could hemadsorb sheep red blood cells (SRBC) coated with rabbit anti-SRBC IgG. The adsorption of IgG-coated SRBC to virus-infected cells was completely abolished if the tests were carried out in the simultaneous presence of rabbit antiserum elicited against CMV. Normal sera of rabbit or human origin as well as purified human IgG but not Fab fragment of human IgG could also abolish the binding of sensitized SRBC to CMV-infected fibroblasts. Active metabolism on the part of CMV-infected fibroblasts proved to be an important requisite for demonstrating binding of sensitized SRBC to their surfaces. By using as indicator Staphylococcus aureus to which rabbit antiserum against normal human IgG, IgM, or IgA was bound via Fc fragments, evidence has been obtained which suggests the existence of receptor(s) on CMV-infected WI-38 cells that react specifically with Fc region of human IgG.
Separation of Populations of Sensitized Lymphoid Cells into Fractions Inhibiting and Fractions Enhancing Syngeneic Tumor Growth in Vivo
Authors: Small Myra , Trainin Nathan
Published: December 2022

Separation of subpopulations of lymphoid cells sensitized against a syngeneic tumor was attempted by means of velocity sedimentation and the fractions were injected together with tumor cells into syngeneic hosts. Spleen cells from tumor-bearing mice or spleen cells sensitized on tumor cell monolayers could be fractionated into a subpopulation capable of inhibiting growth of the same tumor and a separable fraction which enhanced tumor growth. Activity of the tumor-inhibiting lymphocytes was not apparent in the presence of the tumor-enhancing cells. The former activity was associated with small lymphocytes and the latter with injection of larger cells. Preliminary experiments investigated the developmental relation between the cells responsible for these opposing activities.
C1q (C1) Receptor on Human Platelets: Inhibition of Collagen-Induced Platelet Aggregation by C1q (C1) Molecules
Authors: Suba Eva A. , Csako Gyorgy
Published: December 2022

Hemolytically active human C1q incubated with EA before the addition of complement inhibited the immune hemolysis. On the contrary, heat-inactivated preparation (30 min 56°C) was ineffective. Preincubation of EA with bovine collagen also resulted in a decreased hemolysis. When aggregation was measured by a turbidimetric method in citrated human platelet-rich plasma, it was found that hemolytically active human C1q (C1) alone does not induce platelet aggregation. However, in its presence the platelets failed to aggregate or exhibited a significantly reduced aggregation response to bovine collagen. The inhibition by C1q depended on the preincubation time with platelets. Heat treatment (30 min 56°C) destroyed the inhibitory action of C1q (C1). The effect of C1q proved to be highly specific because different C1q preparations at their inhibitory doses in collagen-induced platelet aggregation did not influence the response to other aggregating agents (bovine thrombin, ADP, horse anti-human thymocyte globulin, goat anti-baboon platelet antiserum). The results prove that collagen and C1q are capable of binding to the same site(s); namely, to those of EA and human platelets; furthermore, they suggest the presence of a receptor for C1q (C1) on human platelets.
Biological Expressions of Lymphocyte Activation
Authors: Tadakuma Takushi , Kühner Alice L. , Rich Robert R. , David John R. , Pierce Carl W.
Published: December 2022

Supernatant fluids from murine spleen cell cultures incubated with concanavalin A for 48 hr contain a factor(s), soluble immune response suppressor (SIRS), which suppresses plaque-forming cell responses to sheep erythrocytes by murine spleen cells in vitro. In the present studies, some of the biochemical and biophysical properties of SIRS were investigated. SIRS was non-dialysable; the suppressive activity was stable at 56°C for 30 min, but was destroyed by treatment at 70°C for 30 min, 80°C for 10 min, or at pH 2. The suppressive activity was not absorbed by the stimulating antigen, SRBC, or antisera against murine IgG or µ-chain, suggesting that SIRS does not contain immunoglobulin determinants. Murine spleen and thymus, but not kidney cells, however, absorbed SIRS activity. Enzyme treatments revealed that SIRS was resistant to DNase and RNase, but was destroyed by trypsin and chymotrypsin. In gel filtration with Sephadex G-100, SIRS activity eluted in the fraction corresponding to m.w. in the range between 48,000 and 67,000. With polyacrylamide gel electrophoresis, SIRS activity migrated in the region cathodal to albumin. Isopycnic centrifugation in a cesium chloride gradient suggested that SIRS is a glycoprotein. These supernatant fluids with SIRS activity were also found to contain macrophage migration inhibitory factor (MIF). In the experiments using gel filtration, polyacrylamide gel electrophoresis, and isopycnic centrifugation to fractionate supernatant fluids, SIRS and MIF activity were found in the same fractions, and to date we have been unable to dissociate definitively SIRS activity from MIF activity.
Hybridization Kinetics of Ribonucleic Acid and Deoxyribonucleic Acid from Antigen-Stimulated Mouse Spleen Cells
Authors: Moav Neomi , Goldblatt Drora , Moav Boaz , Frensdorff Asher
Published: December 2022

In an attempt to explore the mechanism by which antigenic stimulation alters gene expression in lymphoid cells in vivo, three different hybridization techniques have been used to compare the complexity of the genome of lymphoid cells from normal and from immune BALB/c mice.

RNA/DNA hybridization experiments at a DNA excess of 1000 demonstrated that normal RNA and immune RNA hybridized identically with DNA extracted from mouse spleen cells before and after immunization and with liver DNA. These findings indicate that DNA sequences complementary to immune RNA or to normal RNA are represented in a number of copies not significantly different in the genome of normal lymphoid cells and in that of immune lymphoid cells.

Hybridizations of normal and of immune RNA with normal and immune pulse-labeled DNA, done at RNA excess, detected no differences between these two DNA. However, significant differences were observed in the percentage of DNA hybridized with normal and immune RNA; 3 to 4% of the DNA hybridized with normal RNA and 8 to 9% with immune RNA. This indicates that more DNA sequences are transcribed 48 hr after immunization than before immunization.

The RNA exhaustion rates caused by normal and immune DNA were found to be identical, indicating that antigenic stimulation did not induce major changes in the number of DNA base sequences complementary to the RNA tested. However, when normal and immune pulse-labeled RNA were compared by exhaustion with DNA, the immune pulse-labeled RNA obtained 48 hr after immunization displayed a slower exhaustion rate than normal RNA or RNA extracted 72 hr after immunization. These results suggest the temporary synthesis, at a higher frequency, of certain RNA species 48 hr after immunization, as compared to the RNA synthesis in normal, nonimmune cells, or that occurring 72 hr after immunization.

Thus, the three experimental approaches used lead to the conclusion that antigenic stimulation does not induce major gene amplification; it does, however, change the transcription rate of certain RNA species.
Antibodies to Guinea Pig Lymphokines
Authors: Geczy Carolyn L. , Geczy Andrew F. , de Weck Alain L.
Published: December 2022

A “second generation” antibody to a highly purified lymphocyte product was raised in a goat against material eluted from a rabbit anti-guinea pig lymphokine immunoadsorbent column. This anti-lymphokine serum, in contrast to anti-lymphocyte serum (ALS) did not appear to contain cytotoxic antibodies directed against membrane antigens on guinea pig lymph node lymphocytes. Furthermore, the anti-lymphokine serum did not inhibit the formation of spontaneous T rosettes nor significantly depress lymphocyte response to mitogens.

The anti-lymphokine serum totally suppressed the delayed skin reactivity to PPD and contact sensitivity to DNCB when injected intradermally around the site of antigen challenge. By contrast, intradermally injected ALS did not appear to suppress the PPD response in sensitized guinea pigs. Intravenously and i.p. administered anti-lymphokine serum was somewhat less effective in suppressing the delayed skin response to PPD. The intradermal injection of the antiserum had no effect on nonspecific inflammation evoked by turpentine-olive oil or on the extravasation of circulating Evans blue evoked by intradermally injected histamine.

Histologic examination of 24-hr DNCB-induced skin lesions from sensitized guinea pigs treated with intradermally injected anti-lymphokine serum showed marked reduction of mononuclear infiltration of the dermis and of epidermal lesions, as compared with skin sites taken from sensitized animals pretreated with normal goat serum. The anti-lymphokine serum injected i.v. also markedly reduced the perivascular infiltration of the dermis and subcutis in skin reaction sites from sensitized animals challenged with PPD. Intravenous treatment with ALS for 3 consecutive days caused extensive depletion of the paracortical areas of peripheral lymph nodes whereas treatment with normal serum and anti-lymphokine serum caused no such depletion.

It is proposed that the anti-lymphokine serum is directed against activated lymphocyte products, one of them being MIF. These products are involved in the mediation of delayed hypersensitivity reactions. This is in marked contrast to ALS, the suppressive action of which appears to be central rather than peripheral.
Cellular Immunity in Chronic Theiler's Virus Central Nervous System Infection
Authors: Rabinowitz Stanley G. , Lipton Howard L.
Published: December 2022

After (IC) inoculation of the DA strain of TMEV, SJL/J mice develop chronic CNS infection with marked mononuclear cell infiltration of spinal cord leptomeninges and white matter and concomitant demyelination. In the present study the temporal course of cell-mediated and humoral immune responses to virus were measured in this infection. It was shown that chronic TMEV infection is associated with the development of immunologically specific spleen cell reactivity as judged by in vitro incorporation of 3H-TdR into DNA in response to inactivated TMEV antigen. Spleen cell reactivity is first detectable about 2 months after infection, persists for at least 1 year, and correlates with the temporal development of serum-neutralizing antibody. The late development of sensitized spleen cells is not the result of an immunosuppressive effect of this virus infection since infected mice exhibit normal spleen cell proliferative responses to T cell mitogens and produce normal antibody responses to a heterologous protein antigen, sheep red blood cells. In addition, anti-viral antibody inhibits virusinduced spleen cell reactivity. Finally, the antigen-reactive lymphocyte subpopulation within the spleen responsible for proliferation to TMEV antigen are T cells and not B cells.
The Inhibitory Effect of Chemotactic Factors on Erythrophagocytosis by Human Neutrophils
Authors: Musson Robert A. , Becker Elmer L.
Published: December 2022

The effect of various chemotactic factors on phagocytosis of sheep erythrocytes sensitized with IgG and complement (EAC1423) by human neutrophils (PMN) was studied. The bacterial chemotactic factor, a butanol extract of an Escherichia coli culture filtrate, the pronase sensitive and insensitive chemotactic substances isolated from this extract, C5a, a chemotactic fragment of the fifth component of complement, and a chemotactic synthetic peptide, formylmethionyl-leucine all significantly reduced the initial rate of ingestion at concentrations that are chemotactic for PMN. The bacterial chemotactic factor produced a 45 to 75% decrease in the initial rate of ingestion, but did not affect adherence of the EAC1423 and PMN. This same substance had no consistent effect on the total number of EAC1423 ingested at 90 min or longer or on the time interval from the addition of the EAC1423 to the start of ingestion. The inhibitory effect of the bacterial factor increased as the amount of bacterial factor was increased and the inhibitory effect was reversible. Inhibition by bacterial factor could be decreased by increasing the concentration of EAC1423; and if the concentration was increased 3-fold, the inhibition was abolished. These results suggest that inhibition by bacterial factor is competitive in nature.
Requirements for Induction of T Cell Tolerance to Dnfb: Efficiency of Membrane-Associated DNFB
Authors: Claman Henry N. , Miller Stephen D.
Published: December 2022

Tolerance to contact sensitization with DNFB,3 a T cell-dependent phenomenon, was induced in mice by preparations of DNFB coupled to mouse RBC or spleen cells. Such tolerance is dose related, wanes with time, and can be transferred to normal animals with lymphoid cells (presumably containing suppressors). Tolerance to DNFB-RBC can be produced by whole DNFB-RBC, by ghosts of these cells, by sonicates of the ghosts, and by detergenttreated DNFB-RBC ghosts. Tolerance cannot be produced by larger amounts of DNFB-RBC components not associated with membrane. The ability of various DNP compounds to stimulate DNA synthesis in DNFB-sensitized cells also correlates with their ability to bind to protein components; i.e., DNFB is a far more efficient stimulator than DNBSO3, whereas DNP-lysine does not stimulate at all. Thus, the ability to sensitize or to tolerize with DNFB congeners is related to their ability to couple to proteins. It appears that the active induction of T cell tolerance requires that tolerogen be coupled to cell membranes. Since both T cell sensitization and tolerance to DNFB are best produced by DNFB-membrane, the actual occurrence of one state or the other must depend on the molecular method of “presentation” of DNFB-membrane.
Isolation of a Murine Leukemia Fc Receptor by Selective Release Induced by Surface Redistribution
Authors: Cooper Sheldon M. , Sambray Yugalkishore
Published: December 2022

A protein which binds to the Fc region of IgG has been isolated from the murine leukemia L1210. The isolation technique involves surface cross-linking of the cell's Fc receptors with the use of aggregated human IgG and anti-human IgG. This results in the redistribution (patch formation and capping) of the cell's Fc receptors. Lactoperoxidase-catalyzed radioiodination of the cells before complex binding indicates that Fc receptor redistribution results in the selective release of surface proteins. SDS-PAGE analyses of the supernatants from cells thus treated reveals a major peak corresponding to a molecular weight of 45,000 daltons. This protein has been purified from the cell supernatants by immunoprecipitation and chromatography of the percipitates on Sephadex G-200 under dissociating conditions. After separation from the immune complex this protein can be bound to heat-aggregated IgG, but not aggregated F(ab′)2 fragments. The 45,000 dalton protein appears to be the Fc receptor which has been released from the cell surface in association with the complex.
Mechanisms Involved in Elimination of Organisms from Experimental Cutaneous Candida Albicans Infections in Guinea Pigs
Authors: Sohnle Peter G. , Frank Michael M. , Kirkpatrick Charles H.
Published: December 2022

Experimental cutaneous Candida albicans infections were produced in guinea pigs either by using occlusive dressings over the organisms or by applying them to the shaved skin directly without occlusive dressings. In either model there was clearance of the infecting organisms from the skin by a process involving profuse scaling of the keratinized layer in which they were confined. However, for each type of infection the mechanisms producing this scaling seemed to involve different parts of the host defense system.

Infections produced under occlusive dressings were characterized by a rapid accumulation of polymorphonuclear leukocytes (PMN) in the epidermis and formation of thick crusts in which organisms were trapped. Sloughing of the crust removed the organisms. In this model, evolution of the lesions and the rate of clearance of the organisms did not depend on prior immunity to Candida. Two possible mechanisms for attraction of PMN into the lesions were direct activation of the alternative complement pathway by the organisms in the lesions and direct chemotactic activity in components of Candida albicans.

In contrast, infections produced without occlusive dressings showed only minimal epidermal PMN infiltration, but also underwent profuse scaling of the keratinized layer. This response appeared to depend on cell-mediated immunity. Only animals with previously-acquired delayed hypersensitivity to Candida antigens could undergo this type of scaling, and, indeed, this response was transferable to nonimmune animals with peritoneal exudate cells from Candida-immune animals. Clearance of the infecting organisms from this type of infection was significantly faster in immune than in nonimmune animals. It is postulated that a lymphokine released from lymphocytes in the upper epidermis acts on epidermal cells to increase the rate of keratin turnover either by increasing the mitotic rate of the germinal cells or by increasing their rate of keratinization.
Cellular Specificity of Plasmacytoma-Induced Immunosuppression
Authors: Zolla-Pazner Susan , Sullivan Bessie , Richardson Deborah
Published: December 2022

The pattern of immunodeficiency in plasmacytoma-bearing mice appears to be unique. Mice bearing these tumors exhibit a severe impairment in their ability to mount a primary immune response to thymus-dependent and -independent antigens. However, cell-mediated immune functions in these mice apparently remain intact. Thus, when T cell activity of lymph node cells from plasmacytomabearing mice was tested in vivo by sensitization with dinitrofluorobenzene and in vitro by responsiveness to phytohemagglutinin, allogeneic cells, and dinitrobenzene sulfonate, cell-mediated immunity was found to be normal.
Histamine Release by Chemotactic, Formyl Methionine-Containing Peptides
Authors: Hook William A. , Schiffmann Elliott , Aswanikumar Srinivasabhat , Siraganian Reuben P.
Published: December 2022

Certain formyl dipeptides and tripeptides containing methionine released histamine from human basophils at concentrations of 10-4 to 10-7 M. However, N-formyl amino acids did not release histamine. Tripeptides, in general, were more active than dipeptides. An acyl group was required for histamine release although an N-terminal position for Met was not essential. Histamine release from human basophils by these peptides correlated well with their chemotactic activity for rabbit leukocytes.
Altered Lymphocyte Functions in Rats Bearing Syngeneic Moloney Sarcoma Tumors
Authors: Veit Bruce C. , Feldman Joseph D.
Published: December 2022

Impairment of mitogen responses to Con A and LPS and of MLR and MLTR was detected in the spleens of rats bearing syngeneic Moloney sarcoma tumors. Depressed responses of both T cell and Ig+ cell populations were observed. During the observation period of 6 to 10 days post-tumor inoculation when maximal T cell-mediated cytotoxicity was observed in spleen and draining lymph node cells, spleen cells showed marked impairment in response to stimuli mentioned above. By contrast, draining lymph node cell activity was either unaltered or somewhat elevated above the level of activity measured in normal control populations. Data presented in this and an accompanying paper strongly indicate that macrophages are activated as immunosuppressor cells in tumor-bearing rats.
Altered Lymphocyte Functions in Rats Bearing Syngeneic Moloney Sarcoma Tumors
Authors: Veit Bruce C. , Feldman Joseph D.
Published: December 2022

Spleens from tumor-bearing rats contained a population of adherent cells that suppressed lymphocyte responses to Con A and LPS and cell-mediated cytotoxicity (CMC). By use of various fractionation procedures, Ig+ cells, T cells, and null cells were excluded as candidates for the suppressor cell activity. Procedures that removed macrophages abolished the suppressive activity whereas those procedures that enriched for or involved direct addition of macrophages resulted in augmented suppression. On the basis of these results, we conclude that the suppressor elements in spleens of tumor-bearing rats were macrophages.
The Homologues of Rabbit b-Allotypes on Hare Immunoglobulin Light Chains: An Evolutionary Puzzle
Authors: Tosi Simonetta Landucci , Mage Rose G. , Tosi Roberto M.
Published: December 2022

Most alloantisera directed against the rabbit allotypes b4, b5, and b6 cross-reacted with hare IgG. The determinants recognized by antisera against the three allotypes were shown to reside on the same hare L chains. Hare immunoglobulins, when injected into b4, b5, or b9 rabbits, elicited the formation of antibodies which reacted with hare IgG and cross-reacted with those rabbit allotypes (except b9) absent from the recipient. The anti-b9 antisera tested lacked reactivity with hare IgG.
Deficient Production of a Thymus-Dependent High Affinity Antibody Subset in Mice (CBA/N) with an X-linked B Lymphocyte Defect
Authors: Gershon Richard K. , Kondo Kazunari
Published: December 2022

Since the original demonstration by Amsbaugh et al. (1) that a sub-line of CBA/H (CBA/N) mice has a recessive X-linked genetic defect which prevents them from responding to type III pneumococcal polysaccharide this sub-line of mice has come under intensive study, particularly by Scher and his colleagues (2–9). These workers have established that the X-linked defect is expressed in B cells (4) and that by a number of criteria the T cells of the mice with the defect are indistinguishable from those of appropriate control mice (4). They have further shown that the defect preferentially inhibits the response to so called “thymus-independent antigens” (1, 2, 5, 9); it leads to a much smaller deficit in the response to “thymus-dependent antigens”. CBA/N B cells are intrinsically defective and are not influenced by the environment in which they reside (4, 9). The defect can best be explained as a failure of maturation or differentiation in that it has been shown that adult CBA/N mice lack a population of B cells which is also lacking in young (but not mature) normal mice (6, 7).
Genetic Control of the Immune Response in Guinea Pigs to the Known Sequence Polymer (Tyr-Ala-Glu-Gly)n
Authors: Zeiger Allen R. , Maurer Paul H.
Published: December 2022

The genetic control of the immune response to randomly polymerized polypeptides containing amino acids such as glutamic acid, alanine, and tyrosine is now well established in inbred guinea pigs (1, 2). Recent advances in the field of peptide chemistry now make possible the synthesis of polypeptides of similar amino acid composition but with defined amino acid sequences. Studies with these polymers may yield information on the specificity of the genetic control at the molecular level.

We have reported the synthesis of (Tyr-Glu-Ala-Gly)n of 53,000 m.w. (3). Under physiologic conditions, it exists primarily in the α-helical configuration and is immunogenic in some Hartley guinea pigs and in inbred strain 13 guinea pigs, but not in strain 2 guinea pigs (4).

We have recently synthesized a polymer of similar amino acid composition but with a different sequence, (Tyr-Ala-Glu-Gly)n, of 33,000 m.w. and have shown that it too is α-helical under physiologic conditions (Zeiger and Maurer, manuscript in preparation).
Bence Jones Proteins and Light Chains of Immunoglobulins
Authors: Solomon Alan , Schmidt Wilhelm , Havemann Klaus
Published: December 2022

Bence Jones proteins can be cleaved specifically by several types of endopeptidases into fragments corresponding to the amino-terminal, variant (VL) portion and to the carboxyl-terminal, constant (CL) portion of the light polypeptide chain. Two types of neutral proteases, designated elastase-like (ELP) and chymotrypsin-like (CLP), have been isolated and purified from human polymorphonuclear leukocytes. Because these proteases have defined proteolytic activity under physiologic conditions for several types of human proteins, we investigated their effect on human Bence Jones proteins. Incubation of κ-type or λ-type Bence Jones proteins with ELP or CLP under appropriate conditions resulted in cleavage of both types of light chains as evident by immunochemical and electrophoretic analyses. Treatment with ELP or CLP of one κ Bence Jones protein resulted in the formation of a single component that had antigenic and electrophoretic properties similar to the VL fragment derived from pepsin digestion of the native protein. No component corresponding to the CL could be detected immunochemically or electrophoretically. Studies of isolated pepsin-labile (37°C) and pepsin-stable (55°C) CL fragments demonstrated the marked susceptibility of the carboxyl-terminal half of the light chain to proteolysis by the leukocyte-derived neutral proteases. Incubation with ELP of three other κ Bence Jones proteins and three reduced-alkylated λ Bence Jones proteins resulted, in each case, in the formation of a homogeneous component which was electrophoretically and immunochemically distinct from the pepsin-derived VL fragment. An identical component could also be formed by incubating a pepsin-derived VL fragment with ELP. In the ELP-treated samples, no CL-related material was detected electrophoretically or immunochemically with antisera possessing specificity for CL antigenic determinants present on the unfolded light polypeptide chain or on the isolated CL. The component formed by ELP or CLP treatment of certain Bence Jones proteins thus appears to be VL-related, but lacks the idiotypic antigenic determinant present on the native protein. In this respect, these neutral protease-derived light chain components are similar to the amyloid-like VL fragments generated in vitro from certain endopeptidase-treated Bence Jones proteins.
Immunochemical Studies of Infectious Mononucleosis
Authors: Fletcher Mary Ann , Lo Timothy M. , Graves William R.
Published: December 2022

A glycoprotein was isolated from goat erythrocyte membranes by extraction with hot 75% ethanol. The glycoprotein was purified by ethanol precipitation, phosphocellulose chromatography gel filtration, ethyl:ether and chloroform:methanol extraction. In aqueous phosphate-buffered saline, pH 7, the glycoprotein was in an aggregated state with a sedimentation coefficient (Sobs) of 21. Addition of 0.5% sodium dodecyl sulphate (SDS) lowered Sobs to 1.5. Electrophoresis of the glycoprotein on polyacrylamide gels containing phosphate-buffered 0.1% SDS gave a single band, staining with both periodic acid Schiff (PAS) and Coomassie Blue (CB). The apparent m.w., calculated from retardation coefficient, was 25,000. Electrophoresis of the glycoprotein on 1% SDS gels buffered with Tris-acetate (pH 7.4) showed a major band of similar (23,500) apparent m.w. plus four other PAS- and CB-staining bands of lower mobility. With 131I-labeled glycoprotein, recovery of bands from gels, sialic acid analysis, heterophile antigen activity, and re-electrophoresis, it was shown that these additional bands were aggregated forms of a single or closely related glycoprotein species. The purified glycoprotein contained 50% carbohydrate with molar ratios of sialic acid: galactose: mannose: galactosamine: glucosamine of 3.1:2.1:0.1:1.6:1. The glycoprotein was highly reactive with the Paul-Bunnell heterophile antibody in the sera of patients with infectious mononucleosis, with Limulus polyphemus lectin and weakly ractive with wheat germ agglutinin. These reactivities were destroyed by neuraminidase treatment or by alkaline sodium borohydride. The native glycoprotein did not react with lectins from Canavalia enisformis, Phaseolus vulgaris, Ricinus communis, or Vicia graminea although it was reactive with the latter two after neuraminidase treatment.
Influence of H-2 on the Ontogenesis of a Spleen Cell Population Which Lacks C3 Receptors and Thy-1 Antigen
Authors: Ferreira Arturo , Nussenzweig Victor
Published: December 2022

During ontogeny there are marked differences in the cellularity of the spleen of mice from different inbred strains. Data from segregation analysis demonstrate that one of the genes involved in the control of the size of the spleen at 15 days lies in the H-2 region. In contrast to previous reports, we find that the cell population under H-2 influence lacks complement receptors.
Nicotinamide: Suppression of Lymphocyte Transformation with a Component Identified in Human Transfer Factor
Authors: Burger Denis R. , Vandenbark Arthur A. , Daves Doyle , Anderson William A. , Mark Vetto R. , Finke Patricia
Published: December 2022

The component in human transfer factor (TF) (Fraction IV, from exclusion chromatography on Sephadex G-25) responsible for suppression of antigen-induced lymphocyte transformation was previously identified as nicotinamide. Commercially available nicotinamide was subsequently shown to produce suppression of antigen-induced responses in vitro previously observed with TF Fraction IV. Nicotinamide was found to be nontoxic at the highest concentrations employed (10-2 M) and suppressive over a relatively broad range (10-5 to 10-2 M). The suppression appeared to be related to the magnitude of antigen- or mitogen-induced transformation and was apparent even when nicotinamide was added as late as 48 hr after stimulant addition.
Purification, Specificity, and Hypervariable Region Sequence of Anti-Pneumococcal Polysaccharide Antibodies Elicited in a Single Rabbit
Authors: Chen Francis W. , Edward Cannon L. , Margolies Michael N. , Donny Strosberg A. , Haber Edgar
Published: December 2022

Four homogeneous antibodies to type VIII pneumococcal polysaccharide (S8) were isolated from the serum of a single rabbit (3322) by affinity chromatography on an S8 immunoadsorbent by utilizing gradient elution with cellobiose and NaCl. The binding properties of these antibodies were determined by a radioimmunoassay with 125I-bovine γ-globulin-S8. Cellobiose (a disaccharide unit of S8) was the immunodominant group of each of the four antibodies, but each antibody bound to this disaccharide with different relative affinities. The amino acid sequences (positions 0–40) of three of the four antibody light chains were each different both in framework and first hypervariable region sequences. The fourth antibody light chain has a blocked amino terminus. These findings indicate that antibodies elicited by a relatively simple antigen and examined at one time during the course of immunization in a single rabbit may exhibit common specificities for an oligosaccharide determinant, yet have different binding affinities for that determinant as well as different primary structures in the complementarity (hypervariable) regions and framework regions.