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It has previously been shown that rats do not expel a primary infection of Nippostronglus brasiliensis during lactation. In the present paper, three aspects of the immune response of the lactating rat to the parasite were examined and compared with the response of non-lactating rats. Protective and reaginic antibodies were present in the circulation of rats first infected during lactation, in titres as high or higher than those in non-lactating controls. The intestinal mast cell response was similar both in timing and magnitude and lactating rats became susceptible to shock with the i.v. injection of antigen. Attention was drawn to the similarity between the response of the lactating rat and that of the neonate to this infection. [ABSTRACT FROM AUTHOR]

This paper describes the induction of immunosuppression by multiple injections of carrageenan-lambda (cgn) in BALB/c mice. While cgn alone induced non-specific suppression that persisted for up to 25 days, priming with sheep red blood cells (SRBC) of mice within l0 days of cgn treatment prolonged the suppressive state. Also, antigen (SRBC)-specific suppression was observed when these mice were siren a secondary challenge 25–30 days after priming. Thus multiple cgn treatment along with priming SRBC generated non-specific and specific suppressive states which were transferable by Thy-l+ Lyt-2+ splenocytes. [ABSTRACT FROM AUTHOR]

As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]

The experiments described in this paper were designed to determine the degradation of soluble IgG aggregates (AIgG) bearing C3b by guinea-pig peritoneal macrophages with different numbers of functional C3b receptors. The number of functional Fc receptors for AIgG containing 40 molecules of IgG per aggregate (AIgG40) were kept constant during these experiments. By increasing the concentration of trypsin for the treatment of normal peritoneal macrophages a dose-dependent inactivation of C3b receptors was achieved as determined by the binding of tetrameric [125I]-C3b([125I]-AC3b). Normal peritoneal macrophages bound 148,500 AIgG40 and 60,300 AC3b per cell. Treatment of the macrophages for 15 rain at 37° with incremental amounts of trypsin from 60 to 1000 µg/ml did not affect the binding of AIgG40 to macrophages but caused a dose-related loss of up to 95% of AC3b binding, indicating functional inactivation of C3b receptors. Degradation of trichloroacetic acid non-precipitable protein of [125I]-AIgG40 by 106 macrophages was 38±6% in medium alone and 60 ±8% in the presence of 10% fresh guinea-pig serum (NGPS) after 60 rain at 37°. The inactivation of 25%, 50%, 72% and 94% of C3b receptors by trypsin did not affect the degradation of AIgG40 in medium alone, but decreased degradation from 69% to 58%, 47%, 32% and 13% of AIgG40 respectively, in the presence of 10% GPS. Macrophages (106) in medium alone degraded 40%, 47%, 65% and 68% of AIgG40 beating 0, 5, 10, 16 and 20 C3b molecules per aggregate, indicating a dose-dependent enhancement of degradation by bound C3b; conversely, inactivation of 95% of C3 receptor on the macrophages resulted in 39%, 30%, 12%, 5% and 6% degradation of these AIgG40-C3b, indicating a dose-related inhibition by aggregate-bound C3b in the absence of cellular C3 receptor. These experiments stress the importance of Fc and C3b receptor co-operation and immune complex bound C3b. [ABSTRACT FROM AUTHOR]

Plaque-forming cell responses and antibody titres to sheep red cells (SRC) were elevated in normally-fed irradiated adult mice reconstituted with spleen cells from young mice which had received a 4% albumin diet, compared with those given cells from normally-fed littermates. This was independent of the dose of cells transferred (5 × 106-4 × 107), the day of assay (3–10) and the duration of protein-deficiency (1 or 3 weeks). It suggests that the depressed responses produced by protein-deficient (donor) mice reported in earlier papers resulted from an impairment of reticuloendothelial function or a shortage of protein reserves, not directly associated with the spleen. As protein-deficiency (of the donor) accelerated the initiation of the adoptive response and increased the cell yields of the recipients it is considered likely that an enhancement of cell proliferation during the first 3-5 days after transfer was responsible for the elevated responses. [ABSTRACT FROM AUTHOR]

Red cells sensitized with naturally occurring or 'immune' fowl antibody were lysed by fresh fowl serum. This fowl complement could not be replaced by that of human, rabbit or guinea pig. Both naturally occurring and 'immune' antibodies to red cells in the mammalian species tested did not lyse with fowl complement. Lysis by fresh fowl serum of sheep red cells sensitized with mammalian antibody is due to the presence of naturally occurrent antibody to these cells in the fowl serum; the enhancement of this lysis by the mammalian antibody will be described more fully in the next paper. Naturally occurring antibody to sheep red cells present in turkey serum and 'immune' antibody to fowl red cells were not lytic with fresh turkey serum, with fowl complement, with guinea-pig complement or with any combination of these. Some properties of fowl complement are given. [ABSTRACT FROM AUTHOR]

A theoretical framework is presented which explores two models of suppressor cell-target cell interactions in T-dependent antibody responses. The first is the full-dominance model, in which a single or limited number of suppressor cells can entirely suppress an immune response irrespective of the multiplicity of other effector cells present. The second is the ratio-dominance model, in which a suppressor cell is capable of inactivating only a certain number of target cells. Thus, the multiplicity of target cells in a given microculture well influences the degree of suppression. Both models are evaluated using limiting dilution analysis and two systems are explored, in the first model, suppressor cells alone are titrated into microculture wells containing all other cells required for an immune response. In the second, suppressor cells are added from populations containing a mixture of helper T cells as well as suppressor cells. This latter type of analysis is similar to that in which populations of T cells primed to alloantigens in mixed lymphocyte cultures are analysed for positive (help) and negative (suppression) allogeneic effects. The analysis allows us to conclude that such suppressor cells operate via a mechanism best described by a ratio-dominance model. [ABSTRACT FROM AUTHOR]

Two methods are described for linking chlorambucil to antibodies. At low pH an association is formed which is not stable under physiological conditions and the cytotoxicity is the result of the independent action of chlorambucil and antibody. At pH 8 a more stable linkage is formed and this complex shows specific toxicity for cells carrying the appropriate antigen. Uncombined chlorambucil and antibody are more cytotoxic than chlorambucil alone, especially if the cells are exposed first to the chlorambucil. [ABSTRACT FROM AUTHOR]

The immunological response of the primitive mammal Tachyglossus aculeatus has been studied. We have shown that this animal responds to flagella from Salmonella adelaide with production of mercaptoethanol-resistant antibodies during both primary and secondary responses. Although an anamnestic secondary response could be demonstrated, it was of much smaller magnitude than that of phylogenetically higher placental mammals. Serological investigations demon- strated the presence of a mercaptoethanol-sensitive antibody of high molecular weight and an antibody of lower molecular weight which was mercaptoethanol resistant. These two antibodies seem to be analogous to IgM and IgG antibodies of higher mammals. [ABSTRACT FROM AUTHOR]

Rabbits made immunologically unresponsive by neonatal administration of HSA, HGG or BSA were given a course of intravenous injections of the respective antigens, adsorbed on alum, after a lapse of 13-27 months since the last administration of antigen. 8/12 responded to HSA, 4/5 to HGG, 9/10 to BSA, as judged by immune elimination of antigen, but this was delayed in onset and slow compared with that in previously untreated rabbits. The antibody formed was small in quantity and usually failed to precipitate with antigen. The sedimentation coefficients of 131I-labelled antigens, in the presence of excess antibody, were measured by ultracentrifugation through a sucrose density gradient. These showed that only small complexes were formed in some of the non-precipitating antisera. In one instance the diffusion coefficient of the complex was also measured, by a technique based on diffusion through agar gel. The calculated molecular weight of the complex, 330,000 indicated the presence of only two combining sites on the antigen. Combination of the anti-HSA sera with an HSA fragment was also measured. Whereas the amount of the fragment bound by ordinary hyperimmune anti-HSA sera was about one-fifth the HSA bound, the amounts bound by the test sera were relatively much less. Some non-precipitating sera failed to bind the fragment, although they bound HSA. These findings indicate that following neonatally induced immunological unresponsiveness the capacity to respond to antigen returns piecemeal in respect of different parts of the antigenic mosaic, and that it may be severely restricted. The theoretical implications are discussed. [ABSTRACT FROM AUTHOR]

The immunological responses of rabbits to HSA, HGG or BSA were tested at various times later in animals which had received the corresponding antigens before or shortly after birth. As judged by the criterion of failure to show immune elimination of antigen, a high proportion of the rabbits remained unresponsive at times when it was calculated that all the originally administered antigen would have been eliminated from the circulation. Furthermore, removal of antigen by passively administered antibody failed to restore the capacity to respond. It is concluded that, in respect of the antigens used, their persistence in the extracellular body fluids is not a prerequisite for maintenance of immunological unresponsiveness.
Further administration of the same antigen to rabbits which had escaped from a state of specific immunological unresponsiveness generally produced a very weak response, and in a few instances resulted in a return to the unresponsive state.
When the cross-reacting antigens HSA and BSA were administered adsorbed on alum to rabbits made unresponsive by neonatal contact with BSA and HSA respectively, and at the same time a further dose of the original antigen was given, antibodies were formed which were specific for the second antigen and did not cross-react with the first. In only 1/9 animals was responsiveness to the first antigen restored. The significance of these results is discussed. [ABSTRACT FROM AUTHOR]

Cold antibodies were separated from the sera of six patients suffering from the cold-haemagglutinin syndrome and from one patient with acquired haemolytic anaemia secondayr to lymphosarcoma by dissociation of the specific antigen-antibody complexes. The eluted antibodies were studied (a) by immuno-electrophoresis along with the parent sera against horse anti-human serum and (b) by double diffusion in agar gel along with electrophoretically separated ‘γ1 globulin’† against anti-19S ‘γ-globulin’ rabbit sera. The protein forming the cold antibody was localized in the β2-M position on immuno-electrophoresis in each instance. It was found by double diffusion in agar gel to be immunologically identical with the protein forming the abnormal ‘γl-globulin’ electrophoretic peak in the parent serum. The results of these experiments indicate that the cold antibodies derived from patients with the cold-antibody type of acquired haemolytic anaemia are macro-molecular globulins. [ABSTRACT FROM AUTHOR]

Cold agglutinins were separated from the sera of eleven patients suffering from the cold-antibody type of acquired haemolytic anaemia by the dissociation of the specific antigen-antibody complexes. The electrophoretic mobility of the cold antibody was found to correspond to that of γl globulin in each case. Ultracentrifugal studies carried out on eluted cold antibodies prepared from the sera of seven patients demonstrated that the antibodies were macromolecules (S20,w∼18.1). In one instance the sedimentation coefficient of the cold antibody was demonstrated to be similar to that of electrophoretically separated ‘γ1 globulin’ prepared from the same serum, indicating their identical physical state. The results of treating the sera of nineteen patients with the cold-antibody type of acquired haemolytic anaemia with mercapto-ethanol further confirmed that the cold antibodies were all macromolecules, whether derived from idiopathic cases or cases secondary to some other known disorder. [ABSTRACT FROM AUTHOR]

A critical review is given of Goldberg's (1952, 1953) theory of Antigen-Antibody reactions in vitro. Goldberg's assumptions and the mathematical development of his theory are described in detail. Comparisons of Goldberg's predictions with experimental results are given in graphical form. Some criticisms are made of Goldberg's use of equations in regions in which the derivations given by him are not valid. [ABSTRACT FROM AUTHOR]

The development of donor‐specific antibodies (DSAs) is a major complication in transplantation, which is associated with inferior graft survival, impaired quality of life, and increased healthcare costs. DSA develop upon recognition of nonself HLA by the recipient's immune system. HLA molecules contain epitopes, which are the surface regions of HLA molecules recognized by antibodies. HLAMatchmaker is an algorithm for assessing donor:recipient HLA compatibility at the level of structurally defined HLA targets called eplets. The consideration of eplets, rather than the whole HLA molecule, could offer some advantages when classifying the immune risk associated with particular donor:recipient pairs. Assessing compatibility at the level of HLA eplets could decrease misclassification of post‐transplant immune risk by improving specificity, when antibodies are confirmed to be directed against donor eplets missing from the recipient's repertoire of eplets. Consideration of eplets may also increase the sensitivity of immune risk assessment, when identifying mismatched eplets that could give rise to new, not previously detected, donor‐specific antibodies post‐transplant. Eplet matching can serve as a rational strategy for immune risk mitigation. Herein, we review the evolution of HLA (in) compatibility assessment for organ allocation. We outline challenges in the implementation of eplet‐based donor:recipient matching, including unavailability of allele‐level donor genotypes for 11 HLA loci at the time of organ allocation and difficulty in assessing the hierarchy of immune risk associated with particular HLA eplet mismatches. Opportunities to address some of the current shortcomings of donor genotyping and HLAMatchmaker are also discussed. While there is a demonstrated benefit in the application of HLAMatchmaker for donor: recipient HLA (in)compatibility assessment, evolving long‐read genotyping methods, compilation of large data sets with allele‐level genotypes, and standardization of methods to verify eplets as determinants of immune‐mediated injuries are required before HLA eplet matching is implemented in organ allocation to improve upon transplant outcomes. [ABSTRACT FROM AUTHOR]

HLA donor‐specific antibodies developed de novo after transplant remain a major cause of chronic allograft dysfunction. Our study main purpose was to determine whether HLA MM, assessed traditionally and by HLA total and AbVer eplet mismatch load (EptMM and EpvMM) assessed with HLAMatchMaker, had impact on dnDSA development after living donor kidney transplantation (LDKT). We retrospectively analysed a cohort of 96 LDKT between 2008 and 2017 performed in Hospital Santo António. Seven patients developed dnDSA‐II and EpvMM and EptMM were greater in dnDSA‐II group compared to the no dnDSA‐II (18.0 ± 8.7 versus 9.9 ± 7.9, p =.041 and 41.3 ± 18.9 versus 23.1 ± 16.7, p =.018), which is not observed for AgMM (2.29 versus 1.56; p =.09). In a multivariate analysis, we found that preformed DSA (HR = 7.983; p =.023), living unrelated donors (HR = 8.052; p =.024) and retransplantation (HR = 14.393; p =.009) were predictors for dnDSA‐II (AUC = 0.801; 0.622–0.981). HLA‐II EpvMM (HR = 1.105; p =.028; AUC = 0.856) showed to be a superior predictor of dnDSA‐II, when compared to AgMM (HR = 1.740; p =.113; AUC = 0.783), when adjusted for these clinical variables. Graft survival was significantly lower within dnDSA‐II patient group (36% versus 88%, p <.001). HLA molecular mismatch analysis is extremely important to minimize risk for HLA‐II dnDSA development improving outcome and increasing chance of retransplant lowering allosensitization. [ABSTRACT FROM AUTHOR]

The authors explore a study which addresses the role of major xenogeneic antigen Ga1 and anti-Ga2 antibody in biological heart valves (BHV) durability and degeneration. They note the key finding of the study about the ability of abundant preformed antibody, universally present in patients, to initiate an antibody-mediated inflammatory reaction without the need for an induced antibody response. They believe that anti-Ga1 antibody plays an important role in the degeneration of BHVs.

The history of regulatory T cells goes back to the realisation that T cells could provide ‘help’ for antibody responses: the obverse of this is their ability to hold them in check. This brief personal overview follows the initial designation of T cells as ‘suppressor’ and the various hypotheses, some now disproved, put forward for their mechanism of action. We now cautiously label them T regulatory cells, but realise they do not control not all immune regulation. They probably operate through several mechanisms, and some of these are discussed. [ABSTRACT FROM AUTHOR]

Immune receptors that show high mutual sequence similarity and have antagonizing signaling properties are called paired receptors, and are believed to fine-tune immune responses. Siglecs are sialic acid-recognizing receptors of the immunoglobulin (Ig) superfamily expressed on immune cells. Human Siglec-5, encoded by SIGLEC5 gene, has four extracellular Ig-like domains and a cytosolic inhibitory motif. We discovered human Siglec-14 with three Ig-like domains, encoded by the SIGLEC14 gene, adjacent to SIGLEC5. Human Siglec-14 has almost complete sequence identity with human Siglec-5 at the first two Ig-like domains, shows a glycan binding preference similar to that of human Siglec-5, and associates with the activating adapter protein DAP12. Thus, Siglec-14 and Siglec-5 appear to be the first glycan binding paired receptors. Near-complete sequence identity of the amino-terminal part of human Siglec-14 and Siglec-5 indicates partial gene conversion between SIGLEC14 and SIGLEC5. Remarkably, SIGLEC14 and SIGLEC5 in other primates also show evidence of gene conversions within each lineage. Evidently, balancing the interactions between Siglec-14, Siglec-5 and their common ligand(s) had selective advantage during the course of evolution. The "essential arginine" critical for sialic acid recognition in both Siglec-14 and Siglec-5 is present in humans but mutated in almost all great ape alleles. [ABSTRACT FROM AUTHOR]

The objectives of the present study was to describe different dynamics of humoral immune responses to experimental infection in piglets of different stages of infection and immunity. Two groups of piglets originating from non-immune (group 1) and immune (group 2) sows at the age of 3 weeks were subdivided as follows: a half of each group of piglets was exposed to a low-dose infection with Actinobacillus pleuropneumoniae (APP) strain 9. At the age of 8 weeks, all four groups of piglets were challenged with a high infection dose of APP of the same strain. Isotype characterization of the specific antibodies in sera and in bronchoalveolar lavage fluids (BALF) to a lipopolysaccharide was carried out, besides monitoring clinical signs and post-mortem examinations. A typical primary immune response was observed in specific antibody-free piglets infected with a challenge infection. Colostrum-derived immunoglobulin-G (IgG) antibodies persisted in sera and BALF of piglets up to the age of 8 weeks. However, they did not prevent induction of specific-primary antibody response, either in 8 or 4 weeks of age, when levels of specific colostrum-derived antibodies were still high. It was demonstrated by the increase of specific IgM antibodies in sera. The infection induced an increase in the levels of IgA antibodies in BALF regardless the severity of infection and presence of specific colostrum-derived antibodies. The specific antibodies of IgG isotype increased only in BALF from piglets without colostrum-derived antibodies. [ABSTRACT FROM AUTHOR]

OX40 ligand (OX40L), a molecule originally identified as human gp34, is an important co-stimulatory molecule during immune response. In this study, we report on five functional mouse anti-human OX40L monoclonal antibodies named as 9H10, 4C12, 8D10, 4H4 and 1G1, characterized by means of flow cytometry, Western blot and competition assay. These monoclonal antibodies bound to distinct OX40L epitopes on activated B cells and dendritic cells (DCs) and two of them could suppress the proliferation of T lymphocytes co-stimulated by mature DCs. Furthermore, we demonstrated that our monoclonal antibodies, such as 9H10 and 4C12, could trigger OX40L reverse signal that enhanced IgG production of B cells and promoted maturation of DCs as evidenced by the upexpression of CD80, CD86, CD83 and CXCR4 and monoclonal antibody 9H10 could also promote anti-CD40 monoclonal-antibody-stimulated DCs in order to induce T cells to secrete more interleukin-2 and interferon-γ, which suggested that OX40L signals could strengthen the effect of CD40 signals on promoting Th1 differentiation. [ABSTRACT FROM AUTHOR]

Domagała A, Kurpisz M. Immunoprecipitation of sperm and somatic antigens with antibodies from sera of sperm-sensitized and anti-sperm antibody-free individuals. AJRI 2004; 51:226–234 © Blackwell Munksgaard, 2004 Immune infertility may result from the presence of anti-sperm antibodies (ASA) in sera of sensitized individuals or in their genito-urinary millieu. According to some authors, sera of pre-pubertal boys with genital disorders may contain ASA, too. When identified and characterized, sperm antigenic components can be employed for diagnostic and/or for immunocontraceptive purposes. Sperm auto- and isoimmune reactive surface antigens were identified by means of immunoprecipitation. Comparative immunoprecipitations of somatic antigens by using antibodies, contained in polyclonal sera of fertile and (immunologically) infertile adults as well as pre-pubertal boys with gonadal failures were performed. Antibodies contained in sera of the all studied populations reacted with a number of sperm as well as somatic antigens. However, we distinguished a panel of antigens localized exclusively on the surface of sperm cells, reacting with ASA positive sera (in the range of molecular weight between 15 and 115 kDa), some of them seem to present novel entities as can be judged by the molecular weight. [ABSTRACT FROM AUTHOR]

The kinetics of parasite-specific antibody responses in relation to worm burden and egg output were investigated in hamsters infected with 25, 50 and 100 Opisthorchis viverrini metacercariae (MC). Levels of antibody to egg, excretory–secretory (ES) and somatic antigens were examined by ELISA on days 1, 3, 7, 14 and month 1 postinfection (p.i.), and repeated monthly up to 6 months. The antibody responses were first detected as early as 14 days after infection. Hamsters that were infected with 100 MC and 50 MC showed higher antibody levels than those of 25 MC, during early infection until 1 month p.i. Then, the antibody levels were increased rapidly to a plateau at approximately month 2 p.i. and, subsequently, were relatively stable in all groups. The average antibody levels to egg and somatic, but not to ES antigens, were significantly higher in hamsters infected with 25 MC than those of 50 MC and 100 MC. These antibody responses, particularly to egg and ES antigens, were not correlated with worm burden or egg output. Overall, higher antibody responses were found in the order: ES, somatic and egg antigens. The significant lower antibody responses in chronic and heavy infections than those with mild infection may a result of immunosuppression. [ABSTRACT FROM AUTHOR]

Exposure to ispaghula dust in a pharmaceutical factory resulted in chest tightness/ wheeze, nasal, and ocular or skin symptoms in 48 of 92 exposed workers. Whilst symptoms were not incapacitating in the majority (44) of these, one worker required antihistamines and three others experienced severe respiratory symptoms when exposed to the dust. These three were atopic, had a positive RAST and skin test to ispaghula; a combination unique to them. There was a significant relationship between work-related symptoms and atopic status, however, smoking did not influence symptoms, total serum IgE and specific anti-ispaghula IgE. We conclude that handling ispaghula produces, an irritant effect in most exposed people, however, sensitization to the dust can occur with severe respiratory symptoms. [ABSTRACT FROM AUTHOR]

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In areas endemic for schistosomiasis, there is great heterogeneity in antibody isotype responses to parasite antigens amongst infected individuals. At the population level, the isotype composition of antibody responses undergoes dynamic changes which are associated with the age of infected individuals. Here we examine the IgG subclass responses to Schistosoma mansoni eggs (soluble egg antigens; SEA) of infected individuals by immunoblot and ELISA. By controlled treatment of SEA-coated ELISA plates and immunoblot nitrocellular strips with sodium periodate, in order to oxidize terminal carbohydrate residues selectively, we were able to relate individuals subjects' isotype responses to the different antigens that they responded to, and to the presence of putative carbohydrate and peptide epitopes on those antigens. IgG2 responses were restricted strictly to sodium periodate-sensitive carbohydrate epitopes and antigens of relatively high molecular weight. These antigens were not usually recognized by other isotypes and, therefore, they were only recognized by individuals who had high levels of IgG2. IgG1 and IgG3 responses were directed against both carbohydrate and peptide epitopes, whereas IgG4 responses were restricted to periodate-resistant epitopes. This suggests that the fall in IgG2 responses, and reciprocal rise in IgG4 antibodies, seen in young children as their intensities of schistosome infection increase, is not the result of isotype switching, and that, if these two subclasses are involved in blocking immunity to schistosomiasis, they are operating independently. [ABSTRACT FROM AUTHOR]

Interferon-γ, (IFN-γ) and interleukin-4 (IL-4) are cytokines with important functions in regulating immune responses. IFN-γ may be produced by cells responsible for delayed-type hypersensitivity (DTH), whereas IL-4 is essential for IgE production. Pertussis toxin (PT) from Bordetella pertussis enhances both DTH and IgE responses, and causes enhancement of both IFN-γ and IL-4 secretion in immunized mice. In the present study, the effects of neutralizing monoclonal antibodies against IFN-γ or IL-4 on DTH, serum IgE and cytokine production were assessed. Treatment with a monoclonal anti-IL-4 antibody at the time of immunization caused a striking increase in DTH responses, and elicited enhanced IFN-γ expression, while inhibition of the production of IL-4 and IgE was observed. By contrast, injection of a monoclonal anti-IFN-γ antibody was followed by significant but not complete suppression of DTH reactions. IFN-γ secretion was also inhibited, whereas IL-4 production and serum IgE were increased. Thus antibodies to IL-4 and IFN-γ, given at the time of immunization, can profoundly influence the nature of short-term immune responses elicited by PT in immunized mice. [ABSTRACT FROM AUTHOR]

The article presents abstracts of research on immunology. They include "Isotype-Dependent Localization of Human Antibody-Secreting Cells in the SCID-TMC-hu Mouse," "Treatment of Visna Infected Sheep With Cyclosporin A," "Human IgG Rheumatoid Factors Induce Mouse IgG1 Rheumatoid Factor Production in NZB Mice in vivo," "Capture ELISA Is Better Than Direct ELISA for PR3-ANCA Detection" and "Human T Cell Responses to Secreted Antigen Fractions of M. tuberculosis."

The role of complement component C5 in the immune response of mice to sheep red blood cells (SRBC) was investigated. Congenic C5-sufficient and C5-deficient B10.D2 mice and genetically C5-defficient DBA/2 mice, as such or supplemented with C5-suffcient serum, were used as experimental animals, C5-substitution of the C5-deficient mice resulted in measurable C5 levels for days. The functional half-life of C5 in C5-deficicnt DBA/2 mice was about 21 h. No significant differences between the IgM-responses of C5 bearing and naive C5-deficient animals were observed. This suggests that C5 does not play a major role in the primary humoral immune response of mice in vivo, although C5 seems to do so in in vitro experiments, even with the same antigen. Antigen-induced C5-produclion by C5-deficient mice as one of the explanations of the in vitro, in vivo discrepancy could not be confirmed experimentally. [ABSTRACT FROM AUTHOR]

We have examined the immunological activity of five affinity-purified protein antigens from Mycobacterium tuberculosis in seven inbred and one outbred guinea pig strains. The test systems were measurements of delayed-type hypersensitivity (Dth) responses, lymphocyte stimulation assays (LS), and antibody response measurements. The results showed significant differences in the immunogenicity of the single-protein antigens and, when the antigens were considered separately, highly significant guinea pig strain differences. The outbred guinea pig strain behaved as a Dth high responder to all antigens studied. The order of magnitude of the Dth responses was not usually correlated with that of the corresponding antibody responses for the individual guinea pig strain-antigen combinations. In particular, when compared with the other strains, strain 2 guinea pigs generally gave the lowest Dth, but the highest antibody responses. A 38,000 molecular weight protein, possessing M. tuberculosis complex-specific B-cell determinants, appeared immunodominant in 5 out of 7 strains. Our Dth data in the inbred strains further suggest the presence of an M. tuberculosis-specific T-cell epitope. A T-cell line, 11D9, derived from the high-responder guinea pig strain 13 reactive to this protein, was shown to be able to confer a tuberculin-like skin reaction in vivo. LS assays with recombinant 38-kDa protein and truncated versions of the protein mapped the 11D9-defined T-cell epitope to the middle part of the molecule. [ABSTRACT FROM AUTHOR]

The predominant selection of CRI-A-bearing antibodies during the anti-arsonate (ARS) response of A/J mice has been used as a model to analyse the mechanism involved in the process of clonal selection and establishment of predominance. In order to assess the importance of the affinity and adaptability of CRI-A clones in this process, we tested the capability of a minor recurrent idiotype (id-IA3). present in a CRI-anti-ARS monoclonal antibody (65-IA3), to develop a normal anti-ARS response. Our results show that the id-1A3 predominance, established by anti-id-IA3 administration was stable during the primary and secondary anti-ARS response and that this predominance occurred concomitantly with low levels of CRI-A. Thus, a change in the idiotype predominance was achieved. In spite of the high levels of id-IA3, the anti-ARS antibody concentration, the affinity values, and the kinetics of the immune response were similar to those of the control group. All these results show that CRI-A clones are not essential in the normal development of the anti-ARS antibody response of A/J mice, and suggest that factors other than affinity could be involved in the stablishment of the CRI-A predominance. [ABSTRACT FROM AUTHOR]

This article focuses on a hypothesis for the activity of immune response genes in the processing and presentation of antigens by macrophages. The major histocompatibility complex (MHC) of higher species contains a set of extremely polymorphic immune responses (Ir) genes, which exert a pervasive control over immune responses. The MHC class 11 molecules, henceforth called the Ia molecules are products of the Ir genes. They are glycoprotein heterodimers expressed on the surface of some of the cells in the immune system. Structural studies of the Ir genes and Ia molecules have revealed homologies with recognition molecules of the immune system such as immunoglobulin and the T-cell antigen receptor.

Bone marrow cells produce soluble mediators with structural and functional heterogeneity. They were found to stimulate antibody production at the peak of the immune response, owing to compounds of a peptide nature (Mr 2000–1300). Active material was isolated by means of gel chromatography and electrophoresis. This material positively reacts with ninhydrin, and has maximum absorption close to 278 nm. Its antibody-stimulating activity decreased or stopped completely after treatment with proteolytic enzymes. Apart from the immunostimulating activity, bone marrow mediators have opiate-like activity. They have an analgetic effect, and interact with the opiate receptors of brain nerve cells. After a physicochemical and functional analysis, we concluded that bone marrow produces regulatory peptides that were previously unknown. We called them myelopeptides. [ABSTRACT FROM AUTHOR]

Immunological reactivity in patients with systemic lupus erythematosus (SLE) was assessed by investigating in vitro trinitrophenyl (TNP)-specific antibody formation by peripheral lymphocytes. Peripheral lymphocytes from 16 patients with SLE were cultured with TNP conjugated with horse erythrocytes (TNP- HRBC) in the presence of 2-mercaptoethanol. The hemolytic plaque assay was used to detect hapten (TNP)-specific antibody-forming cells. Peripheral lymphocytes from normal individuals failed to produce antibody to TNP, whereas SLE lymphocytes produced a significant number of plaque-forming cells. Co-culture experiments with SLE and normal lymphocytes suggested that patients with SLE have a defect in T lymphocytes, leading to abnormal antibody production. [ABSTRACT FROM AUTHOR]

The present experiments were undertaken to delineate the role of LD and SD antigens in terms of memory in cell-mediated immune response (CML), Using recombinants that differ for either the H-2K or H-2D determinants (SD-different) and other recombinants differing for the central region of H-2 (LD different), we have investigated this question. The results indicate that priming to SD determinants leads to a more rapid and higher response when cells are restimulated in vitro with either the same SD antigt-n alone or the same SD plus an LD antigen and tested on target cells that possess either the SD antigen alone or both the LD and SD antigens. Antigens in the central regions of H-2, which includes LD, serve as the stimulus both for the helper T cells and for the c)'totoxic T lymphocjtes. Priming with a high dose of LD antigt-ns leads to memory in the cytotoxic T lymphocyte recognizing the cytotoxic target antigens coded by the central region of H-2. Nevertheless, memory could not be detected when priming was done under the same conditions as for SD antigens. Moreover, a primed helper T-cell response does not facilitate the development of increased CML on restimulation in vitro with the LD antigen used for priming and a new SD antigen. Thus, it seems that memory in CML is in the cytotoxic T lymphocyte and not in the proliferating helper cells. [ABSTRACT FROM AUTHOR]

Evidence is presented that significant numbers of specific anti body-forming cells are released from the spleen into the circulation on the 4th day of the secondary-immune response to sheep erythrocytes. This release results in a transient appearance of specific antibody-forming cells in the blood and implicates a dissemination of specific anti body-forming cells from the spleen to different parts of the body. Also specific antigen-binding cells are released from the spleen, with a peak release on the 4th day of the immune response. [ABSTRACT FROM AUTHOR]

An unclustered molecule, 8-10C5, present on bovine leucocytes, was characterized using a monoclonal antibody (mAb) prepared at the University of Wisconsin-Madison, and the functional and biochemical characteristics of that molecule compared to defined molecules. This molecule was present on a large percentage of peripheral blood cells (84%), including T and B lymphocytes, monocytes and neutrophils, but was absent from immature thymocytes, mAb 8-10C5 blocked proliferation to alloantigen and bovine herpesvirus-1; however, antibody to the 8-10C5 molecule was unable to stimulate proliferation alone or in combination with PMA or a cross-linking agent. These results indicate that this molecule has a role in T-cell activation, but probably not signal transduction. mAb 8-10C5 was unable to block cytotoxic T lymphocyte (CTL) or natural killer (NK) like lysis. mAb 8-10C5 identifies a non-covalently bound heterodimer present on most peripheral lymphocytes with a molecular weight (MW) of 120,000 for the alpha chain (10% glycosylation) and 90,000 MW for the beta chain (16% glycosylation). The beta chain is an acidic molecule (pI=4.5-5.0). Biochemical studies included the CD2 and CD5 molecules and further demonstrated their similarity to equivalent molecules in other species, confirming the phylogenetic importance of these molecules in immune responses. This functional and biochemical information will allow further characterization of these molecules at the RNA and DNA levels. [ABSTRACT FROM AUTHOR]

Sixteen monoclonal antibodies (mAb) were produced against mouSe thymic stromal elements. These mAb fell into two groups of reactivity: (i) thymic epithelial markers (screened and presented according to the guidelines proposed in the 1989 Rolduc Thymic Epithelial Workshop); and (ii) non-epithelial thymic markers. Specificities of these mAb included extensive subpopulations of both epithelial and non-epithelial thymic stromal cells, as well as isolated stromal cells, demonstrating some of the complex microspecificities in existence within the thymic microenvironment. Furthermore, six of these mAb demonstrated shared antigenicity between thymocytes and thymic stromal cells, revealing greater similarities than previously recognized between these two components. Three mAb detected antigens illustrating three consecutive layers of the blood-thymus barrier: the vascular endothelium; connective tissue of the capsule and perivascular spaces; and the connective tissue associated with the basal laminae lining these regions. This study illustrates unequivocably that there are indeed complex and varied microenvironments existing within the thymus, and emphasizes the need for reclassification of these cells. [ABSTRACT FROM AUTHOR]

The idiotypic (Id) diversity of the immune response to phosphorylcholine (PC) was studied by immunization of mice with thymus-dependent (PC-keyhole limpet haemocyanin; PC-KLH) and thymus-independent (S. pneumoniae R36a; Pn) forms of the antigen. Mice with the BALB/c genetic background (BALB/c, C.B20, and BALB.B) were used because their response to PC is dominated by immunoglobulins encoded in VH-1 and Vk 22 genes, which uniformly express the T15 idiotype. The actual repertoire of the antibody was determined by idiotypic markers (Id) defined with monoclonal antibodies designated AB1–2, B36–82, MaId5–4, and B24–44. Previous studies from our laboratory have shown that these Id are present on TI5 (VS107-1/Vk22) immunoglobulins only, but that they differentiate between somatic variants of the antibody molecules. We have measured the serum concentrations of these four Id after primary (1°), secondary (2°), and tertiary (3°) immunization; all of the Id activity was associated with the PC-binding antibody, as shown by specific immunoadsorbents. However, the levels of the Id-bearing (Id+) antibody did not correlate with each other. After immunization with PC-KLH, the AB1–2+ antibody declined precipitously, whereas the levels of B24–44 and B36–82 remained steady. A similar pattern of Id heterogeneity was seen at the level of direct antibody-plaque-forming cells from the spleen, suggesting that the idiotopic (clonal) diversification occurred already during the early IgM response. A significant portion of anti-PC antibody after the 3° PC-KLH immunization was negative for all four Id, implying that the late response to the antigen involved distinct, T15-negative clones. The same idiotope repertoire changes were observed in BALB/c and in congenic strains C.B20 (Ishb) and BALB.B (H-2b). A diversification of T15+ antibody was also detectable upon immunization with a T-independent antigen, Pn, but to a much lesser extent. These observations indicate that the T15+ antibody response in BALB/c mice is heterogeneous, and that there appears to be a selection of specific clonal variants in which the T cells play a role. [ABSTRACT FROM AUTHOR]

Affinity maturation was studied by the analysis of the kinetics of the appearance of antibody subpopulations with different affinities during the immune response, using an hapten-inhibition ELISA. The immune response in KLH-Ar-immunized A/J mice was used as a model system. Five antibody subpopulations of different affinity (103-107 M-1) could be detected, the relative concentrations of which changed during affinity maturation. The high-affinity antibody subpopulations did not represent the major fraction at any stage during affinity maturation. The appearance of the highest affinity subpopulation (107 M-1), despite exhibiting relative concentrations no higher than 12%, produced an important increase in average affinity. On the other hand, its disappearance at the end of the maturation process could explain the average affinity decrease observed at this stage. Our results indicate that affinity maturation cannot be explained by the dominance of high-affinity clones, as proposed by Siskind & Benacerraf (1969). The increase in affinity could rather be due to the progressive appearance of low percentages of high-affinity clones, which are not present in the primary response and never become dominant. [ABSTRACT FROM AUTHOR]

Examines the formation of antibodies to the respective idiotypes of myeloma proteins produced by MOPC plasmocytoma tumours of BALB/c origin. Description of the biological characteristics and morphology of the IR202 transplantable immunocytoma tumour in rats; Presentation of the 202M protein molecules on the macrophage surface; Development of antibodies specific to individual antigenic determinant of the monoclonal IgM.

Passive administration of monoclonal IgM anti-sheep red blood cell antibody 2 hr prior to a low dose of sheep red blood cells (SR BC) markedly enhances the specific antibody response. This IgM enhancement of the response to SRBC is highly reproducible and can furthermore be demonstrated in vitro. The time course and dose dependency of the response indicate that a critical antibody: antigen ratio is necessary for enhancement to occur. The IgM enhancement phenomenon has been demonstrated in several strains of mice, providing strong evidence against an idiotype-related mechanism. [ABSTRACT FROM AUTHOR]

The effect of the injection of a synthetic platelet-activating factor (PAF-acether) upon the fate of exogenous immune aggregates was studied in normal mice. When animals received 0.5 µg of PAF-acether following the administration of 5 µg heat-aggregated human IgG (A-IgG), a 50% increase of clearance velocity was observed during the initial 5 min; thereafter, between 15 and 30 rain, there was a marked increase in blood levels of immune aggregates which paralleled the increase in plasma volume observed at those times. As regards the effect of the infusion of PAF-acether on the distribution of A-IgG in the organs, hepatic uptake was not affected, kidney uptake was reduced during the first 15 min, and lung and spleen showed only minor variations. When animals were injected with 0.5 µg PAF-acether, skin trapped aggregates showed a 73% increase above control values at 5 rain, followed by a fall to control values coincidently with the flood back of the aggregates into the circulation and the increase in blood volume. The injection of lower doses of PAF-acether (0-05 µg) or Diazoxide (1.5 mg) did not induce any change on the skin trapping of aggregates. In conclusion, the powerful action of PAF-acether on vascular permeability allows a reversible deposition of immune aggregates in the skin which is followed by the flood back of this material into the circulation when its pharmacological action subsides. These findings may be of some relevance to the understanding of the dynamic processes involved in the deposition of immune complexes in tissues, especially as regards skin vessels. [ABSTRACT FROM AUTHOR]

Lysine prevented the activation of C I at low ionic strength or by heat aggregated IgG (aggIgG) measured by the hydrolysis of acetyl tyrosine ethyl ester (ATEe) by C1&smacr;. When serum was mixed with aggIgG, complement was activated and consumed. If lysine was present in the serum containing aggIgG, the activation of complement, thus its consumption, was inhibited in a dose-response manner. C1 haemolysis assay which measures the C 1 activity to interact with EA (erythrocytes bound with antibody) was used to study the effects of lysine. The results indicate that 50% of Cl haemolysis was inhibited at 3 mM of lysine. Crossed immunoelectrophoresis indicates that C1 in the serum was activated by agglgG, but C1&smacr; thus formed seemed to be soon complexed with C1 inactivator. The presence of lysine prevented the conversion of Cls to C1&smacr; completely. It might be possible that lysine binds with the binding sites on Clq, thus preventing the interaction of C1q and Cγ2. [ABSTRACT FROM AUTHOR]

Small lymphocyte subsets were characterized radioautographically on the basis of several surface markers, viz. surface Ig (S-Ig), Thy-1 and Lyt (Ly-1, Ly-2 and 3) antigens in host lymphoid organs (thymus, spleen and blood) as well as at the turnout site at various stages of subcutaneous growth of two different syngeneic turnouts—MPC-11 plasmacytoma and WEH I- 164 fibrosarcoma in BA L B/c mice. In both tumour-host combinations there was a rise in the levels of null (S-Ig-, Thy-1-) small lymphocytes as well as the Ly-23+ subset of T small lymphocytes at all the sites examined. The absolute number of these two subsets also increased excepting the case of null cell rise in the thymus which was relative. The functional potentials of Lyt subsets were explored by employing in vitro and in vivo assays. While no appreciable levels of anti-turnout cytotoxic T cells (Tc) were detectable by a 51Crk release assay in the host spleen or the turnout-draining lymph nodes at any stage of growth of MPC-11 tumour, such Tc was generated in vitro by a co-cultivation of unprimed spleen cells with irradiated MPC-11 cells. These Tc were Thy-l+ and Ly-12+, as noted from antibody+C' mediated abrogation of cytotoxicity. These results suggested that the generation of anti-turnout Tc in vivo was suppressed in tumour-bearing hosts. The possibility of a cell-mediated suppression was tested by an adoptive transfer of thymocytes or splenocytes from turnout-bearing mice into naive or pre-immunized recipients which then received fresh turnout transplants. This procedure caused a specific enhancement of turnout growth in three tumour-host combinations: MPC-I 1 or WEHI-164 turnout in BALB/c mice and W-I fibrosarcoma in CBA mice. The suppressor lineage lymphocytes appearing in vivo were found to be Thy-1+ and Ly-1-, 2+, as noted from antibody +C' mediated abrogation of their turnout-growth promoting ability. They appeared earlier (7 days) in the thymus and later (> 2 weeks) in the spleen and then persisted during the turnout lifetime. The parallel kinetics of the increase in the overall level of Ly-23+ cells and the appearance of Ly-2(3)+ suppressor lineage T cells in tumour-bearing hosts may indicate that studies of T-cell surface markers may be useful in predicting changes in the functional lymphocyte subsets. [ABSTRACT FROM AUTHOR]

We have developed a hybridoma cell tine which secretes monoclonal antibody to human basement membrane type IV collagen. The monoclonal antibody secreted by this hybridoma has been obtained in large amounts by either concentrating it from culture supernatants or from the ascites fluid of mice bearing the hybridoma tumour. This monoclonal antibody to type IV collagen does not cross-react with other types of collagens, including types I, III and V, as determined by an enzyme-linked immunosorbent assay (ELISA) and by immunohistochemical staining of corneal and lens sections. Descemet's membrane of mouse, rabbit and human corneal endothetium and lens capsule, both rich in type IV collagen, bind the antibody when stained immunohistochemically. By the indirect precipitation technique, the antibody is found to bind more than three peptides in the basement membrane collagen-rich fraction of human placenta. Based on the observations of other investigators, these peptides are probably derived by proteolysis of the larger polypeptides, since the purification steps involve extensive pepsin digestion. [ABSTRACT FROM AUTHOR]

The influence of serum on phagocytosis related to the complement system was examined by means of a kinetic phagocytosis method using IgG-coated particles, isolated polymorphonuclear neutrophil leucocytes (PMNs), fresh serum, in vitro activated sera and in vivo activated sera. The previously described opsonic properties of C3b and C4b were confirmed by the enhancement of phagocytic rate by the opsonization of IgG particles with C3 and C4. An anti-opsonic effect of serum was revealed by the initial inhibition of PMN phagocytosis of IgG-coated particles in the presence of fresh serum. In vitro activated normal fresh serum and in vivo activated SLE sera mediated a prolonged or even irreversible inhibition of phagocytosis dependent on the degree of complement activation. Investigation of this anti-opsonic effect of serum, which was heat-labile, suggested that it was caused by an inhibition of the interaction between the Fc receptor and IgG mediated by the C1q component of the C1 complex. [ABSTRACT FROM AUTHOR]

The avidity of antibodies against human serum albumin (HSA) and the complement-mediated solubilization of HSA anti-HSA precipitates has been investigated during the immune response in rats, mice, rabbits, and guinea-pigs. The avidity of the anti-HSA antibodies was quantitatively determined and expressed as the amount of HSA required to solubilize 50% of 10 ng HSA anti-HSA precipitate. In rats, from 25 to 100 days after primary immunization the avidity of the anti-HSA antibodies increased approximately 100-fold, whereas the affinity did not change significantly. The increase in avidity was accompanied by a thirty-six-fold decrease in the amount of immune precipitate that could be solubilized by complement. Booster injections of the rats did not prevent the increase in avidity (thirteen-fold) that occurred from 25 to 50 days after the first immunization; however, the subsequent eight-fold increase in avidity from 50 to 100 days could partially or completely be abolished by secondary immunizations. A close, inverse relationship between the avidity of the anti-HSA antibodies and the rate of complement-mediated solubilization was observed. In addition, an increase in avidity without a change in affinity of anti-HSA antibodies and a decrease in the rate of complement-mediated solubilizatíon was found during the immune response against HSA not only in rats, but also in mice, rabbits, and guinea-pigs. [ABSTRACT FROM AUTHOR]

Soluble antigen preparations from Mycobacterium leprae are reported to inhibit the response to other stimuli, of peripheral blood mononuclear cells from lepromatous leprosy cases (BL/LL) and also from tuberculoid cases (TT/BT) and normal donors. We confirm these findings and in addition, report that a similar suppressive effect is exerted by antigen from Mycobacterium vaccae, Mycobacterium nonchromogenicum and, to a lesser extent, Mycobacterium tuberculosis and Mycobacterium kansasii. Moreover, suppression is seen using peripheral blood mononuclear cells from individuals unlikely to have encountered the organism used. The suppression is not due to toxicity of the antigen preparation, and is not indomethacin sensitive. It involves a cell found in the E-rosetting population, which loses its ability to suppress or be suppressed, after 48 hr in culture. Possible explanations include a pharmacological effect of cell wall peptidoglycolipids, or the triggering of suppressor cells specific for common mycobacterial antigens. [ABSTRACT FROM AUTHOR]

Normally circulating human leucocytes were found to consistently lyse rabbit erythrocyte (RRBC) target cells within 24 hr in culture. The reaction is referred to as the naturally-occurring cell-mediated cytotoxic, or NOCC, reaction. Characteristics of this cytotoxic reaction are as follows. (i) The cytotoxic reaction described here can be distinguished from the antibody-dependent cellular cytotoxic (ADCC) reaction as conventional Fc receptors do not appear to play a role. Although the cytotoxic reaction occurs optimally in medium fortified with normal human serum to a final concentration of 1%, neither antibodies nor immunoglobulins in general appear to play a role. Agamma human serum or purified human Serum albumin without detectable immunoglobulins are as capable of facilitating and sustaining the NOCC cytotoxic reaction as is normal human serum. Furthermore, foetal calf serum, which promotes the ADCC cytotoxic reaction, inhibits the NOCC cytotoxic reaction. (ii) The NOCC reaction is not a phagocytic one as phagocytosis of the RRBC could not be detected during the culture period. (iii) Monocytes and neutrophils, but not lymphocytes, are capable of lysing the target cells in the NOCC reaction. The effector mononuclear cell is a monocyte with receptors for Fc and C′3. (iv) The NOCC cytotoxic reaction is dependent upon direct effector cell-target cell contact and not upon soluble mediators secreted by the effector cells since third-party bystander erythrocytes are not lysed in the presence of rabbit erythrocyte target cells and human mononuclear cells. Supernatants from lysed RRBC target cells could not lyse fresh RRBC. It is concluded that the NOCC cytotoxic reaction utilizing rabbit erythrocytes as target cells permits the identification of cytotoxic subclasses of monocytes and neutrophils. [ABSTRACT FROM AUTHOR]