bluuebunny/crossref_metadata_2025 huggingface dataset:
The Specificity of Human Autoantibodies That React with Both Cell Nuclei and Plasma Membranes: The Nuclear Antigen Is Present on Core Mononucleosomes
Authors: Rekvig Ole P. , Hannestad Kristian
Published: December 2022

We have examined the nature of the nuclear antigen recognized by certain natural human antibodies that react specifically with both cell nuclei and plasma membranes from many species. Partial purification of these antibodies, called X-ANA, is achieved by binding to and rapid elution from the surface of viable human leukocytes. Chicken erythrocyte chromatin was solubilized by digestion with staphylococcal nuclease and fractionated into a 0.15 M NaCl soluble fraction that consisted of core mononucleosomes lacking H1/H5, and a 0.15 M NaCl insoluble fraction composed of polynucleosomes with H1/H5 present. No proteins other than histones were detected. Native and reconstituted mononucleosomes displaced IgG of the leukocyte eluates from nuclei of frozen mouse kidney sections and from the walls of plastic tubes coated with polynucleosomes. The reconstituted core mononucleosomes were 4- 10-fold less efficient inhibitors than native mononucleosomes. Trypsin digested mononucleosomes, free high m.w. DNA, and free histones displayed no or very weak inhibitory activity. The data indicate that X-ANA recognize a complex consisting of the core histones H2A, H2B, H3, H4, and DNA of 140 to 200 base pairs in length.
Plasminogen Activator Production by Human Monocytes
Authors: Greineder Dirk K. , Connorton Kevin J. , David John R.
Published: December 2022

Human monocytes, but not nylon wool column-nonadherent lymphocytes, produce plasminogen activator. The activity is found only in association with intact cells. Exposure of monocytes to activated lymphocytes or to lymphokine-rich supernatants enhances monocyte plasminogen activator production. The assay allows assessment of baseline and activated human monocyte function.
Cellular and Genetic Control of Antibody Responses
Authors: Hodes Richard J. , Hathcock Karen S. , Singer Alfred
Published: December 2022

The expression of Ir gene function has been analyzed in the in vitro primary anti-hapten response to TNP-(T,G)-A—L. Helper T cells, B cells, and accessory cells of responder H-2b and nonresponder H-2a origin were individually assessed for the ability to support PFC responses to TNP-(T,G)-A—L.

For the normal B10.A (H-2a) nonresponder, it was found that the accessory cell function of the spleen adherent cell (SAC) population was under H-2 linked Ir gene control, since B10 (H-2b) but not B10.A (H-2a) SAC were capable of reconstituting responses to TNP-(T,G)-A—L by responder T cells and B cells. In contrast, the function of nonresponder B10.A B cells was not under H-2 linked Ir gene control, since nonresponder B10.A B cells were as effective as responder B10 B cells in responding to TNP-(T,G)-A—L.

The ability of B10.A → (B10 × B10.A)F1 (B10.A → F1) chimera spleen cells to respond to TNP-(T,G)-A—L was also investigated. It was demonstrated that B10.A → F1 spleen cells, which were greater than 95% donor (H-2a) origin, were nonresponders, i.e., the overall nonresponder phenotype of B10.A cells was not altered by maturation in the chimera environment. In experiments designed to examine the competence of each cell subpopulation of B10.A → F1 chimera spleen, it was found that nonresponder (H-2a) B10.A → F1 T cells provided effective help for the response to TNP-(T,G)-A—L when cooperating with responder B10 (but not nonresponder B10.A) SAC accessory cells; and that nonresponder (H-2a) B10.A → F1 B cells were similarly effective in supporting the response to TNP-(T,G)-A—L in the presence of responder accessory cells. Finally, B10, but neither B10.A nor B10.A → F1, SAC were competent to reconstitute the response of accessory cell-depleted (B10 × B10.A) F1 spleen cells to TNP-(T,G)-A—L.

Taken together, these results demonstrated that the Ir gene-controlled unresponsiveness of H-2a nonresponder spleen cells was expressed only at the level of the accessory cell, and not by either T cells or B cells. Thus, H-2a spleen cells are nonresponders to TNP-(T,G)-A—L, because the only accessory cells normally available for presenting TNP-(T,G)-A—L are nonresponder H-2a. Whether the defect is intrinsic to nonresponder accessory cells or is due to the functional absence of helper T cells (or B cells) capable of responding to antigen presented by nonresponder accessory cells has not been established.
Characterization of lymphocyte responsiveness in early experimental syphilis. I. In vitro response to mitogens and Treponema pallidum antigens.
Authors: Lukehart S A , Baker-Zander S A , Sell S
Published: December 2022

Lymphoid cells from spleens and lymph nodes of rabbits infected with T. pallidum respond by proliferation to concanavalin A (Con A) and T. pallidum antigens. Spleen cell responsiveness to treponemal antigens appears 6 days after infection, is 100 to 600 fold higher than the response of uninfected control rabbits, and is maintained throughout the 31-day observation period. Specifically responding cells in the inguinal and popliteal lymph nodes of infected animals are demonstrable on day 10, and the magnitude of the response increases throughout the observation period. Specific responsiveness to T. pallidum antigens in vitro is enhanced in purified T cell populations and is abolished by treatment with goat anti-rabbit thymocyte serum and complement. The response of spleen and lymph node cells to Con A is unaffected during syphilitic infection. These results are consistent with a role for T cell-mediated specific immunity to treponemal antigens early after infection and do not support a hypothesis of depressed cellular immunity during syphilitic infection.
Native and activated properdin: interconvertibility and identity of amino- and carboxy-terminal sequences.
Authors: Medicus R G , Esser A F , Fernandez H N , Müller-Eberhard H J
Published: December 2022

The development of a two-step purification procedure of native properdin with good yield has allowed the physical and chemical comparison of native and activated properdin. The two forms of properdin have identical electrophoretic mobility, subunit size, and amino- as well as carboxyl-terminal amino acid sequences. The two forms of properdin can be interconverted by using mild denaturing agents, indicating that the change in biologic activity is conformational. Circular dichroism analysis of properdin reveals a significant variability in the tertiary structure. However, the differences are a result of the method of purification and do not correspond to the biologic activity of the protein, because the spectra of the interconverted forms of properdin do not change. This indicates that the conformational transition that causes biologic activity changes is small, relative to the conformational variations produced by other conditions that do not alter the biologic activity.
Cytotoxicity of human macrophages for tumor cells: enhancement by bacterial lipopolysaccharides (LPS).
Authors: Cameron D J , Churchill W H
Published: December 2022

Bacterial lipopolysaccharide (LPS) stimulates human macrophages derived from peripheral blood monocytes to kill tumor cells in vitro. Maximum cytotoxicity was observed after 8 to 24 hr of incubation with LPS. However, if the macrophages are activated with LPS for 8 hr and then maintained in medium for an additional 16 hr before assay, their cytotoxic capacity is lost. In comparison to normal macrophages, LPS-activated macrophages were cytotoxic to the three malignant cell lines tested but had no effect on the three nonmalignant cell lines. Human macrophages can be made tumoricidal by the addition of greater than or equal to 10 microgram/ml LPS, and the effect is abolished in the presence of polymyxin B.
Elicitation of anti-Sendai virus cytotoxic T lymphocytes by viral and H-2 antigens incorporated into the same lipid bilayer by membrane fusion and by reconstitution into liposomes.
Authors: Hale A H , Lyles D S , Fan D P
Published: December 2022

We have investigated the minimal molecular requirements for elicitation of anti-Sendai virus cytotoxic T lymphocytes (CTL), and the minimal molecular requirements for the recognition and lysis processes associated with anti-Sendai virus CTL-target cell interactions. This report demonstrates a) that the hemagglutinin-neuraminidase and/or fusion glycoproteins of Sendai virus can elicit anti-Sendai virus CTL and b) that these glycoproteins and H-2 antigens must be within the same membrane lipid bilayer for effective elicitation of anti-Sendai-virus CTL and for effective recognition and lysis of target cells by anti-Sendai virus CTL.
A hybridoma from an autoimmune NZB/NZW mouse producing monoclonal antibody to ribosomal-RNA.
Authors: Eilat D , Asofsky R , Laskov R
Published: December 2022

Spleen cells from an unimmunized autoimmune NZB/NZW F1 female mouse were fused to the BALB/c MPC-11 drug-resistant clone 45.6 TG 1.7. One hybrid clone (D4) produced IgG-3 immunoglobulin that bound ribosomal RNA. A high concentration of this antibody was produced in the ascitic fluid of NZB/NZW male mice. DNA, tRNA, and synthetic single- and double-stranded polynucleotides could not bind significantly to the antibody. A Scatchard analysis showed that the rRNA-binding immunoglobulin is monoclonal and has a high affinity (10(9) liter/mole) for the RNA antigen.
The sequential release of granule constitutents from human neutrophils.
Authors: Bentwood B J , Henson P M
Published: December 2022

The degranulation response of human neutrophils to the calcium ionophore A23187, serum opsonized zymosan (ZC), aggregated gamma-globulin (A gamma G), C5a, formyl-methionyl-leucyl-phenylalanine (FMLP), and PMA has been studied as a reaction time course in order to compare the release kinetics of the separate granule types. Cell suspensions were treated with submaximal doses of stimuli for various time intervals, and the isolated supernatants were assayed for granule constituents. Lactoferrin (LF), a unique specific (secondary) granule protein, was measured by radioimmune assay, and the azurophil (primary) granule components, myeloperoxidase (MPO) and beta-glucuronidase (beta-glu), by enzymatic activity. A sequential pattern of first LF release followed by MPO and beta-glu was demonstrated with each of the stimuli examined, with or without cytochalasin B pretreatment. These kinetic studies demonstrate that the extracellular release of the specific and azurophil granules occur sequentially in human neutrophils with both soluble and particulate stimuli. These findings support the concept that the two granule types are subject to separate controlling factors.
Cellular and genetic control of antibody responses. VIII. MHC restricted recognition of accessory cells, not B cells, by parent-specific subpopulations of normal F1 T helper cells.
Authors: Singer A , Hathcock K S , Hodes R J
Published: December 2022

Normal F1 helper T cell populations were analyzed under conditions in which the number of T cells was strictly limiting so that anti-hapten PFC responses to TNP-KLH increased linearly with increasing numbers of T cells. The slope of the response line is a measure of the helper activity of the added T cell population and reflects the number of helper T cells activated. In this way, the recognition and activation requirements of normal F1 helper T cell subpopulations were analyzed. It was determined that the F1 helper T cells specific for recognizing antigen in the context of the MHC determinants of only one parent specifically recognized those determinants expressed on accessory cells, but not on B cells. Indeed, each parent-specific F1 T cell subpopulation was only triggered by one parent's accessory cells; but once triggered, each parent-specific F1 T cell subpopulation was capable of activating either parent's B cells.
Nature of hapten-modified determinants involved in induction of T cell tolerance and suppressor T cells to NDFB contact sensitivity.
Authors: Miller S D , Conlon P J , Sy M S , Moorhead J W , Colón S , Grey H M , Claman H N
Published: December 2022

Unresponsiveness to DNFB contact sensitivity induced by DNP-modified lymphoid cells (DNP-LC) is mediated by two separable pathways: a rapidly induced, long lasting inhibition of reactive T cell clones (donor tolerance), and a transient period of suppressor T cell (Ts) activity. The present report has examined the nature of the hapten-modified determinants responsible for the induction of these pathways by utilizing soluble DNP-LC cell lysate preparations as tolerogens. The results indicate that both DNP-modified MHC and non-MHC encoded determinants can mediate donor tolerance 7 days after tolerization. On the other hand, the induction of Ts requires DNP-modified MHC determinants, since DNP-LC lysates passed over lentil lectin or specific anti-H-2 immunoabsorbent columns lost their ability to induce Ts. Additional experiments showed that the injection of DNP-LC lysate compatible with the recipient strain at the H-2K and H-2D region of the MHC was sufficient for the induction of Ts. We propose that Ts induction involves the direct presentation of DNP-H-2 determinants to Ts precursors, whereas the induction of donor tolerance may involve host processing and presentation of DNP-modified membrane determinants in conjunction with host MHC structures.
Progressive myelopathy in older German shepherd dogs. II. Presence of circulating suppressor cells.
Authors: Waxman F J , Clemmons R M , Hinrichs D J
Published: December 2022

Progressive myelopathy in the German shepherd dog is a degenerative neurologic disease of unknown etiology. Results presented in a previous study indicated a depression in the response to thymus-dependent mitogens by peripheral blood leukocytes obtained from dogs with progressive myelopathy. Data presented here indicate that this depressed response to mitogens was associated with the presence of peripheral blood suppressor cells. Suppressor cell activity was detected in dogs that were severely affected with PM, but was not apparent in dogs that were mildly affected. Peripheral blood leukocytes obtained from dogs with progressive myelopathy suppressed the mitogenic response to autologous lymph node cells as well as allogeneic normal canine peripheral blood cells. The suppressor cells had the capacity to suppress mixed leukocyte reactions. Suppressor cell activity was radioresistant. Both nylon wool-adherent and -nonadherent peripheral blood leukocyte populations contained suppressor activity. Suppressive activity diminished after incubation of the suppressor cells with indomethacin, suggesting that suppression may be mediated by the release of prostaglandins. Although a role for peripheral blood suppressor cells in the disease process has not yet been established, it is possible that this abnormal regulatory activity reflects an attempt by the host to control an autoimmune event.
A mature T lymphocyte marker closely linked to Igh-1 that is expressed on the precursor for the suppressor T cell regulating a primary response to SRBC.
Authors: Owen F L
Published: December 2022

The product of a new genetic locus closely linked to Igh-1 in the mouse has previously been shown to be expressed on T cells by using an in vitro fluorescent antibody assay. In vivo studies reported here show the determinant coded for by that locus is expressed in unimmunized animals on the precursor for a suppressor T cell regulating a primary response to SRBC. Antisera raised in allotype congenic animals by immunization with suppressor T cells (Ts) for the ARS.CRI stimulate Lyt2+3+ suppressor cells for unrelated antigens. The suppressive effects of the serum can be absorbed with T cells but not with B cells. Suppression of an IgM PFC response in allotype congenic animals confirms close linkage of the marker to Igh-1 but not to H-2. This determinant is expressed on Ts cells for many antigens and may represent a heavy chain linked "constant" portion of the antigen-specific receptor.
Flow sorting of antigen-binding B cell subsets.
Authors: Greenstein J L , Leary J , Horan P , Kappler J W , Marrack P
Published: December 2022

Antigen binding was used as a probe in the definition of functional B cell heterogeneity. Unprimed, anti-Thy 1 and complement-treated spleen cells were stained with fluorescent trinitrophenylated bovine serum albumin (FL-TNP-BSA). These cells were sorted, fluorescence negative from fluorescence positive, by using a multiparameter cell sorter and assayed for precursor frequency in antibody responses to TNP by limiting dilution analysis. The cells that bound FL-TNP-BSA were demonstrated to be enriched for antibody-forming precursors to the antigens TNP-lipopolysaccharide (LPS), TNP-sheep red blood cells (SRBC), and TNP- or DNP-Ficoll, whereas the fluorescence negative cells were depleted for these responses. B cells that bound FL-TNP-BSA were then sorted into populations that bound a moderate or high amount of FL-TNP-BSA. The B cells responsive to TNP-LPS and TNP-SRBC were present in both the moderate and high binding populations. In contrast, the B cells responsive to TNP- or DNP-Ficoll were present only in the cells that bound a moderate amount of FL-TNP-BSA. These experiments suggest that there is a population of B cells in adult mouse spleen that binds large amounts of antigen, and that can respond to antigen carried on LPS or SRBC but not carried on Ficoll.
Gangliotetraosylceramide is a T cell differentiation antigen associated with natural cell-mediated cytotoxicity.
Authors: Schwarting G A , Summers A
Published: December 2022

Thymocytes and splenic T cells from C57BL/6 mice were analyzed for their content of glycosphingolipids (GSL) by high performance liquid chromatography. Glucosylceramide and lactosylceramide were shown to be the major GSL of thymocytes from mice 1 to 30 weeks of age, whereas a third GSL, asialo GM1, was found only in trace amounts. In splenic T lymphocytes, however, asialo GM1 was shown to increase in concentration with age. It reached a peak at 5 to 10 weeks of age, at a concentration 10 to 20 times that of thymocytes or neonatal splenic T cells. These studies confirm the previous finding with antibodies to asialo GM1, that this glycosphingolipid is a true differentiation antigen in the mouse. Subsequent analysis of C57BL/6 bg/bg (beige) mice, which lack natural killer function, demonstrates that levels of asialo GM1 in the splenic T cell population do not increase with age but remain at the level of 2- to 3-week-old normal mice, indicating that asialo Gm1 may be an important cell surface component in the generation of natural cell-mediated cytotoxicity.
Influence of adult thymectomy on immunocompetence in patients with myasthenia gravis.
Authors: Wijermans P , Oosterhuis H J , Astaldi G C , Schellekens P T , Astaldi A
Published: December 2022

The influence of adult thymectomy on several parameters of immunocompetence in patients with myasthenia gravis (MG) was investigated. Since incomplete thymectomy may lead to the presence of thymic remnants, we determined the activity of a thymus-dependent factor in the sera of the MG patients. As measured by several parameters, MG patients showed a normal immunocompetence compared with healthy controls, except in the response to DNCB sensitization in vivo. When tested at least 5 years after thymectomy, MG patients were found to have decreased response to mitogens, and a decreased cytotoxic T cell response in cell-mediated lympholysis. The response to challenge with DNCB in vivo was decreased both in thymectomized and nonthymectomized MG patients. No difference was found in a) the percentage of circulating T, B, non-B/non-T cells; b) the response to allogeneic cells (MLR); c) the antibody-dependent lymphocytotoxicity; d) the production of immunoglobulins in vitro by pokeweed mitogen-stimulated cells; and e) the anamnestic response to antigens in vitro. We conclude that adult thymectomy results in a decrease in the function of some subpopulations of lymphocytes.
A B cell subpopulation binds to macrophages: this binding can be disrupted by T cells.
Authors: O'Toole M M , Wortis H H
Published: December 2022

We have investigated the macrophage-binding properties of normal murine B cells and found that only a defined subpopulation of B cells can bind to macrophages. This subpopulation corresponds to the Lyb3--positive subpopulation. A population of T cells exists that disrupts this macrophage-B cell interaction. These findings are discussed in light of the demonstrated dependence on macrophages of several Lyb3+ cell functions.
Heavy chain-specific suppression of immunoglobulin synthesis and secretion by lymphocytes from patients with selective IgA deficiency.
Authors: Schwartz S A
Published: December 2022

A simple, solid-state immunofluorescent assay specific for the heavy chain of human immunoglobulins (Ig) was adapted for studying pokeweed mitogen- (PWM) stimulated Ig biosynthesis and secretion by peripheral blood lymphocytes (PBL) in vitro. PBL from patients with panhypogammaglobulinemia were noted to synthesize and secrete decreased amounts of all classes of immunoglobulin after polyclonal activation of B cells in vitro with PWM. PBL from 14 patients with selective deficiency of IgA were capable of synthesizing and secreting significant levels of IgG and IgM after culture with PWM; however, they did not produce appreciable amounts of IgA. Thus, B lymphocyte differentiation in vitro parallels the clinical status. Several different immunoregulatory phenomena were observed when PBL from patients with selective IgA deficiency were co-cultivated with cells from healthy donors. Most notable was the specific suppression of IgA synthesis and secretion seen in 8 of 14 patients studied, although other modulatory effects including enhancement and suppression of all Ig classes were also observed. These results suggest that the pathologic basis of selective IgA deficiency may be heterogeneous and support a model for the role of Ig class-specific suppressor cells in the pathogenesis of some cases of selective IgA deficiency.
Allelic forms of the immunoglobulin heavy chain variable region.
Authors: Rudikoff S , Potter M
Published: December 2022

The complete variable region sequence of the heavy chain from a phosphorylcholine-binding myeloma protein of C57/BL allotype has been determined. When this sequence was compared with the germ line-coded heavy chain variable region sequence of BALB/c phosphorylcholine-binding proteins, five differences were observed. Four of the substitutions were located in the framework portion of the variable region and the fifth in the "J" or joining segment. Two of the framework substitutions were found at positions 14 and 16. Previous studies have shown that heavy chains from all anti-phosphorylcholine antibodies induced in C57/BL mice have the same amino acids at positions 14 and 16 as the C57/BL myeloma protein described in this communication. It has therefore been concluded that these residues are encoded in the C57/BL germ line in contrast to two alternatives in the BALB/c genome. This finding, in addition to the 96% homology found between the C57/BL and BALB/c sequences, suggests that these structures represent allelic forms of an entire variable region.
Functional differences between cells from MLR colonies grown in soft agar cultures.
Authors: Zeevi A , Chiu K M , Duquesnoy R J
Published: December 2022

This report describes a method of growing soft agar colonies of human T lymphocytes activated in the MLR. Two types of colonies were demonstrated: lower colonies grew within the agar layer, and upper colonies grew on the surface of the agar layer. Three days of priming the lymphocytes in the MLR and the use of supernatants of day-3 MLR cultures to provide T cell colony growth factor were necessary for optimal colony formation. Lymphocytes obtained from colonies were grown in long-term (2 to 4 weeks) cultures to generate sufficient numbers of cells to be tested in different functional assays. Cells from both types of colonies exhibited PLT activity. Upper colony cells showed considerably higher CML activity than lower colony cells (mean percent cytotoxicity 37 +/- 5 vs 6 +/- 3). Cells from both types of colonies contained radiosensitive suppressor cell activity that inhibited the primary MLR. The suppressor cell effect of lower colony cells was specific for the original stimulator, but upper colony cells displayed nonspecific suppressive effects. For both types of colony cells, it appeared that suppressive effects were unrelated to the CML activity of these cells. These data suggest that the soft agar colony assay offers a promising approach to separate subpopulations of lymphocytes activated in the MLR.
Induction of murine B cell proliferation by insolubilized anti-immunoglobulins.
Authors: Puré E , Vitetta E
Published: December 2022

This study demonstrates that intact antibodies specific for mu, delta, or light chains when coupled to Sepharose are effective in delivering proliferative signals to B cells. Furthermore, using Sepharose-coupled anti-delta antibodies, we have shown that hybridoma anti-delta (that is not active as soluble protein) is as effective as rabbit anti-delta in activating murine B cells. However, antibodies directed against two other surface molecules, I-A and H-2K, were not mitogenic. Thus, sIgM and sIgD are comparable in their ability to transmit a proliferative signal to the B cell and sIg seems to play a unique role in this regard.
Lymphocyte surface membrane immunoglobulin in myeloma. II. T cells with IgA-Fc receptors are markedly increased in mice with IgA plasmacytomas.
Authors: Hoover R G , Lynch R G
Published: December 2022

BALB/c mice with established subcutaneous IgA plasmacytomas (MOPC-315, MOPC-167, McPC-603, or TEPC-15) develop large numbers of circulating theta-bearing lymphocytes that have surface membrane receptors for IgA. The extraordinary expansion of T alpha cells in mice with IgA plasmacytomas accounts for the large number of lymphocytes with surface membrane myeloma protein that are found in these mice. The IgA myeloma protein that was originally bound to the T cell receptor in vivo was competitively displaced in vitro by other purified IgA myeloma proteins but not by their F(ab)' fragments. After overnight incubation in vitro, or brief exposure to pronase, IgA was released from the T cell surface, rendering available a surface membrane receptor for IgA. In vitro binding of purified IgA to the T alpha cell receptor was not inhibited by purified IgG1 or IgM myeloma proteins. T alpha cells were not increased in mice with three variant plasmacytomas that did not secrete large amounts of IgA. These observations: i) establish the generality of T alpha cell expansion in mice with IgA plasmacytomas, ii) establish an association between elevated serum IgA levels and T alpha cell expansion, and iii) identify a source of large numbers of T alpha cells that can be specifically purified for structural and functional studies.
Surface immunoglobulin-bearing rabbit lymphocytes express both VH and L chain allotypic determinants.
Authors: Raffel C , Sell S
Published: December 2022

The cell surface distributions of a locus and b lucus rabbit immunoglobulin allotypes have been examined simultaneously, using immunoelectronmicroscopic techniques. Most rabbit lymphocytes that bear surface immunoglobulin express both a and b markers. This is true of lymphocytes from blood, spleen, and lymph node of normal and immunized rabbits. A preponderance of cells bearing VH markers (a locus) but not L chain markers (b locus) was not observed.
The in vitro response of human lymphocytes to Pneumocystis carinii antigen.
Authors: Herrod H G , Valenski W R , Woods D R , Pifer L L
Published: December 2022

Pneumocystis carinii pneumonitis (PCP) is a major complication in the immunocompromised host. Recent evidence suggests that most normal individuals have detectable antibody against this organism. The role of the various components of the immune system in protecting the host from acute PCP is unclear. We have examined the in vitro proliferative response of lymphocytes from normal adults to P. carinii antigen. Fourteen of 16 subjects had a positive response with stimulation indices greater than 3. This response was due primarily to thymus-derived (T cell) lymphocytes and was dependent upon the presence of adherent cells. The response was most likely not due to a mitogenic component in our antigen preparation, since lymphocytes from only 2 of 16 cord blood specimens had stimulation indices greater than 3.
Regulation of expression of a family of cross-reactive idiotypes.
Authors: Hirai Y , Lamoyi E , Dohi Y , Nisonoff A
Published: December 2022

It has recently been shown that anti-p-azophenylarsonate antibodies of A/J mice, which share a common idiotype, are not homogeneous but actually comprise a family of idiotypically related molecules. To obtain additional insight into the degree of relatedness of antibodies within this family, we have determined whether inoculation of any idiotype-positive hybridoma product, conjugated to thymocytes, can activate a regulatory mechanism capable of controlling the entire cross-reactive idiotypic response. In addition anti-idiotypic antibodies were prepared against individual hybridoma products, and their suppressive effects on the idiotypic component of the humoral response were determined. Inoculation of each of the idiotype-positive hybridoma products or anti-idiotypic antisera caused virtually complete suppression of the idiotypic component of the immune response. Furthermore, it was shown that the state of suppression induced by the inoculation of a hybridoma products could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. The results indicate that there are sufficient structural similarities among the family of antibodies comprising the major cross-reactive idiotype to permit their recognition by the same set of elements involved in idiotypic regulation.
Antigen-specific activity of murine leukocyte dialysates containing transfer factor on human leukocytes in the leukocyte migration inhibition (LMI) assay.
Authors: Borkowsky W , Suleski P , Bhardwaj N , Lawrence H S
Published: December 2022

We report on the extension of the direct leukocyte migration inhibition (LMI) test as an assay for antigen-specific activity in human leukocyte dialysates (DLE) containing transfer factor to an evaluation of antigen-specific activity in DLE prepared from inbred mice. Murine DLE was observed to cause antigen-dependent and antigen-specific effects on the inhibition of migration of nonimmune human leukocyte populations. Pulsing of nonimmune human leukocyte with DLE preparations from BALB/c and SJL mice immunized with Candida, diphtheria toxoid, and SK-SD resulted in their inhibition of migration in the presence of the respective antigens. The antigen-specific activity in murine DLE was found to be present in lymph node cell preparations and to be absent from spleen cell preparations of the same donors. The activity of DLE in lymph node cells was found to be present in the theta-cell enriched subpopulation of nonadherent lymphocytes after passage through nylon wool columns. The antigen-specific activity of murine DLE, as we have reported for human DLE, was found to reside in the < 3500 dalton dialysis fraction and not in the < 3500 dalton fraction. We conclude that nonimmune human leukocytes in the LMI test provide a suitable assay for the detection of antigen-specific activity in murine DLE as well as that in human DLE. Additionally, murine DLE is active across species barriers and appears to share properties with human DLE.
Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. II. In vitro killing of TNP-schistosomula by human eosinophils and neutrophils.
Authors: Moser G , Sher A
Published: December 2022

Purified human eosinophils and neutrophils were compared for their capacity to mediate anti-TNP antibody-dependent killing of schistosomula of Schistosoma mansoni surface labeled with TNBS. In contrast with findings from studies employing human anti-schistosome sera and unmodified larvae, neutrophils in addition to eosinophils were found to be potent killers of schistosomula. Indeed, neutrophils proved to be consistently more effective than eosinophils in killing haptenated larvae throughout the dose response of each of the components (i.e., the TNBS surface label, rabbit anti-TNP sera and cells) of the in vitro reaction. The capacity of neutrophils to kill haptenated parasites is not likely to be due to the use of rabbit antibodies in the assays, since these cells were ineffective in killing unlabeled schistosomula when either rabbit or human anti-schistosome sera were employed. Furthermore, the ability of neutrophils to destroy TNP-labeled schistosomula does not appear to result from sublethal damage induced by the labeling procedure, since haptenated parasites were found to be no more susceptible than unmodified worms to killing mediated by anti-schistosome sera plus eosinophils or complement and, like unlabeled parasites, could not be killed by anti-schistosome sera plus neutrophils. The lethal interaction of neutrophils and haptenated schistosomula was preceded by a rapid and marked adherence of the cells to the worms, an effect that was not observed in the nonlethal interaction of neutrophils with schistosomula induced by anti-schistosome sera. The results argue, therefore, that the capacity of different granulocyte populations to kill schistosomula may be determined by the kinetics and intensity with which the effector cells adhere to the parasites. The findings further suggest that a key factor influencing the differential adherence of the cells to the parasites and their subsequent death may be the nature of the specific antigen-antibody interaction occurring at the surface of the larvae.
Role of lymphotoxin in antibody-dependent cell-mediated cytotoxicity (ADCC).
Authors: Kondo L L , Rosenau W , Wara D W
Published: December 2022

The precise mechanism by which human peripheral blood lymphocytes (PBL) lyse antibody-coated target cells in antibody-dependent cell-mediated cytotoxicity (ADCC) is unclear. Antiserum against purified human alpha-lymphotoxin (anti-LT serum) inhibited an ADCC reaction with human PBL as effector cells and antibody-coated mouse P815 mastocytoma cells as targets. This observation suggests that alpha-lymphotoxin is instrumental in the destruction of antibody-coated targets. The inhibition was not due to a cytotoxic effect of the anti-LT serum on the PBL, nor was it caused by the presence of IgG aggregates. PBL incubated with cycloheximide were still cytotoxic in the ADCC system, although to a somewhat lower degree. This finding suggests that de novo protein synthesis not essential in the cytotoxic reaction.
Evidence for homologues of the murine I-A and I-E loci in the rat MHC.
Authors: Shinohara N , Sachs D H
Published: December 2022

Various anti-Ia mouse alloantisera were examined for cross-reactivity with rat lymphocytes. Many of them were found to cross-react with rat spleen cells with anti-Ia-type (40 to 60%) killing. Likewise, mouse antisera raised against rat lymphocytes cross-reacted with mouse cells, and some of these reactions could be mapped within the I-A subregion and some within the I-E/C subregion of the mouse H-2 complex. Using such cross-reactive mouse alloantisera and a defined anti-MHC rat alloantiserum (BN anti-LEW), SDS-PAGE analyses were performed on an NP-40 extract of internally labeled LEW antigen. The cross-reactive mouse alloantisera precipitated Ia-like glycoproteins (35,000 and 28,000 m.w.), which could be completely removed by pretreatment with the rat anti-MHC antiserum. The cross-reactive anti-I-A and anti-I-E/C mouse antibodies were found to react with 2 different classes of rat Ia molecules by sequential precipitation analysis. On the basis of the specificity of the mouse alloantibodies, one Ia molecule appears to be a homologue of the murine I-A antigens and the other a homologue of the murine I-E antigens. Preabsorption of LEW antigen with cross-reactive anti-I-A and anti-I-E/C mouse alloantibodies together did not leave a detectable amount of residual Ia molecules precipitable with the rat alloantiserum, which indicates that there is probably no other major class of rat Ia molecules. These results support the hypothesis that these 2 major classes of Ia molecules have evolved independently from distinct primordial genes.
Phylogeny of NK cell reactivity against human and nonhuman primate lymphoblastoid cell lines: evolving and conserved target antigens.
Authors: Clark E A , Sturge J C
Published: December 2022

Both human and nonhuman primate natural killer (NK) cells display little or no killing against allogeneic B lymphoblastoid cell lines. However, the same B cell lines are killed in baboon-human (B alpha H) or human-baboon (H alpha B) xenogeneic combinations. Competition-inhibition experiments indicate that the xenogeneic determinants recognized by NK cells are found principally if not exclusively on B rather than T target cells. Cell lines from closely related chimpanzee or orang-utan species can block some killing of human target cells, but lines from more distantly related species including gibbon, macaque, baboon, and marmoset do not inhibit cytotoxicity. This suggests that some NK target structures are susceptible to evolutionary change. Gibbon or marmoset lines infected with Epstein Barr virus (EBV) do not block killing, suggesting that host rather than viral determinants are being recognized. In contrast to the foregoing pattern, 2 cell lines derived from the same baboon differed in susceptibility to NK lysis irrespective of the effector cell species. The viral producer line 13CB-1 was more susceptible to lysis than its viral nonproducer partner 26CB-1. Thus, some NK target antigens may be highly conserved whereas others evolve with the species.
Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production.
Authors: Snyder D S , Unanue E R
Published: December 2022

Corticosteroids have profound effects on functions of the macrophage associated with antigen presentation to T cells. The drugs inhibited the expression of surface I-region-associated (Ia) antigens by peritoneal macrophages both in vitro and in vivo, reduced the production of IL 1, and inhibited antigen presentation for T cell proliferation by macrophages. The doses of hydrocortisone and prednisolone that inhibited by 50% Ia expression in cultured macrophages ranged around 2 to 5 x 10(-8) M. These results could explain one mechanism by which corticosteroids suppress the induction of immune responses.
Limited life span of extensively proliferating B cells: no evidence for a continuous class or subclass switch.
Authors: Bergstedt-Lindqvist S , Severinson E , Fernandez C
Published: December 2022

The polyclonal B cell activators (PBA) dextran sulphate (DxS) and lipopolysaccharide (LPS) induce a marked synergistic response in mouse splenic B cells. Such activated B cell blasts could be maintained in culture for a total period of 15 to 20 days, provided the cells were subcultured repeatedly in fresh medium containing the PBA. After this time period activation could no longer be achieved. The B cell blasts responded at all times better to LPS plus DxS than to either PBA added alone. Furthermore, LPS-induced B cell blasts also responded better to LPS plus DxS than to LPS alone. Activated cells secreted IgM and switched to IgG3 and IgG2b secretion. At the end of the culture period, approximately one cell out of four secreted IgG. The kinetics of IgG3 and IgG2b production were similar, and the fraction of cells secreting these subclasses increased at similar rates throughout the culture period. We conclude that high-rate secreting and proliferating B cells have a limited life span. Furthermore, most activated B cells do not seem to go through a continuous subclass switch but keep on secreting the subclass they originally switched to.
Anaphylactic Shock and Mechanical Obstruction of the Hepatic Veins in the Dog
Authors: Simonds J. P. , Brandes W. W.
Published: December 2022

Mechanical obstruction of the hepatic veins of the dog produces a fall in arterial blood pressure similar to, but not so marked as, that which occurs in anaphylactic shock. The injection of the homologous serum into a sensitized dog while the hepatic veins are mechanically obstructed does not cause an additional fall in blood pressure that can be attributed to the onset of anaphylactic shock. Peptone, on the other hand, does induce a further fall in pressure under these conditions as a result of peripheral dilatation. When the homologous serum is injected into a sensitized dog with the hepatic veins mechanically obstructed and, after an interval of from one to three minutes, the hepatic veins are released either indefinitely, or for fifteen to twenty seconds and then reconstricted, the ensuing fall in blood pressure is, in most animals, greater than that induced by the obstruction alone. Fifteen to twenty seconds is sufficient time for enough of the injected serum in the circulating blood of a sensitized dog to pass through the liver to initiate anaphylactic shock. It is suggested that in anaphylactic shock in the dog very little blood escapes from the liver into the vena cava. It is further suggested that in anaphylactic shock in the dog there is a peripheral dilatation such as occurs after injections of peptone. But before this peripheral effect is induced the injected serum must pass through the liver of the sensitized animal, while in peptone shock this is not necessary.
Relation of Anaphylaxis to Immunity
Authors: Manwaring W. H. , Reeves D. L. , Moy H. B. , Shumaker P. W. , Wright R. W.
Published: December 2022

Tissues of actively immunized dogs transplanted by blood vessel anastomosis into hypersensitive recipients show a complete acquired insusceptibility to the hepatic anaphylatoxin.

The hepatic anaphylatoxin, therefore, must be regarded as a secondary antigen, presumably of protein nature, and conceivably a denaturization product of the primary antigen.

The antianaphylatoxic immunity factor is apparently not transferred from one animal to another by even massive immune blood transfusion.
On the Cocto-Immunogen of the Dysentery Bacillus (Shiga Type)
Authors: Torikata R. , Fujimoto A.
Published: December 2022

I. Introduction. Since the publication on “Cocto-precipitinogen and cocto-immunogen” by one of us, Torikata, in 1917 (1), the experiments have been repeated with various bacterial organisms by many investigators. But no one has yet repeated the experiments with regard to dysentery, except Boku (10), who successfully immunized rabbits with cocto-immunogen of the Shiga dysentery bacillus in order to obtain dysentery agglutinating serum. This was the reason that prompted us to undertake the present study.

It is a well known fact that the dysentery vaccine or raw toxin is so extremely strong that it can not be used for immunizing human beings or laboratory animals, such as rabbits. Our primary object was to find out whether or not the cocto-immunogen can be used more advantageously to immunize rabbits and at the same time to test the value of the cocto-immunogen as such.
The Action of Enzymes on the Protective Antibody of Pneumococcus
Authors: Felton Lloyd D. , Kauffmann Gladys
Published: December 2022

It has been shown that the protective antibodies as found in a water-insoluble protein separated from Types I, II, and III antipneumococcus horse serum by dilution in water, were digested by the proteolytic enzymes pepsin, trypsin, and pancreatin, and also papain, with a loss in their protective quality. This loss apparently paralleled the extent of protein cleavage. A prolonged contact of the antibody solution with rennin, ptyalin, amylopsin, taka-diastase, and malt diastase resulted in loss to a varying degree, ptyalin and rennin being the least destructive. Huntoon's antibody was completely destroyed with any of the proteolytic enzymes pepsin, trypsin, or pancreatin.
Experimental Immunisation with Bacteria Detoxicated by Gold Chloride
Authors: Osman M. B.
Published: December 2022

Gold chloride exerts a marked detoxicating effect on various bacteria. The power of such detoxicated bacteria to stimulate agglutinin production is slight. Animals immunised with such detoxicated organisms tolerate large doses of live organisms. By immunising with a large dose of detoxicated organisms, followed after a week by a large dose of live organisms, an agglutinating antiserum of high titer can be readily obtained.
Skin Tests to Extracts of Echinococcus and Ascaris
Authors: Rackemann Francis M. , Stevens Amos H.
Published: December 2022

The skin reaction to echinococcus fluid which is obtained in patients recently suffering from echinococcus disease, is accompanied by circulating antibodies capable of transferring a local sensitiveness to the skin of normal individuals, but not capable of being precipitated by the echinococcus fluid in the test tube. Similarly, the skin reaction to Ascaris extract is likewise accompanied by “reagins” but not by “precipitins.” Hypersensitiveness to Ascaris is not uncommon, and may be acute, even in individuals who give no signs or symptoms of previous infection. These various observations suggest that the intradermal injections of the corresponding extracts may be a method of diagnosis in other forms of helminthiasis, which is worthy of study.
The Influence of Heparin on the Course of Anaphylaxis in the Guinea Pig
Authors: Reed C. I. , Lamson R. W.
Published: December 2022

A decreased coagulability of the blood of the experimental animal during anaphylactic shock has been observed in dogs (1), rabbits (2), guinea pigs (3), and more recently in pigeons (4), (5). This is perhaps most pronounced in the dog (2), although very definite in the other animals mentioned. Few attempts have been made to correlate this phenomenon with the progress of anaphylactic shock. It is the purpose of this paper to report the results obtained when an anticoagulant, heparin, is used to increase the coagulation time of the blood of a sensitized animal before the shock dose of antigen is injected.

In a previous communication (6) it was shown that repeated injections of heparin after suitable intervals did not produce any anaphylactic symptoms in guinea pigs. It was also mentioned that the power of heparin to modify the anaphylactic reaction from horse serum was then under investigation.
A group-specific inhibitor of lysosomal cysteine proteinases selectively inhibits both proteolytic degradation and presentation of the antigen dinitrophenyl-poly-L-lysine by guinea pig accessory cells to T cells.
Authors: Buus S , Werdelin O
Published: December 2022

A limited intralysosomal proteolytic degradation is probably a key event in the accessory cell processing of large protein antigens before their presentation to T cells. With the aid of highly specific inhibitors of proteinases, we have examined the role of proteolysis in the presentation of antigens by guinea pig accessory cells. The proteinase inhibitor benzyloxycarbonyl-phenylalanylalanine-diazomethyl-ketone, which selectively inhibits cysteine proteinases, was used to block this set of enzymes in cultured cells. We demonstrate that the selective inhibition of the cysteine proteinases of antigen-presenting cells causes a profound inhibition of both the proteolytic degradation and the presentation of the synthetic antigen dinitrophenyl-poly-L-lysine. In contrast, the presentation of another synthetic antigen, the copolymer of L-glutamic acid and L-alanine, was enhanced by the same inhibitor. Another inhibitor, pepstatin A, which selectively blocks aspartic proteinases, did not block the presentation of dinitrophenyl-poly-L-lysine. The results identify cysteine proteinases, probably lysosomal, as one of the groups of enzymes involved in antigen processing.