bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphocyte Depletion Induced by Cholera Toxin; Relationship to Adrenal Cortical Function
Authors: Morse Stephen I. , Stearns Carol D. , Goldsmith Susan R.
Published: December 2022

Intravenous injection of cholera toxin (choleragen) into mice caused a profound lymphocytopenia associated with marked cellular depletion of the lymph nodes, spleen, and thymus. After administration of 1 µg of choleragen, lymphocytopenia was most marked at 24 hr; recovery occurred 6 to 10 days later. Similarly, depletion of lymph nodes and spleen was maximal at 24 hr with recovery by 14 days. Choleragen also caused a marked elevation of serum corticosterone and lymphocyte depletion was not observed in adrenalectomized mice. These results suggested that the lymphocytopenic effect of choleragen was mediated by increased production and secretion of adrenal cortical hormones secondary to a rise in intracellular cAMP induced by cholera toxin. The site of action of choleragen may be the adrenal cortex itself and/or the hypothalamic-pituitary system.
Anti-Ig-Triggered Movements of Lymphocytes—Specificity and Lack of Evidence for Directional Migration
Authors: Schreiner George F. , Unanue Emil R.
Published: December 2022

Interaction of anti-immunoglobulin antibodies with the surface Ig of B lymphocytes leads to capping and endocytosis of the immune complexes and to a brief stimulation of translational motility. Lymphocytes are not stimulated to move by interaction with other ligands, such as antibodies to the theta isoantigen, to H2 determinants, or to determinants recognized by heterologous anti-lymphocyte antibodies. Furthermore, anti-lymphocyte antibodies block the motility produced by anti-Ig. This effect was not seen in cells treated with colchicine, suggesting that the antilymphocyte effect may be associated with hyperstabilization of microtubules. Finally, we report on preliminary experiments using chemotactic chambers which show that anti-Ig stimulates random but not directional movement.
The Antigenicity of Myelin Encephalitogenic Protein: Production of Antibodies to Encephalitogenic Protein with Deoxyribonucleic Acid—Encephalitogenic Protein Complexes
Authors: Whitaker John N.
Published: December 2022

Rabbits immunized with monkey encephalitogenic protein (EP) complexed to deoxyribonucleic acid (DNA) formed complement-fixing antibodies that reacted well with EP from monkey, bovine, and human brain and the large EP of rat brain. Reactivity with the small EP of rat brain was much less. The antibodies, analyzed by the quantitative micro-complement fixation test, were of the 7S class, were produced in high titer, and failed to react with histone, lysozyme, or acidic liver extracts. Immunohistochemical studies revealed that the antibodies bound to central nervous system white matter from human, rat, guinea pig, and mouse as well as human peripheral nerve myelin. These findings demonstrate that the immunogenicity of EP is greatly enhanced by attachment to DNA and perhaps other negatively charged molecules. This method makes available anti-EP with which to investigate immunochemically the antigenic and conformational features of EP.
Induction of Tolerance to Nucleic Acid Determinants by Administration of a Complex of Nucleoside d-Glutamic Acid and d-Lysine (D-GL)
Authors: Eshhar Zelig , Benacerraf Baruj , Katz David H.
Published: December 2022

The administration of nucleosides coupled covalently to the copolymer of D-glutamic acid and D-lysine (D-GL) or to its stereoisomer, L-GL, induces a state of nucleoside (NUC)-specific tolerance in inbred SJL and BALB/c mice, irrespective of their immune status at the time of treatment. Such tolerance is characterized by the inability of treated animals to mount either primary or secondary, intact or adoptive, anti-NUC antibody responses following immunization with a highly immunogenic conjugate of NUC-Keyhole limpet hemocyanin. These observations have potential therapeutic importance in autoimmune processes involving anti-DNA antibody production.
Maturation of B Lymphocytes in the Rat
Authors: Strober Samuel
Published: December 2022

Thoracic duct and spleen cells of normal (unimmunized) adult rats were fractionated according to size by 1 × G velocity sedimentation. Fractions were tested for their ability to restore the adoptive antibody response of irradiated hosts to horse spleen ferritin. A constant source of T cells (small numbers of unfractionated thoracic duct cells) was added to each fraction in order to monitor the B cell activity of the latter. Although large and small cell fractions of the spleen showed restorative activity, only the small cell fractions of the thoracic duct lymph showed activity.

The turnover rate of the spleen cell fractions was determined by treating donors with high specific-activity 3H-thymidine for 48 hr before splenectomy. Rapidly dividing cells are preferentially killed by this treatment. The results suggest that a considerable proportion of large, intermediate, and small virgin B cells turn over within 48 hr.

The cell surface of the various spleen cell fractions was examined for the presence of immunoglobulin (Ig) and a receptor for complement. The percentage of Ig-bearing cells in the large cell fractions was similar to the percentage of cells bearing IgM and a receptor for complement. However, the majority of Ig-bearing cells in the small cell fractions did not show the latter two surface markers. Experiments with the fluorescence-activated cell sorter showed that the large functionally active B cells bore surface IgM.

The experimental findings suggest that there are subpopulations of virgin B cells in the spleen of the adult rat which differ with respect to size, migration pattern, turnover rate, and cell surface characteristics. The relationship of these cells to one another is discussed in the framework of an antigen-independent model of B cell maturation in the rat.
Mechanism of Action of Concanvalin A on Human Basophils
Authors: Siraganian Reuben P. , Siragania Patricia A.
Published: December 2022

Concanavalin A (Con A) activates human basophils to release histamine. This reaction has great similarities to that of antigen-or anti-IgE-induced release. It is characterized by a two stage reaction: the initial stage is the binding of Con A to the cell and the second stage is a secretory process of the cell. Cells desensitized by incubation with excess amounts of Con A or by prolonged incubation in the absence of cations cannot be activated to release with antigen or anti-IgE. When the native (tetravalent) Con A molecule is modified by succinic anhydride to become divalent it is much less active in releasing histamine.

There is wide variation in the response of cells from different individuals to Con A. However, a close correlation exists between the histamine release induced by Con A and anti-IgE. Therefore, in general, cells from allergic donors release more histamine with Con A than those from non-allergic individuals.

Evidence is presented to demonstrate that Con A acts by binding to carbohydrate groups on the IgE molecule located on the basophil membrane. On a molar basis, IgE is 4000-fold more active than α-methyl-D-mannoside in inhibiting the Con A-induced histamine release. Succinyl Con A blocks the ability of Con A and anti-IgE equally well and to a lesser extent the ability of antigen to activate cells to release histamine.
Control of Histamine Release: Effects of Various Conditions on Rate of Release and Rate of Cell Desensitization
Authors: Baxter James H. , Adamik Ronald
Published: December 2022

Histamine release from rat mast cells by dextran and by antigen under various conditions was studied in terms of the rate of release and the duration of release, which together determined the total amount released. Reducing the concentration of the releasing agent decreased the rate of release without greatly affecting its duration. Reducing the temperature also decreased the rate, but prolonged the duration. Under all of the various conditions, release stopped as the cells became desensitized to the releasing agent. It appeared, therefore, that the rate of desensitization controlled the duration of release.
Demonstration of in Vitro Lymphocyte-Mediated Cytotoxicity against Measles Virus in Sspe
Authors: Kreth Wolfgang H. , Käckell Mathilde Y. , Meulen Volker Ter
Published: December 2022

Patients with subacute sclerosing panencephalitis (SSPE) are presumed to lack specific cellular immunity against measles virus. In order to test this hypothesis in vitro, the interaction between peripheral lymphocytes and measles virus-infected tissue culture cells was investigated in 10 SSPE patients. Human fibroblasts, either uninfected or carrying a persistent measles virus infection, were labeled with 51Cr and incubated with lymphocytes for 18 to 20 hr in the absence of antibody and complement. Peripheral lymphocytes from measles sero-positive and sero-negative individuals were tested, and the system was found to be virus specific. The lymphocytes from the 10 SSPE patients caused specific cytotoxicity of target cells. A correlation was not found between antibody titer and specific 51Cr release. It could also be demonstrated that target cell destruction was not mediated by monocytes or B lymphocytes. These in vitro studies suggest that SSPE patients do not have a specific defect of cellular immunity against measles virus.
Complement-Mediated Alteration of Antibody Specificity in Vivo
Authors: Drake Walter P. , Mardiney Michael R.
Published: December 2022

The simultaneous injection of heterologous anti-EL4 lymphoma serum and complement results in the rapid disappearance of such antibody from the periphery of non-tumor bearing mice. However, this phenomenon is only observed when a complement source capable of mediating the lysis of EL4 cells sensitized with such heterologous antibody is used. This complement mediated enhancement of anti-tumor antibody absorption was observed in vivo for three strains of mice. Omission of complement or the use of genetically deficient complement sources resulted in no effect on circulating antibody titer when compared to the titer of heterologous anti-tumor antibody observed in the periphery when injected alone. Exogenous complement did not enhance the clearance of heterologous anti-tetanus toxin serum, thereby suggesting that the increased absorption of anti-EL4 in vivo is not related simply to the enhanced clearance of foreign γ-globulin. Confirmatory evidence of the role of complement in altering anti-tumor antibody specificity in vivo was obtained in a guinea pig tumor model as well. The data suggest that anti-tumor serum shown to be relatively specific for the tumor cell gains additional specificity in the presence of functional complement and consequently manifests avidity for crossreactive determinants previously thought to be unrelated.
Immunosuppressive Effects of Glucocorticosteroids: Differential Effects of Acute vs Chronic Administration on Cell-Mediated Immunity
Authors: Balow James E. , Hurley Douglas L. , Fauci Anthony S.
Published: December 2022

The effects of acute vs. chronic glucocorticosteroid administration on established cellular immune responses were studied in guinea pigs previously sensitized to tuberculin. A greater than 50% reduction in circulating lymphocytes was observed 4 hr after injection of soluble hydrocortisone and 24 hr after daily subcutaneous injections of depot cortisone acetate. After a single dose of hydrocortisone, peripheral lymphocyte migration inhibitory factor (MIF) production and antigen and mitogen-induced proliferation were unchanged. However, the peripheral lymphocytes remaining in the circulation after chronic cortisone treatment showed a marked decrease in both antigen-induced MIF and proliferation, although mitogen responses remained normal. Although similar levels of lymphocytopenia were induced by acute and chronic glucocorticosteroid administration, only chronic treatment was associated with depression of certain cell-mediated lymphocyte functions. The available evidence suggests that these changes may depend on GCS-induced selective alterations in the circulation patterns of certain subpopulations of lymphocytes.
Antibody-Dependent Cytotoxicity: Modulation by the Cytochalasins and Microtubule-Disruptive Agents
Authors: Gelfand Erwin W. , Morris Simon A. , Resch Klaus
Published: December 2022

Cytochalasin B was shown to inhibit lysis of antibodycoated target cells by effector cells from rabbit spleen and lymph node. The inhibitory activity was dose-dependent and reversible. At low concentrations of cytochalasin B (0.15 to 0.3 µg/ml) enhancement of antibody-dependent cytotoxicity was observed. The drug appeared to act at an early stage of the lytic pathway after effector cell-target cell interaction, but before triggering of the cytotoxic event. Cytochalasin A was shown to be a more potent but similarly reversible inhibitor of antibody-dependent cytotoxicity. No enhancement of cytotoxicity was seen at non-inhibitory concentrations of cytochalasin A. The microtubule-disruptive agents colchicine (10-4 M), vinblastine (10-5 M) and colcemid (10-6 M) did not influence antibody-dependent cytotoxicity at concentrations which were not toxic to the effector cells. Our results suggest that antibody-dependent cytotoxicity is a surface membrane-initiated process and microtubule-associated functions are not essential.
The Hapten-Carrier Effect in Teleost Fish
Authors: Yocum David , Cuchens Marvin , Clem L. W.
Published: December 2022

The sea robin (Prionotus evolans), a representative teleost fish, was found to undergo the hapten-carrier effect, suggestive of T-B cell cooperativity, in vivo with dinitrophenyl as the hapten and bovine γ-globulin or bovine serum albumin as carriers. In contrast to mammalian systems, the secondary anti-hapten response in the sea robin was found to involve exclusively high molecular weight antibody.
Complement-Dependent Alterations in the Handling of Immune Complexes by NZB/W Mice
Authors: Miller Gary W. , Steinberg Alfred D. , Green Ira , Nussenzweig Victor
Published: December 2022

Serum of normal mammals contains factors which can release antigen-antibody complexes from the surfaces of leukocytes and platelets. This “complex release activity” (CRA) is mediated by the alternative pathway of complement activation, and is measured by a kinetic assay of the release of lymphocyte-bound soluble immune complexes. CRA activity was measured in the sera of NZB/W mice, which develop an autoimmune disease with aging. CRA in these mice declined rapidly after 16 weeks of age, and by 32 weeks was barely detectable. Serum C3 levels also declined in these mice. An association test correlating CRA and C3 concentration was highly significant. The decreased complement levels in the older mice led to profound changes in their handling of injected soluble immune complexes, as demonstrated in studies of the kinetics of distribution of the complexes between plasma and circulating cells. These abnormalities may be related to the disease which occurs spontaneously in NZB/W mice, as well as in human immune complex diseases.
A Radioactive Hapten-Binding Assay for Measuring Antibodies to the Pentapeptide Determinant of Peptidoglycan
Authors: Heymer Berno , Bernstein David , Schleifer Karl H. , Krause Richard M.
Published: December 2022

A major portion of the humoral immune response to peptidoglycans is directed against the non-cross-linked pentapeptide side chains of these ubiquitous bacterial antigens. At present, no specific and sensitive assay for pentapeptide antibody determination is available. Therefore, a radioimmunoassay has been developed which employs the synthetic pentapeptide hapten L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala, labeled by the active ester method of Bolton and Hunter to high specific activities (6.74 to 18.18 µCi/µg) with 125I, and used as a reagent for measuring pentapeptide antibody. A-variant streptococcal antisera, known to contain pentapeptide antibodies as shown by quantitative precipitation, would bind more than 95% of the radiolabeled hapten in contrast to 2 to 3% by preimmune rabbit sera. Specificity of the binding reaction was demonstrated by inhibition experiments employing various synthetic oligopeptides related or unrelated to the pentapeptide in the radioimmunoassay. Binding curves established with serial dilutions of peptidoglycan antiserum were linear from 15 to 500 µg/ml of antibody permitting pentapeptide antibody measurement within this range. Comparative data on pentapeptide antibody determinations by quantitative precipitation and radioimmunoassay are given and the time course of the production of this antibody in 14 rabbits hyperimmunized with A-variant streptococcal vaccine is reported.
Tumor Development after Polyoma Infection in Athymic Nude Mice
Authors: Stutman Osias
Published: December 2022

Nude (nu/nu) mice in a CBA/H background show an age-dependent susceptibility to tumor development after polyoma virus infection (strain LID-1) when compared with nu/+ or CBA/H mice, which is apparent when 15- or 30-day-old mice are used: tumor incidence was 83 to 90% in nudes and 0 to 10% in controls. Latent periods for tumor development were also shortened in nudes. However, with increasing age nude mice become partially resistant and only 25% develop tumors when infected at 120 days of age. This partial resistance could be transferred with spleen cells to newborn mice. The cells in spleen responsible for this transfer can be eliminated by lysis with anti-Ig and complement or by pre-treatment of the donor with 100 mg/kg of cyclophosphamide and were not affected by treatment in vitro with anti-Thy.1.2 or procedures that remove adherent cells and/or macrophages. When the cells in 15-day-old nu/+ spleen were studied, both anti-Ig or anti-Thy.1.2 treatment eliminated tranfer of resistance to newborn. Virus replication in tissues of nude mice was increased 5 days after infection when compared with nu/+ but became comparable by day 15 after infection. Hemagglutination-inhibition antibodies in serum of nude and nu/+ had comparable titers when measured early after infection but higher titers were observed in nu/+ later after infection.
Electrophoretic Fractionation of Guinea Pig Lymphocytes: Evidence for Different Subsets of T and B Cells in Spleen and Lymph Node
Authors: Andersson Leif C. , Nordling Stig , Häyry Pekka
Published: December 2022

Guinea pig lymph node and blood lymphocytes have been physically fractionated in preparative cell electrophoresis into two functionally viable populations, the high mobility cell population (HMC) and the low mobility cell population (LMC). By using cell surface markers and functional tests known to be specific for T and B lymphocytes, respectively, it is shown that the T lymphocytes localize in the HMC population and the B lymphocytes in the LMC population. The spleen lymphocytes do not separate into the two populations. They move into one single broad peak containing both T and B cells. This finding indicates the presence of electrokinetically different subsets of T and B lymphocytes in the spleen on one hand and in the lymph node and blood on the other hand.
Activation of T and B Lymphocytes in Vitro
Authors: Armerding Dieter , Katz David H.
Published: December 2022

In the presence of a preparation of purified thymus extract factors (TEF), spleen cells from athymic nude mice develop in vitro immune responses to soluble DNP-protein conjugates, to particulate sheep red blood cells, and to allogeneic cells. TEF has similar effects also on the in vitro antibody responses of normal mouse spleen cells, enhancing antigen-dependent plaque-forming cells responses to dinitrophenyl carrier complexes of unprimed and primed mice. TEF fails to reconstitute helper cell function in cultures of T cell-deprived spleen cells. The thymic factor increases the reactivity or normal thymus cells in the in vitro mixed lymphocyte reaction and has at high doses mitogenic effects. The role of humoral thymus factors on the differentiation process of T cells is discussed.
Studies on Tolerance Induction in Vitro
Authors: Schaefer Annette E. , Adler Louise T. , Fishman Marvin
Published: December 2022

Tolerance was induced in rabbit spleen cells by incubation with solubilized T2 phage (S-T2)2 at 37°C. Spleen cells thus treated maintained normal responsiveness to an unrelated antigen, S-SP82. Transfer of tolerance was demonstrated in in vitro in that the addition of washed tolerant cells caused suppression of the response of untreated cells to an immunogenic dose of S-T2. Evidence is presented that this suppression is not due to the transfer of tolerogenic quantities of antigen. Spleen cell populations depleted of adherent cells were still capable of being made tolerant and of transferring tolerance.
The Nature of Murine Immune Response to Nucleic Acids
Authors: Fuchs Sara , Mozes Edna , Stollar B. D.
Published: December 2022

The antibody response of mice to nucleic acids appears to be genetically regulated, and may show varying patterns. SJL/J mice and AKR/Cu mice are high responders to denatured DNA complexed with MBSA and produce 7S as well as 19S antibodies. DBA/2 mice respond with low titers to this immunogen which consists of 19S antibody exclusively. C57BL/6 mice are high responders to denatured DNA, but produce only 19S antibodies. Denatured DNA-MBSA is immunogenic when injected without complete Freund's adjuvant, thereby suggesting that this antigen might be thymus independent.

The pattern of immune responses of some strains to the polyribonucleotides poly(I)·poly(C) and poly(A)·poly(U) is opposite to that observed with denatured DNA. Thus, DBA/2 mice are high responders and SJL/J mice are low responders. However, the low responders SJL/J mice produce 7S as well as 19S antibody which suggests that different mechanisms operate for the regulation of immune responses to the two types of nucleic acids.

Whereas no antibody is elicited upon immunization with DNA in the absence of a carrier protein, poly(A)·poly(U) and poly(I)·poly(C) are immunogenic when injected without MBSA. Immunization with complexes of the polyribonucleotides and MBSA enhanced the responses to these immunogens; however, the strain differences were not completely abolished.

Poly(A)·poly(U) did not enhance the low immune responses of DBA/2 mice to denatured DNA when injected i.v. following immunization with the DNA-MBSA. However, simultaneous immunization of DBA/2 and SJL/J mice with poly(A)·poly(U) and denatured DNA-MBSA resulted in high antibody titers to both immunogens in either mouse strain.
Mechanism of the Suppressive Effect of Interferon on Antibody Synthesis in Vivo
Authors: Brodeur Bernard R. , Merigan Thomas C.
Published: December 2022

Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen. It is also possible to effect the late responses of antigen sensitive “memory” cells observed during secondary immunization by administration of interferon prior to primary immunization. The immunosuppressive activity of interferon was time- and dose-dependent. Maximum suppression was produced when animals were given 1.5 × 105 units of interferon between 4 and 48 hr before antigenic stimulation. These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m-RNA translation. In addition, the use of nonadherent spleen cell cultures from interferontreated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes. A variety of soluble “suppressive” factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro. Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression.
Induction of Blood Eosinophilia by Pulmonary Embolization of Antigen-Coated Particles: The Relationship to Cell-Mediated Immunity
Authors: Schriber Robert A. , Zucker-Franklin Dorothea
Published: December 2022

A method of immunization has been described which consists of the i.v. injection into rats of large latex particles coated with human γ-globulin (HGG). The coated particles embolize the pulmonary capillary bed and induce blood eosinophilia, which correlated strongly with the development of lymphocyte responsiveness to HGG in vitro. Sequential histologic studies of the lungs including ultrastructural analysis suggest a delayed hypersensitivity reaction to the coated particles. These studies support the concept that the induction of blood eosinophilia may be mediated by T lymphocytes.
Delayed Clearance of Morphine from the Circulation of Rabbits Immunized with Morphine-6-Hemisuccinate Bovine Serum Albumin
Authors: Hill Jeffrey H. , Wainer Bruce H. , Fitch Frank W. , Rothberg Richard M.
Published: December 2022

Morphine clearance from the circulation of normal rabbits and rabbits with circulating anti-morphine antibody was studied. Individual animals were injected with 14C trace-labeled morphine in saline (6 mg morphine/kg body weight). The rabbits were bled at various times after morphine injection and the amount of morphine present in the serum at each time interval was determined. Morphine could be detected in the serum of normal animals for 1 week following injection and up to 12 weeks following injection in at least one animal with antibodies to morphine. The rate of morphine clearance in animals immunized to morphine-6-hemisuccinate-bovine serum albumin was not significantly different from normal during the first 4 hr after morphine injection. However, by 24 hr after injection, the rate of morphine clearance in morphine-6-hemisuccinate-bovine serum albumin-immunized animals was significantly slower than in normal animals. The amount of morphine present in the sera of the rabbits 24 hr after injection was related to the antigen-binding capacity and independent of antibody avidity. However, the rate of morphine clearance at times greater than 24 hr after injection was related to the average antibody avidity and not related to the antigen-binding capacity.
Role of the Eosinophil in the Allergic Reactions
Authors: Hubscher Thomas
Published: December 2022

An inhibitor of histamine release was found to be associated with the human eosinophilic leukocyte. This eosinophil-derived inhibitor (EDI) was released from eosinophilrich fractions upon sonication or interaction with immune reactants (specific allergens or anti-IgE). EDI was found to exert its inhibitory action at the target cell level by increasing the intracellular levels of cyclic-AMP. Preliminary electron microscopic studies show the presence of IgE on the eosinophilic leukocyte and it is suggested that the allergen or anti-IgE-induced release of EDI might be due to a direct interaction of these immune reactants with the eosinophil-bound IgE antibody.

The results also suggest that by virtue of liberating a histamine release inhibitor such as EDI, the eosinophil assumes a modulating role in the allergic inflammatory reaction.
A Vaccination Procedure Against Trypanosoma Cruzi Infection in Mice by Nonspecific Immunization
Authors: Ortiz-Ortiz Librado , Gonzalez-Mendoza Amado , Lamoyi Edmundo
Published: December 2022

There are previous reports dealing with vaccination against experimental infection with Trypanosoma cruzi in mice. They have varied from the use of avirulent, killed, or irradiated strains to subcellular materials and the use of other kinetoplastic flagellates (1, 2). Although these procedures have been promising, none of the methods presently studied has resulted in absolute protection under conditions of challenge with large numbers of parasites.

The aim of the experiments reported here was to explore the possibility of protecting mice against T. cruzi infection by BCG immunization, a treatment that has been shown in other systems to enhance nonspecifically immunity (3–6).

Mice of the Carworth Farm strain (CF1) aged 1.0 to 1.5 months were used uniformly throughout these experiments. Development of the T. cruzi infection was checked routinely by determination of parasites in blood every 5 days after challenge infection and histopathologic studies of the heart at the time of death.
Interaction between Cells of Peyer's Patches and Cells of Bone Marrow Origin in the Immune Response
Authors: Knudson Kristine C. , France Charlotte M. , Coppola Edward D. , Miller Harold C. , Jones Tobi L.
Published: December 2022

There has been a good deal of interest in Peyer's patches as a part of the gut-associated lymphoid system, but their actual function has not been defined. Much of the early work on Peyer's patches was concerned with defining their role as the mammalian equivalent of the bursa of Fabricius, populated primarily by thymus-independent, bursal equivalent (B)3 lymphocytes (1–5). More recently, however, several studies have provided evidence that Peyer's patches also contain functional T lymphocytes (6–11).

We reported previously that although Peyer's patches of mice do not respond to systemic antigenic stimulation by producing antibody in situ. Peyer's patch cells could act synergistically with spleen cells to produce a 5-fold increase in the number of antibody-forming cells to sheep red blood cells (SRBC) (12). In this communication we report that Peyer's patch cells are able to cooperate with bone marrow cells to produce antibody-forming cells of IgM, IgG, and IgA classes.
Amyloid Fibril Protein Related to Immunoglobulin λ-Chains
Authors: Skinner Marytha , Benson Merrill D. , Cohen Alan S.
Published: December 2022

Amyloid fibrils, isolated from the spleen of a patient with primary amyloidosis, had an N-terminal sequence showing a high degree of homology with λ Bence Jones proteins. Antiserum prepared to the amyloid protein detected a soluble factor, antigenically identical to the isolated fibril preparation.
Experimental Autoimmune Encephalomyelitis in Mice: Immunologic Response to Mouse Spinal Cord and Myelin Basic Proteins
Authors: Bernard Claude C. A. , Carnegie Patrick R.
Published: December 2022

It was confirmed that experimental autoimmune encephalomyelitis EAE, could be induced in SJL/J mice with mouse spinal cord homogenate. It was shown that induction of EAE in mice was critically dependent on the concentration of pertussis vaccine. The encephalitogen present in mouse brain was the basic protein of myelin. The smaller form of the mouse and rat basic proteins induced EAE; thus the mouse like the rat responds to determinants other than the “tryptophan region,” which induces EAE in guinea-pigs.

Mice with EAE developed a cell-mediated immune response to myelin basic protein, as judged by inhibition of peritoneal cell migration. However, levels of antibody to mouse basic protein were low, as judged by radioimmunoassay. The establishment of this autoimmune disease model in the mouse will allow the application of well established techniques for the analysis of the immunologic mechanisms leading to disease manifestation.
Enhancement and Hyperacute Rejection of Skin Grafts in the Mouse
Authors: Jansen Jan L. J. , Koene Robert A. P. , v. Kamp Gerard J. , Gerlag Paul G. G. , Wijdeveld Paul G. A. B.
Published: December 2022

B6AF1 anti-B10.D2 ascites fluid was fractionated by molecular sieving and cation exchange chromatography in an attempt to separate cytotoxic and enhancing antibodies. Five fractions were obtained which showed no overlap on analysis with isoelectric focusing. Despite this complete physicochemical separation all fractions contained detectable amounts of 7S IgG1 and 7S IgG2. Furthermore, enhancement of B10.D2 skin grafts in B6AF1 recipients could be induced with all the fractions. Cytotoxic activity was also present in the fractions. This was not only shown in vitro by the cytolysis of B10.D2 lymphoid cells in the presence of rabbit complement, but also by the ability of the different fractions to induce hyperacute destruction of B10.D2 skin grafted onto B6AF1 mice after i.v. injection together with rabbit complement. Thus, we were unable to separate the alloantiserum in cytotoxic and enhancing fractions by physicochemical means.
Stimulator T Cells: Involvement in the Induction of Cell-Mediated Cytotoxicity
Authors: Dennert Gunther
Published: December 2022

Spleen cells of mice primed by injection of normal or formaldehyde-treated allogeneic or xenogeneic tumor cells show a dramatically enhanced capacity to generate cytotoxic cells in vitro. This effect appears to be due to priming of a relatively anti-Thy-1 resistant T cell, which does not display immunologic specificity.
Repopulation with IgA-Containing Cells of Bronchial and Intestinal Lamina Propria after Transfer of Homologous Peyer's Patch and Bronchial Lymphocytes
Authors: Rudzik R. , Clancy R. L. , Perey D. Y. E. , Day R. P. , Bienenstock J.
Published: December 2022

Transfer of 50 million rabbit allogeneic lymphocytes from either bronchus-associated lymphoid tissue (BALT) or Peyer's patches into 1000 R x-irradiated recipients results, 6 days later, in predominant repopulation of gut and bronchial lamina propria, as well as spleen, with IgA-containing cells.

After repopulation with BALT or Peyer's patch cells, lymphoid follicles in both gut and lung showed peripheral cellular membrane type of fluorescence with fluorescein-conjugated anti-IgA antisera only.

Six days after x-irradiation alone, little evidence of repopulation was seen and immunofluorescent qualitative observations of gut and lung, and quantitative data in the spleen, confirmed these findings. After transfer of 50 million lymph node cells, very few immunoglobulin-containing cells were seen in the gut or bronchial lamina propria.

These results suggest that there may be a common mucosal immunologic system, and that repopulation of gut and lung lamina propria may be through the organized lymphoid tissue therein.
IgG Diphtheria Antitoxin Responses from Human Tonsil Lymphocytes Induced by Anti-γ-Chain Antibodies
Authors: Platts-Mills Thomas A. E. , Ishizaka Kimishige
Published: December 2022

Human tonsil lymphocytes were cultured for 24 hr with purified antibodies specific for human IgG heavy chain determinants (anti-γ-chain) and then cultured for 6½ days in Marbrook tubes. IgG diphtheria antitoxin was measured in the culture supernatants by antigen-binding radioimmunoassay. In cultures from eight tonsils, anti-γ-chain stimulated significant IgG antitoxin formation; in each case parallel cultures stimulated with toxoid gave good responses. The specificity of the antibody produced was established by showing that supernatants from cultures stimulated with anti-γ-chain will neutralize toxin. Total IgG in culture supernatants was measured by radioimmunoassay and it was found that cultures stimulated with anti-γ-chain generally produced less total IgG than unstimulated cultures. In time course experiments IgG antitoxin formation increased rapidly after the 3rd day whereas over 50% of the total IgG was produced in the first 3 days. Evidence is presented which suggests that anti-γ-chain acts differently on different groups of B cells.
Distinction between Malignant L Cells and Normal Mouse Fibroblasts by Rosette Formation with Sheep Red Blood Cells
Authors: Hoch James A. , Dierich Manfred P. , Pellegrino Michele A. , Ferrone Soldano , Reisfeld Ralph A.
Published: December 2022

Murine L cell fibroblasts, and derivatives were found to rosette with sheep red blood cells (SRBC). Primary fibroblast explants from the parent murine strain, C3H, did not possess this potential. No rosettes were observed with primary fibroblast explants from C57BL and B10Br mice, with a human fetal lung fibroblast, with baby hamster fibroblasts or their polyoma transormed derivative, or with a cell line, 1T-22, derived from BALB/c mice. Hybridization of 1T-22 and L cells, by Sendai virus-mediated cell fusion, suppressed the rosette potential of the L cell parent. The receptor for SRBC on L cells appears to result from the expression of a recessive characteristic.
Reversible Restoration by Thymosin of Antigen-Induced Depression of Spleen DNA Synthesis in NZB Mice
Authors: Dauphinee Michael J. , Talal Norman
Published: December 2022

Antigen-induced depression of spleen DNA synthesis was studied in NZB and CBA/J mice. This phenomenon, a measure of T suppressor cell activity, normally decreases as a consequence of aging. However, NZB mice have an accelerated loss of antigen-induced depression that can be restored by treatment with thymosin or injection of 1-month-old NZB thymocytes. The restoration by thymosin declined between 1 and 2 weeks after treatment, but could be induced again after a second exposure to thymosin. These results suggest a potential for reversible but repeatable restoration of suppressor cell activity in NZB mice.
The Structure and Function of Immunoglobulin Domains
Authors: Isenman D. E. , Dorrington K. J. , Painter R. H.
Published: December 2022

The observation that reduction of the inter-chain disulfides in rabbit antibody destroys its ability to interact with complement was confirmed and shown to be true also of human myeloma IgG1 subclass proteins. In the latter case a C1-binding assay was used. Further studies indicated that it was the interheavy chain disulfides which were essential for complement-binding activity: Non-covalently reassembled IgG (LHHL) was devoid of C1-fixing activity whereas molecules formed from covalently linked heavy chain dimers, and reduced and alkylated light chains (ie., LH-HL) were as active as the parent intact IgG. Fc fragments from IgG1 bound C1 and this activity was insensitive to the presence or absence of intact interchain disulfides. These bonds therefore are neither directly involved in C1 binding nor essential for the integrity of the binding site. We have also shown that although IgG4 does not bind C1, Fc fragments derived from this subclass fix C1 with an affinity comparable to that of the corresponding fragment from IgG1. These data suggest that quaternary interaction with other regions of the molecule (ie., Fab) may modulate the activity of the C1-binding site.
Pathogenesis of Rabies in Immunodeficient Mice
Authors: Kaplan M. M. , Wiktor T. J. , Koprowski H.
Published: December 2022

The HEP and ts2 strains of rabies virus inoculated intracerebrally into adult mice normally cause clinically inapparent infection. In the experiments described, this is converted into a lethal infection by immunosuppression with cyclophosphamide, which also prevented induction of immunity with vaccine. Lethal infection of HEP-inoculated mice was also observed in mice treated with antithymocytic serum, and in athymic (BALB/c-nu) nude mice.
Bactericidal Activity of Meningococcal Antisera
Authors: McLeod Griffiss J. , Broud Dennis D. , Bertram Mary Ann
Published: December 2022

Humoral IgA, separated and purified from human sera drawn 12, 27, and 33 days after infection with serogroups B, Y, and C meningococci, respectively, has been shown to inhibit complement-mediated bacteriolysis by IgG and IgM purified from the same sera. Inhibition was dependent on the ratio of lytic to blocking antibody, was strain specific, and was greater for IgG than IgM. IgM was found to be more active than IgG in a bactericidal test. Activity of IgA appeared unrelated to the presence of a prozone in the whole serum. Similar inhibition was noted for IgA separated from rabbit sera.
Human Lymphocyte Cytotoxicity Against Mumps Virus-Infected Target Cells
Authors: Härfast Bengt , Andersson Torbjörn , Perlmann Peter
Published: December 2022

Subpopulations of human lymphocytes were tested for their capacity to kill mumps virus-infected target cells in a 51chromium release assay. Using two different cell fractionation techniques, lymphocytes were fractionated into T cell-enriched (primarily T cells) and T cell-depleted (primarily B cells) subpopulations.

Filtration of lymphocytes through columns coated with human immunoglobulin and rabbit anti-human-immunoglobulin (Ig-anti-Ig) rendered the resulting T-cell preparation mactive as effector cells against target cells carrying mumps virus antigens.

In the second technique, lymphocytes were fractionated by centrifugation into two fractions according to their ability to form spontaneous rosettes with sheep erythrocytes (E). The E-rosette-forming population (primarily T cells) was shown to lack cytotoxic activity against mumps virus-infected target cells. This activity was present in the nonrosetting population. The results suggest that the effector cells involved in this cytotoxic system are of a non-T variety.
In Vitro Studies on Information Transfer in Cells from Allotype-Suppessed Rabbits
Authors: Adler Frank L. , Fishman Marvin
Published: December 2022

Data are presented which show that cells from allotypically suppressed rabbits resist in vitro “rescue” attempts in which informational ribonucleic acid (i-RNA) coding for the suppressed allotypic marker is used. It is shown that peritoneal exudate cells from such thoroughly suppressed animals contain cells that yield i-RNA coding for the suppressed marker, and that central lymphatic tissue possesses cells that produce Ig of the suppressed type.
Immune Responses to a Soluble Schistosomal Egg Antigen Preparation during Chronic Primary Infection with Schistosoma Mansoni
Authors: Colley Daniel G.
Published: December 2022

Murine schistosomiasis mansoni is characterized by an intense, predominantly cell-mediated, anti-egg, granulomatous response to schistosomal egg antigens (SEA). Anti-SEA responses include lymphocyte blastogenesis, the production of the lymphokine eosinophil stimulation promoter (ESP), hemagglutinating antibody, heat-labile and heat-stable, 72-hr passive cutaneous anaphylaxis (PCA) antibodies, and pronounced peripheral blood eosinophilia. These responses were followed during the course of chronic (1 year) infection and analyzed with specific reference to the observed diminution of granuloma formation, in the presence of continued antigenic exposure, which occurs by 10 to 12 weeks after infection and persists during long-term schistosomiasis. Lymphocyte blastogenesis and peripheral blood eosinophilia were positive from the 8th week of infection until the 50th. Lymphokine production and circulating heat-labile PCA antibody were only positive for a few weeks after 8 weeks of infection. In contrast, hemagglutinating antibody and heat-stable, 72-hr PCA antibody increased during weeks 10 to 14 and remained high throughout chronic infection. The development and regression of these various immune responses to SEA indicate that there are several potential mechanisms that could explain the immunoregulatory interactions that result in specifically diminished lesion formation in this chronic infection.
Structural Homogeneity of Human Subacute Sclerosing Panencephalitis Antibodies
Authors: Strosberg A. Donny , Karcher Denise , Lowenthal Armand
Published: December 2022

Three homogeneous immunoglobulin fractions were isolated from the serum of a patient with subacute sclerosing panencephalitis (SSPE). All three fractions reacted in immunodiffusion with measles and SSPE virus preparations. The amino-terminal sequence of the light and heavy chains of one of the antibody fractions was determined by automated Edman degradation. A single amino acid residue was obtained at every step, confirming the homogeneity of this human antibody.
Kinetic Study of T Lymphocytes After Sensitization Against Soluble Antigen
Authors: Durkin Helen G. , Waksman Byron H.
Published: December 2022

Sensitized T cells in inguinal lymph nodes (LN) of rats immunized with ovalbumin and adjuvant can be separated on BSA density gradients from T cells responding to Con A and PHA. Further, these OA-sensitized T cells are separable from B memory cells responsive to OA. On days 9 and 17 after sensitization, OA-reactive cells peak and are found in enriched numbers in the lighter bands A + B (B-band), and C, respectively, whereas Con A and PHA reactive cells, on both days, are concentrated in bands C and D, respectively. On day 9 at least 20 to 30% of B-band cells can reinitiate DNA synthesis and produce high concentrations of lymphotoxin in response to OA in culture, but show only a marginal blastogenic response to Con A or PHA and cannot produce lymphotoxin in response to PHA. These cells are defined as OA-sensitized T cells because a) treatment with rat isoantiserum specific for T lymphocytes plus complement abolished their ability to incorporate 3H-thymidine in response to OA and Con A or PHA; b) membrane-bound immunoglobulin could not be detected with indirect immunofluorescence staining; c) histologic studies demonstrate massive hypertrophy of thymus-dependent paracortical areas and absence of germinal centers in inguinal LN at this time, and d) they produce lymphotoxin after challenge with OA, but not with PHA, whereas cells of the other bands produce lymphotoxin in response to PHA, but not to OA. Addition of purified macrophages to the various cultures did not affect the levels of response observed. Day 17 C-band cells are regarded as B-memory cells because treatment with T-specific antiserum plus complement enhanced their response to OA, many germinal centers now are present in inguinal LN, and a significant proportion of cells of bands B and C, negative on day 9, show positive immunofluorescence staining at this time.
Concanavalin A-Induced Histamine Release from Normal Rat Mast Cells
Authors: Sullivan Timothy J. , Greene Warner C. , Parker Charles W.
Published: December 2022

Concanavalin A- (con A) induced release of histamine from normal rat mast cells was studied. In the presence of phosphatidylserine (PS) con A induced a concentration and temperature-dependent, noncytotoxic histamine release at con A concentrations ranging from 0.1 to 100 µg/ml. The optimal con A concentration, 100 µg/ml, caused a 27.3% (±2.7 S.E.M.) net histamine release. Release began approximately 30 sec after addition of con A and was complete within 45 min. In the absence of PS, no net con A-induced release occurred. The effect of PS was concentration dependent from 1 to 100 µg/ml. PS alone, however, did not cause histamine release. Binding studies indicated that mast cells bound up to 16 × 106 con A molecules per cell without histamine release. Upon removal of unbound con A and the addition of PS, normal histamine release occurred. α-Methyl-D-mannose (50 mM) prevented both con A binding and histamine release and if added after Con A, caused a rapid cessation of histamine release and a reversal of con A binding. This study indicates several important advantages of the con A-induced histamine release system. Binding of con A to mast cells can be dissociated from histamine release by omitting PS from the medium. Release can then be induced by the addition of PS. α-Methyl-D-mannose can be used to terminate rapidly the ongoing release reaction at any phase of the interaction. This system is potentially very useful for investigation of metabolic events during histamine release.
Preparation of IgG-Binding Membrane Vesicles from the Microvillar Brush Border of the Fetal Rabbit Yolk Sac
Authors: Schlamowitz Max , Hillman Kathleen , Lichtiger Benjamin , Ahearn Michael J.
Published: December 2022

A one step procedure is described for the production of membrane vesicles from the endodermal microvillar brush border of the fetal rabbit yolk sac splanchnopleur.

The vesicles, examined by light and electron microscopy, were shown to consist of biomolecular leaflet unit membrane, coated to varying extents with glycocalyx.

By fluorescence microscopy, the homologous immunoglobulin, FITC-IgGR, has been shown to bind to the glycocalyx-coated vesicles as well as the glycocalyx-coated brush border of the intact yolk sac, whereas, the heterologous bovine immunoglobulin, FITC-IgGB, fails to bind under comparable conditions. These observations demonstrate the specificity of the receptors for the homologous IgG.