bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Appearance of Sensitized Lymphocytes in Mice Infected with Listeria Monocytogenes
Authors: Zinkernagel Rolf M. , Blanden Robert V. , Langman Rodney E.
Published: December 2022

These experiments were designed to detect the earliest appearance of cell-mediated immunity (CMI) in primary Listeria infection. Two lines of evidence suggested that CMI was operating by day 3 after infection. First, in the livers and spleens of mice treated with anti-thymocyte serum, a potent suppressor of CMI, bacterial numbers were similar to those in control mice for the first 2 days after primary infection, but were consistently higher on the 3rd, 4th, and 5th days. Second, spleen cells from Listeria-infected donors were capable of conferring an antibacterial effect on infected recipients if transferred 3, 4, or 5 days (but not 2 days) after donor infection. The full expression of the potency of the immune cells was ensured by culturing them in vitro for the 22 hr prior to transfer under conditions which virtually eliminated the large numbers of cell-associated viable Listeria remaining from the immunizing infection.
Studies on Delayed Hypersensitivity with Trachoma Organisms
Authors: Kuo Cho-Chou , Grayston J. Thomas
Published: December 2022

Guinea pigs sensitized via the footpad with inactivated trachoma organisms in complete Freund's adjuvant developed delayed hypersensitivity to trachoma at the 9th day as demonstrated by skin tests and in vitro blastogenic transformation of lymphocytes obtained from the regional lymph nodes. The supernatant of lymph node lymphocytes cultured in the presence of trachoma antigen for 24 hr and concentrated 10-fold induced erythema in the normal guinea pig skin. Similar supernatant cultured for 5 days was shown to inhibit the growth of the mouse L cell at a 1:4 dilution.
Effect of Irradiation and Cyclophosphamide on Anti-KLH Antibody Formation in Mice
Authors: Hoffsten Phillip E. , Dixon Frank J.
Published: December 2022

The effect of cyclophosphamide and x-irradiation on antibody formation in two strains of mice was studied. Cyclophosphamide was found to prevent a primary response if given prior to KLH used as antigen. An established antibody response to KLH was depressed but not ablated even after 9 months of drug administration. Single weekly administered doses of irradiation were found to markedly enhance primary antibody responses at low doses of x-irradiation and suppress only at higher doses. X-irradiation markedly enhanced anti-KLH antibody formation if given after the immune response was established.
Antibodies Specific for the ϑ- and Ly-Alloantigens in Various Rabbit Antisera
Authors: Rabinowitz Ruth , Cohen Ada , Laskov Reuven , Schlesinger Michael
Published: December 2022

Antisera against murine thymus derived (T) lymphocytes were raised by immunizing rabbits with BALB/c thymus cells, boiled thymus, brain homogenate, or SJL/J lymphosarcoma cells. These antisera were tested for the presence of antibodies to the ϑ and Ly alloantigens. Four types of antibodies were found: Cross-reactive ϑ antibodies cytotoxic for lymphocytes of both ϑ-C3H and ϑ-AKR mice were demonstrated in all antisera tested. Antibodies specific for the ϑ-C3H alloantigen were detected in rabbit anti-boiled BALB/c thymus and anti-SJL/J lymphosarcoma sera. Rabbit anti-thymus serum and rabbit anti-lymphosarcoma contained antibodies which seemed to cross-react with various Ly allospecificities. Rabbit anti-thymus serum may also possess a small amount of antibodies specific for the Ly-A.2 Ly-B.2 antigenic determinants.
Antigen-Induced Proliferation of Guinea Pig Lymphocytes in Vitro: Functional Aspects of Antigen Handling by Macrophages
Authors: Waldron James A. , Horn Robert G. , Rosenthal Alan S.
Published: December 2022

Macrophages were incubated in vitro with purified protein derivative (PPD) under various experimental conditions, washed to remove unbound antigen, and assayed for immunogenicity by addition to cultures of purified PPD-immune lymph node lymphocytes. Proliferative responses elicited in the “indicator lymphocytes” served as semiquantitative indices of macrophage-associated immunogenicity. The accumulation of immunogenic activity by macrophages during a 1-hr pulse with PPD exhibited marked temperature dependency; immunogenicity of macrophages pulsed at 37°C exceeded that of cells pulsed at 4°C at every concentration of PPD utilized. The immunogenicity associated with macrophages pulsed with PPD at 4°C could be completely removed by trypsinization of the cells immediately after termination of the pulse. In contrast, only a fraction of the immunogenicity associated with macrophages pulsed with PPD at 37°C could be removed by trypsinization. When macrophages pulsed with antigen at 4°C were incubated at 37°C before trypsinization, the macrophage-associated immunogenicity became progressively more resistant to removal with trypsin. Kinetic studies of the accumulation of immunogenicity by macrophages pulsed with PPD at 37°C revealed that the trypsin-insensitive fraction of the total macrophage-associated immunogenicity became progressively greater with pulses of 0 to 60 min duration. The results suggest that accumulation of relevant antigen molecules by macrophages proceeds by a two step mechanism, involving membrane binding and subsequent metabolic dependent sequestration of bound antigen by the macrophage.
Endotoxin-Stimulated Spleen Cells: Mitogenesis, the Occurrence of the C3 Receptor, and the Production of Immunoglobulin
Authors: Gormus Bobby J. , Crandall Richard B. , Shands Joseph W.
Published: December 2022

Endotoxin (LPS)-stimulated mouse spleen cells were investigated in an attempt to correlate three markers for B lymphocytes: 1) LPS-induced blastogenesis, 2) rosette formation via the C3 receptor site, and 3) immunoglobulin production. After 24 hr stimulation 86% of LPS-induced blast cells formed rosettes indicating that these cells were B lymphocytes. Subsequently there was a progressive decrease in the percentage of rosette-forming blast cells to a low of 39% at 72 hr. The percentage of cells producing IgM increased progressively to a maximum of 54% after 72 hr of LPS stimulation These data indicate that at given times correlations between the three markers vary, and that no one of the three alone allows a strict categorization of cell types. The data presented are consistent with the hypothesis that LPS is a mitogen for B lymphocytes, although the possible involvement of other cell types was not ruled out.
Cell Interactions between Histoincompatible T and B Lymphocytes. V. Failure of Histoincompatible T Cells to Interfere with Physiologic Cooperation between Syngeneic T and B Lymphocytes
Authors: Katz David H. , Hamaoka Toshiyuki , Dorf Martin E. , Benacerraf Baruj
Published: December 2022

We have recently reported a series of experimental studies demonstrating certain genetic requirements for optimal thymus-derived-bone marrow-derived (T-B)2 cell cooperative interactions in the development of antibody responses to hapten-protein conjugates (1–4). Briefly, these studies have shown that in order for optimal physiologic, i.e., antigen-specific, T-B cell cooperation to occur, the interacting cells must share certain genes located in the histocompatibility gene complex. The experimental system employed in these studies was designed specifically to eliminate nonspecific T cell influences, of either an enhancing or suppressing nature, from the potential development of an “allogeneic effect” (reviewed in Reference 5). Indeed, in our initial attempts to investigate this problem, we found that adoptive transfer of spleen cells from donor mice primed to 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH) into unprimed x-irradiated histoincompatible recipients resulted in nonspecific enhancement of anti-DNP antibody responses after challenge with a heterologous DNP-protein conjugate (1).
Failure of Terminal Complement Components to Induce Lysis of Moloney Virus Transformed Lymphocytes
Authors: Cooper Neil R. , Polley Margaret J. , Oldstone Michael B. A.
Published: December 2022

Antibody-dependent complement-mediated lysis of a viral-induced lymphoma cell was confined to the G1 phase of the cell cycle. During the portion of the cell cycle in which the cells were resistant to complement-mediated lysis (S, G2, and M), C5 and C8 became bound to the plasma membrane and ultrastructural lesions characteristic of complement membrane attack developed after incubation of the cells with antibody and complement. Quantitative studies revealed that the plasma membrane of cells bound equivalent numbers of C8 molecules in all phases of the cell cycle. These findings emphasize the importance of events occurring subsequent to activation and attachment of the cytolytic effector system for destruction of this tumor cell.
Local and Systemic Cell-Mediated Immunity after Immunization of Guinea Pigs with Live or Killed M. Tuberculosis by Various Routes
Authors: Spencer James C. , Waldman Robert H. , Johnson Joseph E.
Published: December 2022

Recent studies have suggested that there is compartmentalization of the cell-mediated immune response, i.e., local (nasal) immunization with influenza virus vaccine is more effective in inducing local cell-mediated immunity (CMI) than is parenteral immunization, whereas parenteral immunization is more effective in inducing systemic immunity. This study was undertaken to investigate the development of local respiratory as compared to systemic CMI in response to both nasally and parenterally administered BCG or killed Mycobacterium tuberculosis H37Ra.

CMI was tested with guinea pigs as the animal model and the inhibition of macrophage migration (IMM) technique at various intervals after immunization. Splenic lymphocytes were used as indicators of systemic immunity and pulmonary cells obtained by lung lavage were used to measure local immunity.

The animals immunized via the respiratory tract with either H37Ra or BCG developed significantly greater local respiratory CMI (greater percentage of IMM) than did animals immunized subcutaneously although the parenterally immunized animals developed greater systemic immunity. This compartmentalization of CMI could be overcome partially with higher doses of H37Ra, i.e., both respiratory and systemic CMI resulted from high dose local or parenteral immunization.

The response after BCG (live), as compared to H37Ra (killed organisms), was more prolonged: by 6 weeks after H37Ra immunization, by any route, there was no IMM; however, after BCG, high levels of IMM were present at 6 weeks. When guinea pigs were immunized i.v. with H37Ra, neither systemic nor respiratory CMI was stimulated. I.v. BCG stimulated systemic but not respiratory CMI.

These results could not be explained on the basis of local immunization leading to local irritation and infiltration of lymphocytes into the lung, since cell counts and histologic studies revealed no difference between the animals immunized locally and systemically.

These results may have implications with respect to immunization of humans against tuberculosis.
An in Vitro Study of Exocytosis of Neutrophil Granule Enzymes in Chronic Granulomatous Disease Neutrophils
Authors: Ulevitch Richard J. , Henson Peter , Holmes Beulah , Good Robert A.
Published: December 2022

Neutrophils from chronic granulomatous disease (CGD) patients were compared with neutrophils from normal donors in their ability to release granular enzymes to the outside of the cell (exocytosis), when such cells are placed upon a non-phagocytizable surface coated with soluble aggregates of human γ-globulin. Based upon measurement of both granule and cytoplasmic enzymes CGD patients demonstrated no defect in exocytosis of granular enzymes when compared to normal controls. In addition these studies confirmed that an increase in hexose monophosphate shunt activity is not required for exocytosis of granule enzymes.
Changes in Antigenic Properties of Human C3 upon Activation and Conversion by Trypsin
Authors: Molenaar J. L. , Müller M. A. C. , Engelfriet C. P. , Pondman K. W.
Published: December 2022

C3 conversion by trypsin was investigated with anti-C3a, anti-C3B, anti-C3c and anti-C3d sera in single radial immunodiffusion. In sequence, C3B determinants disappeared within 1 min of incubation and C3a vanished after 5 to 8 min. C3c and C3d, however, increased in concentration. The loose complex C3ab generated after the disappearance of C3B could be dissociated by lowering the pH and by subjection to electrophoresis.

Free C3a production, demonstrated by means of rocket electrophoresis against anti-C3a, skin tests, and gel filtration with radioactively labeled C3, was maximal after 1 min of trypsin treatment.

Isolated C3 activated by trypsin in solution was bound to erythrocytes in a C3b form as could be demonstrated by agglutination with anti-C3c and anti-C3d. This was also the case with C3 bound to erythrocytes after incubation of cold agglutinin serum with fresh normal serum at pH 7.5. Both of these C3 products proved inactive in the biologic test systems used. In contrast, isolated C3 activated by bound and fixed to the cell surface was biologically active. cells obtained in this way were agglutinated not only by anti-C3c and anti-C3d, but also by anti-C3B and anti-C3a sera. The C3 conformation which is assumed to be characterized by the C3B determinants seems essential for the biologic properties. Nevertheless, the C3B antigenicity is not directly related to the biologic activity of C3. Since C3a was detected on cells as well as on IgG1, its activity might possibly be evolved on the surface of an immune complex. From the antigenic properties of C3 during conversion and binding to both erythrocytes and immunoglobulins by trypsin and treatment, it is concluded that both enzyme activities attack the same region of native C3. The antigenic properties of C3 after binding depend on whether the converting enzyme is present in solution or in a solid phase.
Decline and Restoration of Antibody-Forming Capacity in Aging Beagle Dogs
Authors: Jaroslow Bernard N. , Suhrbier Katherine M. , Fritz Thomas E.
Published: December 2022

The production of antibody to coliphage was studied in young (1 1/2 years) and old (7 to 11 years) beagles. In five old dogs given a single injection of T2 coliphage three of them showed a severe deficiency of antibody-forming capacity as compared to five young controls. When three injections of T2 or T4 coliphage were given in 5 days, 15 old dogs produced the same amount of antibody as did 15 young control dogs. Thus, antibody-forming capacity was restored to aging dogs by giving multiple injections of antigens. The relative serum titer to the cross-reacting antigen, T4 coliphage, was equal in young and old dogs given T2 coliphage. Our results are interpreted in accord with the Antigen Selection Hypothesis (33). They showed that one of the age-associated losses in antibody-forming capacity results from a decline in the proliferative activity of antigen-stimulated cells because the proliferative state can be maintained by repeated injections of antigen. We also concluded that the precursor cells suffer no loss with age in sensitivity to antigenic stimulation because there is no relative increase in the fraction of cross-reacting antibody.
Enumeration of B-Lymphocytes in Human Peripheral Blood by a Rosette Method for the Detection of Surface-Bound Immunoglobulin
Authors: Giuliano Vincent J. , Jasin Hugo E. , Hurd Eric R. , Ziff Morris
Published: December 2022

A rosette method is described for the identification and enumeration of B-lymphocytes in human peripheral blood. Sheep red blood cells coated with purified goat anti-human F(ab′)2 were mixed with mononuclear cells separated from blood by density centrifugation on Ficoll-Hypaque. Rosettes were formed by the mononuclear cells with immunoglobulin determinants on their surfaces. The rosetteforming cells were identified as either lymphocytes or monocytes on the basis of their ability to phagocytose polystyrene particles. The percentage and total number of B-lymphocytes in the peripheral blood were calculated after correcting for the rosettes formed by monocytes. The mean values for these determinations in 10 normal subjects were 23% and 485/mm3, respectively.

Elevated values were found in one patient with thymic aplasia and in another with chronic lymphatic leukemia. Markedly decreased values were observed in a patient with congenital agammaglobulinemia.
Mucosal and Glandular Distribution of Immunoglobulin Components: Differential Localization of Free and Bound SC in Secretory Epithelial Cells
Authors: Brandtzaeg Per
Published: December 2022

Immunohistochemistry of saline-extracted human glandular tissue revealed that secretory epithelial cells contain membrane-associated IgA and secretory component (SC). Free SC alone was demonstrated intracellularly in the Golgi region whereas both free and IgA-complexed SC were detected in the cell membranes and in the apical portion of the cytoplasm. The findings support a tentative model for selective epithelial immunoglobulin transmission. It is proposed that SC acts as a specific surface receptor for dimeric IgA, and that the formed complexes become mobilized and at least partially stabilized in the cell membrane. They subsequently enter the gland lumen via the epithelial cell cytoplasm outside the Golgi apparatus, and perhaps, to some extent, directly from the cell membrane.
In Vitro Reconstitution of T Cell Deficient Mouse Spleen Cells by Co-Cultivation with Human Lymphocytes
Authors: Farrar John J.
Published: December 2022

The results presented in this report have shown: 1) that human leukocytes are capable of reconstituting the in vitro PFC response of a population of mouse spleen cells known to be deficient in T helper cells; 2) the active cells in the human leukocyte population are resistant to 800 R x-irradiation; and 3) the cells are not removed by carbonyl iron treatment which is known to remove phagocytic cells. The data therefore support the contention that a radioresistant human T lymphocyte is capable of interacting synergistically with mouse B lymphocytes. A subsequent report (15) will present experiments in which double-chambered culture vessels have been used to demonstrate that HPL mediate this xenogeneic “helper” function via a diffusible factor. A number of other questions will also be considered including the antigenic specificity of the active factor.
Specific Binding of Mouse IgE with Rat Mast Cells
Authors: König Wolfgang , Okudaira Hirokazu , Ishizaka Kimishige
Published: December 2022

Evidence was obtained that the mouse IgE antibody was absorbed in vitro by rat peritoneal mast cells, but not by macrophages. A significant absorption of the antibody was observed at 0°C in the presence of EDTA, although the rate of absorption was faster at 37°C than at 0°C. Mouse IgG1 and IgG2, which combine with mouse mast cells, did not combine with rat mast cells or macrophages at 0°C nor inhibit the binding of mouse IgE with mast cells.
Antigen Binding T and B Lymphocytes
Authors: Hämmerling Günter J. , McDevitt Hugh O.
Published: December 2022

In the present study, conditions are described for the selective detection of specific 125I-(T, G)-A--L binding to peripheral B and T cells. The following observations were made: 1) B cells appear to have at least 5 times more antigen receptors than do T cells. 2) When cells were allowed to react with antigen at 37°C instead of at 4°C, this had no influence on the frequency of B-ABC. In contrast, the number of T-ABC was increased 2- to 3-fold. This increase could be prevented by sodium azide, suggesting that the exposure of antigen-binding receptors on the surface of T cells depends on cellular metabolic activity. 3) Inhibition studies with chemical analogs of (T, G)-A--L revealed a different specificity of B and T cells. Whereas excess unlabeled (T, G)-A--L, (Phe, G)-A--L and (H, G)-A--L could each block 125I-(T, G)-A--L binding to B cells, only unlabeled (T, G)-A--L could inhibit specific T-ABC. Altogether, these observations provide further evidence for profound differences between B and T cell antigen receptors.
Phagocytosis: A Defense Mechanism against Infection with Trypanosoma Cruzi
Authors: Kierszenbaum Felipe , Knecht Eva , Budzko Delia B. , Pizzimenti María C.
Published: December 2022

In mice, depression of reticuloendothelial activity by intravenous injection of silica particles resulted in a decreased resistance to infection with virulent blood forms (trypomastigotes) of Trypanosoma cruzi. In these animals, both the mortality rate and the levels of parasitemia were significantly increased over those of control mice given only the parasites. Accordingly, stimulation of the reticuloendothelial system (RES) with diethylstilbestrol (DES) before infection reduced considerably both the mortality rate and the levels of parasitemia, and prolonged the survival time after infection. Although in low percentages (16 to 25%), survival after the 60-day observation period was observed only among mice which had been treated with DES.

Virulent trypomastigote forms of T. cruzi were found inside mouse peritoneal macrophages shortly after intraperitoneal (i.p.) injection. Many of the parasites were killed within these cells both in vivo and in vitro.

The data reported in this paper indicate that, in the mouse, the RES is involved in the resistance against infection with virulent blood forms of T. cruzi, possibly through the capacity of macrophages to destroy the parasite.
The Reaction of Zymosan with the Properdin System: Isolation of Purified Factor D from Guinea Pig Serum and Study of Its Reaction Characteristics
Authors: Brade Volker , Nicholson Anne , Lee Gerald D. , Mayer Manfred M.
Published: December 2022

On incubation with serum, zymosan (Z) combines with several serum components, collectively designated X, to form an intermediate, ZX, which activates the complement system by cleavage of components C3 and C5. The enzymes, responsible for cleaving C3 and C5 differ from C̄4̄,2̄ and C̄4̄,2̄,3̄, and are collectively designated “properdin enzymes.” In our earlier studies it was shown that these are multi-unit complexes comprising factor B and complement fragment C3b. The present experiments extend our work on the C3-cleaving properdin enzyme with respect to a third component, designated factor D. On extended incubation at 37°C and long storage at 0°C, ZX changes to a severely decayed precursor, designated ZXd2, due to loss of factors B and D. if fresh factor B is supplied, ZXd2 can serve as a reagent for the detection and measurement of D. This method is far more sensitive than assaying with factor B and the cobra venom factor. Rigorous evidence is presented in the present work that the factor detected by each of these assay systems is one and the same despite the large difference in sensitivity. A procedure is described for isolation of D from guinea pig serum in a highly purified state as judged by disc electrophoresis on polyacrylamide gel. The final product was found to have a molecular weight of about 22,000 daltons, and a frictional coefficient, f/fo, of about 1.1, as estimated from its sedimentation rate of ca. 2.6S, its diffusion coefficient of ca. 10.5 × 10-7 cm2/sec, and an assumed partial specific volume of 0.725. The isoelectric point was 9.35. Adsorption of D on ZXd2 is favored by low pH and low ionic strength and proceeds in the absence of divalent cations. The rate of uptake of D on ZXd2 is not influenced greatly by temperature and, therefore, does not appear to involve enzymatic cleavage.
Forssman-Containing Liposomes: Complement-Dependent Damage due to Interaction with a Monoclonal IgM
Authors: Joseph Kenneth C. , Alving Carl R. , Wistar Richard
Published: December 2022

Since 1968 liposomes have been employed as a model for studying the molecular basis of immune lysis (1). The liposomes consist of closed, concentric shells of lipid bilayers alternating with aqueous interspaces (2). The aqueous portions within the liposomes generally contain marker molecules (e.g., glucose) and the membrane damage is measured by release of the marker compound (2, 3). By using liposomes with various amphipathic lipids as antigens, a wide variety of specificities have been described (1, 4). Forssman substance was the first antigen used in these studies and its properties in liposomes have now been thoroughly investigated (5). The initial work demonstrated that liposomes containing Forssman hapten could bind anti-Forssman antibodies (hemolysin) and this led to membrane damage and glucose release due to complement fixation (6, 7). A subsequent report showed that this was a highly specific phenomenon, and anti-Forssman antibodies did not cross-react with globoside I, which is a closely related glycolipid (8).
In Vitro Stimulation of Rabbit Lymphocytes after Immunization with Live and Inactivated Rabies Vaccines
Authors: Wiktor Tadeusz J. , Kamo Isao , Koprowski Hilary
Published: December 2022

Spleen lymphocytes from rabbits immunized with live or inactivated rabies virus were exposed in vitro to rabies antigens. Blastogenesis of sensitized spleen cells was measured by incorporation of 3H thymidine into the DNA of actively proliferating cells. The maximum stimulation ratio by rabies antigens was observed 8 days after immunization and animals remained sensitized for at least 175 days. No differences were noted when either live or inactivated viruses were used for immunization or for stimulation of spleen lymphocytes. Purified rabies virions, “soluble antigens,” and glycoprotein fraction showed a stimulating effect but not the nucleocapsid fraction of rabies virions.
Mitogenic Effect of a Water-Soluble Extract of Nocardia Opaca: A Comparative Study with Some Bacterial Adjuvants on Spleen and Peripheral Lymphocytes of Four Mammalian Species
Authors: Bona C. , Damais C. , Dimitriu A. , Chedid L. , Ciorbaru R. , Adam A. , Petit J. F. , Lederer E. , Rosselet J. P.
Published: December 2022

A water-soluble extract of Nocardia opaca (NWSE) induced a very strong stimulation of rabbit and mouse spleen lymphocytes and a weak, but significant, increase of thymidine incorporation by human peripheral lymphocytes and monkey blood, or spleen cells. As was demonstrated by the migration inhibition factor assay, the strong mitogenic activity observed with mice spleen cells was not related to a state of natural impregnation. In the same experiments, the various lymphocytes were also incubated with M. smegmatis water-soluble adjuvant (WSA) and S. enteritidis lipopolysaccharide (LPS). No mitogenic activity was shown with WSA even when this extract was incubated with the lymphocytes of human tuberculin responders, showing that this preparation is free of tuberculoprotein contaminants.

Finally, it must be noted that, contrary to what is observed in mice, LPS did not induce thymidine incorporation by monkey or rabbit spleen cells.
Homogeneous Immunoglobulins in Sera of Mice During Aging
Authors: Rádl Jiri , Hollander Carel F.
Published: December 2022

One of the striking features of the immune response in man during aging is an increasing tendency to produce homogeneous immunoglobulins, the so-called “idiopathic paraproteins” or “benign monoclonal γ-globulins” (1, 2). The frequency of idiopathic paraproteinaemias is reported by several groups of investigators to be about 1% of the adult population, increasing gradually from 0 in the third decade up to 19% in the tenth decade (3, 4). Although a large amount of clinical data on such cases has been accumulated during the last 15 years, very little is known about the etiology, the mechanisms, and the significance of this particular form of the immunoglobulin production in aging man. No similar findings have been reported in animals. Without an experimental animal model, any attempt at more detailed investigations would be difficult.

We report here the appearance of homogeneous immunoglobulins (H-Ig)1 in the serum of mice during aging that show some features comparable to those described in man under the term “idiopathic paraproteinaemias.”
Characterization of Serum Inhibitors of Neutrophil Chemotaxis Associated with Anergy
Authors: van Epps Dennis E. , Palmer Darwin L. , Williams Ralph C.
Published: December 2022

Forty patients with acute illness and a leukocytosis of greater than 12,000 WBC/mm3 were studied with respect to skin test reactivity and plasma or serum chemotactic activity. Sixteen patients were skin test negative when tested with a battery of six common antigens capable of eliciting delayed-type skin test responses. Serum from 12 of these patients contained chemotactic inhibitors capable of abrogating chemotaxis toward purified C3a, C5a, and kallikrein in addition to normal and immune complex-activated human serum. All patients having inhibitor were skin test negative. The presence of chemotactic inhibitor in patient serum directly paralleled skin test anergy. After clinical improvement, patients became skin test positive to at least one of the six antigens used, and their serum simultaneously lost chemotactic inhibitor. Physical characteristics of a 50% ammonium sulfate-precipitated inhibitor included heat stability, β mobility by zone electrophoresis, elution in the third peak from DEAE with a 0.1 M, pH 5.8, phosphate buffer, and sedimentation coefficients of 6.8 and 10.7S. Functional studies indicated that the inhibitor could not be absorbed by large numbers of leukocytes and could be neutralized by excess normal human serum. The serum chemotactic inhibitory activity and the highly significant association with skin test anergy indicate that chemotactic inhibitors may function as naturally occurring anti-inflammatory agents in patients with systemic illness.
Effector Mechanisms of Cell-Mediated Immunity to Xenogeneic Cell Antigens
Authors: Dennert Gunther
Published: December 2022

The effector cells in mouse and rat spleen performing cell-mediated lysis of xenogeneic target cells in vitro have been identified. In mice injected with either a rat or human cell line, the cytotoxic effector cells are shown to be thymus-derived lymphocytes. Repeated challenge of mice with the human cell line also gives rise to antibody, which induces normal spleen cells to become cytotoxic, indicating that two effector mechanisms of cell-mediated lysis may operate in this model.

In the rat, cell-mediated lysis of a mouse and of a human cell line is brought about by thymus-derived lymphocytes as well as thymus independent cells, as shown by a T cell-specific antiserum. In confirmation of this, antibody, which renders normal spleen cells cytotoxic, is consistently found in the serum of rats injected with these two cell lines.
Modification of NZB/NZW F1 Autoimmune Disease by Development of Tolerance to DNA
Authors: Parker Lewis P. , Hahn Bevra H. , Osterland C. Kirk
Published: December 2022

NZB/NZW F1 mice that received from birth prolonged high dose administration of SDNA-poly-d-lysine, or intermittent SDNA-poly-d-lysine followed by cyclophosphamide lived significantly longer than their controls. In association with the increased survival the following alterations in laboratory parameters were observed: decreased levels of anti-DNA antibodies, decreased numbers of spleen plaque-forming cells against DNA-coated RBC, less histologic and immunofluorescent evidence of glomerulonephritis, and less IgG in kidney eluates. The results suggest that tolerance to SDNA will increase survival and decrease tissue lesions.
Release of Neutral Protease and β-Glucuronidase from Human Neutrophils in the Presence of Cartilage Treated with Various Immunologic Reactants
Authors: Ignarro Louis J.
Published: December 2022

Human neutrophils were studied for their capacity to release cartilage proteoglycan matrix-degrading neutral protease in the presence of rabbit ear cartilage treated with various immunologic reactants. Extracellular discharge of neutral protease and β-glucuronidase from purified neutrophils was provoked by cell contact with cartilage treated with heat-aggregated immunoglobulin G but not normal immunoglobulin G. Neutrophils were incubated also with cartilage treated with both heat-aggregated immunoglobulin G and rheumatoid serum, rheumatoid synovial fluid, or cryoprecipitates from rheumatoid synovial fluid. The greatest amount of lysosomal enzyme release occurred when neutrophils interacted with cartilage that had been treated with both heat-aggregated immunoglobulin G and either rheumatoid synovial fluid or cryoprecipitates from rheumatoid synovial fluid. Methyl prednisolone sodium succinate, triamcinolone acetonide, vinblastine, and colchicine reduced the immunologic discharge of granule enzymes from human neutrophils. Normal serum and synovial fluid inhibited markedly the activity but not the release of neutrophilic neutral protease. Rheumatoid serum and synovial fluid also inhibited neutral protease activity but to a lesser extent. These studies indicate that human neutrophils are capable of releasing cartilage degrading neutral protease during cell contact with immobilized immunologic reactants and that certain anti-arthritic drugs can inhibit the immunologic release of this neutral protease.
Endocytosis by Macrophages of Altered Soluble Protein. The Effect of Binding to Particulate Surfaces and of IgM and IgM Antibody
Authors: Feldman Joseph D. , Pollock E. M.
Published: December 2022

Keyhole limpet hemocyanin (KLH) was bound to homologous rat erythrocytes with CrCl3 or to Bio-Gel beads with carbodiimide. When bound KLH was offered to rat peritoneal exudate cells, in vitro, uptake was 18 to 70 times greater than uptake of free unbound KLH. The augmented uptake was the result of enhanced endocytosis without phagocytosis of the binding particles. Protein in medium containing suspensions of macrophages depressed uptake of bound and free KLH, but depressed the latter significantly more. Endocytosis of bound KLH was not affected by γ-globulin, antibodies to rat IgG, or antibodies specific for and bound to rat macrophages, beyond the depressing effect of protein. IgM antibody to KLH was significantly more effective in increasing uptake of free KLH than was IgG antibody to KLH, whereas both antibodies to KLH had little effect on uptake of bound KLH. The enhanced uptake of bound KLH was probably due to the form and manner in which the protein was offered to macrophages.
The Occurrence of Shared Idiotypic Specificity among the Goat Antibodies That Distinguish Human Hemoglobin S from A1
Authors: Schreiber Robert D. , Reichlin Morris
Published: December 2022

Rabbits have been immunized with the goat antibody population(s) that distinguishes human hemoglobin S (sickle) from A1. After appropriate absorption these rabbit sera bind only the S-specific antibody and not the antibodies that cross-react with hemoglobin A1. S-specific antibody from three individual outbred goats gives reactions of complete immunologic identity in double diffusion reactions in agar with rabbit sera made specific for the antibody that distinguishes hemoglobin S from A1. Quantitative studies of these reactions by radioimmunoassay support the notion that the idiotypic determinants from these three goats have similar antigenic reactivity.
Experimental Allergic Neuritis: Cells Binding Horseradish Peroxidase Conjugates of Myelin Basic Proteins
Authors: dal Canto Mauro C. , Johnson Anne B. , Raine Cedric S. , Wisniewski Henryk M. , Brostoff Steven W.
Published: December 2022

In rabbits with experimental allergic neuritis induced by inoculation with purified bovine peripheral myelin, we have demonstrated mononuclear cells specifically binding a conjugate of horseradish peroxidase and bovine P2 protein. The P2 protein is one of the two basic proteins of peripheral myelin and is unique to the peripheral nervous system. The specifically reactive cells were present in lymph nodes and in infiltrates in dorsal root ganglia, a target organ in this autoimmune disease. Many of the reactive cells in both sites resembled plasma cells and large lymphocytes. No cells bound a conjugate of peroxidase and the encephalitogenic basic protein from bovine central myelin, which appears to be chemically identical and is immunopathologically cross-reactive with P1 protein, the other basic protein of peripheral myelin. These immunopathologic results are consistent with the clinical and histologic findings that peripheral myelin induces only neuritis and not encephalomyelitis despite its content of both P1 and P2 proteins. They suggest that within intact peripheral myelin, the antigenic sites on P1 protein are masked whereas those on P2 protein are free to act as immunogens.

In rabbits immunized with purified P2 protein, lymph nodes also contained cells binding the P2 protein peroxidase conjugate. These animals, however, did not develop definite evidence of experimental allergic neuritis.
Studies on Human Secretory Immunoglobulin A
Authors: Mestecky Jiri , Kulhavy Rose , Wright Genesis P. , Tomana Milan
Published: December 2022

Fragments produced by cyanogen bromide cleavage of human secretory IgA were fractionated before and after the splitting of disulfide bonds on Sephadex G-200 columns in 5 M guanidine · HCl. By electrophoretic, antigenic, amino acid, and carbohydrate analyses of individual fractions it was revealed that J chain was released as a result of cyanogen bromide cleavage. Secretory component remained associated with a large fragment(s) of α chain (approximately 80% the size of the original α chain) to which L chains were also linked. Data indicate that J chain and secretory component are linked to different cyanogen bromide fragments of the α chain(s) and are not mutually connected by disulfude bonds. Although J chain might mediate the binding of secretory component through a disulfide-bond interchange reaction, the J chain is not involved in direct bridging between secretory component and polymeric IgA molecules.
The Production of Specific Antibodies to Native Collagens with the Chain Compositions, [α1(I)]3, [α1(II)]3, and [α1(I)]2α2
Authors: Hahn Eckhart , Timpl Rupert , Miller Edward J.
Published: December 2022

The antigenic properties of collagen are of great interest both from the structural and clinical point of view. It has recently been indicated (1) that the triple-chain collagen molecule is an excellent model for studies designed to elucidate the interrelationships between sequential and conformation-dependent protein determinants. These studies demonstrated that antigenic determinants on the native calf skin collagen molecule (chain composition, [α1(I)]2α2 were either absent or greatly diminished in triple-helical molecules prepared from single types of chains and exhibiting the chain composition, [α1(I)]3 or (α2)3. It was concluded that in addition to the helical conformation of the native collagen molecule, full expression of the antigenic activity requires an appropriate juxtaposition of amino acid side chains from both α1(I) and α2 chains.

The data presented here extend these observations to the genetically-distinct collagen which occurs only in cartilaginous structures. The latter collagen is comprised of three identical chains, designated α1(II), and therefore possesses the chain composition, [α1(II)]3 (2).
Stimulation of Mouse B Lymphocytes by Trypsin
Authors: Vischer Thomas L.
Published: December 2022

BALB/c spleen cells (5 × 106) were cultured in 1 ml of serum-free RPMI 1640 medium for 3 days. Stimulation was assessed after addition of 3H-thymidine for the last 16 hr. Addition of trypsin to the cultures resulted in a stimulation comparable to that induced by endotoxin (LPS). Optimal amounts for stimulation were around 2.5 µg. Trypsin had to be active during at least 24 hr of cultures for stimulation as determined by addition of soybean trypsin inhibitor. Thymus cells from normal or hydrocortisone-treated mice could not be stimulated whereas spleen and lymph node cells from homozygous, athymic, nude mice responded well. Similarly, over 80% of the transformed cells after stimulation of BALB/c spleen cells by trypsin had immunoglobulin surface receptors and are B cells. Removal of adherent cells from the cultures did not diminish the response to trypsin or LPS. It is concluded that trypsin is a potent stimulator of B lymphocytes.
Mouse Bone Marrow Lymphocytes and Their Differentiation
Authors: Ryser Jean-Etienne , Vassalli Pierre
Published: December 2022

About 50% of the mouse bone marrow (BM) small lymphocytes bear neither surface immunoglobulin (sIg) nor lymphocyte differentiation antigens (MBLA, MSLA or θ). These “null” lymphocytes are the most newly formed of the BM small lymphocytes. When purified populations of labeled BM null lymphocytes are transfered into syngeneic recipients, they migrate principally to the spleen and 20 hr after transfer about half of them have acquired characteristics of B lymphocytes (sIg, MBLA). After in vitro cultures, a high proportion of these cells acquire sIg and the MBL antigen, a process which does not require cell division. The null lymphocyte population does not contain detectable precursors of T lymphocytes or pluripotential stem cells. The BM B lymphocytes, which appear to derive directly from BM null lymphocytes, differ in several respects from the B lymphocytes found in peripheral lymphoid organs: a number of them bear light chains without detectable µ, γ, or α heavy chains; they have little or no receptor for complement; their response to Escherichia coli lipopolysaccharide in culture is different from that of spleen B lymphocytes.
Pathophysiologic Effects of Lethal and Immunoregulatory Doses of Cholera Enterotoxin in the Mouse
Authors: Chisari Francis V. , Northrup Robert S.
Published: December 2022

Cholera enterotoxin (CE) can kill mice, produce severe thymic cortical atrophy and depletion of lymphoid cells from splenic red pulp. Furthermore, lethal doses can decrease the viability of spleen cells and thymocytes in vitro and produce severe hypercalcemia which probably is responsible for the lethal effect. However, a sublethal dose known to have the capacity to modulate the immune response exerts a distinct stimulatory effect on cells in the splenic red pulp whereas cortical thymocytes are destroyed even at this lower dose. A lesser degree of serum calcium elevation is also produced. The differential susceptibility of thymus and bone marrow-derived cells to CE and the role which the adenyl cyclase-cyclic AMP system plays in these effects is discussed.
Abrogation of Resistance to Bone Marrow Grafts by Silica Particles
Authors: Lotzová Eva , Cudkowicz Gustavo
Published: December 2022

An attempt was made to assess the role of macrophages in resistance of irradiated mice to parental-strain and allogeneic bone marrow grafts. 1.25 to 5 mg of silica particles injected i.v. (5 µ average size) are specifically toxic to macrophages and resulted in prompt abrogation or reduction of hybrid and allogeneic resistance. The silica was equally effective when given within 2 days before or after transplantation of bone marrow cells. The effectiveness decreased with increasing intervals, but foreign marrow cells could be rescued from rejection as long as 3 days after grafting. The macrophage stabilizer poly-2-vinylpyridine N-oxide injected subcutaneously (150 mg/kg) 1 day before silica entirely prevented the suppression of hybrid resistance. It was concluded that macrophages, or a subpopulation thereof, could be the effectors of hemopoietic graft rejection by irradiated mice. The immunogenetic specificity of these allograft reactions and the suppressive effects of anti-lymphocyte agents suggest, however, that also lymphoid cells participate in this process.
Lectins from Abrus Precatorius and Ricinus Communis
Authors: Olsnes Sjur , Pappenheimer Alwin M. , Meren Roberta
Published: December 2022

When equimolar amounts of purified homologous A- and B-chains from abrin or ricin are mixed and dialyzed to remove 2-mercaptoethanol, the disulfide bridge between the chains reforms and fully toxic molecules are reconstituted. In a similar manner, when heterologous chains are mixed and dialyzed, the toxic hybrid molecules abrin A/ricin B or ricin A/abrin B are formed in good yield. Stable hybrid molecules were not formed between the two A-chains or the two B-chains.

Whereas rabbit anti-abrin and anti-ricin sera each neutralizes only its homologous toxin, neither antitoxin can distinguish between the hybrid toxins. On the other hand, antibodies specifically directed against determinants on A- or B-chains readily distinguish between the two hybrids. Neutralization by antisera of the toxic effects of abrin, ricin, and their hybrids on protein synthesis in HeLa cell cultures has been studied quantitatively.

The results are discussed in relation to other interspecies hybrid molecules and in relation to the mode of action of certain glycoprotein tropic hormones.
The Immunology of Experimental Chagas' Disease
Authors: Teixeira Antonio R. L. , Santos-Buch Charles A.
Published: December 2022

Homogenates of trypomastigote and amastigote forms of the Ernestina strain of Trypanosoma cruzi, derived from tissue cultures, were partitioned by differential centrifugation and yielded six subcellular fractions described by electron microscopy. The soluble supernatant of the 100,000 × G for 90-min fraction, the cytosol, that retained nearly 50% of the proteins of the initial homogenate, showed at least one major antigenic component and these soluble substances gave rise to high titers of hemagglutinins, precipitins, and complement-fixing antibodies. The immunoglobulins in the serum have been characterized as IgG and IgA. In contrast, the lysosome-rich (30,000 × G for 35 min) fraction, and also the ribosome-rich (100,000 × G for 90 min) fraction retained minute amounts of protein and elicited only low titers of humoral antibodies in rabbits. Of interest, high titered sera with complement-fixing antibodies, hemagglutinins and precipitins did not have any demonstrable effect on trypomastigotes of T. cruzi.
Eosinophils and Immune Mechanisms
Authors: Greene Bruce M. , Colley Daniel G.
Published: December 2022

Eosinophil stimulation promoter (ESP) is a soluble product of activated mouse lymphoid cells which increases in vitro migration of mouse eosinophils. Pretreatment of the lymphoid cells, either by freezing and thawing or the lytic action of antithymocyte serum, abolished the ability of these sensitized cells to produce ESP when challenged by specific antigen. Its production is inhibited by the addition of puromycin. ESP is relatively heat stable, with full activity remaining after incubation at 60°C for 30 min, but none after 100°C for 30 min. Dilution markedly reduces its activity. ESP is sensitive to a proteolytic enzyme, chymotrypsin, but insensitive to RNase and to Vibrio cholera neuraminidase. Molecular sieve column chromatography of ESP-containing culture supernatant fluids yields a single peak of ESP activity, associated with only a small fraction of the total protein. The estimated molecular weight of ESP is 24,000 to 56,000 daltons.
The Use of Allogeneic T Lymphocytes and Bacterial Lipopolysaccharide to Induce Immune Responses to Monovalent Haptens in Vitro
Authors: Trenkner Ekkhart
Published: December 2022

Immune responses to monovalent haptens were stimulated in mouse spleen cultures either by the addition of bacterial lipopolysaccharide (LPS) or by T cells reactive against the alloantigens on precursor antibody-forming cells (P-AFC). These findings suggest that P-AFC require two independently delivered signals for the induction of antibody synthesis. One signal is delivered via the interaction of hapten with surface immunoglobulin receptors. A second signal is delivered either by LPS or via the interaction of a T cell with cell surface determinants on P-AFC.