bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparity of IgE Binding Between Normal and Tumor Mouse Mast Cells
Authors: Mendoza Guillermo R. , Metzger Henry
Published: December 2022

The binding constants of rat and mouse IgE to normal and neoplastic rat and mouse mast cells have been measured. None of the cells distinguishes between rat and mouse IgE. Rat normal and neoplastic mast cells and mouse mastocytoma cells show very similar binding properties: k1 ∼ 105, k-1 ∼ 10-5 and, therefore, KA ∼ 1010. Normal mouse mast cells also show a forward rate constant, k1, of 105 but the dissociation rate constant, k-1, is 50 times higher (5 × 10-4). The detergent-solubilized receptors reflect the properties of the cell-bound receptors. The discrepancy in binding by normal and neoplastic mouse mast cells remains unexplained but appears to be a reproducible finding for the cells from three strains of normal mice and three different mastocytomas studied.
Cell Surface Immunoglobulin
Authors: Vitetta Ellen S. , Uhr Jonathan W.
Published: December 2022

The present studies were designed to determine the effect of papain upon IgM and IgD on the surface of murine splenocytes. By using radioiodinated cells, it was shown that IgD is more susceptible to cleavage by papain than IgM. The difference in susceptibility to papain of the two isotypes was not observed when cell lysates were employed, suggesting that attachment to the plasma membrane affects the accessibility of IgM to papain. The major site of attack of the enzyme on IgD appears to be in the hinge region. The possible biologic implications of such a cleavage are discussed.
Regulation of the Primary Immune Response in Vivo by Parathyroid Hormone
Authors: Swierenga S. H. H. , MacManus J. P. , Braceland B. M. , Youdale T.
Published: December 2022

Injection of sheep red blood cells into rats stimulates splenic DNA synthesis, then increases the proportion of plaque-forming cells, and finally raises the circulating antibody level. Removal of the parathyroid glands, which causes hypocalcemia, 24 hr before antigen injection impairs all of these responses, but is without effect after antigen injection. It is suggested that parathyroid hormone and calcium control the immune response, probably by affecting the proliferative phase of this response.
Ontogeny of the Antibody-Forming Cell Line in Mice
Authors: Rosenberg Yvonne J. , Cunningham Alastair J.
Published: December 2022

This paper maps the developmental stage reached by B cells in mouse fetuses of different ages. The “maturity” of these cells was assessed in a functional way by measuring the time taken for cells to generate antibody-forming progeny when injected into carrier-primed irradiated adult hosts and challenged daily with antigen. A steady uninterrupted progression in development of B cells occurred between 13 days of gestation and birth. There was no evidence for a stage during which B cells could only be paralyzed and not induced by antigen.
Contrasting Effects of BCG on Spleen and Lymph Node Antibody Responses in Nude and Normal Mice
Authors: Doft Bernard H. , Merchant Bruce , Johannessen Lynne , Chaparas Sotiros D. , Sher Neal A.
Published: December 2022

Subcutaneous footpad injection of BCG causes a marked augmentation of popliteal lymph node plaque-forming cell (PFC) responses to DNP-derivatized hemocyanin and to sheep red blood cells, both T-dependent antigens, but not to DNP-derivatized Ficoll, a T-independent antigen. This augmentative effect occurs in normal thymus-bearing heterozygous (nu/+) mice, but not in congenitally athymic nude mice (nu/nu). In contrast, intravenous injection of BCG causes a suppressed splenic PFC response to subsequently administered T-dependent or T-independent antigens in both nude and nu/+ mice. BCG's augmenting effect on the lymph node appears to be mediated by a T-helper cell. BCG's suppressive effect in the spleen is not attributable to T cells. The actual mechanism of the BCG-mediated suppressive splenic effect remains incompletely defined at present.
The Involvement of Cyclic Nucleotide Metabolism in the Initiation of Lymphocyte Proliferation Induced by Mitogens
Authors: Watson James
Published: December 2022

Murine lymphocytes incubated with specific mitogens were examined for alterations in levels of intracellular cyclic AMP and cyclic GMP. Mitogenic concentrations of LPS elevate cyclic GMP levels; however, DxSO4, Poly I:C, PPD, Con A, and PHA show little immediate effect on cyclic GMP levels. Higher concentrations of all of these mitogens consistently elevate cyclic AMP levels. Exogenous cyclic GMP stimulates DNA synthesis in homozygous nude (nu/nu) spleen cultures but not in murine thymocyte cultures. Both LPS and cyclic GMP enhance the mitogenic response of thymocytes in the presence of suboptimal concentrations of Con A. Exogenous cyclic AMP inhibits mitogenic responses to both LPS and Con A; however, these inhibitory effects are partially reversed when cyclic GMP is also added to cultures. The mitogenic response of nu/nu spleen cells to LPS can be inhibited by high concentrations of Con A. This inhibition by Con A is also partially reversed by cyclic GMP, indicating that Con A may exert its effect by elevating intracellular levels of cyclic AMP. Thus, while lymphocyte mitogens may affect intracellular levels of both cyclic AMP and cyclic GMP, three effects show a consistent pattern. 1) Exogenous cyclic GMP is either mitogenic for B cells or agents that elevate cyclic GMP levels enhance the mitogenic response of T cells to Con A. 2) Increasing cyclic AMP levels inhibit cell proliferation induced by both B and T cell mitogens. 3) The inhibitory effects of cyclic AMP or cyclic AMP-elevating agents on mitogen-induced proliferation can be partially reversed by the presence of cyclic GMP. The opposing effects of these two cyclic nucleotides may reflect either their involvement in the initiation of cell proliferation or their modulating effects on cell cycle events after the initiation process has been completed.
Abnormalities of Cellular Immune Response in Arthritis Induced by Rubella Vaccination
Authors: Chiba Yasuo , Sadeghi Esmaeel , Ogra Pearay L.
Published: December 2022

The rubella-specific antibody, activity the levels of immunoglobulins and complement in the serum, the number of T cells, and the nature of cell-mediated immunity as measured by lymphocyte transformation (LTF) of circulating lymphocytes in response to rubella virus and phytohemagglutinin (PHA) were studied in 15 children who manifested arthralgia or arthritis after parenteral immunization with HPV-77 DE/5 or RA27/3 live attenuated rubella virus vaccines. Eighteen appropriately matched subjects who developed no post-vaccine complications were included as controls. The immunoglobulins, complement, and rubella antibody levels were similar in all subjects. Although significant rubella specific cell-mediated immunity was detectable in most control subjects, the activity was markedly depressed in subjects with arthritis. The LTF activity in response to PHA was approximately equal in both groups. These findings suggest a selective depression of cell-mediated immunity to rubella virus in subjects with arthritis associated with rubella vaccination.
Carrier-Dependent Selection of Antibody Clones and Classes during the Immune Response
Authors: Kolb H.
Published: December 2022

The selection of antibody clones and antibody classes during the immune response to the hapten oligo-D-alanine was found to be carrier dependent. When the hapten was coupled to a T-independent antigen (streptococci) a restricted immune response of IgM and IgG antibodies was induced. When the hapten was coupled to a T-dependent antigen (ovalbumin) a heterogenous response of only IgG antibodies was found. The carrier had an effect on the affinity of IgG but not of IgM antibodies.

Clonal pattern and class distribution were fixed early in the immune response. Second and third immunizations with a heterologous carrier elicited the same clonal pattern and class distribution in the secondary response as that found with the original carrier.
Evidence for Separate Subpopulations of B Cells Responding to T-Independent and T-Dependent Immunogens
Authors: Jennings John J. , Rittenberg Marvin B.
Published: December 2022

BALB/c spleen cell cultures were double-challenged with optimal doses of TNP-T-independent and TNP-T-dependent immunogens. The anti-hapten response was additive or synergistic in double challenged cultures compared to the response in cultures challenged with either immunogen alone. A high, suppressive dose of either immunogen did not prevent the response to an optimal dose of the second immunogen in the same culture. Spleen cell cultures were also double challenged with combinations of two T-dependent or two T-independent immunogens. Addition or synergy in the anti-hapten response only occurred when the double challenge consisted of a mixture of T-dependent and T-independent immunogens. These results are consistent with the proposed B1B2 classification of B cell subpopulations.
Inhibition of Vaccinia Virus Replication in Skin of Tuberculin-Sensitized Animals Challenged with PPD
Authors: Lodmell Donald L. , Ewalt Larry C. , Notkins Abner Louis
Published: December 2022

Induction of a delayed-type hypersensitivity reaction in tuberculin-sensitized animals by tuberculin purified protein derivative (PPD) at the site of dermal vaccinia virus (VV) infection markedly accelerated elimination of VV and led to clinical recovery. Viral titers were depressed by over 99.9% in the skin of animals given PPD as compared to animals given phosphate-buffered saline or nonspecific irritants. Low concentrations of acid labile interferon were found in the skin of uninfected tuberculin-sensitized animals challenged with PPD. High concentrations of acid stable interferon were found in skin of tuberculin-sensitized animals infected with VV and challenged with either PPD or PBS. The time of appearance of the acid stable interferon was markedly accelerated, however, in the animals challenged with PPD as compared with PBS. It is concluded that recovery from dermal vaccinia infection can be enhanced by induction of a local delayed-type hypersensitivity reaction with an antigen unrelated to the infecting virus.
Studies of Surface Immunoglobulins on Human B Lymphocytes
Authors: Abo Toru , Yamaguchi Tai , Shimizu Fumio , Kumagai Katsuo
Published: December 2022

Surface markers and organ distributions of B lymphocytes bearing surface immunoglobulins (SIg B) and lymphocytes lacking SIg but carrying Fc receptors (SIg-Fc+), and the variations of both the cell populations in the autoimmune diseases were studied. Peripheral blood lymphocytes contained approximately 9% SIg B and 22% SIg-Fc+ cells. Both the populations of SIg B and SIg-Fc+ cells were included in the cells that formed no E-rosettes. When previously treated with neuraminidase, however, the SIg-Fc+ cells formed E-rosettes, whereas SIg B showed no ability to form rosettes. C receptors as detected by human complement were found in the large portions of SIg B but in a minority of the SIg-Fc+ cell population. The tissues that contained the highest concentrations of SIg B and SIg-Fc+ cells were the spleen and peripheral blood, respectively. In the patients with an autoimmune disease in active stages SIg B cells in the peripheral blood markedly increased and, reversely, SIg-Fc+ cells decreased; in contrast, in remission of the diseases SIg B cells dropped down and SIg-Fc+ increased up to their normal levels. A possible relationship between the SIg B and SIg-Fc+ cells in regard to the differentiation of B lymphocytes was presumed.
Analysis of Parameters Affecting the Solid Phase Radioimmunoassay Quantitation of Antibody to Meningococcal Antigens
Authors: Zollinger Wendell D. , Dalrymple Joel M. , Artenstein Malcolm S.
Published: December 2022

An indirect solid phase radioimmunoassay (SPRIA) performed in flexible polyvinyl microtiter plates was modified for quantitative determination of antibodies to various bacterial antigens. Parameters affecting quantitation of the assay were investigated by using meningococcal serotype antigens and rabbit antisera to whole meningococci as a model system. Binding of purified antigens to the plate was essentially complete after 1 hr at 37°C, and only 4 to 8% of the bound antigen was released during the course of the assay. About 90% of the specific primary antibody (PAb) added to the antigen-coated wells was bound after overnight incubation at room temperature, whereas, 10 to 25% of the bound PAb was released before completion of the assay. Under conditions of limiting PAb the time required for saturation binding of 125I-anti-immunoglobulin (secondary antibody = SAb) to the PAb was dependent on the concentration of SAb. At a concentration of 20 ng SAb/25 µl, maximum binding occurred in 12 to 16 hr at 22°C. Under conditions of extreme SAb excess the cpm of 125I-SAb bound was directly proportional to the amount of PAb bound. Under these conditions the cpm of 125I-SAb bound per well can be related to the amount of PAb added per well by a time-dependent calibration coefficient K(t) which is the product of three parameters: 1) the specific activity of the 125I-SAb, 2) the ratio of PAb bound to SAb bound and, 3) the fraction of added PAb remaining bound to the plate. Experimentally determined values for these parameters were used to calculate K(t) and quantitate the specific antibody in nine rabbit antisera with the SPRIA. A close correlation (r = 0.985) was found between these results and the results of quantitative precipitin tests performed by using the same antisera and antigens. Although the SPRIA results were an average of 33% lower, a more accurate value for K(t) can easily be determined by performing the SPRIA on several sera calibrated by the quantitative test. Reproducibility of the SPRIA for 10 replicate determinations was ± 6.7%. The assay described is capable of measuring a minimum of about 0.5 µg antibody/ml of serum and appears to be applicable to many different antigens.
Resistance to Tumor Growth Mediated by Listeria Monocytogenes: Collaborative and Suppressive Macrophage-Lymphocyte Interactions in Vitro
Authors: Youdim Said , Sharman Marti
Published: December 2022

Spleen (SC) and peritoneal cells (PC) from C57BL/6 mice immune to Listeria monocytogenes (LM) have a marked cytotoxic effect on the in vitro growth of B-16 melanoma. Cytotoxicity to B-16 is mediated by the interacting sensitized thymus-derived (T) lymphocytes and macrophages (Mø) or adherent cells. Separation of immune SC or PC into their adherent and nonadherent components, depletion of the adherent cells or elimination of the θ-bearing cells from an enriched T cell population all result in the abrogation of cytotoxicity, whereas, recombination of T cells and Mø re-establishes this effect. Three modes of Mø/T cell interactions occur: 1) LM immune peritoneal or splenic T cells interact or synergize with their respective adherent cells to become cytotoxic to B-16; 2) combination of peritoneal Mø and splenic T cells are noncollaborative and therefore noncytotoxic; 3) the cooperative effect of spleen T cells with Mø are suppressed or inhibited by addition of peritoneal Mø. Splenic Mø, however, are neither uncooperative nor inhibitory when interacting with peritoneal T cells. Normal adherent cells can substitute for immune cells in all the cell-cell interactions with similar end results. These results demonstrate that specifically sensitized T cells interact with Mø for expression of LM-induced nonspecific tumor cell destruction in vitro, however, such interactions may also be noncooperative or suppressive, thus resulting in tumor cell proliferation.
Immunopathogenesis of Autoimmune Tubulointerstitial Nephritis
Authors: Hyman Lawrence R. , Steinberg Alfred D. , Colvin Robert B. , Bernard Eugene F.
Published: December 2022

Immunization of strain XIII guinea pigs with rabbit renal tubular basement membranes (TBM) in CFA consistently results in severe autoimmune tubulointerstitial nephritis (TN). Strain II guinea pigs similarly immunized do not develop this disease. F1 guinea pigs were found to be intermediate between inbred strain II and XIII animals with regard to extent of autoimmune TN and anti-TBM antibody production. The F1 × II backcrosses segregated into two groups with regard to antibody production and disease extent. Those backcrosses tissue typed as II+, XIII+ were similar to the F1 guinea pigs. Those backcrosses typed as II+, II+ demonstrated little disease and low anti-TBM titers similar to the inbred strain II animals. F1 × XIII backcrossed guinea pigs segregated into II+, XIII+ or XIII+, XIII+ subgroups on the basis of lymph node typing. The II+, XIII+ backcross animals resembled F1 guinea pigs with respect to anti-TBM response and disease extent; whereas the XIII+, XIII+ backcrosses developed severe disease and high anti-TBM titers as observed in the inbred strain XIII animals. these experiments suggest that susceptibility to autoimmune TN in the guinea pig is linked to the strain XIII major histocompatibility complex and that an immune response gene governing this susceptibility may be inherited as a single dominant or co-dominant trait.
Antigen-Specific and Nonspecific Mediators of T Cell/B Cell Cooperation
Authors: Hoffeld J. Terrell , Marrack Philippa , Kappler John W.
Published: December 2022

In previously published experiments we have distinguished two subpopulations of helper T cells (specific helper and nonspecific helper) in the spleens of antigen-primed mice. These subpopulations can be differentiated by their modes of action, and their activities and dose-response characteristics in mouse spleens primed with human γ-globulin (HGG). In experiments designed to test whether the two subpopulations were derived from the same pool of precursors, or different pools, mice were injected with limiting doses of a tolerogenic form of HGG. They were subsequently challenged with an immunogenic dose of HGG and their spleens assayed for specific helper and nonspecific helper activities in response to HGG in vitro. Over the dose range of tolerogenic HGG studied, both the helper activities were found to be equally tolerized. The question of the possible involvement of suppressor T cells in the maintenance of the state of unresponsiveness was also addressed quantitatively by the use of this model system. No active suppression was demonstrable in the maintenance of tolerance in either T cell subpopulation. These results suggest that the two types of helper T cells are derived from a common precursor pool, or from different pools with identical susceptibilities to tolerogen. Suppressor cells do not appear to play a role in this form of tolerance.
Specific Extraction of Antigen in Vivo by Extracorporeal Circulation Over Antibody Immobilized in Collodion-Charcoal
Authors: Terman David S. , Petty Donald , Ogden Daryl , Pefley Carol , Buffaloe George
Published: December 2022

A novel extracorporeal immunoadsorbent is described in which anti-bovine serum albumin (anti-BSA) was entrapped in collodion membranes adherent to activated charcoal particles. This immunoadsorbent was capable of specifically removing circulating BSA in vitro and in vivo in an extracorporeal system in dogs. In preparation of the immunoadsorbent, up to 81.2% of added anti-BSA was retained on collodion-charcoal. In vitro circulation studies demonstrated that anti-BSA collodion-charcoal removed 812% more 125I-BSA than control collodion-charcoal. For in vivo studies, an extracorporeal circulation system was established and arterial blood was passaged through a continuous flow celltrifuge wherein plasma which was separated from formed elements of the blood was circulated over anti-BSA and control rabbit γ-globulin collodioncharcoal. 125I-BSA was passively infused into mongrel dogs, and plasma was then circulated over extracorporeal immunoadsorbents for 2 hr. Results showed up to 896% greater uptake of circulating 125I-BSA on the charcoal containing immobilized anti-BSA compared to control charcoal. There was no evidence of release of anti-BSA from the immunoadsorbent since 131I-anti-BSA cpm on the charcoal before and after the experiments were unchanged. In addition, there were no significant alterations in hematocrit, leukocyte counts, serum sodium, potassium, calcium, magnesium, or creatinine levels before and after in vivo procedures. These data suggest that this immunoadsorbent consisting of anti-BSA immobilized in collodion membranes adherent to charcoal particles may specifically withdraw circulating antigens in vivo with minimal release of entrapped antibodies and no significant alteration in the host hematologic and biochemical status.
Acquired Resistance to Infection in an Animal Model of Giardiasis
Authors: Roberts-Thomson Ian C. , Stevens David P. , Mahmoud Adel A. F. , Warren Kenneth S.
Published: December 2022

Infection of the gastrointestinal tract with the protozoan Giardia lamblia is increasingly recognized as a cause of gastrointestinal symptoms, including diarrhea and malabsorption (1–3). Indeed it was the most frequently identifiable cause of water-borne diarrhea in the United States in 1974 (4). Studies of jejunal morphology and function have shown a spectrum of change from normal mucosa with unaltered small bowel absorption to severe mucosal lesions with steatorrhea (1, 5).

The mechanisms that protect man from infection with G. lamblia are largely unknown. Although some persons show spontaneous resolution of infection (6) others may show persistent symptoms for months or years (7). Reports of giardiasis in children with protein-calorie malnutrition (8, 9) and in adults after gastrectomy (5) suggest that susceptibility to infection might be influenced by nutritional factors and changes in gastrointestinal physiology. On the other hand, the importance of normal host immunity is suggested by the high frequency of giardiasis in persons with hypogamma-globulinemia (10, 11).
Cytotoxic Macrophages: A Rapid Nonspecific Response to Viral Infection
Authors: Rodda Stuart J. , White David O.
Published: December 2022

In vitro and in vivo assays have been developed to study the relative contributions of various types of immune cytolysis in the destruction of infected cells after Semliki Forest virus infection of BALB/c mice. Highly cytotoxic activated macrophages, not specific for the infecting virus, appear on day 1, peak on day 2 to 3, and disappear within a week. Specifically sensitized T cells appear around day 3, peak on day 6, and disappear within a month. Cytotoxic antibody appears on day 4 and reaches high titers by day 8. Immune spleen cells greatly reduce the yield of virus from cultured cells. Infected cells rapidly disappear after transfer to infected animals.
Use of Silica to Identify Host Mechanisms Involved in Suppression of Established Friend Virus Leukemia
Authors: Wirth Julia J. , Levy Michael H. , Wheelock E. Frederick
Published: December 2022

Silica, an agent predominantly toxic for macrophages, inoculated i.v. to Friend leukemia virus (FLV)-infected mice, blocks the FLV-leukemosuppressive effects of chlorite-oxidized oxyamylose (COAM)-statolon treatment. FLV-infected, COAM-statolon-treated mice that have received silica and have failed to suppress FLV leukemia produced normal amounts of interferon, but did not make antibodies cytotoxic for FLV leukemic cells. Transfer of untreated spleen cells, splenic T cells, or thymocytes from mice with suppressed FLV erythroleukemia to FLV-infected mice treated with silica and COAM-statolon restores the humoral immune response to FLV antigens and results in leukemosuppression. Thus, T lymphocytes from mice with suppressed erythroleukemia participate in FLV leukemosuppression either directly as effector cells, or indirectly as helper cells in the production of antibodies to FLV antigens.
Subpopulations of Human T Cells Identified by Receptors for Immunoglobulins and Mitogen Responsiveness
Authors: Moretta Lorenzo , Ferrarini Manlio , Mingari Maria C. , Moretta Alessandro , Webb Susan R.
Published: December 2022

Human T lymphocytes in peripheral blood have been shown to have receptors for IgG (Tγ) or IgM (Tµ). Cultured Tγ cells do not express receptors for IgM and purified Tµ cells do not have receptors for IgG, thus they appear to be distinct T cell populations. Although the two subpopulations show similar response patterns to concanavalin A, Tµ and Tγ cells exhibit different dose-response curves to phytohemagglutinin. The normal response pattern to phytohemagglutinin requires a mixture of T cell subpopulations suggesting that synergistic interactions may occur.
Activation of Cytotoxic Function in T Lymphocytes
Authors: Heininger Diane , Touton Mary , Chakravarty Ashim K. , Clark William R.
Published: December 2022

The requirements for activation of cytotoxic function in mouse T lymphocytes were investigated. Initial generation of cytotoxicity in normal lymphocytes was equal in magnitude with either Con A or specific alloantigen, and in either case required DNA synthesis. Cytotoxic function in MLC-primed cells could also be regenerated by Con A, the magnitude and target specificity of the cytotoxicity thus generated being indistinguishable from that recalled by specific alloantigen. Cytotoxicity could also be regenerated by third party-stimulating cells; however, the cytotoxicity evoked by third party cells was always specific only for target cells of the original stimulating cell H-2 genotype.

The data presented suggest that there are a number of ways to activate cytotoxicity in effector T cells, and are most consistent with a model for T cell triggering that minimizes a strict informational function of antigen-receptor interactions.
The Role of Hydroxylation of Proline in the Antigenicity of Basement Membrane Collagen
Authors: Arbogast Bradley W. , Gunson Diane E. , Kefalides Nicholas A.
Published: December 2022

Rabbit antibodies to bovine basement membrane collagen were used to compare the antigenic determinants of rat parietal yolk sac basement membrane [14C]procollagen with [14C]protocollagen. Basement membrane [14C]protocollagen was found to be less antigenic than basement membrane [14C]procollagen. Hydroxylation of basement membrane [14C]protocollagen, either intracellularly or in vitro with protocollagen prolyl hydroxylase, resulted in restoration of antigenicity. The difference in antigenicity observed between basement membrane [14C]procollagen and basement membrane [14C]protocollagen appeared to depend primarily upon the presence of hydroxyproline in the collagen molecule. Glucosylgalactosylhydroxylysine was found to be unimportant for antigenicity.
Minor H Antigens Introduced on H-2 Different Stimulating Cells Cross-React at the Cytotoxic T Cell Level during in Vivo Priming
Authors: Bevan Michael J.
Published: December 2022

The cellular basis of the cross-priming observed with minor histocompatibility antigens on H-2 different cells was investigated. Cytotoxic T cells induced against minor alloantigens show absolute H-2 restriction at the effector level ([51Cr]-release). That is, F1(BALB/c × BALB.B) (H-2d/b) cytotoxic cells induced by immunization with B10(H-2b) cells are not able to lyse B10.D2(H-2d) targets. But an injection of B10 cells does prime F1 mice for a secondary cytotoxic response to B10.D2. The technique of inducing cytotoxic effector function polyclonally with Con A in the absence of alloantigen was used here to establish that such cross-priming reflects what happens at the cytotoxic cell level. It is shown that an F1 animal previously injected with B10 cells has expanded pools of memory cytotoxic cells reactive with B10 and B10.D2. From this it is concluded that: a) minor H structures on B10.D2 and B10 do cross-react at the cytotoxic T cell level during in vivo priming, and b) because normal cells cross-prime whereas tumor cells do not, then the F1 cytotoxic precursors are probably committed to respond to antigen on cells bearing either the maternal or paternal H-2 haplotype before they encounter antigen.

Cross-priming may be explained by foreign minor H antigens being presented to F1 host T cells on the surface of host macrophages. Therefore priming is not restricted to the H-2 type of the injected cells but to both H-2 types of the F1 host.
Immunity to Virus-Free Syngeneic Tumor Cell Transplantation in the BALB/c Mouse after Immunization with Homologous Tumor Cells Infected with Type C Virus
Authors: Al-Ghazzouli Ismail K. , Donahoe Robert M. , Huang Kun-Yen , Sass Bernard , Peters Robert L. , Kelloff Gary J.
Published: December 2022

Syngeneic tumor cell lines free of endogenous type C virus or viral antigen expression were derived from spontaneously occurring tumors of the BALB/cCr mouse. Two cell lines free of endogenous type C virus were examined and found to be highly tumorigenic in tumor growth kinetic studies. In vitro inoculation of these cell lines with Rauscher-murine leukemia virus (R-MuLV) resulted in their chronic infection in which 95 to 100% of the cells were scored as virus positive. These infected lines showed a highly significant increase in their immunogenicity as compared to their uninfected controls. Animals in which these virus-positive tumors regressed were then shown to be highly resistant to challenge with the uninfected tumor cell lines as well as to live R-MuLV. This observed resistance to uninfected tumor cell lines could not be induced by immunization of the mouse with uninfected tumor cells and R-MuLV simultaneously at the same injection site, nor could it be induced with lethally irradiated virus-infected tumor cells, subtumorigenic doses of uninfected cells, or inactivated R-MuLV or Gross leukemia virus (G-MuLV). Cell-mediated cytotoxicity studies revealed that spleen cells obtained from animals whose virus-infected tumors regressed were cytotoxic to homologous infected and uninfected tumor cells as well as to other uninfected tumor cell lines syngeneic to the BALB/c mouse. Correlation of in vitro cytotoxicity with in vivo immunity was provided by the Winn assay, by inoculation into susceptible mice of immune and nonimmune spleen cells premixed with uninfected tumor cells. The immune cells were highly effective in preventing this tumor cell transplantation. It was concluded that type-C virus infection of these syngeneic tumor cells resulted in their acquiring strong transplantation antigens that were in part due to the virion, but were at least in part due to alterations of antigens or haptens that are present in a less immunogenic form on the uninfected tumor cell.
The Effect of Locally Injected Vasoactive Amines on the Elicitation of Delayed-Type Hypersensitivity
Authors: Schwartz Anthony , Askenase Philip W. , Gershon Richard K.
Published: December 2022

In previous work monoamine depletion due to treatment with reserpine was shown to decrease the elicitability of DTH responses in mice. In addition, treatment with monoamine oxidase inhibitors prevented the reserpine-induced decrease. These findings led to the suggestion that serotonin-induced increased vascular permeability is necessary to the development of DTH reactions, perhaps by allowing bone marrow-derived macrophage precursor cells, which are obligate components of DTH responses, to migrate through specialized venules into the site of the reaction. We have compared classical drug tachyphlaxis (temporary inhibition of the effects of a drug by prior treatment with agonists) to serotonin in vessels of mouse feet with local inhibition of DTH after serotonin pretreatment of mice. During the tachyphylactic period, DTH responses are depressed. This suggests that serotonin-induced tachyphylaxis of local endothelial receptors can be responsible for DTH inhibition. In contrast, local injection of histamine has no effect on DTH and this drug is a much less potent inducer of tachyphylaxis to serotonin-mediated vasoactive reactions. On the other hand, histamine can inhibit in vitro T cell reactions, which are not affected by serotonin. These data help to further the concept that serotonin plays an important role in the regulation of DTH in mice and that it probably does so by acting on vascular endothelium.
Cytophilic Antibodies in Experimental Autoimmune Myasthenia Gravis
Authors: Martinez Ruben D. , Tarrab-Hazdai Rebeca , Aharonov Aharon , Fuchs Sara
Published: December 2022

Macrophage-cytophilic antibodies, with acetylcholine receptor specificity, are present in rabbits with experimental autoimmune myasthenia gravis (EAMG). Such antibodies may have a significant role in the immunologic mechanism involved in the pathogenesis of myasthenia gravis.

The induction of EAMG in rabbits was performed by injection of purified AChR from the electric organ of Torpedo californica. Both the binding of AChR specific cytophilic antibodies to normal macrophages and the presence of such antibodies bound in vivo to macrophages of sick animals were demonstrated in vitro. The amount of cytophilic antibodies was determined by measuring cell-associated radioactivity after the addition of 125I-AChR. Cytophilic antibodies capable of binding to normal alveolar macrophages were detected in all animals 14 days after immunization, and were maintained through the severe stages of the disease. In addition, cytophilic anti-AChR antibodies were shown to be bound in vivo to alveolar macrophages drawn from severely sick rabbits, as was measured by a direct 125I-AChR binding to such macrophages.

The role of cytophilic antibodies and in particular of macrophage-associated cytophilic antibodies in the pathogenesis of autoimmune diseases is not clear yet. The availability of AChR specific cytophilic antibodies can now be utilized for studying their role in the immunopathogenesis of EAMG.
Monocyte Function in Man
Authors: Territo Mary C. , Cline Martin J.
Published: December 2022

The monocyte-macrophage cell line is an important member of the host defense system. This report describes a series of assays that can be applied routinely in the evaluation of human monocyte function and gives information as to the activity of normal monocytes in these systems. Tests were chosen to assess various aspects of monocyte function that give some insight into the host defense status and the degree of “activation” of the monocyte. The assays outlined in this report are relatively simple to perform and include measurements of human monocyte chemotaxis, phagocytosis, fungal and bacterial killing, adhesion, and spreading.
C5̄6̄7̄-Initiated Cytolysis of Lymphoid Cells: Description of the Phenomenon and Studies on Its Control by C5̄6̄7̄ Inhibitors
Authors: Baker Patricia J. , Lint Thomas F. , Mortensen Richard F. , Gewurz Henry
Published: December 2022

Cells of the Raji human lymphoblastoid line, when pretreated with the metabolic inhibitor puromycin, were found to be susceptible to killing by the isolated proteins of the complement attack mechanism (C5–9). Incubation of 51Cr-labeled lymphoblastoid cells with purified C and C7 resulted in the formation of a lymphoblast- (LC) intermediate, and the addition of purified human C8 and C9 resulted in release of 51Cr from these cells. Serum C inhibitors (-INH), purified human lipoproteins, and dextran sulfate, each previously shown to inhibit the attachment of the trimolecular complex to erythrocytes, also inhibited the formation of LC and as a consequence, C-initiated cytotoxicity; the polycation protamine sulfate counteracted the inhibitory effect of dextran sulfate. Thus, the potential for damage of bystander nucleated cells exists when C is generated in solution, and is influenced by agents known to modulate the hemolytic activity of . It is suggested that these mechanisms may be involved in the control of the function as well as the viability of various nucleated cells.
Tolerizing Effect of DNP-Ficoll on IgE Antibody Production
Authors: Watanabe Naohiro , Kojima Somei , Ovary Zoltan
Published: December 2022

A/J and DBA/1 mice were infected with 750 third-stage larvae of Nippostrongylus brasiliensis and immunized with 1 µg dinitrophenylated N. brasiliensis extract (DNP-Nb) with 1 mg Al(OH)3 to produce high titers of anti-hapten IgG1 and IgE antibody. Partial tolerance to the production of anti-hapten IgG1 and IgE antibody could be induced by DNP-Ficoll from 5 weeks before to 1 week after the DNP-Nb immunization. The tolerized state persisted through the duration of the experiments. However, no tolerizing effect could be demonstrated on secondary anti-hapten IgE antibody production induced by DNP-Nb. Moreover, DNP-Ficoll failed to evoke anti-hapten IgG1 or IgE antibody production.
Defense Mechanisms Against Primary Influenza Virus Infection in Mice
Authors: Iwasaki Tatsuo , Nozima Tokukiti
Published: December 2022

To investigate the defensive roles and production of interferon and antibodies, C3H/He mice were subjected to various immunosuppressive treatments and infected with influenza virus. In infected normal control mice the pattern of pulmonary viral growth can be divided into three phases. The first phase is characterized by an exponential increase of virus titer, the second by a rapid decrease, and the third by a moderate decrease. At the time of transition from the first phase to the second in pulmonary virus growth, interferon could be detected in the tracheobronchial washings of infected mice, but neutralizing antibodies could not.

In infected B cell-deprived mice and infected anti-µ-treated mice, the transition from the first phase to the second occurred without any detectable antibody production, and interferon could be induced in the early stage of infection. However, the pulmonary virus in these mice increased again exponentially until the death of the mice. In infected T cell-deprived mice which could not induce interferon, but produced IgM-neutralizing antibodies, the second phase was not observed after the first phase, but a transient plateau phase could be demonstrated, and then the pulmonary virus increased again exponentially until the death of the mice. In anti-γ-treated infected mice, pulmonary virus growth and production of interferon and neutralizing antibody were almost similar to those of infected normal control mice except for the absence of IgG neutralizing antibody production. Although anti-α-treated infected mice produced interferon and no IgA antibody, the transition from the first exponential increase of pulmonary virus to the second rapid decrease was seen, but then the virus increased exponentially again until the death of the mice.

These results suggest that interferon plays an important role in the transition from the first phase to the second, and that T cells are required for interferon induction in mice infected with influenza virus. These data also suggest that IgA antibodies play an important role in the inhibition of virus propagation in the lungs after the disappearance of interferon. Moreover, infected T cell-deprived mice could produce only IgM neutralizing antibodies, but not IgG and IgA antibodies. Therefore, T cells are required for the production of IgG and IgA antibodies and eventually for defense functions in mice infected primarily with influenza virus.
The Immunologic and Molecular Profiles of HLA Antigens Isolated from Urine
Authors: Reisfeld R. A. , Pellegrino M. A. , Ferrone S.
Published: December 2022

Human urine was shown to be a good source for the isolation of immunologically functional HLA-A9 antigens. The use of complex solubilization procedures can be avoided since the antigens are present in soluble form and are not complexes with membrane fragments. Purification in excess of 400-fold could be achieved by the application of cellulose ion exchange chromatography, isoelectric focusing, and acrylamide gel electrophoresis. The purified HLA-A9 antigen is composed of a glycoprotein of m.w. 38,000 and β2-microglobulin, a peptide of m.w. 12,000. HLA-A9 antigens isolated from urine proved to be immunologically functional since they not only reacted specifically with anti-HLA-A9 alloantibody but also elicited anti-HLA-A9 xenoantibodies. These antibodies when covalently attached to Sepharose 4B specifically bound HLA-A9 antigens isolated from both serum and urine.
Quantitative Immunoassay of Adenosine Deaminase in Combined Immunodeficiency Disease
Authors: Carson Dennis A. , Goldblum Randall , Seegmiller J. E.
Published: December 2022

We have developed a quantitative immunoassay for the measurement of human adenosine deaminase that requires neither purified enzyme nor monospecific antibody. With this technique, cultured fibroblasts from three immunodeficient patients were shown to contain adenosine deaminase as detected both catalytically and immunochemically. In one patient the level of immunoreactive enzyme exceeded the amount of catalytically active adenosine deaminase, suggesting a structural alteration in the enzyme molecule.
The Formation and Fate of Virus Antigen-Antibody Complexes
Authors: Perrin Luc H. , Oldstone Michael B. A.
Published: December 2022

We report the fate of 125I human IgG measles virus antibodies complexed to virus antigens expressed on the surfaces of HeLa cells persistently infected with measles virus. Each HeLa cell expressing viral antigens on its surface bound about 7.5 × 106 IgG molecules under saturation conditions. Three hours after 125I antiviral IgG bound to and saturated all antigenic sites on infected cells, 30% of the counts were released (85% TCA ppt), after 12 hr 60%, and after 24 hr 75% (30% TCA ppt). By linear sucrose density centrifugation about 30% of the counts released from infected cells at 3 hr sedimented faster than 7S IgG, 60% sedimented at the 7S position whereas 10% (non-TCA ppt) were found at the top of the gradient. Using specific rabbit antibody to measles virus hemagglutinin or nucleocapsid, we found that hemagglutinin, but not nucleocapsid antigen, was present in the heavy complexes. These experiments show that after anti-measles virus antibody binds to cell surface measles viral antigens (i.e., hemagglutinin), immune complexes form and are shed into culture fluids. In addition part of the immune complex is endocytosed and broken into small m.w. components. Shedding of virus antigen-antibody complexes from the cell's surface may be an important source of the circulating complexes found in virus-infected humans and animals.
Isolation and Characterization of Canine Secretory Immunglobulin M
Authors: Thompson Russell E. , Reynolds Herbert Y.
Published: December 2022

Canine secretory immunoglobulin M, isolated from both colostrum and bronchial secretions, contained the unique glycoprotein bound secretory component. The presence of this extra subunit accounted for the differences in size, quaternary structure, and antigenicity observed upon comparison of secretory immunoglobulin M with its serum counterpart. Approximately 90% of the isolated secretory immunoglobulin M contained covalently bound secretory component while, in the remainder of the population, secretory component was loosely attached and easily dissociated from the immunoglobulin. Following peptide bond cleavage with cyanogen bromide, the release of bound secretory component and J chain from secretory immunoglobulin M was not detected. Because cyanogen bromide cleavage of secretory immunoglobulin A results in the release of these subunits, differences in the primary structure of secretory immunoglobulin M and secretory immunoglobulin A must exist around the binding sites for secretory component and J chain.
F1 Resistance to AKR Lymphoma Cells in Vivo and in Vitro
Authors: Schmitt-Verhulst Anne-Marie , Zatz Marion M.
Published: December 2022

AKR × DBA/2 (AKD2F1) mice resist growth of injected spontaneous AKR lymphoma cells. In vitro, normal F1 responder cells generate Thy-1 positive effector cells specifically cytotoxic for the sensitizing antigens of parental AKR normal or lymphoma cells. The possibility is considered that the homozygous normal and neoplastic AKR cells express antigenic determinants, analogous to hemopoietic histocompatibility (Hh) antigens, which are recognized by the F1 hybrid, resulting in in vivo tumor resistance and in vitro cell-mediated cytotoxicity.
Cholesterol-Dependent Human Complement Activation Resulting in Damage to Liposomal Model Membranes
Authors: Alving Carl R. , Richards Roberta L. , Guirguis Adel A.
Published: December 2022

Human (but not guinea pig) complement was activated spontaneously by liposomes containing a high concentration (71 mol %) of cholesterol. This occurred in the absence of any recognizable antigen or antibody, and did not occur at a low concentration (43 mol %) of cholesterol. Activation of complement resulted in membrane damage and release of trapped liposomal glucose. The complement activity was inhibited by preheating (56°C, 30 min), 10 mM Mg2EDTA3 or EGTA, and by prior adsorption with insoluble immune complexes. Almost all human sera had some reactivity, but it ranged from very low levels (<7% liposomal glucose release) to very high levels (τ;50% glucose release). Complement activation appeared to be mediated by a serum factor which could be removed by adsorption and which was partially heat labile. The factor was transferred by adding heated high reacting human serum to unheated low reacting human serum, or to guinea pig serum. The serum factor, although quantitatively diminished in potency due to heat lability, caused equal activation of each of these two latter complement sources in the presence of high cholesterol liposomes. It did not cause activation of C4-deficient guinea pig complement. These data suggested that the classical complement pathway was activated. The liposomal membrane composition had an influence on this phenomenon. Activities of about half of the human sera were enhanced when galactosyl ceramide, or ceramide alone, was present in the liposomes. Activity was enhanced by longer fatty acyl chain lengths of lecithin when dimyristoyl-, dipalmitoyl-, or distearoyllecithin was employed in the liposomes. Liposomes containing sphingomyelin as the only phospholipid were not sensitive to cholesterol-dependent complement-mediated damage. It was concluded that human complement was activated in the presence of high concentrations of membrane cholesterol and that this was caused by an uncharacterized serum factor and was influenced by the lipid composition of the membrane.
Immunologically Specific Cytolytic Activity Induced in Long-Term Mixed Leukocyte Culture Cells by Concanavalin A
Authors: Tartof David , Fitch Frank W.
Published: December 2022

Stimulation of cells from long-term primary MLC with Con A resulted in the generation of CTL activity comparable in magnitude to that induced by reexposure of the cells to the original stimulating cellular antigen. CTL generated by stimulation of long-term MLC cells with ConA had lytic activity specific for the original stimulating alloantigen used in primary MLC. The pattern of stimulation of long-term MLC cells with Con A differed from that of restimulation with alloantigen in that there was no detectable CTL activity the first 24 hr after Con A stimulation and the peak lytic activity occurred later. Unlike restimulation with alloantigen early lytic activity after Con A stimulation was dependent on DNA synthesis. PHA also proved to be an effective agent for stimulating cytolytic activity in long-term MLC cells. The response to PHA was comparable in magnitude to that generated by Con A. Stimulation of long-term MLC cells with T cell mitogens gave decreased cell recoveries relative to restimulation with alloantigen, however, the lytic activity per cells recovered was generally greater in the mitogen-stimulated cultures.