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Studies have been conducted to characterize M. leprae antigens from purified Ieprae bacilli derived from infected armadillos. First, the proteins of the mycobacterial extracts were fractionated by SDS-PAGE. Subsequently, the proteins in the gel were electrophoretically transferred on a strip of nitrocellulose paper by the technique of 'electrophoretic blotting'. The separated bacterial protein bands, thus immobilized on the nitrocellulose paper were made to react immunologically with sera from the lepromatous patients, infected armadillo sera and other experimental mycobacterial antisera. It was observed that a majority of M. leprae proteins contained antigenic determinants also present on proteins of BCG. In addition, only two specific antigen bands of 33KD and 12KD were conspicuously detected by the patients' sera and the infected armadillo sera. These substances were further identified as polysaccharides or glycoproteins since they could only be stained by Schiff's reagent or alcian blue. Only 12KD glycoprotein band reacted with concanavalin A, whereas wheat germ agglutinin (WGA) did not show any reaction with them. These 33KD and 12KD glycoprotein antigens were found to lose their antigenicity after pepsin treatment and can be considered as glycoproteins. Further, radiolabelling experiments showed that 12KD antigen underwent radioiodination under usual conditions, but 33KD glycoprotein Failed to be similarly radiolabelled. It is suggested that these protein antigens have M. Ieprae specific determinants on a cross-reacting component. [ABSTRACT FROM AUTHOR]

In this paper we provide a detailed description of an experimental method for investigating the induction and resolution of recall immune response to antigen in humans in vivo. This involves the injection of tuberculin purified protein derivative ( PPD) into the skin, followed by inducing suction blisters at the site of injection, from which leucocytes and cytokines that are involved in the response can be isolated and characterized. Using this technique we found that although the majority of CD4+ T cells in the skin that are present early in the response express cutaneous lymphocyte antigen ( CLA), the expression of this marker is reduced significantly in later phases. This may enable these cells to leave the skin during immune resolution. Furthermore, interleukin ( IL)-2 production can be detected both in CD4+ T cells and also in the blister fluid at the peak of the response at day 7, indicating that mediators found in the blister fluid are representative of the cytokine microenvironment in vivo. Finally, we found that older humans have defective ability to respond to cutaneous PPD challenge, but this does not reflect a global immune deficit as they have similar numbers of circulating functional PPD-specific CD4+ T cells as young subjects. The use of the blister technology enables further characterization of the skin specific defect in older humans and also general mechanisms that govern immune regulation in vivo. [ABSTRACT FROM AUTHOR]

SUMMARY The addition of a foreign antigen to an inoculum completely inhibits the development of collagen-induced arthritis (CIA). However, the mechanism of this phenomenon, antigen -inhibition, is incompletely understood. Previous studies have demonstrated that the inhibition of arthritis is not mediated through suppression of the antibody response to cartilage antigens. In this paper we investigated cytokine mRNA levels in lymph nodes cells recovered 3, 7 or 16 days from animals immunized with either collagen II in IFA or OVA + collagen II in IFA. At day 7, but not at other time-points, IL-4 mRNA was up-regulated in the lymph nodes of OVA-inhibited non-arthritic animals compared to control animals which all developed arthritis. No significant differences between the two groups could be detected when expression of IFN-γ , IL-2, TNF-α , IL-1β or IL-10 mRNA was analysed. Flow cytometry analysis of draining lymph node cells demonstrated that the T cell marker Ox40 was up-regulated in the OVA-inhibited group. Our results indicate that the complete inhibition of CIA caused by addition of OVA to the collagen II inoculum is due to the presence of a TH2 environment resulting from an increased production of IL-4 mRNA and a parallel increase in Ox40+ T cells. [ABSTRACT FROM AUTHOR]

Investigates the characterization of the antigens identified by the anti-endothelial cell antibodies (AECA) in patients with systemic sclerosis. Prevalence and clinical significance of AECA; Affinity purification of antibody from nitrocellulose paper; Analysis of antinuclear antibodies.

The article presents various research papers related to complement deficiencies, published in an earlier issue of the journal "Clinical & Experimental Immunology". One of the abstracts talk about acquired deficiency in C1-inhibitor associated with an undifferentiated gastric adenocarcinoma. Acquired deficiency in C1-inhibitor (C1-INH) clinically manifests similar to hereditary angioedema and is usually associated with a B cell malignancy or is sometimes characterized by an autoantibody towards the C1-INH molecule.

Recently, we reported on the importance of food antigens on the pathogenesis of an experimentally-induced model of, and some patients with, IgA nephropathy. In this paper, the glomerular deposition of food antigens (casein, lactalbumin, peanut protein, soy bean protein, rice protein, ovalbumin) was investigated by an immunofluorescence technique in 28 patients with IgA nephropathy and 32 controls (ten with lupus nephritis, three with Henoch-Schoenlein purpura nephritis and 19 with other glomerulonephritis). Glomerular IgA deposition was demonstrated in all IgA nephropathy and Henoch-Schoenlein purpura nephritis, and in four lupus nephritis. Positive findings of food antigens, observed as mesangial pattern, were obtained in eleven cases (39.3%) with casein, 21 (75.0%) with soy bean protein and one (3.6%) with rice protein in IgA nephropathy, even though no such findings were seen in the control group. Eleven of 28 patients with IgA nephropathy were positive with soy bean protein alone, nine were positive with soy bean protein+casein, one was positive with soy bean protein + casein + rice protein, and one was positive with casein alone. The deposition of food antigens was not observed in six cases only. Furthermore, no correlation was noted between the deposition of food antigens and the deposition of IgA1, IgA2 or J chain, in vitro binding of the secretory component, or histopathological grades. These results suggest that the exact meanings of glomerular deposition are unclear. Food antigens are postulated, however, as possibly participating strongly in the pathogenesis and as being localized in the glomerular mesangium as an antigen in some patients with IgA nephropathy. [ABSTRACT FROM AUTHOR]

The binding of EPF to lymphocytes stimulates the release of soluble mediators, active in T cell dependent reactions, namely the rosette inhibition test and the adoptive transfer of contact sensitivity. On the basis of their ability to inhibit the delayed type hypersensitivity reaction in this latter assay, they have been classified as suppressor factors. This paper describes the identification of two EPF-induced suppressor factors. Unlike EPF which is neither species-restricted nor strain-restricted, these factors are genetically restricted in their action in the rosette inhibition test EPF-S1 (estimated Mr 14,000) is restricted to the I region of the mouse MHC, while EPF-S2 (estimated Mr 55,000) is restricted to a locus (or loci) outside the MHC. Like other antigen non-specific factors, release of these suppressor factors can be stimulated also by Con A. [ABSTRACT FROM AUTHOR]

Freshly isolated B cells from chronic lymphocytic leukaemia patients (B-CLL) have been previously shown to induce a strong proliferative response and high levels of NK-like activity in lymphocytes from healthy donors. The present paper deals with the origin, mitotic state, target spectrum and cell surface phenotype of the NK-like effectors generated after stimulation with B-CLL. Experiments using large granular lymphocytes (LGL) and T cells as responders demonstrated that most of the precursors of the newly generated NK-like effectors express the CD3 antigen. The induction of NK-like activity paralleled cell activation, as judged by blast transformation, thymidine uptake and appearance of cell surface activation markers. The newly generated NK-like effectors displayed a T cell phenotype and a broader target repertoire than native NK cells. [ABSTRACT FROM AUTHOR]

Patients with the S. aureus hyper IgE syndrome (SAHIGES) have an abnormal IgE response to cell wall and surface antigens of S. aureus. In this paper we describe the detection of IgE antibodies to soluble antigens of staphylococci (S. aureus and S. epidermidis) and qualitative abnormalities of the IgG response lo soluble S. aureus antigens in patients with SAHIGES. These findings may be of pathogenetic importance and help to delineate SAHIGES from other diseases. [ABSTRACT FROM AUTHOR]

Prolonged exposure to antigens may result in high IgG4 antibody titres as was shown in a previous paper (Aalberse et al., 1983b). In novice bee keepers, a shift in the IgGI/IgG4 ratio of the response against phospholipase-A (PLA; a major component of bee venom) occurred. This resulted in an IgG4-dominated response after approximately 2 years of bee-keeping experience. Subject of the present study was the influence of relatively high concentrations of IgG4 antibodies on the biological activity of immune complexes. In the PLA antigen model, it was demonstrated (a) that IgG4-containing immune complexes do not activate complement and (b) that lgG4 antibodies effectively inhibit immune precipitation and complement activation by IgG1 antibodies. Evidence is provided that lgG4 antibodies inhibit binding of Clq to IgG1 in mixed, IgG1- and lgG4-containing complexes. It is proposed that IgG4 antibodies protect against the biological effects of the complement-fixing IgG subclasses. For this reason, determination of the total IgG response or just determination of antibody activity in the complement-fixing isotypes is insufficient in immune-complex diseases. The modulating effect of the non-complement-fixing isotypes should be taken into account to predict the biological activity of the immune complexes. [ABSTRACT FROM AUTHOR]

The antigen-induced DNA synthesis in vitro in lymphocytes from patients with acute Plasmodium falciparum malaria was investigated. The patients and healthy controls from Sweden or Colombia were the same as those studied in the accompanying paper (Troye-Blomberg el al., 1983). The malarial antigens used were sonicated membrane preparations or purified and concentrated supernatants from in vitro cultures of P. facliparum, similar preparations derived from normal human erythrocytes served as control antigen. In the patients' lymphocytes P. falciparum antigens induced a weak or moderate but significant stimulation of DNA synthesis, peaking after 3-4 days of incubation. This early response was specific for P. faleiparum since it was not obtained with lymphocytes from healthy donors nor with those from patients with acute P. vivax or P. ovale malaria. No antigen-induced response was seen in about half of the P.falciparum patients. However in a few negative eases, available for consecutive testing, positive reactions were seen with lymphocytes taken 2 weeks after infection when the blood of these patients was free of parasites. The early response induced in patients' lymphocytes to the P. falciparum antigens was not obtained with RBC antigen, however, these preparations frequently induced a response rising to significant levels later during incubation (day 5-6)- Similar delayed responses were obtained when either- patients' or control donors' lymphocytes were exposed to the P. falciparum antigens. This indicates that both the RBC and the parasite preparations contained mitogenic substances affecting human lymphocytes in general and easily obscuring the P, falciparum specific responses seen only in the patients. This latter response was relatively low and short lived, suggesting that it reflected a secondary in vitro stimulation of in vivo primed lymphocytes and that it was regulated by suppressor mechanisms. [ABSTRACT FROM AUTHOR]

In the present paper we demonstrate that there is an antigenic determinant common to two different types of human teukaemia-associated antigens. i.e. human thymus Ieukaemia-associated (HTL) antigens and common acute lymphoblastic leukuemia (cALL) antigen. In addition, there are distinct antigenic determinants which are unique to the HTL antigens or to the cALL antigen. The new, common antigenic determinant will be useful as a new differentiation marker of human haematopoietic cells as well as a new Ieukaemia-associated marker. In the present study. we used several different anti-human leukaemia antisera which include those prepared by immunizing rabbits (Nos. 7549 and 7550) with purified HTL antigens. The antisera 7549 and 7550, without any absorption1 showed strong specificity as well as strong antibody activity toward Ieukaemia cells. These are the first anti-human leukaemia antisera, except for the monoclonas hybridoma antibodies, that show good specificity for leukaemia cells without prior absorption. [ABSTRACT FROM AUTHOR]

In this paper we use a sensitive, 125I-anti-immunoglobulin-binding assay, recently adapted for use with tissue homogenates as targets, to demonstrate autoantibodies to brain, liver and heart in the sera of normal persons. Quantitative absorption analyses demonstrated that the autoantigens detected were in each case organ-specific, and the brain autoantigen was shown to be present In equal amounts on cerebral cortex, cerebral white matter and cerebellar cortex. The autoantibodies were shown to be IgM in nature by gel filtration studies and experiments where IgM was reduced to monomers, and were found to bind equally well at 4, 20 and 37 C. Cross-reactions with brain, liver and heart of rat and dog were unpredictable and usually weak. Parallel studies with kidney homogenates failed to detect anti-kidney autoantibodies, but immunofluorescence studies on frozen sections revealed large amounts of immunoglobulin in normal kidneys, mainly on glomerular and tubular basement membranes, raising the possibility that autoantibodies to kidney are present but that the autoantigen sites are saturated in vivo. Sera from patients with multiple sclerosis were indistinguishable from normal sera in their binding to brain homogenate, and CSF from five patients with multiple sclerosis did not bind at all to brain homogenate. The theoretical and practical significance of multiple IgM autoantibodies in normal persons, and the organ specificity of the autoantibodies, is discussed. [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes from 105 subjects with different forms of leprosy and healthy contacts of leprosy patients were stimulated in vitro with different preparations of mycobacterial antigens alone or in combination with a suboptimal dose of phytohaemagglutinin (PHA). In nearly all individuals sonicated leprosy bacilli and PHA together gave a lower 3H-thymidine incorporation than did the same dose of PHA alone. There was no difference in the degree of inhibition seen in the different patient groups or the healthy contacts. High doses of whole, washed Mycobacterium leprae, combined with PHA led to an increased thymidine incorporation in borderline tuberculoid leprosy patients who had experienced a reversal reaction, and in healthy contacts with more than 6 months of exposure, while most lepromatous patients and contacts with less than 6 months exposure did not show an augmentation of the PHA-induced thymidine incorporation. The inhibition exerted by sonicated M. leprae was dose-dependent, seen even with very low doses of antigen, and was not due to direct cytotoxicity. M. bovis, strain BCG, was weakly suppressive in combination with PHA, and sonicated M. duvalii had a very marked suppressive effect. There was no correlation between the suppressive effect of M. leprue antigens and the other mycobacteria neither was there any correlation with the responses to the mycobacterial antigens alone. Many lepromatous leprosy patients showed significant suppression of background incorporation with addition of M. leprae antigens. This paper discusses whether the apparent `non-responsiveness' in lepromatous leprosy could be due to active suppressor mechanisms operative in vivo. [ABSTRACT FROM AUTHOR]

This paper reports the properties of purified human F antigen (liver-specific antigen). Homgenates of liver in 0.25 M sucrose were centrifuged at 105,000 g. The supernatants were chromatographed on Sepharose 6-Band tour major peaks were separated. The third peak proved to be predominantly F antigen. This fraction was subsequently subjected to DEAM-cellulose column chromatography and F antigen was eluted at a concentration less than 0.2 M NaCl in 0.01M sodium phosphate huller (pH 7.2). Finally, purified F antigen was obtained alter preparative isoelectric focusing. Purified human F antigen was found to have a mol. wt between 40,000 and 80,000, a pl of 6.5-6.7 and a density of 1.26. It is a protein antigen and contains on detectable carbodhydrate or lipid. No differences were found in purified F-antigen preparations from several species when tested by sodium dodecyl sulphate (DS) disc gel electrophoresis. Immunofluorescent studies showed that F antigen was homogeneously distributed in the cytoplasm of liver cells but was not present on the cell surface. Immunization of guinea-pigs with purified human liver-specific protein did not induce antibody to the F antigenic determinant defined by mouse anti-F antiserum. It did, however, induce antibodies to two human liver antigens. One of these seems to be a human-specific determinant on the F antigen molecule and the other appears to be a separate molecule which is similar in molecular weight and electrophoretic mobility to the F-antigen molecule. [ABSTRACT FROM AUTHOR]

This paper describes immunofluorescence studies on liver cell surface localization of hepatitis B surface antigen (HBsAg) and of IgG in acute and chronic hepatitis and in cirrhosis. In acute hepatitis B, HBsAg was found at the surface of hepatocytes in an early phase of the disease, hut not during the recovery. This finding is consistent with the hypothesis that immune reactions to HBsAg may be responsible for the liver cell lysis. In HBsAg-positive chronic hepatitis and cirrhosis the antigen was found in the cytoplasm, but not on the surface of the hepatocytes, while in HBsAg-negative cases the antigen could not be detected in the liver cells. Both in HBsAg-positive and in HBsAg-negative chronic active hepatitis (CAH) and cryptogenic cirrhosis, IgG bound to the membrane of the hepatoeytes could be detected, suggesting a role of antibodies in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

This paper describes the application of parallel bioassay to the measurement of lymphocyte mitogenic, inflammatory and macrophage migration inhibitory activities present in guinea-pig lymphokine preparations. Seven lymphokine preparations were made under similar conditions by antigen activation of sensitized guinea-pig peritoneal exudate cells; and one of these was prepared in sufficient quantity as a 'working standard' for the repeated assay of the three lymphokine activities in the other six 'test' preparations. Mean potency ratios of the separate lymphokine activities were calculated for the test preparations by reference to those of the standard preparation (designated as unity). Although the seven preparations were made under operationally similar circumstances, χ² analysis of the assay results revealed that the three separate lymphokine activities occurred in different absolute amounts and relative proportions in the different preparations. This demonstration by parallel bioassay of heterogeneity and dissociation of lymphokine activities implies that these biological activities cannot be ascribed to a single substance. This type of analysis has general application in the characterization and separation of biologically active substances present in preparations exhibiting multiple activities. [ABSTRACT FROM AUTHOR]

Two liver-specific antigens are known: a water soluble protein (LP-2) and a water insoluble macromolecular low density lipoprotein (LP-1). In this paper the relative role of the two antigens in the development of experimental immune hepatitis has been investigated. Immunization of rabbits with a human preparation containing both antigens, led in all animals to lesions characteristic of an immune hepatitis. Immunization of the animals with a purified water soluble liver protein proved less efficient: only two out of six animals developed characteristic lesions which were less severe than those in the first group. It was deduced that although not a prerequisite, the liver-specific lipoprotein plays an important supportive role in the development of immune hepatitis, [ABSTRACT FROM AUTHOR]

Target cell killing by lymphocytes can be induced by appropriate antibody complexed to target cell antigens. In this paper it is shown that this form of lymphocyte mediated cytotoxicity is susceptible to inhibition by third party immune complexes which compete with target cell bound antibody for receptors for immunoglobulin on the cytotoxic lymphocytes. The physical state of the complexes is investigated in relation to their inhibitory efficiency. Evidence is presented to show that soluble complexes which exist in antigen-antibody equilibrium or slight antigen excess are the most effective inhibitors. No evidence could be obtained to support the hypothesis that soluble immune complexes can induce indiscriminate cytotoxic activity in lymphocytes. The biological significance of this effect is discussed in relation to chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Partial purification of soluble products of guinea-pig lymphocyte activation (LAP) was undertaken by fractional precipitation with ammonium sulphate, ion-exchange and Sephadex chromatography, and by immune precipitation of inducing antigen and of contaminating serum protein. During these purification steps the activity of macrophage migration-inhibition factor (MIF) was concentrated up to 1300-fold and separated from inducing antigen and serum protein. An endpoint assay was devised for expressing antigen-induced MIF activity of LAP fractions as weights of material giving 30% inhibition of migration (MI30 doses). MIF activity precipitated between 50% and 80% saturated ammonium sulphate and eluted from DEAE-cellulose at pH 7-9 at intermediate salt concentrations (0-03-0-2 M phosphate). On Sephadex gel filtration MIF activity was concentrated in fractions of molecular weight range 56,000-82,000 with a smaller amount of activity eluting from 20,000-56,000. After immune precipitation of extraneous protein and elution from DEAE-cellulose, LAP material was found to have an MI30 dose of 0-4 /μg. Materials representative of antigen and serum protein-depleted MIF were selected for intralymphatic injection in order to determine whether MIF-rich LAP fractions were able to induce paracortical distension in guinea-pig lymph nodes (see following paper). [ABSTRACT FROM AUTHOR]

The mononuclear cells from. the joint fluid of certain patients with inflammatory arthritis are shown to be more cytotoxic to a polyploid strain of homologous liver cells than were equivalent numbers of peripheral blood lymphocytes From the same donors. The diagnostic categories of these patients are essentially similar to those of a group of patients studied by Hedberg (1967) in whom joint fluid mononuclear cells were cytotoxic to monolayers of human foetal fibroblasts. Evidence is presented to show that this cytotoxic activity is attributable to lymphocytes, as opposed to polymorphonuclear leucocytes or phagocytic mononuclear cells which adhere to glass. It is not excluded that the latter population may also have some cytotoxic potential. It is argued that the target cell damage described in this paper is probably not induced by any antigen on the target cell. The implications of this suggestion are discussed in relation to the pathogenesis of inflammatory joint disease. [ABSTRACT FROM AUTHOR]

The article presents an index related to subject terms that appear in papers published in the 1991 issue of the journal "Clinical & Experimental Immunology." Some of the terms are anti-mitochondrial antibodies, anti-phospholipid antibodies, antibodies, antibody production, antigens, apheresis, arthritis, atopic dermatitis, autoantihodies, autoantigen, autoimmune diseases, autologous mixed leucocyte reaction, autoreactive T cells, cancer, carrier detection, cell cycle, cell-mediated cytotoxicity and cerebrospinal fluid.

This article presents information on research papers related to immunology. In the paper "Modulatory Effects of Oestrogen on Immunological Responsiveness. Suppression of Tumour-Associated Immunity in Patients With Prostatic Cancer," the authors wish to point out that retrospective evaluation of the patients in this study has disclosed an effect of hormonal therapy, i.e. orchiectomy and or oestrogen on tumour-associated immunity independent of the effect of in vitro preincubation of patients' leucocytes with DES-P. While in "Migration of Sensitized Mouse Spleen Cells by Cell-Associated Transplantation Antigens: Effect of Method of Antigen Presentation," the authors wish to point out that they have been unable to repeat the MIF assay technique.