bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the human classical complement pathway by a mouse monoclonal hybrid IgG1-2a monovalent anti-TNP antibody bound to TNP-conjugated cells.
Authors: Couderc J , Kazatchkine M D , Ventura M , Duc H T , Maillet F , Thobie N , Liacopoulos P 
Published: December 2022

Abstract
A mouse hybridoma selected and cloned for anti-TNP specificity produced three distinct monoclonal antibody species that were separated on protein A-Sepharose by stepwise acid elution. The IgG1 kappa product of the parental myeloma was eluted at pH 6.0. An IgG2a kappa bivalent anti-TNP antibody was eluted at pH 4.5, whereas elution at pH 5.0 yielded a hybrid IgG1-2a kappa monovalent anti-TNP antibody. The IgG2a molecules agglutinated TNP-conjugated sheep erythrocytes (TNP-ES) and lysed TNP-ES in the presence of normal human serum (NHS). Hybrid IgG1-2a antibody was also capable of lysing the cells in NHS, although it did not agglutinate TNP-ES. A threshold in monovalent antibody input was necessary for the lysis of TNP-ES, indicating a requirement for a minimal density of bound monovalent IgG to trigger complement activation. Lysis occurred in NHS-VBS++ but not in NHS-MgEGTA, and it was associated with a dose-dependent consumption of C1, C4, and C2 hemolytic activities. Quantitation of the antibody bound to TNP-ES when using radiolabeled rabbit anti-mouse Fab antibody demonstrated that for similar inputs, 5.4 times as much bivalent as monovalent antibody bound to TNP-ES. When similar amounts of antibody were effectively bound to TNP-ES, monovalent hybrid IgG1-2a was five times less efficient than bivalent IgG2a to yield 50% cell lysis in the presence of NHS. These results indicate that neither bivalent binding nor the presence of two identical heavy chains are necessary requirements for antibody-dependent activation of the classical complement pathway.
Human C3a-mediated suppression of the immune response. I. Suppression of murine in vitro antibody responses occurs through the generation of nonspecific Lyt-2+ suppressor T cell.
Authors: Morgan E L , Thoman M L , Weigle W O , Hugli T E 
Published: December 2022

Abstract
C3a derived from the third component of human complement was found to suppress in vitro murine anti-SRBC responses. C3a-mediated suppression occurs through the generation of nonspecific Lyt-2+ suppressor T cells. The generation of suppressor cells occurs at an early phase in the response because incubation of naive T cells with C3a for as little as 30 min results in suppression of the anti-SRBC response. The generation of suppressor T cells requires the interaction of T cells, C3a, and a Sephadex G-10-adherent cell, presumably a macrophage. Although the mechanism of action of these suppressor cells has not been elucidated, several possibilities have been eliminated. C3a-suppressor T cells do not apparently release inhibitory lymphokines, nor is helper cell activity inhibited by a 2-day co-culture with these suppressor cells. The observation that interleukin 2 (IL 2)-containing lymphokine preparations could overcome C3a-induced suppression led us to investigate the interaction of the suppressors with IL 2 producer cells. However, neither C3a nor C3a-generated suppressor T cells can block the synthesis of IL 2.
Characterization of the effects of phorbol esters on rat mast cell secretion.
Authors: Heiman A S , Crews F T 
Published: December 2022

Abstract
When applied to the skin, phorbol esters (PEs) elicit signs of acute inflammation, suggesting they may induce the release of mediators from mast cells. Therefore, we have studied the effects of PEs on purified rat peritoneal and thoracic mast cells both alone and in conjunction with the calcium ionophore, A23187, and various other secretagogues that interact with immunoglobulin E (e.g., anti-IgE and Con A) or other cell surface receptors, e.g., somatostatin and compd 48/80. PEs alone caused little or no release of histamine. However, the PE 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/ml) tremendously potentiated release induced by the calcium ionophore A23187, reducing the EC50 for A23187 from 832 ng/ml to 56 ng/ml. In the presence of suboptimal A23187 (50 ng/ml), only active tumor promoting PEs elicited histamine release. The EC50 values of the various active PEs were: TPA 5 ng/ml; 4 beta-PDD, 83 ng/ml; and 4-O-methyl-TPA, 807 ng/ml, with maximal histamine release ranging from 54 to 80%. TPA synergistically enhanced stimulation of histamine release by anti-IgE and Con A over the entire concentration-response range. In contrast, this synergism was absent when cells were stimulated with somatostatin and compd 48/80. Phorbol esters may act by increasing the activity of a calcium/phospholipid-dependent protein kinase (Ca/PL-PK). Mast cells do have Ca/PL-PK activity, and TPA in the presence of suboptimal A23187 induces protein phosphorylation comparable with other secretagogues. These results suggest that in the purified mast cell, PE-induced mediator release increases the sensitivity of release mechanisms for calcium, acts syngergistically with secretagogues interacting with IgE, and as suggested from structure-activity relationships, occurs via a specific mechanism of action perhaps involving the Ca/PL-PK.
Identification of an antigen specific to Trypanosoma congolense by using monoclonal antibodies.
Authors: Parish N M , Morrison W I , Pearson T W 
Published: December 2022

Abstract
Using indirect immunofluorescence assays on acetone-fixed smears of a series of different parasites, we have shown that two monoclonal antibodies bind specifically to Trypanosoma congolense organisms. The antibodies bind to both bloodstream trypomastigotes and procyclic culture forms of the parasite and are thus not stage specific. Immunoprecipitation and immunoblot analysis showed that both monoclonal reagents bound a protein of approximately 31,000 m.w. This antigen appeared to be located on the plasma membrane of T. congolense, but the epitope was not exposed on the surface of living bloodstream or procyclic organisms. The antigen was detectable on acetone-fixed organisms or in trypanosome lysates in enzyme-linked immunosorbent assays and may therefore by useful as a species-specific marker in field assays for epidemiologic and clinical investigations.
Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice.
Authors: Lehmann-Grube F , Assmann U , Löliger C , Moskophidis D , Löhler J 
Published: December 2022

Abstract
Adult mice were infected by i.v. inoculation with 10(3) mouse infectious doses of lymphocytic choriomeningitis virus (LCM virus). Despite widespread replication of the agent, overt illness did not develop; histopathologic alterations were moderate. High virus concentrations were attained in the spleen, which was chosen for further study. Cytotoxic spleen T cell responses were found to vary among inbred mouse strains, and as a rule, these were correlated with other virus-specific cell-mediated immune phenomena. However, high- and low-responder mice eliminated the virus equally fast and already at times when spleen cytotoxic T lymphocytes were just beginning to appear (and before delayed-type hypersensitivity could be demonstrated). Adoptive transfer experiments showed that very few immune T lymphocytes were capable of reducing virus replication in the recipients' spleens and, furthermore, that protection was rapidly induced; when low numbers of cells were transferred, the effect was apparent 8 hr later, and with higher numbers diminished virus replication was evident after an interval as short as 6 hr. In fact, the data suggest that virus was actually inactivated. In spite of this marked efficiency, morphologic alterations in spleens of adoptively immunized mice were absent. Attempts to reveal expansion of immune cells in the recipients have failed, and the observation that adoptive transfer was as efficient in nude mice as in their furred counterparts makes it unlikely that the recipients' T lymphocytes participated to any extent. The low number of T lymphocytes causing reduction of virus, the short interval after which the effect became measurable, and the lack of histopathologic alterations has led to a working hypothesis in which it is assumed that immunologically activated T lymphocytes secrete lymphokines that directly interfere with virus replication in neighboring cells.
Mechanism of action of thymosin. I. Thymosin fraction 5 increases lymphokine production by mature murine T cells responding in a mixed lymphocyte reaction.
Authors: Zatz M M , Goldstein A L 
Published: December 2022

Abstract
The effect of thymosin on the murine thymocyte mixed lymphocyte response was studied. Thymosin fraction 5 (TF5) caused a two- to threefold enhancement of the proliferative response and production of IL 2 when murine thymocytes were cultured with alloantigenic stimulator cells. Production of a second lymphokine, CSF, was increased up to sevenfold. The target cell for thymosin was a mature T cell, because the PNA- subpopulation of thymocytes, as well as peripheral lymph node lymphocytes, responded to culture with TF5 and alloantigen by enhanced proliferation and lymphokine production. The active component of TF5 appears to be one or more as yet unidentified peptides, because neither of the well-characterized TF5 component peptides, alpha 1 or beta 4, were active. After incubation with TF5 in primary culture, cells remaining after 10 to 14 days were increased both in number and in secondary response to alloantigen, as measured by lymphokine production. These results suggest that TF5 contains one or more biologically active components which can modulate mature T cell activity and lymphokine production, and which provide the basis for understanding some of the previously reported diverse effects of thymosin.
Heterogeneity and specificity of human anti-insulin antibodies determined by isoelectric focusing.
Authors: Thomas J W , Virta V J , Nell L J 
Published: December 2022

Abstract
Anti-insulin antibodies are present in the majority of insulin treated diabetics, and in some cases these antibodies have been found to be highly specific for limited epitopes on the molecule. To determine how the human response differs from that seen in inbred animals, we have examined the heterogeneity and specificity of human anti-insulin antibodies by isoelectric focusing (IEF). In addition, we have used human insulin to examine the extent of autoreactivity in the serum of subjects treated with animal insulins. The majority of diabetic sera exhibited complex IEF spectra that were composed of discrete bands and unresolved smears. Autoradiography using 125I-beef, pork, and human insulin revealed some affinity differences; however, the predominant antibodies were capable of binding all insulins, including human. These specificity studies were extended by comparing competitive inhibition with excess cold insulins, and sera with highly specific binding of the A chain loop of beef insulin were identified. The spectra by IEF of these highly specific sera were found to be variable. Our results indicate that the majority of insulin-treated diabetics develop a heterogeneous antibody response that is more complex than the response of inbred animals and includes reactivity with autologous insulin. Although infrequent, individuals having antibodies directed at limited regions of the molecule can be identified and will provide valuable tools for dissecting this complex response.
Shared idiotypy between phosphorylcholine-specific antibody and acetylcholinesterase detectable by a monoclonal antibody.
Authors: Strickland F M , Hamilton S L , Blalock E , Cerny J 
Published: December 2022

Abstract
Studies were undertaken to detect structural similarities between immunoglobulins and other proteins that bind to choline-containing ligands. Such proteins may share serologically detectable determinants that may not be predicted from the amino acid sequence alone. A monoclonal antibody was used that recognizes an idiotope near the phosphorylcholine binding site of the IgA myeloma TEPC15. This monoclonal anti-TEPC15 idiotopic antibody (anti-Id) also bound the enzyme acetylcholinesterase (AChE) as well as the nicotinic acetylcholine receptor from Torpedo californica. The anti-Id antibody also significantly decreased the AChE catalytic activity but did not affect the activity of an unrelated enzyme, horseradish peroxidase. These findings suggest that nonimmunoglobulin molecules share antigenic determinants with immunoglobulin that are associated with binding to structurally related ligands, and immune regulation may inadvertently affect the function of nonimmune systems.
Recognition and display of the predominant idiotype among members of the regulatory circuitry controlling the anti-lysozyme immune response.
Authors: Araneo B A , Yowell R L , Sercarz E E 
Published: December 2022

Abstract
The in vitro suppression of lysozyme (HEL)-primed helper T cell function (AgTh) is dependent on both suppressor inducer T cells (Tsi) (bearing the Lyt-1 and I-J surface antigens) and suppressor effector T cells (Tse) (bearing the Lyt-2 and I-A cell surface antigens). The AgTh and Tsi appear in draining lymph nodes of antigen-primed mice within 10 days of footpad immunization, whereas the Tse is detected in the lymph node around 21 days. Tse are localized to the spleen after i.p. immunization and represent the predominant functional T cell subset. In an attempt to understand the idiotypic relationships that exist among the three T cell types associated with anti-HEL responses in genetic low responder mice, each subset was characterized for expression of the predominant idiotype of anti-lysozyme antibodies, IdXL, by treatment with a cytotoxic anti-IdXL antibody and for IdXL-specificity by binding to IdXL-coated plates. Only the Tse was found to bear IdXL. The Tsi, on the other hand, binds to IdXL, and the AgTh belongs to a distinct idiotypic universe. These results suggest that the mode of communication between the Tsi and Tse is via idiotypic complementarity.
Localization of the conglutinin binding site on the third component of human complement.
Authors: Hirani S , Lambris J D , Müller-Eberhard H J 
Published: December 2022

Abstract
The binding site on the human third complement component for bovine conglutinin has been located. C3 fragments were purified to homogeneity by preparative SDS-polyacrylamide-gel electrophoresis. Only the N-terminal 27,000 dalton (Da) fragment of the alpha'-chain and the beta-chain were found to be glycosylated, and the carbohydrate was susceptible to endo-beta-N-acetylglucosaminidase H. This finding indicates that only high mannose or hybrid-type oligosaccharide chains are present on the C3 molecule. Binding to conglutinin was determined by an enzyme-linked immunosorbent assay and occurred with C3b, iC3b, C3c, the alpha-chain, and the 27,000 Da fragment of the alpha'-chain, but not with C3d or the C-terminal 40,000 Da fragment of the alpha'-chain. The beta-chain displayed very weak interaction. Binding to conglutinin could be inhibited by EDTA, N-acetylglucosamine, and to a lesser degree by mannose. Enzymatic removal of the carbohydrate from the C3 molecule abolished binding to conglutinin. It is concluded that bovine conglutinin binds to the carbohydrate moiety located on the N-terminal 27,000 Da polypeptide of the alpha-chain.
Inhibition of cytotoxic T lymphocyte-mediated lysis by ETYA: effect independent of arachidonic acid metabolism.
Authors: Taylor A S , Howe R C , Morrison A R , Sprecher H , Russell J H 
Published: December 2022

Abstract
Cytotoxic T lymphocyte (CTL)-mediated lysis of target cells was inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA) and other inhibitors of the lipoxygenase pathway at concentrations that inhibited arachidonic acid metabolism in mixed lymphocyte cultures. Inhibition was reversible and selective for the "lethal hit" stage in the CTL-target interaction. Studies to define CTL-specific arachidonic acid metabolites demonstrated that cloned CTL populations have little or no capacity to metabolize arachidonic acid. Therefore, inhibitor actions appear to be independent of the effects on CTL arachidonic acid metabolism. Alternative explanations for inhibitory effects are discussed.
Immunoradiometric assay to measure the in vitro penetration of sporozoites of malaria parasites into hepatoma cells.
Authors: Zavala F , Hollingdale M R , Schwartz A L , Nussenzweig R S , Nussenzweig V 
Published: December 2022

Abstract
We describe here an immunoradiometric assay to quantitate the in vitro invasion of hepatoma cells by sporozoites. The assay measures levels of circumsporozoite (CS) antigen that remain associated with the hepatoma cells after their incubation with the parasites. Several observations show that these measurements reflect internalized rather than extracellular antigen. For example, when incubations were performed with nonviable parasites (sonicated or heated), or in the presence of metabolic inhibitors, such as sodium azide and deoxyglucose, the amounts of CS antigen found in hepatoma cell extracts were greatly diminished. Moreover, Western blotting experiments revealed a striking difference in the pattern of CS proteins of infected cell extracts as compared with those of free parasites. The assay was used to measure the amounts of intracellular CS antigen for several days after infection of the hepatoma cells. The results confirmed previous microscopic observations, made by using immunofluorescence techniques, showing that the CS antigen in the host's liver cells diminishes progressively while the parasite develops into the exoerythrocytic stage. The immunoradiometric assay should facilitate the evaluation of the effects of drugs on sporozoites and also on studies aimed at the identification of a sporozoite receptor on the hepatocyte.
Dissociation between aggregation and superoxide production in human granulocytes.
Authors: Whitin J C , Cohen H J 
Published: December 2022

Abstract
Aggregation and the activation of the granulocyte (PMN) superoxide (O2-) generating system occur when certain stimuli are added to resting cells. It had previously been postulated that PMN aggregation is essential for maximal O2- production. This study was undertaken to test the hypothesis that PMN aggregation is required for full expression of PMN O2- production. We examined aggregation and O2- production induced by four stimuli; concanavalin A (Con A), phorbol myristate acetate (PMA), N-formylmethionyl-leucyl-phenylalanine (FMLP), and ionophore A23187. Cytochalasin B enhanced aggregation by all four stimuli but only enhanced the rate of O2- production by Con A; 2-deoxyglucose inhibited aggregation by all stimuli. Dissociation of PMN aggregation and O2- production was achieved by using NEM, TPCK, and divalent cations. NEM and TPCK prevent Con A-induced O2- production but have no effect on Con A-induced aggregation. PMA-stimulated PMN generate O2- in the presence or absence of Ca++ and Mg++. In contrast, PMA stimulated maximum PMN aggregation only in the presence of both Ca++ and Mg++. Thus PMN can generate O2- without aggregating, and PMN can aggregate without producing O2-. PMN from patients with chronic granulomatous disease do not generate O2- or undergo membrane potential depolarization in response to PMA. These PMN aggregated when stimulated with PMA, providing evidence that depolarization is not required for PMN aggregation. We conclude that aggregation and the activation of the O2- generating system, though temporally related, are not necessarily causally related.
A role for mast cells and the vasoactive amine serotonin in T cell-dependent immunity to tumors.
Authors: Van Loveren H , Den Otter W , Meade R , Terheggen P M , Askenase P W 
Published: December 2022

Abstract
The involvement of mast cells in anti-tumor resistance was studied by employing 2 strains of mast cell deficient but otherwise immunocompetent mice on a C57BL/6 (H-2b) background (W/Wv and Sl/Sld) and their respective normal +/+ littermate controls. Sensitization of control mice with irradiated semisyngeneic B16 melanoma cells (H-2b) resulted in protection against subsequent challenge with viable B16 cells, in contrast to sensitization of either W/Wv or Sl/Sld mice. The involvement of serotonin in antitumor resistance was studied by employing 2 serotonin active drugs: reserpine, that depletes mast cells of serotonin; and methysergide, a serotonin antagonist. Sensitization of BDF1 mice with irradiated B16 cells and sensitization of DBA/2 mice (H-2d) with irradiated SL2 cells (H-2d) resulted in protection against subsequent challenge with viable B16 cells and viable SL2 cells, respectively. Treatment with either reserpine or methysergide resulted in a decreased protection. Delayed-type hypersensitivity (DTH) footpad responses to allogeneic L5178Y (H-2d) tumor cells in C57BL/6 mice showed a biphasic reaction pattern, similar to that found in DTH responses to simple reactive haptens, such as picryl chloride. Moreover, the early swelling responses were also dependent on T cells and on mast cells. BDF1 mice carrying a semisyngeneic L5178Y tumor on the chest showed an early swelling response after footpad challenge but no late response, possibly indicating that selective down regulation of the late component of DTH was associated with progressive tumor growth in these animals. The biphasic patterns of DTH to both tumor cells and picryl chloride and the T cell and mast cell dependence of both antitumor resistance and DTH to tumor cells suggest that T cell-dependent activation of mast cells to allow entry of mononuclear leukocytes into sites of tumor growth is similar to the mechanism that occurs in DTH.
Enhancement of tumor growth correlates with suppression of the tumor-specific cytolytic T lymphocyte response in mice chronically infected by Trypanosoma cruzi.
Authors: Plata F 
Published: December 2022

Abstract
The immunity of BALB.B mice to syngeneic Gross murine leukemia virus (MuLV)-induced B.GV cells was studied at various times after infection by Trypanosoma cruzi. BALB.B mice chronically infected by the parasite do not develop an effective immune response against B.GV tumor cells, and B.GV tumor growth in vivo is consequently facilitated. The tumor-specific cytolytic T lymphocyte (CTL) compartment in these mice was studied in vitro because CTL are known to participate actively in syngeneic tumor rejection. These analyses showed that: a) CTL differentiation is suppressed in mice with chronic T. cruzi infections; b) suppression is at the level of CTL precursor cell activation; c) suppression is not antigen-specific; and d) suppression is mediated by macrophages and Lyt-2+ T lymphocytes.
Cell-mediated T lymphocyte responses against syngeneic cells modified with amino-reactive hapten (AED-NH2): H-2Dk serves as an element for cell-mediated lympholysis to amino-reactive hapten (AED-NH2)-modified self.
Authors: Mizuochi T , Fujiwara H , Takai Y , Hamaoka T 
Published: December 2022

Abstract
Spleen cells from C3H/He mice immunized to the newly synthesized amino-reactive hapten, 5-sulfo-1-naphthoxy acetic acid N-hydroxysuccinimide (AED-NH2), were stimulated in vitro with AED-NH2 modified syngeneic cells. After 5 days of culture, effector cells were assayed for their cytotoxic activity against AED-NH2-modified target blast cells. In contrast to other amino-reactive haptens reported so far, a strong cytotoxic activity against AED-NH2-modified syngeneic cells was found in H-2b mice as well as in H-2k mice. Furthermore, Dk-restricted anti-AED-NH2 CTL recognition was observed in H-2k mice as shown by cold target inhibition. Previous studies have demonstrated the predominant influence of K over D region self determinants, and of the chemical reactivity of the haptenic reagent in Ir gene control of CTL response to hapten-self. The present report illustrates the importance of the hapten itself in genetic regulation of these CTL responses.