bluuebunny/crossref_metadata_2025 huggingface dataset:
Migration Inhibition Factor (MIF) and Migration Stimulation Factor (MSF) in Fetal Calf Serum
Authors: Fox Roy A. , Gregory Douglas S. , Feldman Joseph D.
Published: December 2022

Non-heat-inactivated fetal calf serum contains a factor, FCS-MIF, that inhibits in vitro the migration of guinea pig peritoneal macrophages. FCS-MIF is partially or completely inactivated by dialysis, repeated freezing and thawing, heating to 56°C for 30 min, and changes of pH beyond the range of 6.0 to 7.7. Chromatography in different gels and with different buffers suggests that several fractions may have MIF activity.

FCS also contains a factor, FCS-MSF, that stimulates the migration of guinea pig macrophages. It is detected after MIF is removed by chromatography on DEAE-Sephadex A-25. A stimulatory factor is also present in supernatants of sensitized guinea pig lymphoid cells stimulated with antigen and is detected when the supernatants are treated in the same fashion as FCS to uncover FCS-MSF.
Periodate-Induced Lymphocyte Transformation
Authors: O'Brien Richard L. , Parker John W. , Paolilli Patricia , Steiner Joan
Published: December 2022

If lymphocytes are inactivated with mitomycin C, 60Co irradiation, or ultraviolet (UV) irradiation, and treated with sodium periodate (NaIO4), they are capable of inducing transformation of autologous lymphocytes in vitro. The optimal ratio of IO4--treated stimulator cells to untreated autologous lymphocytes is 1:2 or 1:4. Maximum incorporation of tritiated thymidine (3H-TdR) in autologous mixed lymphocyte cultures (A-MLC) occurs after 3 days. As with direct NaIO4 transformation of lymphocytes, the transformation in the A-MLC can be blocked by sodium borohydride (NaBH4). Overoxidation of the cells by NaIO4 also diminishes their ability to induce an autologous mixed lymphocyte reaction (A-MLR). Incubation of the stimulator cells after treatment with NaIO4 results in a progressively declining ability to induce transformation in the responder cells. We failed to find any evidence of a blastogenic factor released into the medium by the treated cells during periods ranging from 2 hr to 72 hr after NaIO4 treatment. NaIO4 treatment of autologous red blood cells does not render them capable of inducing transformation of autologous lymphocytes.
Distinctive Medullary and Germinal Center Proliferative Patterns in Mouse Lymph Nodes after Regional Primary and Secondary Stimulation with Tetanus Toxoid
Authors: Buerki Heinz , Cottier Hans , Hess Max W. , Laissue Jean , Stoner Richard D.
Published: December 2022

In an attempt to gain more insight into antigen-induced generation of plasma cells and memory B cells, respectively, we compared medullary proliferative responses and germinal center development in popliteal lymph nodes of young adult mice with antibody production as a function of time after primary and secondary stimulation with fluid tetanus toxoid (FTT) via the hind leg footpads. Differences in the time course of primary and secondary antibody responses correlated with the time sequence and magnitude of medullary proliferative activity rather than with germinal center formation and growth. Initial labeling indices of lymphoid and plasmocytoid cells were determined after injection of 3H-thymidine. After primary antigenic stimulation, medullary-labeling indices showed moderate oscillations with a maximum (8%) on day 6 and subsequent variations above control levels to day 32. In contrast to this limited but sustained primary proliferative response, medullary-labeling indices after booster injection of the antigen rose to a sharp, high peak (30%) on day 3 and then fell abruptly to almost control values between days 5 and 6. Germinal center activity, as expressed in both numerical increase and expansion of individual centers, was at least as important after primary stimulation as after the booster injection, although the latter evoked formation of these structures 2 to 3 days earlier than the primary stimulus. Variations in numbers and total mass of germinal centers during the anamnestic response were characterized by a maximum on day 5, followed by a rapid decline to day 6, i.e., when serum antibody titers attained a high plateau, and a second rise to day 12. This pattern differed significantly from that after primary injection of FTT showing a more sustained germinal center deployment between days 6 and 14. These observations support the view suggested previously by other authors that germinal centers are predominantly involved in the generation of memory B cells, and do not contribute markedly to antibody production elicited by the same antigen which evoked their de novo formation and expansion.
The Proliferative Response of Bronchus-Associated Lymphoid Tissue after Local and Systemic Immunization
Authors: Clancy Robert , Bienenstock John
Published: December 2022

The rate of DNA synthesis has been examined in vitro in lymphocytes obtained from the bronchial mucosa (bronchus-associated lymphoid tissue or BALT), washings of the bronchial tract, and the spleen, in animals immunized locally and systemically with dinitrophenylated human γ-globulin. The spontaneous rate of DNA synthesis of lymphocytes isolated from the BALT or washings of the bronchial tract was considerably greater in animals immunized via the bronchial lumen when compared with systemically immunized animals. Bronchial washing lymphocytes and BALT responded selectively to local antigen, with a similar time course. Antibody-containing cells were detected in the spleen, particularly after footpad immunization, but could not be detected in either the BALT or the lamina propria of the bronchus after local or systemic immunization.
Distribution of Antibody-Binding Affinity
Authors: Kim Young Tai , Werblin Theodore P. , Siskind Gregory W.
Published: December 2022

It has been shown that when a direct binding assay, such as equilibrium dialysis, is used to measure antibody site concentration an underestimate of the concentration of low affinity antibodies may occur in the presence of small amounts of high affinity antibody. Removal of high affinity antibody by use of a solid immunoadsorbent permits detection of more low affinity antibody than was detected by assaying the original serum sample. It appears likely that immune sera frequently contain considerably larger concentrations of low affinity antibodies than can be detected by conventional assay methods.
Distribution and Mobility of β2-Microglobulin on the Human Lymphocyte Membrane: Immunofluorescence and Immunoferritin Studies
Authors: Bismuth Alain , Neauport-Sautes Catherine , Kourilsky François M. , Manuel Yves , Greenland Timothy , Silvestre D.
Published: December 2022

β2-Microglobulin (β2-µ) was detected on the surface of human peripheral blood cells by direct or indirect immunofluorescence methods and by indirect immunoferritin labeling in electron microscopy with specific anti-β2-µ sera and conjugates. β2-µ was expressed, although not with the same intensity on the membrane of all lymphocytes, including B and T derived cells, on polymorphonuclear leukocytes, but not on erythrocytes. The antibody-induced redistribution and capping of β2-µ on the membrane of living lymphocytes could not be obtained at 37°C by bivalent anti-β2-µ antibodies alone, but was readily provoked upon addition of anti-Ig sera to anti-β2-µ antibody-coated cells. The technical conditions for the redistribution of all detectable β2-µ were defined by double immunofluorescence techniques. In such conditions, β2-µ migrates independently of surface Ig on the membrane of B lymphocytes, indicating that these molecules are independent on the cell surface.
The Ability of Chemotactic Factors to Induce Lysosomal Enzyme Release
Authors: Becker Elmer L. , Showell Henry J. , Henson Peter M. , Hsu Long S.
Published: December 2022

The complement-derived chemotactics factors, C3a, C5a, and C567, as well as the chemotactic factor obtained from culture filtrates of Escherichia coli, induce release of the lysosomal enzymes, β-glucuronidase and lysozyme, from rabbit peritoneal neutrophils. Under the same circumstances, there is little or no release of the cytoplasmic marker, lactic dehydrogenase, indicating that the release is a form of induced secretion.

The release occurs to an appreciable extent only when the neutrophils settle on filters of average pore size of 0.60 µm or greater; however, increasing the pore size of the filters from 0.60 to 5 µm does not increase the amount of lysosomal enzyme secretion. The requirement for an appropriate surface suggests that enzyme release by chemotactic factors is a form of induced secretion on non-phagocytosable surfaces studied previously.

No statistically significant correlation was found between the chemotactic responsiveness of neutrophils from different rabbits and their ability to give lysosomal enzyme release when stimulated by the same chemotactic factor. This suggests, at least, that a critical step or steps in the biochemical sequence or sequences governing chemotaxis and induced secretion of lysosomal enzymes in neutrophils is different or has a different quantitative importance.
Natural and Acquired Epidermal Autoantibodies in Man
Authors: Ackermann-Schopf Christl , Ackermann Rolf , Terasaki Paul I. , Levy Joshua
Published: December 2022

Sera from normal humans were cytotoxic to autologous and allogeneic epidermal cells. Sera from newborns were not cytotoxic, which is consistent with earlier results suggesting the gradual development of autoantibodies in animals. With anti-human IgG fluorescein-labeled conjugate staining, it was shown that the outer layers of the epidermis were stained by the natural autoantibody. No staining, however, was noted with sera from newborn cord blood. Another autoantibody induced by burns associated with autograft rejection was found to stain specifically the cells of the basal layer of the epidermis. The basal layer cells were not stained by HL-A antibodies. It is concluded that autoantibodies to the outer layers of the human epidermis occur naturally, and autoantibodies to the basal layer can be induced by burn injury associated with autograft rejection.
Lymphocyte Receptors for Myxoviruses and Paramyxoviruses
Authors: Woodruff Jack F. , Woodruff Judith J.
Published: December 2022

Rat thoracic duct lymphocytes which are predominantly thymus-derived (T) cells have surface receptors for myxo and paramyxoviruses. Thus B, A(H2N2) and A(H3N2) influenza, Newcastle disease, and Sendai viruses agglutinated T lymphocytes in vitro. In contrast, the cells were not agglutinated by certain A(HON1) and A(H1N1) influenza viruses. Evidence was obtained suggesting that bone marrow-derived lymphocytes have viral receptors that were not detected on the surface of T lymphocytes. Moreover, T cell receptors for myxo and paramyxoviruses were found to differ. Fetuin, sialic acid, and periodate treatment of cells selectively inhibited lymphocyte agglutination. Also after elution of Newcastle disease virus (NDV) from lymphocytes the cells were still agglutinated by influenza virus but not by NDV and Sendai virus. Similarly Sendaipretreated lymphocytes agglutinated when incubated with influenza or NDV but not when re-exposed to Sendai. It appears that specific determinants on lymphocytes mediate their interaction with viruses.
Sites of Localization and Synthesis of Ss Protein in Mice
Authors: Saunders David , Edidin Michael
Published: December 2022

Ss, a serum protein whose structure and level in serum are determined by genes of the mouse H-2 complex, has been localized to a variety of cell types, using immunofluorescence and radiolabel techniques. Peritoneal macrophages and liver parenchymal cells appear to synthesize Ss for export to serum. These cells stain in the cytoplasm for Ss and release labeled Ss into the medium of cultures fed 14C amino acids. Other cultured cells, fibroblasts of Ss high strains, bear the protein only on their membranes. The membrane-bound form of Ss has at least one antigenic determinant masked; this determinant is exposed when membrane-as-sociated Ss is released into culture medium. At least in some cells then, Ss, like the other products of H-2 region genes, is membrane associated.
Plaque Assay for the Detection of Alloantibody-Producing Cells in Mice
Authors: Wong A. K. C. , Sabbadini E.
Published: December 2022

A method was developed for the detection of alloantibody plaque-forming cells (PFC) in the mouse based on the use of red blood cells as indicator cells and of normal rabbit serum as the source of complement. Up to 510 PFC per spleen (34 PFC per 107 spleen cells) were detected in primary reactions involving the combination of strains B10.A to C57BL/10 which differ at the H-2 locus and up to 1610 PFC per spleen (115 PFC per 107 spleen cells) in secondary reactions involving the combination A to C57BL/6 which differ at both H-2 and non-H-2 loci. In the latter combination, the assay was shown to detect both cells producing antibodies to H-2 and non-H-2 antigens. The antigens determined by the H-2D region induced the formation of larger numbers of plaques than the antigens determined by the H-2 K region.
Chain Interactions and Idiotypic Specificities of Homogeneous Rabbit Anti-Lactose Antibodies
Authors: Ghose Asoke C. , Karush Fred
Published: December 2022

Functionally homogeneous fractions of rabbit anti-lactose IgG antibody have been characterized with respect to their idiotypic specificity and the effect of homologous recombination of isolated chains on the recovery of functional homogeneity and idiotypic determinants. Dimeric heavy chains and monomeric light chains were obtained from homogeneous antibody fractions and used for the preparation of reconstituted IgG molecules in high yield. The isolated chains were also evaluated with respect to binding affinity and inhibition of anti-idiotype antibody. The most significant observation was the recovery of idiotypic specificity in the homologous recombinants as well as binding affinity and functional homogeneity. These results provide strong evidence that the homogeneous antibody fractions are monoclonal products.

The isolated chains exhibited little or no specific activity. With respect to binding, the dimeric heavy chain bound a lactosyl-containing ligand with an association constant about 100-fold less than that of the parent antibody. Although the binding was homogeneous only one binding site per dimer was expressed. The heavy chain was also found to inhibit slightly the anti-idiotype reaction. The isolated monomeric light chain, on the other hand, showed no reactivity in either kind of experiment. The anti-idiotype reaction was subject to inhibition with lactose and p-amino-phenyl-β-lactoside with some antisera, depending on the form in which the homogeneous antibody was presented for immunization. It is suggested that the major portion of the idiotypic determinant is constituted of amino acid residues located along the periphery of the binding site rather than the contact residues in the groove or cleft of the site. This proposal would account for the inhibition by ligands as the result of the inability of ligand and anti-idiotype antibody to be accommodated simultaneously at contiguous sites because of overlapping volumes. Those cases in which ligand inhibition is not observed could be attributed to unusual geometric relationships between the contiguous sites.
Extraction and Partial Purification of the Histamine-Sensitizing Factor of Bordetella Pertussis
Authors: Lehrer Samuel B. , Tan Eng M. , Vaughan John H.
Published: December 2022

The histamine-sensitizing factor (HSF) of Bordetella pertussis has been recovered in soluble form by treatment of bacterial cells with 4 M urea, 1 M NaCl buffered with 0.1 M sodium phosphate at pH 6.4. Besides histamine-sensitizing activity, this extract has leukocytosis-promoting activity and is a potent adjuvant for hemagglutinating and reaginic antibodies. Through extraction and gel filtration column chromatography, a 280-fold purification of HSF has been achieved resulting in a purified preparation with a 50% sensitizing dose (SD50) of about 60 ng. Chemical analysis of this purified extract demonstrated protein and lipid to be the major components. Since other pertussis biologic activity such as leukocytosis-promoting and adjuvant activities in addition to histamine-sensitizing activity were still present in this highly purified extract of HSF, it is possible that one molecular species might be responsible for all these activities.
Tissue Distribution of I Region-Associated Antigens in the Mouse
Authors: Hauptfeld Věra , Hauptfeld Miroslav , Klein Jan
Published: December 2022

Antiserum (A.TL × B10)F1 anti-B10.HTT, obtained after skin grafting and immunization with spleen and lymph node cells, contains antibodies against antigens controlled by the I region of the H-2 complex (Ia antigens). Two additional Ia antigens have been identified, antigen Ia.3 which is restricted to the H-2s haplotype and its recombinant derivatives H-2t2 and H-2t3, all showing the same Ir-1As subregion, and antigen Ia.4 which is shared by H-2 haplotypes f, r, and u. The anti-Ia antibodies react in a direct cytotoxic test with about 40 to 50% lymph node cells and 50 to 60% spleen cells, but do not react with thymus or bone marrow cells. However, the anti-Ia antibodies can be absorbed in vitro with large numbers of cells by both thymus and bone marrow cells; they cannot be absorbed with muscle, erythrocytes, and brain tissue. After specific removal of anti-Thy-1.1-sensitive cells from the spleen cell suspension, the proportion of cells killed by the anti-Ia sera increases to almost 90%. Pretreatment in vivo with cyclophosphamide abolishes the anti-Ia reactivity of spleen cells. Suspensions filtered through a nylon fiber column are enriched in Ia-negative cells, the Ia-positive cells being retained on the fibers. Pretreatment in vivo with hydrocortisone results in the appearance of a small fraction of Ia-positive cells in the thymus. Thus, the Ia antigens are probably restricted to lymphocytes with predominant expression on B cells; if T cells express these antigens at all they do so either with a very low surface density or only in a minor subpopulation.
Alteration of Rabbit PCA Reaction by Drugs Known to Influence Intracellular Cyclic AMP
Authors: Kravis Thomas C. , Zvaifler Nathan J.
Published: December 2022

Pharmacologic agents which are known to modulate the immunologic release of mediators of anaphylaxis in vitro were analyzed for their effect on the rabbit passive cutaneous anaphylactic (PCA) reaction. Intravenous propranolol increased the diameter of the skin lesions. Isoproterenol in combination with aminophylline inhibited the PCA reaction. Prostaglandin (PGE1) and histamine phosphate caused marked decrease in diameter of skin blueing. These studies support the hypothesis that control of mediator release may be modulated in vivo by drugs which are known to influence intracellular concentrations of cAMP. Because of the complex pharmacologic events which accompany these agents when introduced in vivo, the results are interpreted to include mechanisms in addition to the cAMP system.
Spin-Label Studies of a Hapten-Combining Site of Rainbow Trout Antibody
Authors: Roubal William T. , Etlinger Howard M. , Hodgins Harold O.
Published: December 2022

The hapten-combining site for trout anti-DNP antibody has been compared with that of rabbit by using spin-labeled haptens and electron paramagnetic resonance spectroscopy. The average depth of the combining sites in both trout and rabbit was calculated to be 11.5 A.
Demonstration of Molecular Individuality of HL-A Antigens
Authors: Thieme Thomas R. , Raley Richard A. , Fahey John L.
Published: December 2022

Partially purified HL-A antigens, isolated by papain digestion from membranes of cultured lymphocytes, were subjected to a combination of immunoabsorbance and polyacrylamide gel electrophoresis. With four alloantisera, specific for the HL-A antigens characteristic of the cell line, each antigen could be completely separated from the other three. The results prove that the four HL-A antigens determined by a single genotype are present on four distinct molecular species.
Crossed Immunoelectrophoresis and Electroimmunoassay of IgG
Authors: Grubb Anders O.
Published: December 2022

Simple procedures for crossed immunoelectrophoresis and electroimmunoassay of IgG are described. It is shown how crossed immunoelectrophoresis can readily be used to demonstrate different types of IgG immune responses as well as the formation of complexes between IgG and other molecules.
Effect of Distamycin A on the Immune Response in Vitro Against Sheep Red Blood Cells
Authors: Rossi Guido , Zaalberg Otto Brocades
Published: December 2022

The effect of distamycin A (DMC) on the immune response in vitro has been studied. The addition of DMC to dissociated mouse spleen cells, obtained from unprimed animals and cultured in the presence of sheep red blood cells as an antigen caused a marked inhibition of the plaque-forming cell response when the drug was added during the first 24 hr of culture, but not when it was added later. The response of spleen cells taken from primed mice was more resistant to the immunosuppressive effect of DMC than was the response of unprimed cells. When the effects of DMC were compared to those of cytosine arabinoside and actinomycin D it was found that neither of the latter two compounds could reproduce the effects of DMC.
Application of Transformations to Normalize the Distribution of Plaque-Forming Cells
Authors: Gottlieb Charles F.
Published: December 2022

In the past, it has been tacitly assumed that the distribution of the plaque-forming cell response in mice is approximately normal; that is, it would provide the usual bell-shaped normal distribution curve if enough replicate samples were collected. We address this point directly, by using the plaque-forming cell response generated in a total of five in situ, in vivo, and in vitro experimental systems. The Gaussian distribution assumption was tested on the untransformed data and on the same observations transformed by logarithms or square roots. We conclude that the log transformation provides a close approximation to normality for all the systems studied.
Production of an Immunoglobulin-Binding Factor (IBF) by Antigen-Stimulated Lymph Node Lymphocytes
Authors: Fridman Wolf H. , Nelson Robert A. , Liabeuf André
Published: December 2022

Lymph node lymphocytes from rats immunized with a guinea pig encephalitogenic protein (GEProt) were incubated in vitro with the immunizing antigen in a serum-free medium. They released a factor which had the property to combine with IgG antibodies complexed with antigen, but not IgM antibodies, inducing hemagglutination of IgG-sensitized erythrocytes and protecting IgG-sensitized erythrocytes, but not IgM-sensitized erythrocytes from complement-induced hemolysis. A similar activity was found in supernatants from mixed leukocyte cultures between allogenic mouse strains. This factor was named immunoglobulin-binding factor (IBF). IBF was separated in rat from migration inhibitory factor, blastogenic factor, and lymphotoxin upon column fractionation techniques. IBF activity was found in fractions of about 150,000 m.w. and with a pH of about 6.30.
Heterologous Recombination between Mouse Myeloma 315 Heavy Chains and Rabbit Antibody Light Chains: Structural and Functional Properties of the Hybrid Molecules
Authors: Hoessli Daniel , Olander Jitka , Little J. Russell
Published: December 2022

7S recombinant molecules have been obtained from the heavy (H) chains of mouse myeloma protein 315 (which binds 2,4 dinitrophenyl (DNP) ligands) and the light (L) chains from rabbit anti-DNP antibodies or normal rabbit IgG. H- and L-chain antigenic determinants were detectable on these recombinants, and they displayed structural properties that closely resembled those of the parent molecules with respect to sedimentation coefficient, H- to L-chain ratio, and gel filtration characteristics. Recombinants containing L-chains from anti-DNP antibodies showed significantly greater binding of ε-DNP-lysine than hybrids made with nonspecific L-chains. Idiotypic determinants characteristic of the intact protein 315 were not recovered on any of these recombinants to any greater extent than were expressed on 315 H-chains alone. These results indicate that a DNP-binding site structure can be obtained by interaction between immunoglobulin subunits from different species, provided that they originate from anti-DNP molecules. Also, these data indicate that monoclonal H-chains reconstituted with polyclonal L-chains display binding properties resembling a polyclonal (heterogeneous) antibody population.
Granulomatous Hypersensitivity to Schistosoma Mansoni Eggs in Thymectomized and Bursectomized Chickens
Authors: Davis Bernard H. , Mahmoud Adel A. F. , Warren Kenneth S.
Published: December 2022

Early studies in which immunoglobulin was found in the Schistosoma mansoni egg granuloma led to the assumption that antibody played a major etiologic role in the development of this lesion (1, 2). Subsequent investigations, however, revealed that granulomatous hypersensitivity to S. mansoni eggs could be passively transferred with cells and not with serum (3). Further studies confirmed the latter findings in that: 1) complete granulomas consisting largely of macrophages, eosinophils, and lymphocytes form in the absence of any detectable IgG1 or IgG2 antibodies (4, 5); 2) the onset of granuloma formation correlates with the development of delayed dermal reactivity and in vitro correlates of delayed hypersensitivity (4, 5); and 3) suppression of cell-mediated reactivity markedly diminishes granuloma formation (6–8) whereas suppression of antibody formation via x-irradiation (9) or Friend virus leukemia (8) has no effect. In spite of considerable evidence suggesting that the immunologic etiology of the S. mansoni granuloma is virtually wholly cell-mediated, claims for an important role for antibody have continued (10).
Modulation of Immune Reactivity by Phenylimidothiazole Salts in Mice Immunized by Sheep Red Blood Cells
Authors: Renoux Gerard , Renoux Micheline
Published: December 2022

Two phenylimidothiazole salts, racemic tetramisole and l-isomer, levamisole, modulate mouse immune responsiveness. They produce either enhancement or depression of the number of plaque-forming cells (PFC) to sheep red blood cells (SRBC), depending on the dose and on time of administration of the drugs in relation to antigenic stimulus. They can render antigenic a quantity of SRBC which was insufficient in itself to immunize mice. These effects are not accompanied with an increase of serum antibody level. Immunostimulation does not modify the horse red cell background response. Enhanced immune responses are associated to splenocontraction, whereas the number of nucleated cells per spleen remains unchanged. Steric configuration of phenylimidothiazole salts plays a role, in that the d-optic isomer is almost completely devoid of immuno-modifying activities. The possible relationships between immunologic and pharmacologic activities of phenylimidothiazole salts are discussed.
Evidence for the T Cell Specificity of Sodium Periodate-Induced Lymphocyte Blastogenesis
Authors: Thurman Gary B. , Giovanella Beppino , Goldstein Allan L.
Published: December 2022

Sodium periodate (NaIO4) treatment of lymphocytes can induce blastogenic transformation similar to that caused by plant lectins. In this study we have found that spleen cells from congenitally athymic (nude) mice do not undergo blastogenesis when treated with NaIO4, in contrast to the extensive blastogenesis observed with NaIO4-treated spleen cells from normal littermates (heterozygous for the nude gene) and CBA/J mice. Prior treatment with NaIO4 only partially reduced the capacity of nude spleen cells to respond to a B cell mitogen. Lack of stimulation of nude spleen cells treated with NaIO4 indicates the possible T cell specificity of this mitogenic agent.
Evidence That Different Antibodies Are Involved in the Production of Immunologically Induced Teratogenesis and Nephritis
Authors: Leung Christopher C. K. , Urdaneta Antonio , Jensh Ronald P. , Jensen Marcela , Brent Robert L.
Published: December 2022

Since it has been well established that heterologous antiserum against whole rat kidney is both teratogenic and nephrotoxic, it is important to determine if these two separate pathologic effects are caused by the same or a different group of antibodies. Two antisera were prepared from the following groups of soluble antigens: (1) GBM antigens were obtained by solubilizing isolated rat glomerular basement membrane with trypsin, (2) PBS-soluble kidney antigens were obtained from the supernatant of homogenized, perfused whole rat kidneys following centrifugation at 105,000 × G. Both antisera were assayed for teratogenicity and nephrotoxicity. Nephrotoxicity of the antisera was evaluated by measuring proteinuria and examining light and electron microscopic preparations of kidneys following the injection of antisera into male rats and pregnant rats. The antiserum to trypsin-solubilized GBM antigens was nephrotoxic but not teratogenic while the antiserum to PBS-soluble kidney antigens was teratogenic but not nephrotoxic. In addition, the results of absorption studies utilizing antiserum against whole rat kidney indicate that a) the teratogenic effect of the antiserum against whole rat kidney can be abolished by incubating the antiserum with PBS-soluble kidney antigens, b) the nephrotoxic effects of the antiserum against whole rat kidney still persists after absorbing the antiserum with PBS-soluble kidney antigens. In vivo immunofluorescent studies demonstrated that the antibodies to PBS-soluble kidney antigens localized in the maternal GBM, Reichert's membrane, and visceral yolk sac endodermal cells whereas the antibodies to trypsin-solubilized GBM antigens localized only in the maternal GBM. These data indicate that the teratogenic antibodies present in the classical (Masugi) nephrotoxic serum are not the same group of antibodies that are responsible for nephrotoxicity.
The Role of Suppressor Cells in Avian Allogeneic Tolerance: Implications for the Pathogenesis of Marek's Disease
Authors: Rouse Barry T. , Warner Noel L.
Published: December 2022

Chicken embryos injected with pooled spleen cells from outbred embryos are tolerant to histocompatability antigens of the donor population. Tolerance can be shown by the failure of peripheral blood cells (PBC) from tolerant birds to produce graft versus host lesions on the chorioallantoic membrane of outbred chicken embryos. It is shown that PBC from tolerant chickens can reduce by up to 85% the GVH reactivity of PBC from normal chickens. These results are interpreted to indicate that the PBC of birds tolerant to allogeneic cells contain active suppressor cells that can reduce the activity of normal cells in their response to allogeneic stimulation.

The implications of these results are discussed in relation to the pathogenesis of Marek's disease—a common herpes virus-induced lymphoid neoplasm of chickens. It is suggested that resistance to neoplasia in this disease occurs because of the establishment of a population of active suppressor cells that prevents a neoplastic lymphoid proliferation.
Identification of a Highly Specific Memory T Cell Population: Lack of a B Cell Counterpart
Authors: Krüger Jürgen , Gershon Richard K.
Published: December 2022

We immunized chimeric mice, which had chromosomally marked (T6) T cells, with sheep red cells (SRBC) or saline and then gave them injections of 3H-thymidine every 6 hr for 4, 8, or 12 days. At intervals thereafter, we reimmunized them with SRBC, horse RBC (HRBC), KLH, or saline, and did autoradiographic and karyotypic studies of their spleen cells. We identified a population of T cells which synthesize DNA within the first 4 days after immunization and then remain relatively quiescent until a further immunization, at which time they divide again. No B cell population behaves similarly, even when the period of labeling is extended to 12 days. The T cell response is highly specific in that HRBC immunization fails to activate cells labeled after SRBC immunization. A major portion of the T cells dividing in the secondary response are unlabeled. Control studies indicate that most of these unlabeled cells did not divide in the primary response nor were they naive T cells making a simple concomitant primary response. We conclude that some long-term memory T cells are generated by antigen-induced division of precursor cells. The cellular basis for T cell memory, however, cannot be ascribed entirely to the proliferation of a clone of cells. Either memory cells are generated by nonproliferative mechanisms and/or T memory cells recruit other T cells to respond.
The VHIII Subgroup of Immunoglobulin Heavy Chains: Phylogenetically Associated Residues in Several Avian Species
Authors: Wasserman Richard L. , Kehoe J. Michael , Capra J. Donald
Published: December 2022

Pooled IgG immunoglobulin heavy chains from five avian species were subjected to Edman degradation on an automated protein sequencer. Over 50% of each preparation was “unblocked” and suitable for automated sequencing. A single amino acid was present in greater than 90% of the positions studied. Analysis to position 24 or beyond showed unequivocally that these proteins belong in the VHIII subgroup.

The sequence studies allowed the derivation of a prototype avian sequence for the VHIII subgroup. When this avian prototype was compared with the mammalian prototype VHIII sequence, a high degree of sequence conservation was apparent. Such conservation, considered with the presence of phylogenetically associated residues in both the avian and mammalian proteins, strongly suggests that only limited numbers of germ line genes code for proteins of the VHIII subgroup.
Migration Inhibition Test in Leukocytes from Patients Allergic to Penicillin
Authors: Ortiz-Ortiz Librado , Zamacona Guillermo , Garmilla Clara , Arellano Maria T.
Published: December 2022

Leukocytes from patients with an allergy to penicillin failed to migrate when exposed in vitro to penicillin coupled to human γ-globulin. On the other hand, leukocytes from nonallergic individuals showed no inhibition of migration when exposed to the same antigen.

The sera from the allergic patients were able to sensitize leukocytes obtained from nonallergic individuals. Inhibition of migration of these sensitized leukocytes is produced upon exposure to penicillin-γ-globulin. However, a reversal of the latter inhibition of leukocyte migration was observed when the allergic sera were previously treated with penicillin G alone. The allergic sera able to sensitize leukocytes contained antibodies to penicillin. These antibodies were demonstrated by their ability to neutralize bacteriophage T4 coated with penicillin.
Peculiar Secretory IgA System Identified in Chickens
Authors: Watanabe Hiroshi , Kobayashi Kunihiko
Published: December 2022

IgA was purified from chicken bile and intestinal secretions by using Sephadex G-200 gel-filtration and DEAE-cellulose chromatography. The molecular structure of biliary IgA in chickens resembled the serum type of high polymeric IgA since it lacked a secretory component (SC), and had a molecular weight of 800,000 to 900,000. On the other hand, IgA in chicken intestinal secretions was different from the biliary IgA but was quite similar to mammalian secretory IgA (SIgA) since it was associated with a protein homologous to mammalian SC and had the value of 300,000 to 500,000. It can be predicted that the two types of chicken IgA show phylogenically intermediate characteristics of SIgA system.
Immunologic Evidence for Horizontal Transmission of MTV
Authors: Blair Phyllis B. , Lane Mary-Ann
Published: December 2022

Adult BALB/c female mice raised in the laboratory colony possess spleen cells capable of significant cytotoxic activity against target mammary tumor virus-(MTV) induced mammary tumor cells. If BALB/c females are raised in isolation, their spleen cells are not reactive. Reactivity can be induced in isolated females by caging them with a mouse neonatally infected with MTV. These data provide immunologic evidence for the horizontal transmission of MTV.
The Genetic Control of Antibody Binding Constants and Specificities in Inbred Rats
Authors: Ruscetti Sandra K. , Kunz Heinz W. , Gill Thomas J.
Published: December 2022

The binding constants of antibodies to poly(Glu52Lys33Tyr15) from several strains of high and low responding rats and their various hybrids were measured by equilibrium dialysis. High responders produced antibodies with higher binding constants than low responders. Breeding studies showed that the ability to produce high affinity antibodies is under genetic control and is linked to the major histocompatibility locus. Aggregation of the antigen increased the quantity of antibody and its binding constant in the low responders and decreased both in the high responders. Precipitin reactions using various related synthetic polypeptides indicated that the antibodies produced by the high responders were more cross-reactive than those produced by the low responders. Breeding studies showed that this ability is also inherited in a dominant manner and is linked to the major histocompatibility locus.
Alterations of Murine Immunologic Responses after Silica Dust Inhalation
Authors: Miller S. D. , Zarkower A.
Published: December 2022

The alteration of cell populations and functions related to immunologic responses were examined in the mouse after inhalation of silica dioxide (SiO2). Such exposure produced changes in the T and B lymphocyte population, in the macrophages, and in functions associated with each of these cell types. The possible nature of the immunologic alterations induced by silica dust inhalation is discussed.

In halation of silica dust enhanced the transformation of concavalin A responsive cells, the T lymphocytes, in the spleens of exposed mice, while decreasing the response in the cells of the mediastinal lymph nodes (MLN). Mice exposed to silica dust by inhalation for 2 weeks before and 3 weeks after aerosol or subcutaneous immunization with Mycobacterium tuberculosis H37Ra exhibited enhanced uptake of 3H-thymidine upon culture of their spleen lymphocytes with purified protein derivative (PPD) of tuberculin.

The lipopolysaccharide (LPS) responsive cell population, B lymphocytes, of both spleen and MLN cultures exhibited decreased uptake of 3H-thymidine at all times of assay after silica dust inhalation. Silica-exposed mice also had much lower numbers of plaque-forming cells (PFC) in the spleen, decreased serum agglutinin activity, and generally lower numbers of PFC in the MLN when assayed with Escherichia coli LPS-coated sheep red blood cells after aerosol immunization with whole E. coli O55:B5. Similar immunodepression was noted in exposed mice immunized i.v. with whole E. coli, but to a lesser degree than via aerosol immunization. Depressed B lymphocyte immunocompetence was demonstrated with the adoptive transfer of spleen lymphocytes from exposed and control animals into irradiated recipients.

Alveolar macrophages from silica exposed mice had less ability to phagocytize E. coli, in vitro. Both alveolar and spleen macrophages from exposed animals exhibited decreased capacity to phagocytize antigen and initiate antibody formation, when compared to control animals, upon transfer of in vitro antigen “fed” macrophages from exposed mice to normal syngeneic recipients.
Depression of Human Monocyte Chemotaxis by Herpes Simplex and Influenza Viruses
Authors: Kleinerman Eugenie S. , Snyderman Ralph , Daniels Charles A.
Published: December 2022

To determine the effect of virus infection on monocyte chemotaxis, we isolated mononuclear leukocytes (MNL) from human peripheral blood on a Ficoll-Hypaque gradient and quantitated the chemotactic responsiveness in modified Boyden chambers. The MNL were exposed to herpes simplex (7 plaque-forming units/MNL) or influenza virus (103.0 hemagglutinin units/106.7 MNL) before quantification of chemotactic responsiveness of the cells to a chemotactic lymphokine. Incubation of these viruses with human MNL depressed monocyte chemotaxis by 62 to 85% (p <0.001) as compared to MNL incubated with non-infectious (UV-irradiated) viruses or a control tissue culture preparation. Similar amounts of vaccinia, polio, and reovirus were not inhibitory, and suggested that the inhibition was not a universal effect of viruses. Depressed chemotaxis was not caused by virus-induced cytotoxicity (as measured by trypan blue exclusion) since greater than 95% of the MNL were viable at the end of the assay period. The data suggest that one mechanism for the depression of cell-mediated immunity seen in certain viral infections can be due to the ability of viruses to inhibit monocyte chemotactic responsiveness.
Specificity of the Local Secretory Antibody to Influenza a Virus Infection
Authors: Richman Douglas D. , Murphy Brian R. , Tierney Eveline L. , Chanock Robert M.
Published: December 2022

In animals immunization against influenza A virus via the respiratory tract provides protection against homologous virus challenge that is superior to immunization via a parenteral route although equivalent levels of specific serum antibodies are induced by both procedures (1–3). The evidence for superiority of local immunization in man is less definitive but several studies have shown at least comparable, if not superior, effectiveness of immunization with viral antigen via the respiratory route compared with the parenteral route (4–6). With a series of other respiratory tract viruses the local production of neutralizing antibody of the IgA subclass in the respiratory tract appears to be related to resistance to infection and disease in man; however, a definitive demonstration of the biologic role of local IgA antibody in resistance to influenzal disease has not yet been achieved (7–9). Recently, evidence was presented which suggested the respiratory tract possesses a local cell-mediated immune mechanism which is distinct from systemic cell-mediated immunity (10).
Letters To th Editor
Authors: Cunningham A. J. , Hapel A. J.
Published: December 2022

Sir: The article by Scibienski, Harris, Fong, and Benjamini in the July issue of your Journal demonstrates suppressor tolerance in a way which is analogous to classical helper experiments: an animal tolerized to A and challenged with A-B dimer responds poorly to B. Since the tolerance was induced neonatally, there is a strong possibility that self-tolerance may operate in the same way, i.e., a foreign molecule coupled to a self antigen would invite a suppressed response. Some evidence exists for poor immunogenicity of haptens attached to self-components.

This has a number of interesting implications. Tumors are autologous cells with (sometimes) new antigens attached. The fact that they so often are poorly immunogenic may reflect a mechanism of the kind described by Scibienski et al.: suppressor cells, recognizing the self antigens, damp down the response to the tumor-specific antigens. Thus the tumor survives.
Variation in T and B Cell Deficiency in Different Mouse Allogeneic Radiation Chimeras
Authors: Urso Paul , Gengozian Nazareth
Published: December 2022

The immunologic deficiency of allogeneic radiation chimeras was examined in vitro by culturing spleen cells of the chimera with allogeneic or syngeneic (to donor-type cells of the chimera) activated thymus-derived (T) cells (ATC) or bone marrow-derived (B) cells. The plaque-forming cell (PFC) response to sheep RBC of spleen cells from 100% of the CD2F1 → C3BF1 chimeras was improved considerably (27-fold) with allogeneic ATC but syngeneic ATC gave only a 2-fold increase. Allogeneic B cells induced a moderate increase (4-fold) in the response of spleen cells from only 19% of the chimeras while syngeneic B cells were ineffective. With spleen cells from the reciprocal C3BF1 → CD2F1 chimera there was only a 7-fold increase in the response with allogeneic ATC in 38% of the chimeras and only a 2- to 3-fold increase in 18% with syngeneic ATC. In contrast, there was a 27-fold increase in PFC in about 45% of these latter chimeras with allogeneic B cells while syngeneic B cells failed to improve the response. The PFC generated in mixtures involving both types of chimera spleen cells cultured together were typed with specific isoantiserum and shown to be of CD2F1 origin. These results demonstrate that deficiency in the interacting cellular components of the spleen will vary in different chimeras. Thus, CD2F1 → C3BF1 chimeras are primarily T cell deficient while those of the reciprocal combinations, C3BF1 → CD2F1, are deficient primarily in the B cell population.
Presence of Antigen-Binding Cells for Five Diverse Antigens at the Onset of Lymphoid Development: Lack of Evidence for Somatic Diversification during Ontogeny
Authors: Decker Janet M. , Clarke Jessica , Bradley Linda M. , Miller Alexander , Sercarz Eli E.
Published: December 2022

Cells capable of binding antigen can be detected by half term in mouse, rabbit, and chick embryos, preceding the appearance of most organized lymphoid tissue, some other surface markers, and most immune function (help, antibody synthesis). Binding cells for five diverse antigens are all present at this early stage of development and in approximately the same order of magnitude, depending on the size of the antigen. The number of antigen-binding cells increases during ontogeny, although their frequency in the thymus decreases from the time the organ can first be assayed to the time of birth.

Antigen binding occurs via specific, Ig-like receptors. A proportion of cells is able to bind two antigens noncompetitively when both are added to the cell suspension.

The ability of the lymphoid system to recognize a diverse array of epitopes early in development suggests that genes coding for most antibody specificities are present in the germ-line complement.
Nucleic Acid Antibodies in African Trypanosomiasis: Studies in Rhesus Monkeys and Man
Authors: Lindsley Herbert B. , Kysela Susan , Steinberg Alfred D.
Published: December 2022

Trypanosoma rhodesiense infections in rhesus monkeys led to development of antibodies to nucleic acids. The most dramatic response was to single-stranded DNA (ssDNA); lesser but significant responses were directed to native DNA (nDNA) and double-stranded RNA (dsRNA). Maximum responses occurred at approximately 4 weeks. The antibodies to ssDNA were largely in the 19S fraction early in the course of infection, whereas later they were predominantly in the 7S fraction. Antibodies to nDNA were present almost entirely in the 7S fraction. Trypanosoma gambiense infections in humans were associated with the development of antibodies to ssDNA but not nDNA or dsRNA. These studies demonstrate that antinucleic acid antibodies develop during the course of African trypanosomiasis. The antigenic nucleic acids and any possible relationship to glomerulonephritis remain to be determined.
Relative Insensitivity of Spleen Cells to Interferon
Authors: Gifford George E.
Published: December 2022

Spleen cell cultures were markedly resistant to the antiviral effects of interferon. At least 500 times more interferon was required to inhibit vesicular stomatitis virus replication in such cultures as compared to L-929 cells. Inhibition of virus replication was found only when sufficient interferon was employed also to partially inhibit the incorporation of tritiated thymidine. The data suggest that the inhibition of virus replication was due to an inhibition of the stimulating effects of the mitogens on the cells as well as an inhibition of the low levels of thymidine incorporation in nonstimulated cells.