bluuebunny/crossref_metadata_2025 huggingface dataset:
Factores que influyen en el proceso de enseñanza-aprendizaje en profesores y estudiantes de nivel superior durante la pandemia por covid19
Authors:   Instituto Politécnico Nacional, Escuela Superior de Cómputo, México, Ruiz Ledesma Elena Fabiola , Tovar Corona Blanca ,   Instituto Politécnico Nacional, Unidad Profesional Interdisciplinaria en Ingeniería y Tecnologías Avanzadas, México, Rivero Ángeles Mario Eduardo ,   Instituto Politécnico Nacional, Centro de Investigación en Computación, Méx
Published: January 2023

Como parte del proyecto de investigación que se estaba desarrollando en el año 2020 (con número de registro 20200832), y con el apoyo de la Secretaría de Investigación y Posgrado, se trabajaron acciones que permitieran contribuir al propósito de la investigación reportada en este capítulo de libro, que fue determinar y categorizar los factores que influyeron en el proceso de Enseñanza-Aprendizaje de docentes y estudiantes, durante sus clases a distancia en la primera etapa de confinamiento (abril-septiembre del 2020), con la finalidad de proponer estrategias que incentiven al docente y al estudiante de nivel superior, para atender sus clases en línea o en un modelo híbrido en la nueva normalidad. La metodología que se empleó fue de carácter mixto, se aplicó un cuestionario a una muestra de 226 estudiantes de una Unidad Académica del IPN. Las preguntas de los cuestionarios se clasificaron en 4 factores: emocional, académico, recursos y administración del tiempo. De acuerdo al puntaje obtenido en cada uno, tanto los estudiantes como los maestros fueron considerados en una de las 4 categorías determinadas: critico, inestable, estable y satisfactorio. El análisis arrojó que 31 % de la muestra se encontró en estado crítico, 23 % en estado inestable, 43 % en un estado estable y solo 3 % en un estado satisfactorio.
En la mar ab los mantellets: una milicia municipal de ballesteros en defensa de la frontera marítima de la Barcelona bajomedieval (c. 1356-1516)
Authors: Badia Arroyo Pere
Published: January 2023

El objetivo del presente trabajo es el de dar a conocer las particularidades de una fuerza municipal a sueldo surgida en la Barcelona bajomedieval ante la necesidad de control y protección militar de la franja litoral: los llamados mantellets. Como contingente de ballesteros se les denominó así por los tableros defensivos que empleaban para protegerse en el combate naval. A través del estudio de privilegios reales, ordenanzas municipales, crónicas, dietarios y otros fondos preservados mayoritariamente en el Arxiu Històric de la Ciutat de Barcelona (AHCB) queremos tratar los hechos directamente vinculados a su surgimiento y pervivencia.
Fernando el Católico ante la sublime puerta: presagio y conquista del imperio otomano en el Memorial de Pedro Navarro (1506-1507)
Authors: Fernández de Córdova Álvaro
Published: January 2023

La relación de los Reyes Católicos con el imperio otomano se construyó a base de ideales proféticos, utopías universalistas y proyectos de conquista que se entretejieron a lo largo de su reinado. El desplazamiento de Fernando II de Aragón al reino de Nápoles (1506-1507) marcó una etapa decisiva en la percepción de la vecindad turca, pues humanistas, eclesiásticos y militares exhortaron al monarca a recuperar el Oriente cristiano con la ayuda de Venecia y el papado. En este trabajo nos centramos en el inédito Memorial de un colaborador del capitán Pedro Navarro que desarrolló por vez primera un plan estratégico para reconquistar los territorios otomanos, incluida Jerusalén. Con los mimbres del mesianismo hispano, la experiencia de las guerras de Italia y una renovada eclesiología, se tejió el proyecto más ambicioso presentado hasta entonces al rey Católico: unir Oriente y Occidente reinventando los límites del Mediterráneo cristiano.
Espadas persas muy curvadas: propiedades y especificaciones estructurales
Authors: Moshtagh Khorasani Manouchehr , Arjmandi Nima
Published: January 2023

Las espadas persas muy curvadas, denominadas shamshir (šamšir), alcanzaron su máxima curvatura y popularidad en los siglos XVI-XVII y seguían siendo el tipo de espada preferida en los campos de batalla por los ejércitos persas. Aunque se han llevado a cabo numerosas investigaciones sobre sus materiales y métodos de forja, hasta donde sabemos, no existe ninguna investigación científica sobre su rendimiento mecánico general ni ningún análisis científico de su excepcional forma. El siguiente artículo ofrece un análisis exhaustivo de la curva alta de las espadas persas y demuestra que esta curva alta proporcionaba una fuerza de corte máxima de la espada y también permitía ciertas formas de empuje que pasaban por encima y por debajo del escudo del adversario en el campo de batalla.
Methods in the Quantitation of Antigen-Antibody Reactions Measured by Radioimmunoassay: Application to the Gastrin System Revealing Large and Restricted Binding Energies
Authors: Goldenberg Kim , Berkowitz Jesse M. , Praissman Melvin
Published: January 2023

Quantitative methods are presented for defining antigen-antibody interactions in the radioimmunologic assay system when only the bound to free ratio of labeled antigen and the concentration of unlabeled antigen are known. From these methods the equilibrium constant (K), the antibody site concentration (AbT), the number of binding sites (n), and the extent of binding energy heterogeneity (α) are derived for the gastrin-antiporcine gastrin antibody interaction by using human synthetic gastrin for both the labeled and unlabeled antigen. In one method, models of various orders of interaction are applied to the data and suggest a univalent homogeneous gastrin-antibody reaction. In two other methods a form of the Scatchard equation and Sips distribution are applied to the experimental data to obtain an n of one and an α close to one, respectively. Values for K are found by all three methods. The interaction was studied at six different antibody dilutions and the equilibrium constant and effective antibody site concentration at the largest dilution were 2.71 × 1011 M-1 and 1.09 × 10-12 M, respectively.
Induction of Cellular Immunity to Herpes Simplex Virus: Relationship to the Humoral Immune Response
Authors: Rosenberg Gary L. , Notkins Abner Louis
Published: January 2023

In vitro lymphocyte stimulation and virus-neutralization techniques were employed to study the relationship between the cellular and humoral immune responses to herpes simplex virus (HSV) in rabbits. Lymphocytes specifically sensitized to HSV were detected as early as 3 days after infection, generally before the appearance of neutralizing antibody. Neutralizing antibody levels continued to rise over the next several weeks, whereas the ability of sensitized lymphocytes to respond to viral antigens markedly decreased. Reinfection 60 days after the primary infection resulted in a sharp increase in the responsiveness of the lymphocytes to viral antigens.

The induction of cell-mediated immunity and the responsiveness of sensitized lymphocytes to viral antigens appears to be intimately related to the physical state of the virus. Animals inoculated with infectious HSV developed both cellular and humoral immunity; animals inoculated with UV-inactivated HSV developed a cellular immune response, but little if any neutralizing antibody; animals inoculated with HSV complexed with anti-HSV antibody developed neither a cellular nor a humoral immune response. In vitro, specifically sensitized lymphocytes could be stimulated by virus and by virus bound to cells, but not by cell-bound virus that had been incubated with antiviral antibody. These observations suggest that antiviral antibody can affect both the induction of cell-mediated immunity and the responsiveness of specifically sensitized lymphocytes to viral antigens bound to cells.
Allotypes of Rat Immunoglobulins
Authors: Bazin Hervé , Beckers Andrée , Vaerman Jean-Pierre , Heremans Joseph F.
Published: January 2023

The inheritance and strain distribution of a genetic marker of the α-chains of rat IgA, which we propose to call Iα(1a), was tested by means of a precipitating anti-allotype antiserum obtained by immunizing August rats with a monoclonal IgA protein from a LOU/Wsl rat immunocytoma.

The presence or absence of the Iα(1a) character appeared to be controlled by a single pair of codominant alleles, which appear to govern the biosynthesis of virtually all the rat serum IgA.
Isolation and Characterization of a Blood P1 Active Carbohydrate Antigen of Echinococcus Granulosus Cyst Membrane
Authors: Russi Serena , Siracusano Alessandra , Vicari Giuseppe
Published: January 2023

A glycoprotein antigen was isolated from the membrane of hydatid cysts of sheep and human origin. The constituent sugars of the carbohydrate moiety of this antigen are galactose, galactosamine, and glucosamine. The antigen shows a high P1 blood group activity when tested by hemagglutination-inhibition assay with anti-P1 sera. Moreover, it precipitates 11 out of 21 sera of human patients with echniococcosis. However, none of these sera has complete or incomplete agglutinating anti-P1 antibodies. The immunochemical analysis shows that P1 determinants reactive with anti-P1 sera, and antigenic determinants reactive with human precipitating antibodies are on the same macromolecule. Patients with cyst pulmonary localization show a higher reactivity as compared with those with hepatic localization. The immunodominant group involved in the precipitin reaction appears to be an α-galactosyl residue.
In Vitro Study of Antiviral Activity of Immune Spleen Cells in Experimental Venezuelan Equine Encephalomyelitis Infection in Mice
Authors: Rabinowitz Stanley G. , Proctor Richard A.
Published: January 2023

VEE-immune spleen cells from C57BL/6 mice exert a potent inhibitory effect on VEE viral growth in vitro when co-cultivated with infected L cell cultures. This inhibitory effect is both immunologically specific and dependent on time of spleen cell harvest after donor immunization with attenuated VEE virus. Neither interferon nor neutralizing antibody appear to be responsible for this specific antiviral activity. Studies with purified spleen or peritoneal cell populations demonstrate that only immune macrophages alone, or the combination of immune lymphocytes with normal macrophages, are active in inhibiting VEE-virus growth in cell culture. Finally, treatment of VEE-immune spleen cells with cytotoxic antisera directed at eliminating T cells removes the inhibitory effect on VEE replication in cell culture. Hence a two-cell system involving immunocompetent T cells and activated macrophages is proposed for the inhibition of VEE viral growth.
Biosynthesis of the Second and Fourth Components of Complement: Inhibition in Vitro by Chemical Carcinogens
Authors: Colten Harvey R. , Borsos Tibor
Published: January 2023

Several chemical carcinogens and non-carcinogenic analogues were tested in vitro for their capacity to affect the biosynthesis of the second (C2) and fourth (C4) components of complement. Of the compounds tested, 4-nitroquinoline-n-oxide, effective at 10-7 M, was the most potent inhibitor of C2 and C4 biosynthesis. Propriolactone and two nitroso-compounds also inhibited C2 and C4 synthesis, whereas their non-carcinogenic analogues had no effect. These findings suggest that some carcinogens interfere with at least one normal function of the immune system.
The Production of Interferon by Malignant Plasma Cells from Patients with Multiple Myeloma
Authors: Epstein Lois B. , Salmon Sydney E.
Published: January 2023

To help define the types of immunocytes capable of producing interferon, bone marrow cultures from patients with multiple myeloma were studied. Such cultures contained large numbers of plasma cells, the end stage in the differentiation of bone marrow-derived or B lymphocytes. Quantitative studies of in vitro interferon and immunoglobulin synthesis rates were performed. The results were as follows: a) Interferon was detected within 24 hr in supernatant fluids of cultures from 10 of 12 patients with myeloma studied. These included six patients with IgG myeloma, two with IgA myeloma, one Amyloid myeloma, and one κ light chain myeloma. b) The amount of interferon produced was unrelated to the immunoglobulin synthesis rate, total body tumor cell number, sensitivity of the tumor to chemotherapy, or the clinical status of the patient. c) The plasma cell origin of such interferon was demonstrated by a study in which enrichment of the myeloma cells by gradient techniques resulted in increased interferon production. No interferon was detected in cultures in which there were low or no plasma cells, i.e., those prepared from peripheral blood leukocytes of patients with myeloma, or bone marrow from normal individuals. Interferon synthesis was not detected from bone marrow cells from two patients with Waldenstrom's macroglobulinemia.
Failure to Induce Tolerance to 2,4-Dinitrochlorobenzene Contact Sensitivity with a 2,4-Dinitrophenyl (DNP) Conjugate of a Copolymer of D-Glutamic Acid and D-Lysine, a Specific Tolerogen for DNP B Cells
Authors: Benacerraf Baruj , Katz David H.
Published: January 2023

In the present study, we have investigated the ability of the non-metabolizable tolerogen, 2,4-dinitrophenyl (DNP)-d-glutamic acid-d-lysine (D-GL) to induce tolerance in normal and sensitized guinea pigs to dinitrochlorobenzene (DNCB) contact sensitivity. The data show that treatment with DNP-D-GL, which very efficiently suppresses anti-DNP antibody responses in virgin and primed guinea pigs, does not affect the ability of these animals to develop and to display contact sensitivity to DNCB. These observations confirm the suggestions from earlier studies that important operational differences exist in the induction of tolerance in thymus derived and bone marrow-derived lymphocytes “presumed” to be concerned with the same DNP specificity.
The Purification of Detergent-Solubilized HL-A Antigens by Affinity Chromatography with the Hemagglutinin from Lens Culinaris
Authors: Dawson Jeffrey R. , Silver Jonathan , Sheppard Laura B. , Amos D. Bernard
Published: January 2023

The hemagglutinin from Lens culinaris (LcH) when covalently bound to CNBr-activated Sepharose 4B is capable of binding 75 to 80% of the HL-A serologic activity solubilized from tissue culture cells with sodium deoxycholate (DOC). Serologically specific HL-A antigens may be recovered in highly purified form by elution of the bound antigens from LcH-Sepharose columns with buffer containing α-methylglucopyranose. In some experiments up to 25% of the serologic activity is not bound to the LcH-Sepharose columns and is also not bound when reapplied to freshly prepared or re-equilibrated LcH-Sepharose columns. This finding indicates that there may be an additional form of the HL-A antigen which lacks carbohydrate or contains a carbohydrate moiety not bound by LcH.
Aggregation and Release Reaction Induced in Human Blood Platelets by Zymosan
Authors: Zucker Marjorie B. , Grant Robert A.
Published: January 2023

When citrated platelet-rich plasma was shaken with zymosan particles, platelet aggregation and 14C-serotonin release occurred within 15 min. The platelet response occurred much more rapidly if the zymosan was first incubated with heparinized or citrated plasma for 20 to 30 min. After such incubation, the activity was on the zymosan; the plasma had no effect on platelets and could not generate further activity when incubated with fresh zymosan. Plasma was not necessary for the reaction between washed active zymosan and platelets. However, albumin enhanced the response. The usual ratio of zymosan to platelets was 1:20, and mixed aggregates formed after a delay of a minute or more. ADP, ATP, and heparin neutralizing activity were released from the platelets but beta glucuronidase and lactic dehydrogenase were not. Aggregation and release were inhibited by aspirin or by enzymes which remove ADP, and did not occur with thrombasthenic platelets. The reaction between zymosan and plasma required magnesium ions, and failed to occur in plasma incubated with cobra venom factor or hydrazine or heated to 50°C for 30 min. A mixture of hydrazine-treated and heated plasma generated activity on zymosan as did plasma from a patient with congenital C6 deficiency. Serum was much less effective than plasma in generating activity on zymosan unless fibrinogen was added or more than 15 µg/ml of residual fibrinogenfibrin-related antigen was present. This antigen was detected on zymosan prepared from citrated plasma but not on that prepared from serum or EDTA plasma. Thus the release-promoting activity of zymosan particles depends on their exposure to both the properdin (complement-bypass) mechanism and to fibrinogen.
Cellular Immunoadsorbents: a Simplified Technique for Separation of Lymphoid Cell Populations
Authors: Kedar Eli , de Landazuri Manuel Ortiz , Bonavida Benjamin
Published: January 2023

A simplified and efficient technique for separating T lymphoid cells from non-T cells of mouse, rat and man has been developed. The fractionation procedure is based on the capacity of non-T lymphoid cells to bind antigen-antibody complexes through an Fc receptor. Lymphoid cells are adsorbed on antibody-coated sheep erythrocyte (EA) monolayers prepared in polystyrene Petri dishes previously treated with poly-l-lysine. Adsorption of spleen cells on these monolayers, assisted by a 5-min centrifugation, resulted in 90 to 98% depletion of the Fc receptor-bearing cells (mostly B lymphocytes, but also macrophages and polymorphonuclear leukocytes) in the non-adherent cell population. Eighty to 90% of the adherent cells were capable of forming EA rosettes and could be recovered after lysis of the erythrocytes. The non-adherent fraction comprised at least 90% T-cells. This was determined for mouse and rat spleen cells by lysis with anti-thymocyte serum and complement, and by the absence of immunoglobulin-bearing cells.

The specificity of the adsorption was further substantiated by the following observations: 1) lymphoid cells lacking an Fc receptor were not adsorbed; 2) the adsorption to EA monolayers was inhibited by antigen-antibody complexes or by aggregated γ-globulin; and 3) only 10 to 15% of the Fc receptor-bearing cells were attached to non-sensitized erythrocyte (E) monolayers.

Fractionation of spleen cells obtained from rats immunized against a syngeneic tumor yielded two separate fractions of cytotoxic lymphoid cells: one (non-adherent, T cells) mediating direct target cell destruction, and the other (adherent, non-T cells) mediating lysis of antibody-coated target cells.
Lymphopoietic Potential of Bone Marrow Cells from Aged Mice: Comparison of the Cellular Constituents of Bone Marrow from Young and Aged Mice
Authors: Farrar John J. , Loughman Barbara E. , Nordin Albert A.
Published: January 2023

Cell transfer systems have been used to study the capacity of aged mouse bone marrow to generate functional bone marrow-derived (B) lymphocytes. The progeny of the B lymphocytes in these systems were detected as anti-sheep erythrocyte antibody-producing cells. These in vivo transfer systems suggested that bone marrow from aged mice contained a significantly greater number of differentiated immunocompetent cells than marrow from young mice. Increased frequencies of theta and IgM-bearing cells in the aged marrow were detected by immunofluorescent techniques. Immunofluorescent studies and cell transfer systems demonstrated that pre-treatment of the aged bone marrow donors with anti-lymphocyte serum physically depleted the marrow of contaminating thymus-derived lymphocytes and reduced the relative responsiveness of the cells. Anti-lymphocyte serum did not decrease the number of bone marrow stem cells as measured by the colony-forming unit assay. The results suggested an age-associated alteration in lymphocyte circulation dynamics and a decreased ability of aged marrow to generate B lymphocytes.
Carrier Function in Immune Deviation
Authors: Neveu P. J. , Borduas A. G.
Published: January 2023

The specificity of the immune deviation was studied by testing delayed, Arthus, and anaphylaxis hypersensitivity with hapten-carrier conjugates. Intravenous injections of high doses of carrier protein lowered delayed hypersensitivity to the carrier as well as antibodymediated hypersensitivity to the hapten, whereas the injection of high doses of homologous hapten-carrier conjugate also lowered delayed hypersensitivity to the carrier but did not affect the humoral reactions to the hapten.
Autoimmune Murine Thyroiditis
Authors: Tomazic Vesna , Rose Noel R. , Shreffler Donald C.
Published: January 2023

The immune response to mouse thyroglobulin in mice is associated with the centromeric (left) side of the H-2 region. Thyroid infiltration is strongly controlled by a major gene, probably located between the K-end and the Ir-1 region, but other genes at the D-end of H-2, or outside of the H-2 region, may modify the response. Antibody formation is less strongly influenced by this major gene and may involve additional genetic or non-genetic factors.
Phosphatidylserine Enhancement of Antigen-Induced Mediator Release from Rat Mast Cells
Authors: Stechschulte Daniel J. , Austen K. Frank
Published: January 2023

Phosphatidylserine (PTS) enhances the antigen-induced release of preformed vasoactive amines from rat mast cells both in vivo and in vitro without enhancing the release in vivo of slow reacting substance of anaphylaxis (SRS-A). The duration of mediator release from mast cells is not prolonged by PTS but enhancement is observed when PTS is added before and for as long as 3 min after antigen challenge. PTS enhancement requires intact glycolysis and the presence of calcium ions; it is inhibited by magnesium ions and oligomycin. Antigen-induced release and PTS enhancement are suppressed by agents which increase intracellular levels of cyclic adenosine 3′5′-monophosphate and by the addition of exogenous cyclic AMP in the dibutyryl form.
Counterimmunoelectrophoresis with Adenovirus Type-Specific Anti-Hemagglutinin Sera As a Rapid Diagnostic Method
Authors: Hierholzer John C. , Barme Michel
Published: January 2023

The complex antigenic properties of adenovirus-soluble complete and incomplete hemagglutinins were utilized to study the specificity of adenovirus anti-hemagglutinin sera in immunodiffusion and counterimmunoelectrophoresis tests. Pentons, penton dimers, fiber dimers, and/or dodecons of adenovirus types 2, 3, 5, 7a, 8, and 11 were extensively purified by ion-exchange and exclusion chromatographies. Components were determined to be purified proteins by immunologic, electron microscopic, and polyacrylamide gel electrophoretic criteria. Specific antigenic components were identified by immunoelectrophoresis and by various biologic characteristics. Rabbit antisera prepared against these hemagglutinating components were type-specific in standard serologic, Ouchterlony immunodiffusion, immunoelectrophoretic, and counterimmunoelectrophoretic tests. Counterimmunoelectrophoresis was particularly well suited to a rapid identification and typing of adenovirus isolates for diagnostic purposes.
Suppressor T cell circuits in contact sensitivity. I. Two mechanistically distinct waves of suppressor T cells occur in mice tolerized with syngeneic DNP-modified lymphoid cells.
Authors: Miller S D , Butler L D , Claman H N
Published: January 2023

Suppressor T cells induced by the i.v. injection of syngeneic DNP-LC were studied at varying times after tolerization. It was found that 7 days after tolerization both the spleen and lymph nodes of tolerant mice contained Ts active in suppressing the efferent (effector) phase of the contact sensitivity response (Ts-eff). At 14 days after tolerization, however, only the spleen showed significant suppressive activity that was active on the afferent (induction) phase of the contact sensitivity response. This second wave of afferent suppression was shown to be mediated by an antigen-specific, Ia-positive T cell (Ts-aff). Ts-aff could also be induced in normal, but not in CY-pretreated mice transfused with lymphoid cells containing primed Ts-eff, provided an appropriate induction period was allowed. Also the activity of Ts-aff, but not of Ts-eff, could be eliminated by treatment with anti-DNP antibody (i.e., idiotype) and C. Thus, Ts-aff appears not to be a maturation stage of Ts-eff. It was also shown that Ts-eff and Ts-aff interacted in an antagonistic fashion; cotransfer of these populations along with DNFB-immune TDH cells neutralized the efferent suppressive activity of Ts-eff for the immune cells, allowing successful passive transfer of immunity. The exact role of this antagonistic interaction is not clear, but it may play a part in maintaining the balance of suppression in the intact animal. The data are discussed in terms of a cellular network in immune suppression and are compared and contrasted to other suppressor systems in which network interactions have been described.
Natural cytotoxicity of isolated rat liver cells.
Authors: Cohen S A , Salazar D , Nolan J P
Published: January 2023

Unfractionated liver cells and parenchymal liver cells from untreated male Lewis rats were tested for natural cytotoxicity in a 4-hr 51chromium-release assay against YAC-1. Minimal cytotoxicity was observed. Nonparenchymal liver cells obtained by either differential centrifugation or metrizamide gradient centrifugation exerted strong cytotoxicity against YAC-1 and P815. Resident peritoneal exudate cells and spleen cells displayed cytotoxicity only against YAC-1. Furthermore, the cytotoxicity of these nonparenchymal liver cells was diminished by carbonyl iron treatment. Therefore, on the basis of these and other characteristics, the majority of the effector cells in the liver resemble tumoricidal macrophages. Finally, parenchymal liver cells or their cellfree supernatants were able to inhibit the cytotoxicity of these tumoricidal nonparenchymal liver cells, suggesting that the tumoricidal capacity of the liver was under some regulatory control.
Regulatory mechanisms in the mixed lymphocyte reaction: evidence for the requirement of two T cells to interact in the generation of effective suppression.
Authors: Chaouat G , Mathieson B J , Asofsky R
Published: January 2023

The cellular requirements for suppression of a mixed lymphocyte reaction (MLR) by in vivo alloantigen-activated spleen cells were investigated. We found that the suppression was mitomycin-resistant at days 3 and 5 after antigen injection. By contrast, it was radiation-sensitive on day 3 but not on day 5. Cell fractionation studies using a plate separation technique monitored by flow microfluorometry were performed. We found that neither purified Lyt-2- cells nor purified Lyt-2+ cells independently could suppress an MLR. By contrast, the reconstituted T population was still suppressive. It also was found that culture supernatant factors from allogeneically in vitro restimulated Lyt-2- cells could suppress an MLR if Lyt-2+ cells were present in the responding population. These data obtained by positive selection and reconstitution show that at least two surface immunoglobulin-negative cells interact for the generation of effective MLR suppression. The possibility that we are dealing with a suppressor-inducer, suppressor-effector system is discussed.
Interleukin 2 production by lymphoid cells from congenitally athymic (nu/nu) mice.
Authors: MacDonald H R , Lees R K , Glasebrook A L , Sordat B
Published: January 2023

The ability of lymphoid cells from congenitally athymic (nu/nu) mice to produce interleukin 2 (IL 2) was investigated. Spleen or lymph node cells (superficial or mesenteric) from nude mice on an N:NIH(S)II or BALB/c genetic background were stimulated with concanavalin A (Con A) or with irradiated allogeneic (DBA/2) spleen cells that had been depleted of T cells by treatment with monoclonal anti-Thy-1.2 antibody plus complement. After 24 hr, supernatants were harvested and assayed for their ability to support the proliferation of a cloned IL 2-dependent cytolytic T cell line. With this quantitative microassay, IL 2 production was not detectable in spleen and lymph nodes of 6-wk-old N:NIH(S)II nude mice; however, by 12 mo of age, IL 2 production increased more than 100-fold to reach levels comparable to control (nu/+) animals. Con A was more potent than alloantigen in the induction of IL 2 in either nude or control (nu/+) animals. Furthermore, differences in the genetic background of nude mice resulted in corresponding differences in both numbers of T cells (defined by monoclonal anti-Thy-1 antibody) and IL 2 production. By using negative selection with monoclonal antibodies plus complement, IL 2 production in aged nude mice was shown to depend upon a subpopulation of cells that expressed Thy-1 but not Lyt-2. These data thus demonstrate that a subpopulation of IL 2-producing cells with a Thy-1+ Lyt-2- surface phenotype can develop in the apparent absence of thymic influence.
Lymphocyte dysfunction in cartilage-hair hypoplasia: evidence for an intrinsic defect in cellular proliferation.
Authors: Pierce G F , Polmar S H
Published: January 2023

Individuals with cartilage-hair hypoplasia (CHH), an autosomal recessive form of short-limbed dwarfism, have markedly reduced lymphocyte proliferative responses and cutaneous delayed hypersensitivity reactions, but normal humoral immunity. In the present study we investigated the cellular basis of the immunodeficiency in CHH. Defective lymphocyte proliferation could be due to a) an imbalance of immunoregulatory lymphocyte subpopulations, b) defective accessory cell function, or c) an intrinsic cellular defect in lymphocytes from CHH individuals. The absolute numbers of B cells and immunoregulatory (OKT4+, OKT8+) T cells were markedly diminished, but the proportions of these populations were the same as in the normal controls. OKM1+ lymphocytes were increased in proportion, and OKM1+ macrophages had normal adherence, helper, and phagocytic properties. Co-culture experiments failed to reveal any evidence of suppression by CHH mononuclear cells. CHH lymphocytes could not be stimulated to proliferate normally with B and T cell activators, mitogenic monoclonal antibody (OKT3), allogeneic cells, or chemical activators (Ca++ ionophore A23187 and phorbol myristate acetate). Fibroblasts from three CHH individuals also proliferated at a significantly decreased rate, compared to two normal lines. These results demonstrate a selective loss of B and T lymphocytes in CHH, as well as an intrinsic proliferative defect in CHH lymphocytes distal to the initial events in the lymphocyte activation sequence. These findings in CHH fibroblasts and lymphocytes may reflect a generalized defect present in multiple cell types in CHH.
Modulation of Tac antigen on activated human T cells by anti-Tac monoclonal antibody.
Authors: Tsudo M , Uchiyama T , Takatsuki K , Uchino H , Yodoi J
Published: January 2023

A monoclonal antibody termed anti-Tac antibody is reactive with activated and functionally mature human T cells, but not reactive with resting T cells or B cells. We found that the expression of Tac antigen on activated T cells was inhibited by the addition of anti-Tac antibody in the culture of T cells activated with Con A or alloantigen. In the mixed lymphocyte culture, the expression of Ia-like antigen on allo-activated T cells was also inhibited by anti-Tac antibody, although the antibody does not recognize Ia-like antigen. However, anti-Ia monoclonal antibody did not suppress the expression of either Tac or Ia-like antigen. In addition, Tac antigen expressed on activated T cells was modulated by anti-Tac antibody cultured with activated T cells at 37 degrees C for 48 hr. Antigenic modulation, which means a specific loss of Tac antigen from the cell surface of T cells, was detected by the indirect immunofluorescence method. Tac antigen was reexpressed on T cells after restimulation when the anti-Tac antibody was removed, whereas Ia-like antigen already expressed on allo-activated T cells was not modulated by anti-Tac antibody. These results suggest that Tac and Ia-like antigens are carried on different molecules, both of which are closely linked in expression on activated T cells. The expression of Tac antigen may be essential for the following expression of Ia-like antigen.
The alloantibody response in the allogeneically pregnant rat. III. The location of the alloantibody-forming cells.
Authors: Smith R N , Sternlicht M
Published: January 2023

We determined the location of alloantibody formation in the allogeneically pregnant rat. Greater than 95% of the alloantibody-forming cells were found in the spleen. A few were found in the paraaortic, renal, and parathymic lymph nodes. None were found in other lymphomyeloid organs. In addition, in vitro alloantibody synthesis was largely confined to splenic cells. We conclude that the alloantibody response in the allogeneically pregnant rat is largely peripheral to the uterus and to the lymph nodes that drain the uterus. Therefore, the alloantibody response in the allogeneically pregnant rat cannot be considered an example of a local immune response. In addition, we confirmed that the anti-paternal humoral response against RT1Aa caused by pregnancies by DA males differs dramatically from conventional and secondary pregnancy-induced alloimmunizations because the hierarchy of the number of alloplaques that are developed by these four methods of detecting alloplaques is different for primary pregnancy-induced responses as compared with conventional or secondary pregnancy-induced alloimmunizations.
Ablation of immunity to Amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs.
Authors: Brown S J , Galli S J , Gleich G J , Askenase P W
Published: January 2023

Basophils infiltrate the skin and other tissues as part of T lymphocyte and/or antibody-mediated immune responses to certain protein antigens, viruses, tumors, and parasites. Although basophils may comprise a significant fraction of leukocytes in these reactions, their precise role has been poorly understood. Guinea pigs expressing acquired immunity to the tick Amblyomma americanum develop basophil- and eosinophil-rich cutaneous inflammatory responses at tick feeding sites, and tick rejection is associated with extensive local basophil degranulation. We report that a specific anti-basophil serum (ABS) eliminate basophils at tick feeding sites and abolished immunity to A. americanum. ABS does not react with eosinophils and did not reduce blood or bone marrow eosinophils; however, ABS-treated animals had diminished eosinophils at tick feeding sites, perhaps because these sites were deficient in basophil-derived eosinophil-chemotactic factors. AES treatment markedly reduced feeding site eosinophils, did not affect basophil levels, and partially impaired tick resistance. Taken together, our experiments suggest cooperation between basophils and eosinophils in the expression of immunity to ticks in guinea pigs.
A role for oxygen-dependent mechanisms in killing of Leishmania donovani tissue forms by activated macrophages.
Authors: Haidaris C G , Bonventre P F
Published: January 2023

Leishmania donovani, the causative agent of visceral leishmaniasis, infects macrophages (M phi ) of susceptible vertebrates. Immunologically activated M phi are leishmanicidal, but the mechanisms involved in the killing process are not well defined. We sought to investigate the role of reactive oxygen intermediates in the killing of L. donovani. Both the free-swimming promastigote and the intracellular amastigote forms were found to be susceptible to killing in vitro by hydrogen peroxide and other oxygen intermediates. Upon phagocytosis by mouse peritoneal M phi, promastigotes elicited a significantly stronger respiratory burst compared with amastigotes as measured by release of superoxide anion. Although amastigotes do not elicit a strong burst of M phi oxidative metabolism during the initial phagocytic event, immunologically activated M phi that acquired leishmanicidal capacity could be triggered to release substantial amounts of H2O2. Hence, the development of leishmanicidal capacity was correlated temporally with enhanced H2O2 generation by the M phi. In contrast, M phi that lost their ability to release significant amounts of H2O2 after several days in culture were unable to eliminate their parasite burden. Catalase markedly inhibited the elimination of amastigotes by lymphokine-stimulated M phi. In toto, the results implicate reactive oxygen intermediates in killing of the tissue form of L. donovani by its host cell, the mononuclear phagocyte.
A role for the spleen in the appearance of IgM in the bile of rats injected intravenously with horse erythrocytes.
Authors: Jackson G D , Walker P G , Schiff J M , Barrington P J , Fisher M M , Underdown B J
Published: January 2023

The i.v. injection of the particulate antigens horse red blood cells (HRBC) and Salmonella enteritidis into rats results in the appearance of high levels of IgM agglutinating antibody in the serum and bile. This is in contrast to the appearance of specific IgA antibodies in bile after the injection of antigen into the Peyer's patches. At the height of the response, a fivefold to 10-fold increase in total IgM was found in bile, whereas there was no increase in IgA or in total protein levels. The biliary IgM was not associated with secretory component. Studies aimed at revealing the source of the IgM showed that neither immunized nor nonimmunized rats were able to transport 131I-rat IgM, but both groups were equally efficient at transporting 125I-rat IgA. Furthermore, specific anti-HRBC antibody could not be detected in the bile of rats that were injected with a high titer serum, indicating that blood is unlikely to be the source. Splenectomy of rats at the time of the injection of antigen, at 3 days after immunization had abrogated the biliary response, and at 5 days resulted in rapid decline in existing specific antibody level. Involvement of the spleen was additionally implicated when it was shown that injection of animals with immune spleen cells gave rise to specific antibodies in serum and bile. On the basis of these experiments, it is proposed that antigen entering the blood stream can stimulate a population of cells in the spleen that emigrates to the liver, where the cells localize and secrete IgM into bile.
Specificity of T lymphocyte lines for peptides of myelin basic protein.
Authors: Vandenbark A A , Offner H , Reshef T , Fritz R , Chou C H , Cohen I R
Published: January 2023

T lymphocyte lines specific for myelin basic protein (BP) can mediate experimental autoimmune encephalomyelitis (EAE), or can protect against the active induction of the disease. To investigate the antigenic fine specificity of guinea pig (GP) BP-specific T cell lines raised from different rat strains, and to determine whether functionally different T lymphocyte lines and clones recognized the same or different regions of the BP molecule, the proliferation responses of line cells were assessed after stimulation with purified peptides of GP-BP. Lewis rat T cell lines and clones selected for responses to whole GP-BP responded selectively to the 68-88 amino acid sequence of GP-BP, but not to the 1-37, 43-67, or 89-169 sequences. The region of GP-BP recognized by Lewis T cells was additionally defined to include the 75-80 amino acid sequence, because a T cell clone responded equally to GP and rat BP which differed by only one amino acid at position 79, but did not respond to human or bovine BP, which had a Gly-His insertion in this region. T lymphocyte lines derived from the F344 and PVG (Weizmann) rat strains shared the same selective response to peptide 68-88, but lines from BN rats responded to an epitope(s) outside of the 68-88 sequence. The functional capacity of the various T cell lines to mediate experimental autoimmune encephalomyelitis (EAE) or to induce resistance against EAE was independent of their specificity for the different GP-BP peptides; lines specific for epitope(s) within or excluded from the 68-88 sequence could be encephalitogenic depending on their strain of origin, and various lines specific for the 68-88 peptide could induce both disease and protection, disease only, or neither activity.
Monoclonal anti-acetylcholine receptor antibodies with differing capacities to induce experimental autoimmune myasthenia gravis.
Authors: Gomez C M , Richman D P
Published: January 2023

To study the characteristics of the individual autoantibodies that are important in the development of an autoimmune disease, we produced 26 anti-acetylcholine receptor (anti-AChR) monoclonal antibodies (mcAb) and studied the experimental autoimmune myasthenia gravis (EAMG) induced by a number of them. The mcAb reactive with mammalian acetylcholine receptor (M-AChR) exhibited a wide range of dissociation rates from in situ M-AChR of motor endplates. All anti-M-AChR mcAb were capable of producing at least some degree of histopathologic change at the endplate indicative of EAMG, but their potencies varied markedly. One mcAb induced, even at large doses, only minor macrophage invasion without clinical or electromyographic effect. Others induced severe EAMG, and even death, at 1/200th the dose. Low potency was associated with high rate of mcAb dissociation from antigen. High potency was associated with intermediate avidity, not high avidity. These observations suggest that in EAMG, and perhaps in myasthenia gravis, the characteristics of the individual antibodies making up the autoimmune response can determine the severity of the autoimmune disease.
Monoclonal antibodies reactive with human T cell lymphotropic virusI (HTLVI) p19 internal core protein: cross-reactivity with normal tissues and differential reactivity with HTLV types I and II.
Authors: Palker T J , Scearce R M , Ho W , Copeland T D , Oroszlan S , Popovic M , Haynes B F
Published: January 2023

Three monoclonal antibodies to human T cell lymphotropic virus type I (HTLVI) p19 internal core protein, designated as alpha HTLV-2, 3, and 4, have been developed. In indirect immunofluorescence (IF) assays, these antibodies reacted with acetone-fixed cytocentrifuge preparations of culture HTLVI-infected peripheral blood leukocyte (PBL) from a patient (SD) with Japanese adult T cell leukemia and with infected HUT-102 T cells but not with cultured normal PBL. Anti-p19 antibodies alpha HTLV-2, 3, and 4 all reacted with the same HTLVI p19 identified both by antibodies in HTLVI+ patient sera and by antisera raised against two synthetic peptides encoded by the p19 gag region of HTLVI. Partial proteolytic cleavage of p19 immunoprecipitates obtained with antibodies alpha HTLV-2, 3, and 4 produced a 17,000-dalton cleavage product, in agreement with the size of the fragment predicted from the nucleic acid sequence of the HTLVI p19 gag region. Antibodies alpha HTLV-3 and 4 reacted with HTLVI but not HTLVII proteins and were useful diagnostic probes in identifying HTLVI- but not HTLVII-infected lymphoid cells in immunofluorescence assays. In addition to reacting with HTLVI p19, antibodies 2 and 4 also cross-reacted with a wide variety of HTLV-uninfected normal and neoplastic cells and tissues. In addition, HTLVI+ patient sera contained antibodies that competed for binding to the antigenic site on p19 recognized by antibody 4. Thus, anti-p19 monoclonal antibodies alpha HTLV-2 and 4 reacted with a 19,000-dalton viral-encoded protein of HTLVI and cross-reacted with normal host tissues, while anti-p19 antibody alpha HTLV-3 was specific for HTLVI p19 core protein.
Protein-antigen specific Ia-restricted cytolytic T cells: analysis of frequency, target cell susceptibility, and mechanism of cytolysis.
Authors: Tite J P , Powell M B , Ruddle N H
Published: January 2023

We previously showed that cloned, antigen-specific, Ia-restricted L3T4a+ T cell lines can be cytolytic for antigen-pulsed B cell lymphoma targets. Such cells can also, under different experimental conditions, activate B cells to proliferate and secrete immunoglobulin. In the present experiments, we show that this functional phenotype is a common one among a panel of cloned T cell lines. In keeping with this finding, freshly isolated, antigen-activated lymph node T cells show similar functional properties. Such cytolytic L3T4a+ T cells differ from classical H-2K/D-restricted cytolytic T cells in two distinct ways. First, Ia-restricted cytolytic T cells can kill bystander targets, whereas H-2K/D-specific cytolytic T cells do not. Second, in testing a panel of target cells by using lectin-mediated cytolysis, Ia-restricted cytolytic clones reveal large differences in target cell susceptibility, whereas all targets are similarly susceptible to H-2K/D-specific killer cells. Finally, evidence is presented that both direct and bystander killing effected by L3T4a+ T cells are mediated by the same soluble factors, in that there is a strong positive correlation of these two activities for individual cloned lines. The relevant mediators appear to be lymphotoxin and IFN-gamma, although the latter molecule by itself is not cytolytic on our target lines.
Induction of infectious immunodeficiency in BALB/c mice by serial transfer of lymphocytes immune to alloantigens.
Authors: Kim B S , Hui K M
Published: January 2023

Serial transfer of spleen cells immune to allogeneic or semi-allogeneic cells induced transferable splenomegaly and general immune deficiencies, including the lack of proliferative responses to T and B cell mitogens and antibody responses to specific antigens. Parallel experiments with spleen cells from mice that had been administered rectally with allogeneic spleen or sperm cells also resulted in a similar immunodeficiency. The immune deficiencies were transferable into normal mice by injection of spleen cells, cellfree extracts, or culture supernatants of spleen cells from immunodeficient mice. The particle responsible for transmission of immunodeficiency appears to be a high m.w. (greater than 2 X 10(6], 1.14 g/ml density agent. These results suggest strongly that serial transfer of lymphocytes immune to alloantigens triggers the release of a transmissible virus-like agent, which results in an immunodeficiency similar to acquired immune deficiency syndrome (AIDS) of humans. Therefore, this system may provide a valuable animal model system for studying AIDS.
The characteristics of binding of human recombinant interferon-gamma to its receptor on human monocytes and human monocyte-like cell lines.
Authors: Finbloom D S , Hoover D L , Wahl L M
Published: January 2023

Interferon-gamma (IFN-gamma) induces many effector functions in macrophages, presumably through binding to cell surface receptors. Such receptors have been documented in murine macrophages. This report demonstrates that IFN-gamma interacts with a specific receptor on human monocytes and monocyte-like cell lines, U937 and HL60. Recombinant IFN-gamma (rIFN-gamma) was radioiodinated by using Bolton-Hunter reagent to high specific activity. 125I-rIFN-gamma bound in a specific and saturable manner. Saturation of binding sites occurred at 10(-9) M (300 U/ml); there were 4000 specific binding sites per cell for both monocytes and the cell lines. Purified lymphocyte-derived IFN-gamma as well as rIFN-gamma competed for binding sites with 125I-rIFN-gamma. There was no inhibition of binding of the 125I-rIFN-gamma by rIFN-alpha or rIFN-beta. The forward rate constant, k1, at 4 degrees C was about 8 X 10(5) M-1 sec-1 for each cell type studied. In the presence of excess ligand, the dissociation rate constant, k-1, was about 2 X 10(-4) sec-1. The Ka calculated from these constants (4 X 10(9) M-1) agreed closely with that calculated from experiments performed at equilibrium (8 X 10(9) M-1). Because the dissociation of rIFN-gamma from cells was enhanced in the presence of ligand, interactions between binding sites of a negative cooperative type could be operative. These studies demonstrate that rIFN-gamma binds in a specific and saturable manner and with high affinity to a receptor on human monocytes as well as monocyte-like cell lines.