bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular events in the induction of experimental allergic encephalomyelitis in rats.
Authors: Ortiz-Ortiz L , Weigle W O
Published: June 2004

Although both the T and B cells of the Lewis rat have immunoglobulin receptors for basic protein (BP) of myelin, and both cell types are required for antibody production to BP, the present results demonstrate that the T cells are the only cells required for the induction of experimental allergic encephalomyelitis (EAE). Both EAE and anti-BP were readily induced in thymectomized, irradiated Lewis rats reconstituted with normal thymus and bone marrow cells and challenged with BP in complete Freund's adjuvant. If the thymus cells were first treated with BP heavily labeled with 125I so as to eliminate (sucide) specific T cells, the recipients neither develop EAE nor produce antibody to BP. On the other hand, if the thymus cells were untreated and the specific B cells of bone marrow were eliminated by treatment with 125I-BP, EAE was not inhibited, although no antibody was produced. These results strongly suggest that the T cell is responsible for the induction of EAE although both the T and B cells are competent to respond to BP. Evidence was presented which suggests that neither suppressor T cells nor circulating antibody are involved in the inhibition of EAE by injection of Lewis rats with nonencephalitogenic preparations of BP. The immune status of T and B cells of the Lewis rat to BP was compared with the immune status of these cells in other species to thyroglobulin, where only the B cells appear to be competent. In this context, Brown Norway rats, which are resistant to the induction of EAE, also appear to lack T cells reactive to BP, although competent B cells are present.
Activation of human B lymphocytes. I. Direct plaque-forming cell assay for the measurement of polyclonal activation and antigenic stimulation of human B lymphocytes.
Authors: Fauci A S , Pratt K R
Published: June 2004

A model for the detection of single cell antibody production by human tonsillar lymphocytes after stimulation with either sheep red blood cells (SRBC) or polyclonal B-cell activators has been described. The culture system is a modified Mishell-Dutton technique with certain critical factors identified. The assay is a sensitive and resproducible hemolysis-in-gel system employing an ultra-thin layer gel technique measuring plaque-forming cells (PFC) against SRBC targets. Several factors essential for optimal responses are described, but the critical feature of the culture system is the use of selected lots of human AB serum supplements which are extensively absorbed with SRBC. This removes a blocking factor present in most human serum which suppresses the B-cell response to SRBC targets after stimulation with either SRBC or several polyclonal B-cell activators. In addition, absorption of serum with SRBC eliminates the presence of artifactual plaques. Background PFC are extremely low and stimulated cultures show significant and reproducible responses. These studies provide a simple, sensitive, and reproducible model for probing the complex events associated with activation of human B lymphocytes.
Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis.
Authors: Lindstrom J M , Einarson B L , Lennon V A , Seybold M E
Published: June 2004

Immunization of Lewis rats with acetylcholine receptor (AChR) purified from either Electrophorus electricus electric organ or syngeneic rat muscle induced experimental autoimmune myasthenia gravis (EAMG). This was demonstrated by clinical signs of weakness and by electromyographic evidence of imparied neuromuscular transmission. The amount of rat AChR required to induce an autoimmune response was comparable to the amount of eel AChR required. In vitro complexing of rat AChrR with antibody reduced its immunogenicity. Autoantibody to muscle AChR was present in serum and complexed with AChR in muscle. Antibody was not bound to the ACh binding site of AChR, since antibody-AChR complexes extracted from muscle could still bind 125I-alpha-bungarotoxin. The amount of AChR extracted from muscle of rats with EAMG was diminished. The amount of AChR and antibody-AChR complexes in muscle was measured at intervals after immunization with eel AChR. The amount of AChR decreased in rats with acute EAMG, then transiently increased to more than normal amounts during remission, and finally decreased to only about 20% of normal in rats with chronic EAMG. At least half of the AChR remaining in animals with chronic EAMG was complexed with antibody. Thus, both a decrease in amount of AChR and the formation of antibody-AChR complexes contribute to impairment of neuromuscular transmission in rats with EAMG. The possible mechanisms involved in the changes in AChR content are discussed.
Suppression of the antistreptolysin O response by cholesterol and by lipid extracts of rabbit skin.
Authors: Kaplan E L , Wannamaker L W
Published: June 2004

Lipids extracted from rabbit skin block the hemolytic capacity of SO and also suppress the neutralizing antibody response to this streptococcal extracellular antigen in rabbith immunized intravenosly. The modification in antibody response is specific for SO; the antibody responses to streptococcal DNase B and to streptococcal NADase are not affected. Cholesterol, a lipid present in abundance in skin, has a similar specific effect on the antigenicity of SO and may be the component responsible for the demonstrated effects of these lipid extracts of skin. In vitro experiments indicate that lipid extracts of rabbit skin have a greater capacity to block the hemolytic capacity of SO than do lipid extracts of rabbit heart, kidney, lung, liver, or spleen. These data support the view that the feeble ASO response observed in patients with streptococcal pyoderma is a result of the abundance of a local lipid inhibitor, such as cholesterol, in the skin. They may also bear on the pathogenesis of rheumatic fever, a complication which apparently does not occur following group A streptococcal pyoderma. Two possible explanations for this remarkable epidemiologic observation, both related to the presence of a local inhibitor, are considered: (a) suppression of the ASO response, the magnitude of which has been correlated with the risk of developing rheumatic fever after streptococcal infection of the throat, and (b) inhibition of the toxicity of SO, which has been shown to have a direct toxic effect on the mammalian heart and on isolated beating myocytes.
Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice.
Authors: Goidl E A , Innes J B , Weksler M E
Published: June 2004

The magnitude and heterogeneity of the immune response to dinitrophenylated bovine gamma globulin was measured in aged and young mice at a cellular level using an inhibition of plaque-forming cell assay. The primary and secondary responses of 24-mo-old mice were markedly depressed in magnitude and restricted in avidity for the DNP determinant when compared to 2-mo-old animals. Bacterial lipopolysaccharide given at the time of immunization increased the restriction in heterogeneity seen in 12- and 24-mo-old mice. Indirect PFCs were more severely depressed than direct PFCs in 24-mo-old mice. Syngeneic, lethally irradiated, 2-mo-old mice reconstituted with aged spleen cells exhibit the depressed and restricted response to DNP-BGG seen in old mice. When 10(8) young thymus cells were given together with old spleen cells the heterogeneity of the response was increased. When 2-mo- and 24-mo-old spleen cells were transferred together into young recipients the magnitude of the response to the young spleen cells markedly reduced. Thus, there appears to be a loss of thymic-helper cells and an increase in suppressor activity in aged animals.
Inherited structural polymorphism in human C2: evidence for genetic linkage between C2 and Bf.
Authors: Alper C A
Published: June 2004

Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races. Three forms of C2 have been identified by isoelectric focusing in polyacrylamide gel and development of patterns in agarose gel containing antibody-sensitized sheep red cells and C2-deficient serum: C2 C (common), C2 A (acidic), and C2 B (basic). The C2 variants were shown to be inherited as autosomal codominant traits, and suggestive evidence for close linkage between C2 and Bf was obtained.
In vitro stimulation of lymphocytes by neutral proteinases from human polymorphonuclear leukocyte granules.
Authors: Vischer T L , Bretz U , Baggiolini M
Published: June 2004

Two neutral proteinases from human polymorphonuclear leukocytes (PMN), an elastase and the chymotrypsin-like cathepsin G, were purified, and their actions on lymphocytes in culture were studied. Both PMN proteinases stimulate lymphocytes from human peripheral blood and from mouse spleen in vitro, but do not affect thymic cells from either normal or hydrocortisone-treated mice. In stimulated mouse spleen cell cultures, most of the developing blast cells bear surface immunoglobulins, and subsequently appear to engage in antibody synthesis. In their stimulatory action, the two PMN proteinases thus resemble the classic B-cell mitogen LPS and neutral pancreatic proteinases such as trypsin, chymotrypsin, and elastase. The effects of proteinase inhibitors indicate that lymphocyte stimulation is dependent on the proteolytic activity of the enzymes. This work suggests that PMN proteinases, which are released at sites of inflammation, may modulate the function of lymphocytes.
Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes.
Authors: Hough D W , Eady R P , Hamblin T J , Stevenson F K , Stevenson G T
Published: June 2004

The idiotypic determinants of surface immunoglobulins on B-cell lymphomas and lymphocytic leukemias represent tumor-specific antigens, individually unique for each tumor. As such they have both diagnostic and therapeutic potential, particularly for those neoplasms with no serum monoclonal immunoglobulin arising from synthesis of the protein for export. We describe the raising in animals of anti-idiotype sera directed against two examples of a nonexporting neoplasm, human chronic lymphocytic leukemia. The procedure involves exposing the cells to papain so as to remove the Fab fragments (containing the idiotypic determinants) from the surface immunoglobulin, recovering the Fab on cellulose immunosorbent particles, and immunizing animals with the immunosorbent-Fab complex.
Lysis of RNA tumor viruses by human serum: direct antibody-independent triggering of the classical complement pathway.
Authors: Cooper N R , Jensen F C , Welsh R M , Oldstone M B
Published: June 2004

In earlier studies we found that human serum, but not serum from multiple other species, inactivated and lysed oncornaviruses from a number of diverse sources in the apparent absence of antibody. A detailed analysis of the role of the human complement (C) system in mediating this lytic process indicates that human C1q interacts directly, in the absence of immunoglobulin, with oncornaviruses. Binding of C1 via C1q in this manner leads to activation of C1r, C1s, and thus of the classical C pathway. Integrity of the classical pathway is an absolute requirement for lysis although activation of the alternative pathway considerably amplifies the amount of lysis obtained, possibly through involvement of the C3b-dependent feedback mechanism. Activation of C is accompanied by deposition of C components on the viral surface and lysis on completion of the C reaction sequence. Thus in this system, the C1q subunit of C1 subserves a specific recognition function normally associated with antibody. This ability of human serum to inactivate oncornaviruses may represent a natural defense mechanism operative in vivo which deters expression of intact oncornaviruses in human malignancies.
Allogeneic carrier-specific enhancement of hapten-specific secondary B-cell responses.
Authors: Pierce S K , Klinman N R
Published: June 2004

We have analyzed the capacity of carrier-specific T cells to enhance the immune response of hapten-specific secondary B cells which do not share genes in the H-2 complex with the T cells. For this analysis we have used the in vitro splenic focus technique which allows assessment of monoclonal responses of B cells isolated in splenic fragment cultures of irradiated reconstituted carrier primed mice. A previous report from this laboratory demonstrated that syngeny in the I region of the H-2 complex was necessary between collaborating hapten-specific primary (nonimmune) B cells and carrier-specific T cells for responses yielding IgG1 but not IgM antibody. These findings lead up to postulate that the expression of I-region gene products on the surface of primary B cells and I-region syngeny with collaborating carrier-specific T cells were essential elements in the triggering events leading to IgG1 synthesis by primary B cells. The results presented in the present report indicate that, unlike primary B cells, the majority of secondary B cells can be stimulated to produce IgG1 antibody in carrier-primed allogeneic recipients. Although the enhancement of secondary IgG1 responses is slightly greater with syngeneic T cells, the allogeneic collaborative interaction requires both carrier priming of recipient mice and stimulation with the homologous hapten-carrier complex and thus appears to be specific. These findings clearly discriminate secondary from primary B cells and indicate that the mechanism of stimulation of secondary B cells to yield IgG1-producing clones differs fundamentally from the stimulation of primary B cells in that the requisite for I-region syngeny is obviated.
Expression of equivalent clonotypes in BALB/c and A/J mice after immunization with phosphorylcholine.
Authors: Rudikoff S , Claflin J L
Published: June 2004

Analysis of A/J antibody to phosphorylcholine (PC) revealed a striking degree of similarity to PC-binding myeloma proteins of BALB/c origin. By quantitative idiotypic analysis A/J anti-PC antibody was composed to antibodies bearing binding site idiotypic determinants indistinguishable from two different BALB/c myeloma proteins, T15 and M511. Idiotypic determinants of three other PC-binding proteins, W3207, M167, and M603 were not detected. Isoelectric focusing of the light chains verified the presence of antibodies similar to T15 and M511 and indicated the presence of a third antibody whose light chains had a pI identical to that of M603. When the sequence of A/J heavy chains were compared to the heavy chains of T15, M511, and M603, both the framework and first complementarity regions were identical in all cases. Sequences analysis of the light chains through part of the first complementarity region revealed three chains, one similar to each of the myeloma proteins T15, M603, and M167-M511. The latter two sequences differ by only a single amino acid (a single base substitution) in the first 23 residues, suggesting that the two light chains may be very similar if not identical. Thus, BALB/c and A/J mice which differ genetically at multiple loci including the heavy chain allotype complex locus show a remarkable preservation of their anti-PC antibodies. These results indicate that the genes encoding these antibodies are contained in the germ line.
Analysis of the stimulation-inhibition paradox exhibited by lymphocytes exposed to concanavalin A.
Authors: McClain D A , Edelman G M
Published: June 2004

High doses of Concanavalin A (Con A), which normally inhibit T-lymphocyte stimulation as measured by increases in DNA synthesis, cause these lymphocytes to become committed to mitogenesis while also generating a dominant but reversible negative growth signal. The observed response to the stimulatory signal as measured by the rate of commitment to enter the S phase (i.e., the rate at which the stimulation becomes lectin independent) increases with lectin concentration even in the inhibitory range. The generation of this positive signal is prevented by treating the cells with colchicine. Cells that have become committed but are also simultaneously blocked from entering the S phase by the high doses of Con A can begin synthesizing DNA if the lectin is released by adding a competitive inhibitor of binding. Experiments done in agarose cultures in which lymphocytes are kept from contact with each other suggest that the reversible inhibitory signal is mediated by structures in the individual cells rather than as a result of agglutination. Continuously dividing cells of the lymphoid line P388 are also individually and reversibly inhibited by Con A. These findings are considered in terms of the relation of the inhibitory signal to the microtubular components of cell surface modulating assemblies made up of submembranous arrays of microtubules, microfilaments, and associated proteins.
Cross-reactive lysis of trinitrophenyl (TNP)-derivatized H-2 incompatible target cells by cytolytic T lymphocytes generated against syngeneic TNP spleen cells.
Authors: Burakoff S J , Germain R N , Benacerraf B
Published: June 2004

Normal spleen cells, when cultured with irradiated trinitrophenyl (TNP)-derivatized syngeneic spleen cells, develop cytotoxic effectors that lyse most effectiviely a TNP-derivatized target that is H-2 compatible with the effector. However, these effectors also lyse to a lesser extent TNP tumor and TNP spleen targets that are H-2 incompatible. This cross-reactive lysis correlates with the degree of cytolysis seen on the TNP-derivatized syngeneic target; it appears to be medicated by Thy 1.2-bearing cells and is inhibited by antisera to the K and/or D loci of the target cell and not by antisera to non-K or non-D surface antigens. Nonradiolabeled TNP-derivatized lymphoid cells syngeneic to either the stimulator or the target are able to competitively inhibit cross-reactive lysis, while TNP chicken red blood cells are unable to specifically inhibit lysis. These data on cross-reactive lysis of TNP-conjugated targets are most consistent with the altered-self hypothesis.
Effect of sodium butyrate on lymphocyte activation
Authors: Kyner D , Zabos P , Christman J , Acs G
Published: June 2004

Butyrate, in relatively low concentrations, has been shown to induce synthesis of enzymes, cause changes in cell morphology, and inhibit growth of a variety of mammalian cells in tissue culture (reviewed in [1]).

In this communication, we report our observations on the effect of butyrate on lymphocyte activation. Butyrate completely and reversibly inhibits mitogen-induced blast formation. We present evidence that it does not interfere with the binding of mitogens, that it does not inhibit a number of the early reactions involved in activation, and that it does not affect ongoing DNA synthesis for an extended period of time. However, butyrate rapidly inhibits any increase in the rate of DNA synthesis.
Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice.
Authors: Huber B , Gershon R K , Cantor H
Published: June 2004

CBA/N mice have an X-linked B-cell maturation defect which is reflected in part in an absence or dysfunction of a subclass of mature B cells. We have immunized the defective male offspring of the mating (CBA/N female X BALB/c male) with BALB/c spleen cells. The resulting antiserum (alphaLyb3) selectively reacts with a component on the surface of a portion of B cells from a panel of H-2 different mouse strains. Binding of alphaLyb3 serum to this B-cell subclass results in substantial (10- to 20-fold) enhancement of the antibody response to low doses of SRBC. Both binding and enhancing activity are removed by absorption with B cells from B6 and BALB/c, but not CBA/N mice. Absorption of the serum with bone marrow cells, T cells, or thymocytes from Lyb3+ strains does not remove activity. Since the enhanced plaque-forming cell (PFC) responses are specific for the immunizing antigen, and since no PFC response is produced by injection of the antiserum alone, this enhancement probably reflects a second signal produced by specific interaction between antibody and the surface Lyb3 component. Moreover, this signal can partially replace the requirement for T cells in the production of antibody to a "thymus-dependent" antigen. These findings (taken in conjunction with the previously described immune defects in CBA/N mice and other studies of B-cell maturation) suggest to us that Lyb3 is a cell surface component expressed selectively on a mature B-cell subclass. This component is important in B-cell triggering by antigen and fails to develop in CBA/N mice, due to a dysfunction of a regulatory gene on the CBA/N X chromosome.
Genetic control of the immune response to staphylococcal nuclease. III. Time-course and correlation between the response to native nuclease and the response to its polypeptide fragments.
Authors: Berzofsky J A , Schechter A N , Shearer G M , Sachs D H
Published: June 2004

The progression of the Ir gene-controlled antibody response to staphylococcal nuclease in mice with repeated immunizations has been examined. H-2-linked control of the response to a single immunization with 100 mug of nuclease in complete Freund's adjuvant was confirmed. However, among strains of the high responder H-2a haplotype, the response of the A/J mice was about 10-fold higher than that of the B10.A, indicating additional non-H-2-linked control. In addition, the low responder C57BL/10 (H-2b) strain produced antibody levels as high as or higher than those of the congenic high responder B10.A (H-2a) strain when both strains were repeatedly immunized, indicating complexity even in the H-2-linked control of the response to this small monomeric protein. Polypeptide fragments of nuclease were also studied as immunogens. The antibody response to one fragment (residues 99-149) was found to follow the same pattern among five strains tested as that to whole nuclease. However, in this case the C57BL/10 was found to be a nonresponder rather than a low responder, failing to develop a response despite repeated immunizations. In contrast, the C57BL/10 showed a low but significant response to another fragment (residues 1-126) of nuclease. These results suggest that the apparent H-2-linked control of the response to whole nuclease is a reflection of the ability to recognize a determinant(s) in the region from residues 99 to 149, and that the eventual response of the C57BL/10 strain after hyperimmunization reflects the recognition of other determinants. If these observations reflect the common recognition of a determinant on native nuclease and on a random-conformation fragment, they have implications about the conformational specificity of the receptors, or the flexibility of the determinants, involved in H-2-linked Ir-gene control. In addition, evidence is presented for a possible second H-2-linked gene (or genes) controlling the response to other determinants of nuclease expressed on the polypeptide fragments.
The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. I. Proliferative response.
Authors: Kong A S , Morse S I
Published: June 2004

The lymphocytosis-promoting factor of Bordetella pertussis is a potent mitogen for murine lymphocytes in vitro. The stimulatory response was not the result of specific antigen stimulation. Spleen and lymph node cells were responsive, whereas normal thymocytes were unresponsive. However, DNA replication was induced in cortisone-resistant thymocytes by lymphocytosis-promoting factor (LPF). Bone marrow cells were not stimulated by LPF.
Distribution of maternal immunoglobulins in the mouse uterus and embryo in the days after implantation.
Authors: Bernard O , Ripoche M A , Bennett D
Published: June 2004

The distribution of maternal immunoglobulins in the mouse uterus and embryo in the days after implantation has been studied on sections incubated with sheep Fab anti-mouse immunoglobulins labeled with peroxidase. At the time of implantation the blastocyst is already surrounded by immunoglobulins that are also present in the blastocoel and early endoderm; uterine glands contain large amounts of immunoglobulins. Later, immunoglobulins are concentrated in the vacuolated endoderm, then the visceral yolk sac and the embryonic gut. They are also present in the various cavities of the embryo. Trophoblast cells progressively contain increasing amounts of immunoglobulins. In the decidua, immunoglobulins coat the cells and also occasionally appear as cytoplasmic granules. The early presence of maternal immunoglobulins may represent the transfer of serum proteins as a means of nutrition for the embryo. It is also very likely to have an immunological significance in the protection of the embryo.
Studies on delayed hypersensitivity in mice. III. Evidence for suppressive regulatory T1-cell population in delayed hypersensitivity.
Authors: Morikawa S , Baba M , Harada T , Mitsuoka A
Published: June 2004

T-T-cell interactions involved in delayed hypersensitivity (DH) response have been studied by employing delayed foot pad assay to methylated human serum albumin in C57BL/6J mice. The DH response, one of the T-cell manifestations of cell-mediated immune response is suppressively regulated by T cells and such observation was based on studies of age-associated kinetics of foot pad reaction and effects of cell transfer and adult thymectomy on developing DH response. These suppressively regulatory T cells in DH have a life span of less than 4 wk and a constant derivation from the thymus is required. Such cells are numerous in the young mouse thymus and few in the spleen and thymus of old mice. On the one hand, the presence of a long-lived effector T-cell population was suggested in DH. These cells are numerous in the spleen and are low responders to phytohemagglutinin in vitro. It is assumed that these suppressive T cells interact with antigen-reactive cells at their proliferating stage by recognition of the iodiotypic difference through surface receptors. As in the case of graft-vs.-host and humoral response in vivo, three different subsets of immune competent cells participate in the DH response. These cells consist of one specifically antigen-reactive T cell, one suppressive regulatory T cell, and one bone marrow-derived cell, a macrophage that responds to a chemical mediator from sensitized effector T cells and that develops a DH skin lesion nonspecifically.
T-cell-mediated concomitant immunity to syngeneic tumors. I. Activated macrophages as the expressors of nonspecific immunity to unrelated tumors and bacterial parasites.
Authors: North R J , Kirstein D P
Published: June 2004

Progressive growth of the SA1 sarcoma was shown to result in the generation of a state of concomitant resistance to growth of a second implant of the same tumor. The responding lymph nodes of concomitantly immune mice were shown to contain theta-positive T cells that could specifically neutralize the growth of tumor cells in a normal test recipient. Nevertheless, the concomitantly immune host itself was capable to a limited extent of suppressing the growth of unrelated tumors. The generation of immunity, moreover, was associated with the generation of a powerful state of macrophage-mediated, nonspecific resistance to the bacterial parasite, Listeria monocytogenes. It was concluded that systemic macrophage activation was the consequence of the generation of T-cell-mediated immunity to the progressively growing tumor, and that this not only gave the host the capacity to inhibit the growth of unrelated tumors, but also to protect itself against microbial infection. The results gives credence to the view that macrophages play a central role in defense against microbial and neoplastic growth.
Concanavalin A-mediated activation of antigen-primed lymphocytes into secondary cytotoxic lymphocytes.
Authors: Bonavida B
Published: June 2004

A secondary specific cytotoxic response is obtained when lymphocytes primed in vivo to a tumor allograft are exposed to Con A in culture. The secondary cytotoxic cells generated are specific to target cells bearing antigens of the primary sensitizing cells and are qualitatively indistinguishable from the response obtained upon secondary antigenic stimulation. The cell-mediated cytotoxicity is independent of concanavalin A (Con A) and is not affected by the Con A-specific inhibitor, alpha-methyl-D-mannose pyranoside. Furthermore, cultures containing a mixture of submitogenic concentrations of Con A and stimulating antigens showed synergy and augmentation of cytotoxic activity. It is suggested that activation of prekiller cells by Con A into CTL may be mediated via the same or similar receptors normally triggered by the stimulating antigens. Functional similarities between ConA and the lymphocyte-defined antigens of the major histocompatibility complex region are discussed.
The role of membrane receptors for C3b and C3d in phagocytosis.
Authors: Ehlenberger A G , Nussenzweig V
Published: June 2004

In this paper we re-examine the roles of particle-bound IgG and C3 in phagocytosis of sheep erythrocytes (E) by monolayers of purified human monocytes and polymorphonuclear leukocytes (PMN). We conclude that two fragments of the C3 molecule, that is, C3b and C3d, can function as opsonins if the phagocyte has the appropriate membrane receptors. Monocytes, that bind both C3b and C3d, respond to both as opsonins. PMN, which do not bind C3d, respond only to particles opsonized with C3b. C3 and IgG have separate roles in phagocytosis. IgG, through its Fc fragment, directly stimulates particle ingestion, but is relatively inefficient at inducing particle binding. On the other hand, C3 primarily mediates the binding of the particle via complement receptors. A marked synergy exists between C3 and IgG in inducing phagocytosis. Thus, opsonization of the particle with C3 can be a necessary condition for particle ingestion, although by itself C3 does not trigger phagocytosis. The opsonic effect of C3 can be mimicked by a variety of nonimmunologic agents which enhance binding of the particle to the phagocyte without directly stimulating ingestion. The contact-inducing agents used include centrifugation of particle and phagocyte, high molecular weight dextran, protamine, and treatment of E with neuraminidase. These results suggest that the role of C3 in opsonization is mainly or exclusively one of establishing contact between particle and phagocyte.
Hapten-specific hemolytic plaque assays usually fail to detect most of the diversity in the anti-hapten response.
Authors: Merchant B , Inman J K
Published: June 2004

Immunization of rabbits or mice with a single, chemically defined hapten elicits populations of plaque-forming cells (PFC) detectable not only on sheep erythrocytes (SRBC) bearing the immunizing hapten, but also on SRBC bearing structural analogues of the immunizing hapten. Most of these analogue-reactive PFC preferentially lyse analogue-conjugated SRBC and cannot be detected on erythrocytes bearing the immunizing hapten. Thus, they represent heretofore largely unstudied components of the secretory B-cell response to haptenic immunization, and they have been termed alloreactive PFC. Such alloreactive PFC are detectable using either classical small haptens or tripeptide-enlarged counterparts of these classical haptens. They are present in large numbers both in direct and in indirect PFC assays, and they are elicited in response to both thymic-dependent and thymic-independent antigens. Relatively few alloreactive PFC can be attributed to cells producing hapten-carrier or "bridge area"-specific antibodies. Since the antibodies released by alloreactive PFC can also be detected by passive hemagglutination, their presence does not appear attributable to vagaries of complement activation. Numerous coexisting alloreactive PFC populations are detectable after haptenic immunization. In early direct PFC responses it is not nucommon for a single alloreactive PFC population to outnumber the population of PFC detectable on SRBC bearing the actual immunizing hapten. These alloreactive PFC may be the source of at least some of the new "nonspecific" Ig which is formed at the time of immunization but about which little is known for lack of available techniques. Some possible implications of these findings on the specificity of B precursor cell activation are discussed.
Surface properties related to concanavalin A-induced agglutination. A comparative study of several Entamoeba strains.
Authors: Trissl D , Martínez-Palomo A , Argüello C , de la Torre M , de la Hoz R
Published: June 2004

Pathogenic strains of Entamoeba histolytica are more easily agglutinated with concanavalin A (Con A) than strains isolated from human asymptomatic carriers. All three pathogenic strains studied here were found to agglutinate with low concentrations of Con A in contrast to various nonpathogenic axenic strains of amebas, characterized by their ability to grow at room temperature. Our present observations suggest that the extreme susceptibility of pathogenic strains of E. histolytica to agglutinate with Con A is related to their higher capacity for lectin binding and to their lack of detectable repulsive charges at the cell surface. The amount of fluorescein-tagged Con A bound to the surface was much higher in pathogenic strains. Only nonpathogenic strains showed a detectable negative surface charge as studied both by means of cell microelectrophoresis and by labeling cells with cationized ferritin at 0 degrees C. The mobility of surface Con A receptors estimated as the percentage of caps was comparable in all strains. Results of one strain cultured in axenic and monoxenic conditions suggested that bacteria can modify the behaviour of E. histolytica trophozoites by altering surface properties of the amebas.
Generation of T-helper cells in vitro. I. Cellular and antigen requirements.
Authors: McDougal J S , Gordon D S
Published: June 2004

A sequential mouse cell culture system is described for the induction and assay of T-helper cells. Unprimed, cortisone-resistant, nylon wool-purified thymocytes cultured with adherent peritoneal exudate cells can be primed in vitro with soluble carrier protein to generate carrier-reactive helper cells. These cultured cells enhance the anti-hapten plaque-forming response of hapten-primed spleen cell cultures to hapten carrier conjugates. The culture conditions, cellular manipulations, and antigen requirements for the optimal induction of helper cells with these purified cell populations is presented. The active helper cell generated in this culture system is a thymus-derived cell which requires macrophages for its induction and must be proliferate in vitro before the manifestation of helper-cell function. Helper cells generated in vitro stimulate both carrier-specific and nonspecific enhancement of splenic anti-hapten responses. The carrier-specific and nonspecific enhancement can be distinguished by the requirement for antigen in the helper cell and spleen cell cultures, the dose of helper cells added to the spleen cell cultures, and by the requirement for additional splenic adherent accessory cell interactions.
Cell surface antigens of human malignant melanoma. III. Recognition of autoantibodies with unusual characteristics.
Authors: Shiku H , Takahashi T , Resnick L A , Oettgen H F , Old L J
Published: June 2004

The sera of three patients with malignant melanoma showing reactivity with surface antigens of cultured autologous melanoma cells were analyzed by mixed hemadsorption and immune adherence assays in conjunction with absorption tests. In contrast to the melanoma-specific antigens demonstrated previously, the surface antigens detected by these sera occurred on a broad range of nucleated cells, both normal and malignant, from human, monkey, mouse, and chicken sources. Each serum had a characteristic pattern of reactivity in absorption tests, indicating the detection of distinct antigenic systems. Two sera showed auto-, allo-, and xenoreactivity, as well as the capacity to distinguish different cell populations in the same individual. The other serum reacted with an antigen apparently universally present on nucleated cells from a variety of species, but absent on erythrocytes. As these patients had been treated with chemotherapy, this may have played a role in the emergence of these broadly reactive autoantibodies.
The capsule of the gonococcus.
Authors: James J F , Swanson J
Published: June 2004

16 strains of Neisseria gonorrhoeae were subjected to several established techniques for capsule demonstration by light microscopy. In all strains examined, encapsulation of the gonococcus was demonstrated. Although the capsules were somewhat more easily seen in strains recently isolated from clinical material, organisms that had been passaged for several years also were encapsulated as were all the colony types within these strains. The gonococcal capsule is easily disrupted by mechanical forces.
Histocompatibility antigens and genetic control of the immune response in guinea pigs IV. Specific inhibition of lymphocyte proliferation by auto-anti-idiotypic antibodies.
Authors: Geczy A F
Published: June 2004

The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 guinea pigs could be specifically blocked by the serum of guinea pig (*305) which had been repeatedly immunized with BPO-BGG over a period of 9 mo. The antibodies which appeared in the serum of this animal (*305) were functionally similar to the strain 2 anti-idiotypic antibodies (a strain 2 BPO-BGG) raised by immunizing strain 2 guinea pigs with immuno-adsorbent column-purified BPO-BGG. Animal *305 had no detectable antibodies to BPO-BGG and failed to give a delayed hypersensitivity skin response when challenged with BPO-BGG.
Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) III. Immunochemical properties of the GAT-specific suppressive factor.
Authors: Theze J , Kapp J A , Benacerraf B
Published: June 2004

The GAT-specific suppressor T-cell factor (GAT-TsF) extracted from lymphoid cells from GAT-primed, nonresponder DBA/1 mice has been partially characterized. It is a protein that has affinity for GAT and determinants encoded by the I region of the H-2 complex. On the basis of specificity and avidity, GAT-TsF resembles anti-GAT-MBSA antibodies produced by DBA/1 mice in spite of the fact that it is too small to be classical antibody and has no constant-region determinants of heavy or light chains. Further, GAT or a fragment of GAT is associated with the GAT-TsF. GAT-TsF has been partially purified from the crude extract by absorption to GAT-Sepharose and elution with 0.4 to 0.6 KCl. GAT-TsF purified on the basis of its affinity for GAT bears I-region determinants but not detectable GAT or GAT fragment.
Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro.
Authors: Schimpl A , Wecker E , Hünig T
Published: June 2004

The involvement of a nonantigen-specific T-helper factor in the anamnestic immune response to dinitrophenyl keyhole limpet hemocyanin is demonstrated employing cultures of unseparated spleen cell populations. In such cultures of primed and boosted spleen cells, a good IgG anti-DNP response could be obtained if the hapten was presented on a heterologous carrier, provided that the homologous carrier was added simultaneously. T-cell depletion and reconstitution experiments show that such a factor, presumably identical with T-cell-replacing factor is produced by primed helper cells upon rechallenge and helps primed B cells, stimulated by soluble heterologous carrier hapten conjugates, to become IgG-secreting cells.
Prostaglandin production by rheumatoid synovial cells: stimulation by a factor from human mononuclear Cells.
Authors: Dayer J M , Robinson D R , Krane S M
Published: June 2004

Human peripheral blood mononuclear cells (lymphocyte-monocyte) in culture release a solube factor which can stimulate, up to 200-fold, production of prostaglandin E2 by isolated, adherent, rheumatoid synovial cells. Production of the factor by the mononuclear cells is enhanced by phytohemagglutinin. This factor is similar in apparent mol vt (10,000-20,000) to that which also stimulates collagenase production by the same cells.
Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes
Authors: Ho YK , JR Faust , Bilheimer DW , Brown MS , Goldstein JL
Published: June 2004

The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were incubated for 48-72 h in the absence of lipoproteins, the rate of cholesterol synthesis increased by 5-15-fold. The subsequent addition of plasma LDL, but not HDL, rapidly suppressed cholesterol synthesis in the lymphocytes from normal subjects. In contrast, lymphocytes from the FH homozygotes, which have been shown previously to be deficient in cell surface LDL receptors, were resistant to LDL-mediated suppression of cholesterol synthesis.

In addition to its ability to suppress cholesterol synthesis after it had been elevated by incubation of the cells in the absence of lipoproteins, LDL was able to suppress the induction of the enhanced rate of sterol synthesis when added to normal lymphocytes immediately after their isolation from the bloodstream. In contrast to the former action of LDL, the latter action of LDL-i.e., the suppression of induction of sterol synthesis-also occurred to a limited extent in lymphocytes from FH homozygotes. However, the FH lymphocytes, but not the normal cells, could be made resistant to this action of LDL by inclusion in the incubation medium of lipoprotein-deficient serum (30 percent, vol/vol) plus HDL (1 mg protein/ml). Considered together with previous data demonstrating a deficiency of LDL receptors in freshly isolated lymphocytes from FH homozygotes, the current studies provide evidence in support of the hypothesis that the interaction of plasma LDL with its cell surface receptor serves to regulate cholesterol synthesis in human lymphocytes.
H-2 mutation affecting immune response to Thy-1.1 antigen
Authors: Zaleski M , Klein J
Published: June 2004

Mouse thymus, thymus-derived lymphocytes, and brain share an antigen determined by gene at the Thy-1 locus in chromosome 9 (1). Two alleles have been identified at this locus: Thy-1(a), coding for antigen Thy-1.1 (or θ-AKR) present in AKR and seven other strains; and Thy-1(b), coding for antigen Thy-1.2 (or{teta}-C3H) and present in C3H and all the remaining inbred strains. Injection of AKR thymocytes into inbred mice carrying the Thy-1(b) allele results in an immune response that can be measured either serologically by determining the level of antibodies in the recipients serum (1) or by counting plaque- forming cells (PFC) detectable in spleens of the recipients by means of an assay, with AKR thymocytes as target cells(2). The magnitude of PFC and serum antibody responses after a single thymocyte injection depends on the genetic make-up of the recipient. Three genes controlling the PFC response to the Thy- 1.1 antigen have been identified: Ir-Thy-1A and Ir-Thy-1B, which are closely linked to the major histocompatibility complex (H-2) of the mouse (3-6), and Ir-5, which is located at a distance of 17 cm to the right of the H-2 complex on chromosome 17 (6). Previous genetic mapping with H-2 recombinant strains has indicated that the two Ir-Thy-1 loci are located to the left of the IC subregion (7). Further experiments strongly suggested that either one or both Ir-Thy-1 loci map to the K rather than the I region of the H-2 complex (8). In this report, the study of an H- 2 mutant, CBA-H-2(ka) (M523) (9), and its parental strain, CBA/LacStoY (CBA) provided further evidence that one of these loci apparently resides in the K region and might even be identical with the H-2K locus in that region.
Suppression of cell-mediated immunity by street rabies virus.
Authors: Wiktor T J , Doherty P C , Koprowski H
Published: June 2004

Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.
Histocompatibility linked immune responsiveness and restrictions imposed on sensitized lymphocytes.
Authors: Miller J F , Vadas M A , Whitelaw A , Gamble J , Bernard C
Published: June 2004

Delayed-type hypersensitivity (DTH) transfer to GAT was restricted by the I-A region of the major histocompatibility complex (MHC). Sensitized cells from F1 hybrid mice between responder and nonresponder strains transferred DTH to syngeneic F1 mice and to naive parental strain recipients of the responder but not of the nonresponder haplotypes. These results are interpreted to favor the postulate that the MHC-linked Ir genes exert their effects by coding for components which allow interactions between particular I region gene products and the region to form stable structures immunogenic for DTH T cells.
B-lymphocytes activation by the Fc region of IgG.
Authors: Berman M A , Weigle W O
Published: June 2004

Strong stimulation of DNA synthesis (up to 150-fold) and blast transformation can be induced in mouse spleen cells by Fc fragments of human IgG. The mitogenic response is optimal on day 5 of culture and is dependent on the concentration of Fc fragments with a sedimentation rate of 3-5S. Intact IgG is also stimulatory, but only when modified by heat aggregation, and produces only a 10-fold increase in [3H]thymidine uptake. The stimulation by aggregated IgG is dependent on the Fc portion, since aggregated (or soluble) Fab or F(ab')2 fragments are inactive. The results show that the response is T-cell independent and that it is a function of nylon wool adherent, surface Ig-positive, Fc receptor-bearing B lymphocytes. Fc fragments do not induce plaque-forming cells to human IgG in normal mouse spleen cell cultures, but rather trigger polyclonal antibody synthesis (anti-goat erythrocytes, anti-2,4,6-trinitrophenyl). It is postulated that the Fc region of antibodies plays a role in the regulation of the humoral immune response by triggering clonal expansion of B lymphocytes.