bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a purified glycoprotein from Schistosoma mansoni eggs: specificity, stability, and the involvement of carbohydrate and peptide moieties in its serologic activity.
Authors: Hamburger J , Lustigman S , Siongok T K , Ouma J H , Mahmoud A A
Published: December 2022

A major egg glycoprotein (MEG) was purified from a crude soluble extract of Schistosoma mansoni ova (Egyptian strain) by successive steps of lectin affinity and ion-exchange chromatography. Radioiodinated MEG exhibited a single precipitation band upon immunodiffusion against antiserum from chronically infected mice, and ran as a single band on PAGE (Rf 0.38) and SDS-PAGE (Rf 0.36). Its estimated m.w. was 70,000. The degree of stage and species specificity of MEG and the effect of various treatments on its serologic reactivity were determined by radioimmunoassay (RIA). A low degree of cross-reactivity between MEG and similarly prepared soluble antigens from adult worms and cercariae was demonstrated by RIA inhibition tests, whereas a high degree of cross-reactivity was found between MEG and a crude soluble S. haematobium egg antigen. In similar RIA inhibition tests, the Puerto Rican S. mansoni had a lower degree of cross-reactivity with S. haematobium than the Egyptian strain. MEG was four times more abundant in SEA from a Puerto Rican strain of S. mansoni than in SEA from the Egyptian strain. The serologic reactivity of MEG was stable to heat at 100 degrees C for 60 min, to 0.1 N NaOH or HCl, and to 10% TCA. Treatment of MEG with pronase caused a limited fragmentation of the molecule and some loss of its serologic reactivity. Periodate oxidation resulted in a substantial loss of molecular mass and of serologic reactivity, leaving a low residual activity that is only partially cross-reactive with the bulk of MEG. These results suggest the importance of both carbohydrate and peptide moieties of MEG for its serologic reactivity.
Immunologic regulation of experimental cutaneous leishmaniasis. V. Characterization of effector and specific suppressor T cells.
Authors: Liew F Y , Hale C , Howard J G
Published: December 2022

Resistant CBA mice infected with Leishmania tropica promastigotes develop concomitant and convalescent immunity against reinfection. This can be adoptively transferred by splenic and lymph node T cells with a threshold dosage of 1 to 2.5 x 10(7). The effector cells are of Thy-1+, Lyt-1+2- phenotype. The same immune cell population also adoptively transfers specific DTH to L. tropica, which is restricted by the major histocompatibility complex. On the other hand, highly susceptible BALB/c mice infected with L. tropica develop antigen-specific suppressor T (Ts) cells (previously shown to inhibit the induction and expression of DTH), which are capable, on transference, of reversing the healing of lesions induced by prior sublethal irradiation of BALB/c mice. As few as 10(6) of these T cells are effective in abrogating the potent prophylactic effect of 550 rad. The Ts cells are of Thy-1+, Lyt-1+2-, and I-J- phenotype. Sublethally irradiated and infected BALB/c mice produce antibody responses quantitatively and isotypically similar during the critical first 40 days after infection whether or not they are injected with 10(7) Ts cells (nonhealing vs healing). Thus, impairment of DTH and curative immune responses in BALB/c mice cannot be attributed to a helper function of these Thy-1+, Lyt-1+2- cells for the formation of suppressive antibody.
A mitogen for human B cells: anti-Ig coupled to polyacrylamide beads activates blood mononuclear cells independently of T cells.
Authors: Fothergill J J , Wistar R , Woody J N , Parker D C
Published: December 2022

The F(ab')2 fragment of rabbit anti-human F(ab')2 antibodies covalently linked to polyacrylamide beads (anti-Ig beads) acts as a polyclonal mitogen for human B cells in whole peripheral blood mononuclear cells (PBM) or tonsil cells. Activation, measured by the rate of DNA synthesis, is the result of an interaction between the anti-Ig beads and membrane immunoglobulin found on B cells. Excess soluble human F(ab')2 blocks activation with anti-Ig beads. Immunospecifically purified antibodies against IgM or IgD bound to beads activate lymphocytes. Also soluble anti-IgM or anti-IgD can block activation with insolubilized anti-IgM or anti-IgD, respectively, by modulating membrane immunoglobulin. Irrelevant rabbit antihapten antibodies bound to beads failed to activate PBM or tonsil cells. Anti-Ig beads act independently of T cells. The anti-Ig beads lead to activation of B cells without further maturation to polyclonal immunoglobulin secretion.
Lipopolysaccharide receptor on rabbit peritoneal macrophages. I. Binding characteristics.
Authors: Haeffner-Cavaillon N , Chaby R , Cavaillon J M , Szabó L
Published: December 2022

The Bordetella pertussis endotoxin, labeled with tritium ((3H)-LPS), bound irreversibly and nonspecifically to rabbit lung macrophages, but bound reversibly and specifically to both resident and elicited rabbit peritoneal macrophages. The specific binding capacity of the macrophages was saturated with about 3 X 10(4) LPS molecules per cell. The binding was inhibited with the homologous unlabeled endotoxin, but not at all with endotoxin from Proteus mirabilis, thus assessing ligand specificity. Endotoxins from other bacteria gave intermediate inhibition value. Binding of tritium-labeled pertussis endotoxin was significantly inhibited by one of the two polysaccharides (PS-1) present in this endotoxin, but neither the other polysaccharide (PS-2) nor the Lipid A fragment exhibited such activity. These results strongly suggest the presence of a lectin-like receptor for LPS on the membrane of rabbit peritoneal macrophages.
The interaction of human plasma fibronectin with a subunit of the first component of complement, C1q.
Authors: Pearlstein E , Sorvillo J , Gigli I
Published: December 2022

Fibronectin is a normal plasma protein that enhances reticuloendothelial system functioning, and may participate in immune complex clearance. The interaction of 125I-fibronectin with human C1 and C1q in vitro was investigated by employing a highly reproducible solid-phase binding assay in microtiter wells. We demonstrated that although fibronectin does not bind to antigen-antibody complex (BSA-anti-BSA) or immune complexes containing C1, a 20-fold increase in binding was obtained when the complexes contained C1q alone. In the absence of antigen-antibody complexes, fibronectin binds to the C1q fixed to the wells in a dose-response fashion but not to intact C1. C1q in the fluid phase inhibits 85% of the fibronectin binding to immobilized C1q. The amount of fibronectin bound by immobilized C1q or gelatin is approximately equal. The binding of fibronectin to C1q could be inhibited by the restoration of C1r + C1s to the C1 macromolecular complex before the addition of fibronectin. The inhibition was dependent on the concentration of C1r + C1s and achieved a maximum of 70% at 100 micrograms/ml. This inhibition could be reversed by the removal of C1r and C1s subunits with EDTA or C1 inhibitor. Digestion of C1q with pepsin resulted in an 85% loss of fibronectin binding. It therefore appears that at least one site of fibronectin binding to C1q is in the globular portion of this complement component.
Evidence that antisera that react with products of the human HLA-DR locus may block in vitro antigen-induced proliferation by inducing suppression.
Authors: Muchmore A V , Decker J M , Mann D L
Published: December 2022

It is widely recognized that antisera that interact with determinants encoded by the Ia region of the mouse and its counterpart, the DR locus of man, are capable of interfering with the ability of monocytes and lymphocytes to respond in vitro to an antigenic stimulus. Using an in vitro assay that measures antigen-specific proliferation of human lymphocytes, we found that both a heteroantiserum raised in rabbits (anti-P29,34) and alloantisera which recognize determinants encoded for by the human DR locus dramatically block in vitro antigen-specific proliferation. These anti-DR antisera appear to act at the level of the monocyte; monocytes pulsed and washed free of excess antisera fail to promote proliferation in the presence of soluble antigen and untreated T cells whereas identically pulsed and washed T cells respond normally with untreated monocytes. Furthermore, the addition of unpulsed monocytes fails to restore in vitro antigen-specific reactivity. Our data suggest that membrane-bound anti-DR-specific antisera on monocytes is profoundly suppressive, and also suggests simple steric hindrance may not account for all of the observed effects such antisera have on monocyte-T cell interactions.
Mechanisms of immune lysis. III. Characterization of the nature and kinetics of the cytotoxic T lymphocyte-induced nuclear lesion in the target.
Authors: Russell J H , Masakowski V , Rucinsky T , Phillips G
Published: December 2022

The experiments reported here demonstrate that the event leading to CTL-induced nuclear disintegration is kinetically similar (t1/2 = 3.1 +/- 0.8 min) to that reported for CTL-induced plasma membrane disintegration as measured by 51Cr release. However, the expression of the lethal event by detergent-soluble 125I release occurs so rapidly that the time between the initiation of the lesion and its expression is 15 min instead of the 90 to 120 min time course for plasma membrane disintegration measured by 51Cr release. In addition, we have demonstrated that the rapid 125IUdR release characteristic of CTL-lysed targets is specific for the nucleus within the target cell itself. Isolated nuclei cultured with effectors and targets during a lytic reaction are not rapidly damaged by the lytic process. Finally, we have characterized the CTL-induced nuclear lesion as a degradative process occurring within the plasma membrane of the target cell. The significance of these events and their relationship to the CTL's role in the host defense system is discussed.
Studies on the surface antigenicity and susceptibility to antibody-dependent killing of developing schistosomula using sera from chronically infected mice and mice vaccinated with irradiated cercariae.
Authors: Bickle Q D , Ford M J
Published: December 2022

Changes in the surface antigenicity and susceptibility to in vitro killing during development of schistosomula of Schistosoma mansoni were studied using serum from chronically infected mice (CIS) and from mice vaccinated with highly irradiated (20 krad) cercariae (VS). Binding of these sera was quantitated by counting the number of P388D1 cells (a transformed, macrophage-like cell of mouse origin, bearing Fc receptors for IgG) binding to the parasite surface. Compared with schistosomula derived in vitro by mechanical transformation (MS), schistosomula recovered 3 hr after skin penetration in vitro (SS) showed a significant loss in surface binding of CIS. Schistosomula recovered 3 hr after skin penetration in vivo (SRS) showed even less binding, and this trend continued such that parasites recovered from the lungs 5 days after infection (LS) showed only minimal binding, and 10-day-old worms from the portal system showed no significant binding. In contrast, VS, which bound significantly less well to MS than CIS, showed enhanced binding to SS, and in the face of their declining antigenicity with respect to CIS, 3- to 24-hr SRS maintained this raised level of antigenicity. Although there appeared to be a decline in binding of VS thereafter, LS remained antigenic, still binding as many cells as MS did despite the fact that they also expressed host antigens detected using antisera raised against mouse RBC. In spite of this persistence of VS binding up to the lung stage, resistance to eosinophil-mediated killing in vitro had developed by 48 hr post-infection, and LS were totally resistant to both eosinophil- and C-mediated killing.
Generation of cytotoxic lymphocytes by SV40-induced antigens.
Authors: Chang C , Chang R , Mora P T , Hu C P
Published: December 2022

In order to study the correlation of in vivo tumor transplantation immunity and in vitro immunologic assays, cell-mediated cytotoxicity against SV40-transformed cells was studied in AL/N strain mice by using 51Cr-release assay. Killing of SV40-transformed AL/N fibroblast cells was observed by spleen cells of AL/N mice immunized with syngeneic SV40-transformed cells. Immunization with the solubilized SV40 tumor-specific transplantation antigen (TSTA) that induced transplantation immunity in vivo did not elicit cytotoxic spleen cells in vitro. However, the spleen cells from mice immunized with solubilized TSTA and then sensitized in vitro with SV40-transformed cells became cytotoxic against SV40-transformed fibroblasts. Similarly, SV40 TSTA (T antigen) purified by immunoprecipitation was able to prime the lymphocytes in AL/N mice: the primed lymphocytes could differentiate into cytotoxic lymphocytes upon in vitro stimulation by SV40-transformed cells. These data indicate that SV40 TSTA (T antigen) plays a role in the induction of cytotoxic lymphocytes.
Lymphoepithelial interactions in the mouse thymus: phenotypic and kinetic studies on thymic nurse cells.
Authors: Kyewski B A , Kaplan H S
Published: December 2022

Thymic nurse cells (TNC), complexes between epithelial cells and thymocytes, are further characterized. Our results show that TNC are predominantly located in the subcapsular and outer cortical region of the mouse thymus. The enveloped thymocytes display the characteristics of cortical thymocytes. They are PNA+, Thy-1+, Lyt-123+, TL+, ThB+, H-2K+, IA+, and cortisone and radiation sensitive. In vitro cultivation of TNC in the presence of interleukin 2 induces a phenotype change to Lyt-1-, ThB-, Lyt-23+. The yield of TNC is highly dependent on the isolation conditions. Moreover, the thymocytes enveloped by an individual TNC do not constitute a single clone. The latter findings strongly suggest that complete envelopment is probably an isolation artifact. However, the cellular composition of the complexes is not random but rather the result of a preexisting in vivo association between an immature thymocyte subpopulation and outer cortical epithelial cells. TNC represent the in vitro correlate of this in vivo interaction. The implications of these results for intrathymic T cell differentiation are discussed.
Membrane attach complex of complement (MAC): three-dimensional analysis of MAC-phospholipid vesicle recombinants.
Authors: Podack E R , Müller-Eberhard H J , Horst H , Hoppe W
Published: December 2022

The three-dimensional structure of recombinants of the isolated membrane attack complex (MAC) of complement with single bilayer dioleoyllecithin (DOL) vesicles and with dimyristoyllecithin (DML) vesicles was determined. A total of four MAC-vesicle complexes were analyzed by imaging negatively stained specimens at various defined tilting angles under minimal dose conditions in the electron microscope and by computer-aided three-dimensional reconstruction. The information on electron micrographs obtained at 6 degrees angular increments from +60 degrees to -60 degrees was digitized by densitometric scanning, Fourier-transformed, corrected for imaging errors, cross-correlated, and synthesized to the three-dimensional image. All four MAC-vesicle recombinants showed stain penetration into the interior of the vesicle, indicating increased permeability of the bilayer to negative stain. The MAC appeared as a hollow structure of 16-nm height, 2.0-nm wall thickness, and a 3.0-nm torus at the free end with an outer and inner diameter of 20.0 nm and 10.0 nm. In MAC-DOL vesicles the hollow core of the MAC terminated at the membrane-binding site, and only small pores of up to 2.0-nm in diameter penetrated the bilayer. In one MAC-DML vesicle lipid discontinuities on the outer circumference of the MAC binding site mediated stain penetration. The second MAC-DML vesicle showed a channel of approximately 4.0 nm connecting the hollow core of the MAC across the bilayer with the vesicle interior. The results suggest the MAC may mediate increased membrane permeability by protein channel formation in addition to lipid reorientation.
Cell-mediated immunity in aged mice: an underlying lesion in IL 2 synthesis.
Authors: Thoman M L , Weigle W O
Published: December 2022

It is well established that immune potential declines with age and that aged animals are unable to mount vigorous cell-mediated immune responses. Production of the lymphokine, Interleukin 2 (IL 2) in response to the T cell mitogen concanavalin A or allogeneic stimulation is also diminished in aged individuals. This lesion in IL 2 synthesis in aged mice underlies their deficiency in cell-mediated responses. Mixed lymphocyte responses, cell-mediated lympholysis, and antigen-induced T cell proliferation are all markedly enhanced by supplementation with this lymphokine.
Spontaneous activation of the first component of human complement (C1) by an intramolecular autocatalytic mechanism.
Authors: Ziccardi R J
Published: December 2022

For biochemical characterization, the first component of human complement (C1) was reconstituted from physiologic concentrations of purified C1q, 125I C1r, and 131I C1s. Upon incubation at 37 degrees C, C1 spontaneously activated, as evidenced by the characteristic proteolysis of the C1r and C1s polypeptide chains as detected by SDS-PAGE analysis. This spontaneous C1 activation followed first-order kinetics (t 1/2 = 4 min and k = 0.173 min-1) with an activation energy of 19.1 kcal/mol. Spontaneous C1 activation was unaffected by the general protease inhibitor phenylmethylsulfonylfluoride (PMSF) but reversibly blocked by a known inhibitor of C1 activation, nitrophenylguanidinobenzoate (NPGB). Spontaneous C1 activation was measured at C1 concentrations ranging from 9 to 160 nM (i.e., 0.05 to 1.0 times physiologic concentrations). The data indicate that C1 spontaneously activates by an intramolecular autocatalytic mechanism, for first-order kinetics were observed over the entire concentration range with t 1/2 = 4 min at each concentration. However, the percentage of activable C1 decreased with dilution due to C1 dissociation (i.e., C1qr2s2 leads to C1q + C1r2s2). The observed concentration of C1 that spontaneously activated at each dilution equalled the concentration of C1 present as macromolecular C1. When reconstituted C1 was mixed with normal human serum (NHS) and then incubated at 37 degrees C, spontaneous C1 activation was completely inhibited. Pretreating NHS at 56 degrees C for 30 min destroyed its inhibitory activity. In conclusion, C1 spontaneously autoactivates at 37 degrees C by an intramolecular mechanism. This activation is suppressed in NHS.
Preferential idiotype-isotype associations in antibodies to dinitrophenyl antigens.
Authors: Scott M G , Fleischman J B
Published: December 2022

Murine IgG antibodies to DNP-protein are predominantly IgG1 and IgG2 whereas those against DNP-Ficoll (DNP-F) are mainly IgG3. Isotype restriction in this and other systems may mean that certain heavy chain variable regions (VH) are preferentially associated with particular constant regions (CH) in the immune response. We studied idiotypes of several monoclonal antibodies to DNP in an effort to identify VH regions that may be restricted in this way. Two idiotypes, 7-17 and 8-11, identified on IgG3 hybridomas raised against DNP-Ficoll, were expressed prominently both in immune sera and by IgG3-secreting plaque-forming cells (PFC) against DNP-F. By contrast, these idiotypes were barely detectable in antisera to DNP-proteins and were not expressed by IgG1- or IgG2-secreting PFC. Thus, the 7-17, and 8-11 idiotypes may be restricted to IgG3 and to responses to T-independent DNP antigens. Conversely, the 460 idiotype was expressed prominently in antisera to DNP-proteins but only weakly in antisera to DNP-F. The 460 idiotype was found on IgG1 and IgG2 PFC but not on PFC secreting IgG3. These results suggest that in heterogeneous immune responses to a single antigenic determinant, certain VH regions may be preferentially associated with particular CH isotypes.
A reevaluation of the putative association between the Fc gamma receptor and histocompatibility antigens on human mononuclear leukocytes.
Authors: Pulleyblank B M , Falk J A , Letarte M , Dorrington K J , Falk R E
Published: December 2022

The controversial question of an association between human Ia antigens and the FcR for immunoglobulin G has been examined. The experimental basis upon which such a relationship has been predicted was reevaluated. Human allosera with specificity for classical transplantation antigens, HLA-DR, and the related supertypic specificities MB and MT have been tested for their capacities to inhibit homologous EA rosette formation by PBM and B-CLL cells. Both immune and "nonimmune" sera inhibited rosette formation. Sera were normalized with respect to IgG concentration, and no significant quantitative differences in the observed inhibition were seen. Positive reactivity of the antisera with Ia, HLA-A, or HLA-B antigens did not influence EA binding to FcR. Furthermore, F(ab')2 of IgG from reactive sera did not inhibit rosette formation. These observations have been extended using murine reagents. A.TH anti-A.TL serum, which reacts with human Ia in binding and immunoprecipitation studies, and five monoclonal antibodies, which have been raised against human Ia and bind to monomorphic determinants, were tested for an effect on EA rosette formation. When these reagents were tested at concentrations at which they could be shown to bind to antigens on the target cell population, no inhibition of EA rosette formation by human PBM, MON or B-CLL cells could be demonstrated. The studies provide no evidence to suggest the existence of an association between Ia and the human FcR.
Selective suppression of human B lymphocyte differentiation into IgG-producing cells by soluble Fc gamma receptors.
Authors: Bich-Thuy L T , Revillard J P
Published: December 2022

Receptors for the Fc part of IgG were isolated by affinity chromatography from supernatants of unstimulated human lymphocytes or polymorphonuclear neutrophils. When added to cultures stimulated by polyclonal activators, these soluble receptors selectively depressed the maturation of B lymphocytes into IgG-producing cells, whereas the number of IgM-producing cells was either increased or unchanged. The number of IgA-containing cells was not changed. The data support the concept of class-specific control of Ig synthesis by Fc receptors.
Two loci in I-J subregion of the H-2 complex controlling molecules selectively expressed on suppressor and helper T cells.
Authors: Ochi A , Nonaka M , Hayakawa K , Okumura K , Tada T
Published: December 2022

Different batches of alloantiserum directed at the I-J subregion products of the H-2 major histocompatibility complex (anti-I-J) induced either suppression or augmentation of the in vitro secondary antibody response when added in a minute quantity to the culture of primed spleen cells. The suppressive or augmenting effect of the individual antiserum was found to be determined by its predominant specificity for either one of the two different molecules, both encoded in the I-J subregion, that were selectively expressed on functionally different subsets of T cells, i.e., suppressor (Ts) and helper (Th2) T cells. This was determined by the differential absorption of antiserum with Lyt-1+ and Lyt-2+ T cells as well as with suppressor hybridomas that express an I-Jk product. It was found that the absorption of an anti-I-J antiserum with Lyt-1+ T cells resulted in the loss of activity to eliminate a set of helper T cells (Th2) while leaving the ability to affect antigen-specific suppressor T cells (Ts). The absorption of the same antiserum with either Lyt-2+ T cells or suppressor hybridomas eliminated the activity to kill Ts but not Th2. Thus, the results indicate that the I-J subregion accommodates two or more loci that code for discrete molecules expressed on functionally different subsets of T cells. Because the simple addition of a minute quantity of antisera to the culture resulted in the modulation of antibody response presumably by affecting these two sets of T cells, it is suggested that I-J subregion products act as functional molecules in regulatory cell interactions.
The induction of alloreactive cytotoxic responses in vivo are inhibited by pretreatment with M is-disparate cells.
Authors: Hayes R L , Claman H N
Published: December 2022

Alloreactive cytotoxic cells (CTL) are subject to regulation. These experiments were designed to study the in vivo down-regulation of CTL. Mice injected with allogeneic lymphoid cells (responders) develop CTL that are assayed in vitro by their ability to lyse 51Cr-labeled target cells of an appropriate H-2 haplotype. However, if CBA/J responder mice (H-2k, mls d) are pretreated with spleen cells from C3H/HeN mice, which are H-2 compatible (H-2k) but Mis- and minor antigen-disparate (mis c), there is virtually complete inhibition of the ability to develop CTL against A/J cells (H-2a, mls c) in vivo. In a similar manner, pretreatment of CBA/J responders with B10.BR (H-2k, mls b) cells resulted in the inhibition of the CTL response against B10.A(4R) (H-2h4, mls b). The state of CTL responsiveness appears to be H-2 restricted and requires that the allogeneic cells used for immunization share minor histocompatibility antigens with the strain of mouse selected for pretreatment.
Immunity to herpes simplex virus type 2. IV. Impaired lymphokine production during recrudescence correlates with an imbalance in T lymphocyte subsets.
Authors: Sheridan J F , Donnenberg A D , Aurelian L , Elpern D J
Published: December 2022

Cell-mediated immunity (CMI) to herpes simplex virus type 2 (HSV-2) was studied in patients with recurrent disease. Peripheral blood lymphocytes (PBL) obtained during recrudescence (0 to 3 days post-onset of lesion), convalescence (4 to 14 days), and quiescence (greater than 14 days), which were cultured in vitro in the presence of UV-inactivated HSV-2 (G) antigen, demonstrated similar, virus-specific lymphoproliferative responses. However, the production of the lymphokine, leukocyte migration-inhibition factor (LIF), was completely suppressed during recrudescence. During convalescence, LIF production returned to levels similar to those of PBL from seropositive controls (without a history of recurrent subsets revealed a significant increase in the proportion of T8+ and Ia+ cells during recrudescence and at prodrome (24 to 48 hr before onset of lesions). Glass adherence reduced the proportion of both T8+ and Ia+ cells and restored early (1 day) LIF activity, and recrudescent PBL suppressed the proliferation of autologous T cells in presence of UV-HSV-2 (G) antigen. The expression of both phenotypes and LIF production returned to control levels during convalescence.
Potentiation of the primary humoral immune response in vitro by C5a anaphylatoxin.
Authors: Goodman M G , Chenoweth D E , Weigle W O
Published: December 2022

The effect of the anaphylatoxin C5a on the primary humoral immune response to SRBC was studied in culture of spleen cells from C3H mice. The addition of human C5a to antigen-stimulated cultures resulted in a significant, dose-dependent augmentation of the primary PFC response to antigen. The specificity of this effect was affirmed by the ability of C5ades Arg, but not of the structurally analogous C3a anaphylatoxin, to act in a parallel fashion. Enhancement could be observed over a range of doses of antigen. Brief preincubation of macrophages, but not of lymphoid cells, with C5a was sufficient to cause subsequent enhancement of the primary humoral immune responses. The duration of preincubation required for this effect closely paralleled that for binding of C5a to peritoneal cells. Immunopotentiation by C5a appears to involve the function of C5a receptor-bearing, Ia- accessory cells as well as Ia+ antigen-presenting cells. Immunopotentiation could be observed when the addition of C5a was delayed for up to 24 hr after initiation of culture. Additionally, augmentation of tritiated thymidine uptake in mixed lymphocyte reactions was enhanced by the addition of C5a in a fashion parallel to that for the primary response to SRBC. These observations support a role for C5a as a modulator of cellular immunity in addition to its role in acute inflammation. Possible cellular mechanisms and implications for immunomodulation of immune responses are discussed.
Inhibition of antibody synthesis by histamine in concanavalin A-treated mice: the possible role of glucocorticosteroids.
Authors: Badger A M , Griswold D E , DiMartino M J , Poste G
Published: December 2022

Administration of histamine (50 mg/kg) to BALB/C mice injected with concanavalin A (Con A) (100 micrograms, i.v.) 24 hr previously, results in a marked decrease in antibody synthesis to sheep red blood cells (SRBC) injected 2 hr later. This phenomenon occurs with nonimmunosuppressive doses of Con A and is strain-specific. It does not take place in the response to the T-independent antigen polyvinylpyrrolidone (PVP) or if histamine is administered after the antigen. Adoptive transfer of normal syngeneic cells at the same time as antigen does not reverse this effect. Excess suppressor cell generation was excluded by co-cultivation of treated spleen cells with normal cells in vitro and by determining their antibody response to SRBC 5 days later. 2-Methylhistamine, a histamine type 1 (H1) receptor agonist, mimicks the effect of histamine whereas dimaprit, a histamine type 2 (H2) receptor agonist, does not. Because histamine interaction with H1 receptors causes the release of adrenocorticotropic hormone (ACTH), we examined the effects of ACTH and corticosterone in this system and found that both could mimick the effect of histamine. These results suggest that the interaction of histamine with H1 receptors causes the release of glucocorticosteroids that may interfere with either Con A-activated T helper cell function or macrophage processing of T-dependent antigen.
Monocyte receptors for the Fc portion of IgG studies with monomeric human IgG1: normal in vitro expression of Fc gamma receptors in HLA-B8/Drw3 subjects with defective Fc gamma-mediated in vivo clearance.
Authors: Fries L F , Hall R P , Lawley T J , Crabtree G R , Frank M M
Published: December 2022

The Fc gamma receptors of reticuloendothelial cells are presumed to play an important role in the clearance of circulating particles opsonized with IgG. In order to quantify these receptors and assess their contribution to the clearance phenomenon in man, Scatchard analysis has been applied to 125I-IgG1 myeloma protein binding by a model mononuclear phagocyte, the peripheral blood monocyte. Close compliance to the criteria for linear Scatchard plots has been obtained. The kinetics of binding at 37 degrees C were consistent with a simple, reversible, bimolecular reaction. A saturable, single class of high-affinity binding sites was discerned with a Ka of 2.61 +/- 0.13 x 10(8) M-1 and a mean of 35,500 +/- 1700 receptors per monocyte. These receptors expressed approximately equal affinities for IgG subclasses 1 and 3, with progressively lower affinities for IgG subclasses 4 and 2, respectively. Parameters of IgG1 binding to monocytes of patients with dermatitis herpetiformis and normal individuals of HLA-B8/Drw3 haplotype were not significantly different from controls, despite the previous demonstration of retarded IgG-mediated clearance in one-half of such subjects. Receptor number and affinity failed to correlate with T 1/2 for sensitized erythrocyte clearance in vivo. Functional defects in in vivo clearance, even in the absence of circulating immune complexes, are not necessarily related to abnormal expression of Fc gamma receptors by phagocytes.
Proliferative responses of normal human B lymphocytes. Development of an assay system for human B cell growth factor (BCGF).
Authors: Muraguchi A , Fauci A S
Published: December 2022

A simple and reproducible system for inducing and measuring proliferation of normal human peripheral blood B lymphocytes was developed and employed as an assay for BCGF activity contained in supernatants of cultured human mononuclear cells. SAC was used to activate human peripheral blood B cells to develop into blasts with low levels of proliferation, and a marked synergistic effect on the proliferation of these activated B cell blasts was demonstrated when various culture-derived supernatants containing exogenous growth factors were added to the system. Substantial BCGF activity was obtained from culture supernatants of co-cultures of pooled allogeneic mononuclear cells from two donors, who were also stimulated with PHA. Kinetic studies demonstrated that maximal BCGF activity was produced in cultures carried for 72 hr or longer. A linear relationship was observed between the logarithm of dilution of added factor and incorporation of 3H-thymidine in the responding SAC-stimulated B cell blasts, suggesting the applicability of this system in screening and quantitating BCGF activity in supernatants of various sources, such as T cell clones, T cell neoplasms, and functional human T-T hybridomas. Furthermore, the system could potentially be adopted to the long-term culture of proliferating normal human B cells.
Enhancing effect of concanavalin A on the hemolytic activity of anti-Forssman IgG: the role of C1.
Authors: Langone J J , Sandor M , Ejzemberg R
Published: December 2022

Native tetravalent Con A and the divalent acetylated derivative increased the hemolytic titer (i.e., the reciprocal of the antibody dilution required to give an average of one lytic site per sheep erythrocyte) of IgG antibodies against Forssman antigen by up to 225% with guinea pig and human complement. Although the average number of lytic sites generated at each antibody concentration increased, the slope of the titration curve did not change. Other lectins with the same or different sugar specificity either augmented or inhibited hemolysis but were less potent than Con A. Augmentation by Con A was consistent with the ability of lectin on the cell surface to bind but not activate guinea pig C1. Thus it appears that cell-bound Con A and IgG yield a complex that behaves like a doublet of IgG antibody molecules in its ability to fix and activate C1, when activation is dependent on the IgG component. In contrast, the highest dose of Con A inhibited by at least 50% the hemolytic activity of IgG antibodies against either a sugar-free protein (HSA) or a protein reactive with Con A (human myeloma IgE) using cells to which these antigens were coupled with chromic chloride. This suggests that the identity, density, and/or mode of presentation of the antigen on the cell surface may be important determinants of lectin-induced augmentation. Although both the enhancement or inhibition by Con A in the presence of whole C correlated with the number of C1 molecules bound and activated, there was no correlation with the ability of the lectin to agglutinate the cells.
T cell and IR gene regulation of expression of a cross-reactive idiotype.
Authors: Bekoff M C , Levine H , Schlossman S F
Published: December 2022

The immune response to the chemically defined DNP-oligo-L-lysine antigens is under Ir gene control in the guinea pig. Strain 2 (responder) guinea pigs mount a highly specific T cell-mediated and humoral immune response capable of discriminating closely related DNP-peptides. In contrast, strain 13 (nonresponder) animals fail to mount a cell-mediated response, and produce antibody that is only DNP-specific. In these studies a common idiotypic determinant is defined on highly specific anti-epsilon,DNP-Lys10 antibody produced by strain 2 guinea pigs. Ir gene nonresponder antibody is idiotype-negative. The presence of the idiotypic determinant distinguishes responder anti-epsilon,DNP-Lys10 antibody from responder antibodies elicited by structurally related antigens such as epsilon,DNP-Lys9 and alpha,DNP-Lys10-. Investigation of the regulation of idiotype expression demonstrated that production of idiotype-positive antibody requires the presence of viable, antigen-responsive T cells. Moreover, genetic analysis revealed that expression of the shared idiotype correlates directly with the phenotypic expression of I region genes (DTH responsiveness, Ia antigens) in (2 x 13)F1 x 13 backcross and randomly bred Hartley guinea pigs. Thus, Ir gene regulation of the immune response may be reflected in the v region specificities expressed by antigen-specific B cell clones.
Non-H-2-linked genetic control of murine cell-mediated lympholysis to autologous cells modified with fluorescein isothiocyanate (FTC-self).
Authors: Arora P K , Shearer G M
Published: December 2022

Spleen cells from mouse strains expressing the H-2b haplotype (C57BL/6J, C57BL/6N, C57BL/10J, and C3H.SW) were compared for their ability to generate primary in vitro cytotoxic responses to autologous cells modified with either fluorescein isothiocyanate (FITC) (FTC-self) or trinitrobenzene sulfonate (TNBS) (TNP-self). The resulting hapten-specific cytotoxic T lymphocyte (CTL) responses were assayed on hapten-self Con A blast target cells. Among the four H-2b strains tested, C57BL/6J and C57BL/6N were high responders, whereas C57BL/10J and C3H.SW were low responders for CTL generated against FTC-self. Studies using (C57BL/6J x C3H.SW)F1 responding cells and F1 or parenteral-modified stimulating cells indicated that the F1 cells generated cytotoxic activity equivalent to that of the high-responder strain C57BL/6J. Further comparisons of the C57BL/6J and C2H.SW strains indicated that C57BL/6J is a high responder to both FTC-self and TNP-self, whereas C3H.SW is a high responder to TNP-self but a low responder to FTC-self. The results of this study indicate that non-H-2-linked genetic control of CTL response to hapten-self depends not only on the self determinant but also on the foreign antigens.
The Basenji-Greyhound dog model of asthma: leukocyte histamine release, serum IgE, and airway response to inhaled antigen.
Authors: Peters J E , Hirshman C A , Malley A
Published: December 2022

To understand the immunologic mechanisms underlying the variation in airway response to inhaled Ascaris antigen (AA) in Basenji-Greyhound (BG) dogs having hyperreactive airways, we examined the relationship between leukocyte histamine release, Ascaris-specific serum IgE, changes in pulmonary resistance (RL), and decreases in dynamic compliance (Cdyn). All Ascaris-sensitive BG dogs showing airway responses to AA aerosol challenge exhibited an antigen dose-dependent release of leukocyte histamine, with total leukocyte histamine ranging from 68 to 123 ng/10(7) cells. Airway response to inhaled antigen more closely correlated with antigen dose releasing 50% total leukocyte histamine (RL, r = 0.94); Cdyn, r = 0.82), than with circulating levels of antigen-specific IgE (RL, r = 0.68; Cdyn, r = 0.69). We conclude that the airway response of sensitized BG dogs to AA inhalations is more dependent on factors affecting mediator release from pulmonary sources than circulating specific reaginic antibody.
Parasite- (antigen) specific stimulation of B and T cells in African trypanosomiasis.
Authors: Campbell G H , Esser K M , Phillips S M
Published: December 2022

C57BL/6J mice were immunized with irradiated Trypanosoma rhodesiense organisms. Splenic lymphocytes were subsequently obtained from immunized animals and were tested for blast transformation in vitro after exposure to soluble trypanosome antigens. Immune T lymphocytes were found to be the cells responsible for antigen-mediated blastogenesis to trypanosome antigens. In addition, trypanosome antigen preparations in higher concentrations stimulated B lymphocytes obtained from normal nonimmunized animals.
Deficiency of interferon-gamma but not interferon-beta in Arabian foals with severe combined immunodeficiency.
Authors: Yilma T , Perryman L E , McGuire T C
Published: December 2022

The results of a study on the induction of IFN-alpha, IFN-beta, and IFN-gamma in normal and SCID foals showed a deficiency of IFN-gamma but not IFN-beta in SCID foals. The ability of SCID mononuclear cells to produce IFN-alpha in response to poly I:C but not to NDV may indicate a partial deficiency of IFN-alpha in SCID foals. The deficiency of IFN-gamma and presence of IFN-beta in SCID foals supports the classification of IFN-gamma and IFN-beta as immune and nonimmune interferons, respectively. Furthermore, the deficiency of IFN-gamma in SCID foals may in part explain the high susceptibility to infections observed in SCID foals.
Formation of IgE-binding factors by rat T lymphocytes. V. Effect of adjuvant for the priming immunization on the nature of IgE binding factors formed by antigenic stimulation.
Authors: Uede T , Huff T F , Ishizaka K
Published: December 2022

Rats were immunized with keyhole limpet hemocyanin (KLH) included in complete Freund's adjuvant (CFA) or with the same antigen absorbed to aluminum hydroxide gel. Incubation of their spleen and MLN cells with homologous antigen resulted in the formation of IgE-binding factors. The nature of IgE-binding factors formed by antigenic stimulation was different depending on the adjuvant employed for priming and the period after immunization. If the lymphoid tissues were obtained 2 to 4 wk after antigen priming, IgE-binding factors derived from lymphoid tissues of KLH-alum-primed animals selectively potentiated the IgE response, whereas those produced by the lymphoid tissues of KLH-CFA-primed animals suppressed the IgE response. Analysis of purified IgE-binding factors from KLH-primed spleen cells revealed that the factors were heterogeneous with respect to their m.w., and that IgE-binding factors of a m.w. of 13,000 were responsible for the biologic activities. Thus, the 13,000-dalton factors obtained from KLH-alum-primed spleen cells selectively potentiated the IgE response, and those from KLH-CFA-primed spleen cells suppressed the IgE response. The selective formation of either IgE-potentiating factors or IgE-suppressive factors by KLH-primed spleen cells was observed only when the cells were stimulated by specific antigen. When the same KLH-primed spleen cells were incubated with IgE, IgE-binding factors formed in the cultures neither potentiated nor suppressed the IgE response. It was also found that stimulation of a mixture of BCG-primed spleen cells and KLH-alum-primed spleen cells with PPD resulted in the formation of IgE-suppressive factors; the stimulation of the same mixed cell suspension with KLH resulted in the formation of IgE-potentiating factors. The results collectively indicate that the nature of IgE-binding factors is decided by antigen-primed cells.
Idiotypic analysis of a monoclonal anti-Sm antibody.
Authors: Pisetsky D S , Lerner E A
Published: December 2022

Among murine models of autoimmunity, MRL mice are unique in their expression of antibodies to the nuclear antigen Sm. To assess genetic mechanisms in the control of this response, the idiotypes borne by a monoclonal anti-Sm antibody of MRL-Ipr/Ipr origin were investigated. Rabbit antisera were prepared against Y2, a hybridoma product with anti-Sm activity, and were rendered specific for idiotype by extensive absorption with normal globulins from BALB/c mice. In assays of idiotype by an inhibition ELISA, Y2 was shown to share idiotypes with Y12, another monoclonal anti-Sm derived from the same fusion as Y2; other monoclonal autoantibodies of MRL origin but different antigenic specificity failed to display idiotype activity in this assay. The presence of other anti-idiotypic specificities was revealed by absorption and elution of the anti-idiotype from an MRL globulin column; sera from both anti-Sm-positive and negative mice demonstrated these idiotypes. These results suggest that the predominant specificities detected by the anti-idiotype were unique to the monoclonal antibodies of the same animal, although there was also activity to idiotypes not related to anti-Sm binding molecules.
Structural and functional studies in C1q deficiency.
Authors: Chapuis R M , Hauptmann G , Grosshans E , Isliker H
Published: December 2022

The sera of two brothers were found totally lacking hemolytic C activity. One of them, a 16-yr-old male, presented a severe lupus-like syndrome, whereas the other was apparently healthy. Immunochemical quantitation of C components in both sera showed depressed levels of C1q, whereas the levels of C1r, C1s, and C1 inhibitor were elevated. C4, C3, C5, factor B, and beta 1H levels were in the normal range. Hemolytic C1 activity was totally lacking. C4 titers were elevated (150% of normal). C2 hemolytic activity was about one-third of normal, and the titers of the terminal components C3-C9 were also reduced in the two siblings. Double immunodiffusion against anti-C1q antiserum showed a partial loss of C1q antigenic determinants in the two siblings. Furthermore, the C1q of both siblings was unable to interact with immunoglobulins or to associate with C1r and C1s. Addition of purified human C1q to the sera restored their total C and C1 hemolytic activity. The dose response to the C1q addition was linear, indicating that the functional deficiency was not due to the presence of a serum inhibitor. Although antigenically deficient in comparison with normal C1q, the abnormal C1q appeared to have a larger m.w., as determined by gel chromatography. Investigation of other members of this family suggests a genetically linked disorder, because four out of six siblings had the same dysfunctional C1q in their serum.
Evidence for genetic control of microwave-induced augmentation of complement receptor-bearing B lymphocytes.
Authors: Schlagel C J , Ahmed A
Published: December 2022

The genetic control of 2450 MHz microwave-induced increase in complement receptor-bearing B lymphocytes (CRL) was studied using congenic, backcross, and recombinant inbred (RI) strains of mice. Mice were exposed to 2450 MHz microwaves (0.6 W; 10-14 W/kg) in an environmentally controlled waveguide and were assayed for CRL on days 3 or 6 post-exposure. Genetic studies of responder X nonresponder F1 mice and backcross analysis of nonresponder X (responder X nonresponder) F1 mice indicated that microwave susceptibility was controlled by a single, dominant Mendelian gene. Crosses between two nonresponder strains failed to restore the responder state. The dichotomy in microwave susceptibility between two strains congenic at the H-2--T1a region on chromosome 17 (AKR-responder and B.6-H-2k-nonresponder) indicated the noninvolvement of the Crl-1 gene and that the essential gene was located outside the H-2 region. This was confirmed by the responsiveness of the C3H-H-2o strain, which possesses a nonresponder H-2 haplotype and responder background genes. The strain distribution of microwave responsiveness in the BXH RI lines demonstrated that the microwave-induced increase in CRL was controlled by a single regulatory gene located on chromosome 5. We also analyzed the microwave responsiveness of two congenic strains of mice that possess different C3H/HeJ segments of chromosome 5 inserted into a C57BL/6J background. The JGBF/LeTy strain exhibited an increase in CRL indicating it possessed the segment of C3H/HeJ chromosome 5 that controls microwave responsiveness. The C57BL/6JTy-le strain remained nonresponsive. This places the essential regulatory gene to the right of the PgM-1 locus and to the left of the rd locus on chromosome 5.