Showing papers on "Antigen published in 1972"

Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes.

Abstract: In the DNP system, the specificity of the reaction was assessed by inhibition with hapten. The reaction of immune serum against DNP with DNP-protein, adsorbed to the tubes, was completely inhibited by hapten in solution.

Histocompatibility-Linked Immune Response Genes

Abstract: Publisher Summary This chapter provides information on histocompatibility-linked immune response genes. The genetic study of the capacity to form specific immune responses has revealed that the recognition of antigens as immunogens by individual animals and inbred strains is governed by the product of individual dominant genes located in the genome in close relationship with the genes coding for the molecules bearing the major histocompatibility specificities. These genes are termed as “histocompatibility,” or “H-linked Ir genes.” The presence of relevant genes permit immune responses to be formed, characterized by cellular immunity and antibody synthesis against the determinants on the antigens concerned. Three types of antigens are most useful in the identification of H-linked Ir genes: (1) synthetic polypeptides with limited structural heterogeneity; (2) alloantigens that differ slightly from their autologous counterparts, and (3) complex multideterminants antigens administered in limiting immunizing doses in conditions where only the most immunogenic determinants are recognized. Thus, the discovery of specific H-linked Ir genes depends upon experiments wherein the immunological system is presented with a challenge of highly restricted heterogeneity and specificity. The chapter presents a description of the specific immune responses that are under the control of H-linked Ir genes in guinea pigs, mice, and rats.

Replacement of t-cell function by a t-cell product.

Abstract: WE have recently shown that the immune response to sheep red blood cells (SRBC) in vitro is T-cell dependent, that is, it can be abrogated by pretreatment of the spleen cells with anti-θ serum and complement1. We further reported that reconstitution of the system can be achieved by, among other things, the addition of allogeneic thymocytes2, while syngeneic thymocytes failed to function as helper cells. Positive allogeneic effects were only obtained if the added thymocytes could recognize the remaining B-cells as foreign. One of the explanations evoked for this allogeneic effect was the participation of a potentiating factor2,3. It seemed possible that on the heavy antigenic stimulation provided by the histocompatibility antigens carried by the B-cells, added T-cells produce a soluble factor which stimulates the immune response of B-cells to unrelated antigens. We now want to report the existence of two distinct factors, one of which can completely replace T-cells.

The regulatory role of macrophages in antigenic stimulation.

Abstract: Publisher Summary This chapter focuses on the role of the macrophage in removing antigen from extracellular fluids, degrading the larger part of this antigen while presenting a small part of it in persisting immunogenic form. This handling of antigen is done without contributing to the specificity of the immune response, which is determined by the antigenreactive T and B lymphocytes. During the process of uptake of antigen, macrophages appear to retain a few molecules of antigen, undegraded or with few chemical changes. Macrophage-associated antigen becomes an effective immunogenic stimulus mainly in conditions that require two types of lymphocytes to meet with antigen molecules. These lymphocytes are specifically antigen-committed and few in number. The positive immunogenic role of macrophages is related to their capacity to (1) remove extracellular antigen, which might be capable of interacting with and eliminating isolated T or B lymphocytes and (2) retain antigen in lymphoid tissues and promote its necessary meeting with both T and B cells.

Role of the K88 Antigen in the Pathogenesis of Neonatal Diarrhea Caused by Escherichia coli in Piglets

Abstract: The role of the K88 antigen of Escherichia coli in neonatal diarrhea of piglets was studied by comparing a K88-positive strain with three K88-negative strains derived from the K88-positive strain. K88 antigen was produced by the K88-positive strain in the intestinal tract of gnotobiotic piglets, whereas K88-negative strains did not regain the ability to synthesize K88 antigen. Synthesis of the antigen conferred different colonization characteristics on the four strains; K88-positive bacteria adhered to the mucosa of the small intestine, whereas K88-negative bacteria did not attach and were distributed throughout the lumen. Adhesion of K88-positive bacteria to tissue from the small intestine of gnotobiotic piglets was demonstrated in vitro and was inhibited by antisera that contained K88 antibodies. Attachment did not occur with bacteria grown at 18 C. Adhesion of cell-free K88 antigen was also demonstrated. The K88-positive strain and one of the K88-negative strains were equally virulent in gnotobiotic piglets. In contrast, the K88-positive strain killed 50% of conventionally reared piglets, whereas the K88-negative strain killed only 3%. Adhesion of the K88-positive strain, but not of the K88-negative strain, to the mucosa of the small intestine was demonstrated. Our results show that K88 antigen is responsible for attachment of K88-positive bacteria to the wall of the small intestine, and that adhesion is essential for the virulence of K88-positive bacteria in conventionally reared piglets.

New Specificities in Australia Antigen Positive Sera Distinct from the Le Bouvier Determinants

Abstract: Evidence for new antigenic specificities in Australia antigen positive sera, for one of which we have proposed the designation e, has been obtained in immunodiffusion tests according to Ouchterlony. These specificities co-occur with Au antigen and are distinct from the a, d, y and x determinants of the Au antigen complex according to Le Bouvier and occur on particles other than those carrying the a determinant. It was found in 18 out of 23 persistent carriers of Au antigen from hemodialysis units, in 6 out of 43 Au positive hepatitis cases but in none of 17 Au antigen-carrying blood donors. In the latter group, however, antibodies against the specificities described herein occurred in 13 out of 17 individuals. In five of these cases the antibody was directed against the e specificity. Some evidence is presented for the possible association of this antigen complex to contagiousness.

Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides.

Abstract: Lipopolysaccharides (LPS) from E. coli bacteria were found to be mitogenic for bone marrowderived (B) lymphocytes, but had no effect on thymusderived (T) lymphocytes. When added to normal spleen cells in culture, LPS selectively stimulated the secretion of 19 S proteins, whereas there was no demonstrable increase of 7 S protein synthesis. Spleen cell cultures treated with various doses of LPS exhibited atypical dose response curve with regard to induction of DNA synthesis, 10 μg/ml being optimal, higher and lower concentrations giving lower responses. When direct antibody producing cells to horse and sheep red cells were studied in normal spleen cell cultures exposed to different concentrations of LPS in vitro, it was found that their number increased in parallel with stimulation of DNA synthesis. In contrast, the number of antibody producing cells to LPS itself did not parallel activation of DNA synthesis. Spleen cells from LPS tolerant animals responded with increased numbers of antibody producing cells to heterologous red cells after treatment with LPS in vitro to the same extent as normal spleen cells. Thus, a B cell mitogen, such as LPS, could activate division in B cells, resulting in an increased number of cells producing antibodies to non-cross-reacting antigens, mimicing the effect of specific antigen.

Epstein-Barr Virus: Transformation, Cytopathic Changes, and Viral Antigens in Squirrel Monkey and Marmoset Leukocytes

Abstract: Blood leukocytes of two species of new world primates, other than human, transform following exposure to Epstein-Barr virus. The transformed simian cells produce Epstein-Barr virus antigens and infectious (transforming) virus. The simian lymphoblastoid cells form multinucleate giant cells that appear to be selective sites for the production of Epstein-Barr virus. Multinucleate cells reveal intranuclear inclusions; in both species, a large proportion of giant cells contain Epstein-Barr virus antigen detectable by immunofluorescence.

A receptor for antibody on b lymphocytes : i. method of detection and functional significance

Abstract: Evidence is presented for the existence on all B lymphocytes, but not on T lymphocytes, of a membrane-associated receptor for antibody. The receptor was detected by a radioautographic technique in which lymphoid cells were incubated with antibody followed by the corresponding radioiodinated antigen. The ease with which antibody eluted during washing indicated that the bond between antibody and cell was weak. The formation of an antibody-antigen complex on the cell surface, however, stabilized the bond and permitted accurate quantitation of cells with adherent antibody. The ability of several combinations of antibody and antigen to adhere to the cells demonstrated the nonspecificity of the phenomenon and emphasized the need for care in interpretation of antigen-binding studies particularly when immune cells are being used. The identity of antibody-binding lymphocytes was established by two different approaches. In the first, mouse lymphocyte populations greatly enriched for either T cells or B cells were examined. Their T cell content was assessed by means of well-established markers such as the θ C3H isoantigen. When this was compared with the number of antibody-binding cells, an inverse relationship was obtained in each instance; thus almost all thoracic duct cells from athymic mice labeled with an immune complex although none were θ positive. The striking reduction in antibody-binding cells observed in bursectomized chickens provided a second and independent line of evidence suggesting that B cells, not T cells, bind antibody. The ability of B cells from primed animals to bind antibody in vivo made it important to test whether this phenomenon was related to the carriage of immunological memory. No correlation was, however, found between membrane-bound antibody and memory. It was proposed that the existence of a receptor of this kind may provide a rational explanation for antibody-dependent killing of target cells and may prove of importance in antigen concentration particularly during the secondary response.

Mechanism of Immunologically Specific Killing of Tumour Cells by Macrophages

Abstract: THE increase in anti-microbial activity of macrophages which occurs in animals that have been infected with living microorganisms is frequently non-specific1. In contrast, the anti-tumour activity of macrophages from immunized animals has been demonstrated in vitro to be immunologically specific2,3. The experiments to be described may throw light on this paradox. They show that the killing of tumour cells by macrophages is made up of an immunologically specific interaction which is followed by a non-specific lethal reaction. A similar pattern has been described for the bactericidal action of immune macrophages3. We have described three ways of obtaining immunologically specific macrophages cytotoxic to tumour cells3,5. These are (1) from the peritoneal cavity of suitably immunized mice (see later); (2) “arming” in vitro by contact of non-immune macrophages with spleen cells from hyperimmunized mice, and (3) “arming” in vitro by exposure of non-immune macrophages to the cell-free supernatant obtained when spleen cells from immunized mice are cultured with the specific antigen. All such macrophages, on coming into contact with specific antigens, undergo a transformation (referred to as “activation”) which renders them capable of killing. The actual destruction of the target cell following direct contact with the “activated” macrophages is non-specific. Moreover, this non-specific killing may also be demonstrated by macrophages “armed” against tubercle bacilli (BCG) which are “activated” after exposure to the solubilized protein derivative from tubercli bacilli, PPD, and are able to kill tumour cells. In the original experiments3,5 in which target lymphoma cells were added to “armed” macrophages the immunologically specific stage and the non-specific stage of the cytotoxic reactions were not separated and occurred sequentially (Fig. 1).

Prevalence of hepatitis B virus antigen as revealed by direct radioimmune assay with 125 I-antibody.

Abstract: A two-step direct radioimmune test was used to detect hepatitis B virus associated antigen in human serum or plasma. The procedure involved the use of polypropylene tubes coated with hyperimmune guinea pig serum, and 125 I-labeled specific hepatitis B virus antigen immune globulin. The technique appeared to be more sensitive than other immunologic assays, including indirect radioimmune methods based on competition of unlabeled antigen with 125 I-labeled antigen. Various blood donor populations were tested for antigen by the direct radioimmune test, by complement fixation, agar gel diffusion and counterimmunoelectrophoresis. The increased sensitivity of the radioimmune procedure resulted in the detection of about 3 to 8 times as many positive sera as the above three immunologic methods. The percentages of positive sera by radioimmune assay were: about 1% in volunteer blood donors, about 2% in commercial blood donors and about 40% in hepatitis-implicated patients.

Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy.

Abstract: HL-A phenotypes were determined in 24 unrelated patients with gluten-sensitive enteropathy (GSE) using a lymphocyte microcytotoxicity test 21 of the 24 patients had HL-A8 in the second segregant series, a frequency of 0875 In contrast, the HL-A8 frequency in 200 normal individuals was 0215 (difference significant at P < 0002), and in 6 patients with villous atrophy due to tropical sprue or hypogammaglobulinemia the HL-A8 frequency was 017 (difference from normal not significant) The HL-A types in the families of three HL-A8 positive patients with GSE indicated that the HL-A8 antigen was inherited as an autosomal dominant Frequencies of the other HL-A antigens in the GSE group did not differ significantly from that of the normal group These findings are compatible with the hypothesis that GSE is due to the presence of an abnormal "immune response (Ir) gene," leading to the production of pathogenic antigluten antibody or, alternatively, to the presence of a particular membrane configuration leading to the binding of gluten to epithelial cells with subsequent tissue damage

Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor.

Abstract: Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens. A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values. In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence.

Identification of an Antigen from Normal Human Tissue That Crossreacts with the Carcinoembryonic Antigen

Abstract: A glycoprotein present in normal human tissue is characterized that is neither organ- nor tumor-specific (nonspecific crossreacting antigen) and that crossreacts (by the Ouchterlony double-diffusion technique) with the carcinoembryonic antigen. This immunological relationship indicates common determinants on the molecules of both antigens. We demonstrate that the nonspecific crossreacting antigen is not a fragment of the carcinoembryonic antigen molecule.

Genetics of the antibody response to dextran in mice.

Abstract: The immune response to dextran having the alpha-1,3 linkage may be under the control of antibody structural genes. Mice that respond well to this antigen produce antibody restricted with respect to light chain class (lambda) and to an antigenic determinant resulting from a particular heavy and light chain interaction. The response to dextran is controlled by a locus linked to the-heavy chain locus.

Genetic control of the immune response. Mapping of the Ir-1 locus.

Abstract: The influence of immunization with (T,G)-A--L on the frequency and characteristics of [125I] (T,G)-A--L-binding cells (ABC) was investigated in high and low responder mice, whose ability to respond to (T,G)-A--L is under control of an H-2 -linked immune response gene, Ir-1 . Unimmunized high and low responder mice have about the same number of ABC in spleen and lymph nodes (6–12 ABC/104). However, after immunization with (T,G)-A--L in aqueous solution, ABC in high responders increase to a much greater extent than they do in low responders. By inhibition of ABC with class-specific anti-Ig sera, it was demonstrated that in nonimmune and primed mice antigen is bound to IgM receptors, which is in agreement with the exclusive production of 19S anti-(T,G)-A--L antibody in primed animals. In contrast, after secondary challenge with antigen, ABC in high and low responder mice have mainly IgG receptors, although under the conditions used for immunization, low responders are not able to produce detectable amounts of 7S anti-(T,G)-A--L antibody. From these results and from the evidence that low responders very probably have a T cell defect, it is suggested that the switchover from IgM to IgG precursor cells can be induced by antigen itself, without the action of specific T cells. Furthermore, the failure of marked proliferation of ABC in low responders after antigenic stimulation is explained by the lack of stimulation by specific T cells. By independent methods it has been shown that all ABC detected in this study are B cells. Preliminary experiments indicate that purified peripheral T cells bind antigen, but much less per cell than do B cells.

Association of Serum Anti-Neuraminidase Antibody with Resistance to Influenza in Man

Abstract: The role of serum anti-neuraminidase antibody in resistance to influenzal illness was investigated by administration of wild-type influenza A/Hong Kong/1968 (H3N2) virus to volunteers who possessed varying levels of this antibody but who lacked antibody for the hemagglutinin surface antigen of the virus. Clinical response to the wild-type virus was related to the level of serum anti-neuraminidase antibody. Volunteers in whom influenzal disease with fever developed possessed low levels of serum antibody prior to challenge, whereas men who underwent inapparent infection had a significantly higher mean level of antibody for neuraminidase. Those with afebrile illness had an intermediate level of anti-neuraminidase antibody. Duration of virus excretion and maximal level of virus shed were also inversely related to the titer of serum anti-neuraminidase antibody. These findings provide evidence that antibody directed against influenzal neuraminidase is associated with resistance to clinical expression o...

Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation

Abstract: The primary and secondary immune responses to thymus-dependent and -independent antigens were evaluated in normal male and female mice and in castrated male mice. Both IgM antibody production in the primary response and IgG antibody production in the secondary response were enhanced in females vs. males of equivalent age. Castration of the male converted this animal to a female in terms of responsiveness to the thymus-dependent group of antigens, while inducing equivalent or even greater enhanced responsiveness over the female to the thymus-independent antigen, polyvinylpyrrolidone. Further characteristics of the changes in lymphoid organs were determined in the castrated animal vs. normal males and females. It was shown that the spleen and thymus became markedly hyperplastic, the organ weights exceeding the female, which in turn were greater than in the male. The enhanced weight of the thymus was shown to be due to increased numbers of cortisone-sensitive cells, the absolute number of cortisone-resistant cells remaining equivalent to normal males and females. Thus, the increased thymic weight of the female also resided in the cortisone-sensitive population. Peripheral lymphocyte counts in castrated animals exceeded both normal males and females. Further experiments in gonadectomized males provided evidence that increased thymic cell activity per se played a role in enhanced response to thymus-dependent antigens, but that a thymic-derived hormone mediated the enhanced effect to the thymus-independent antigen in the castrated animal. The capacity for loss of androgenic hormone-producing tissue to generate enhanced differentiation of stem cells was denoted by experiments in which numbers of spleen colonies and uptake of 59Fe, employed as an index of hematopoiesis 1 wk after reconstitution of lethally irradiated castrated and normal recipients, were enhanced in gonadectomized male animals. Thus, in summary, changes in sex hormone levels exerted a marked influence on immune responsiveness and stem cell differentiation, by increasing numbers of functioning cells, by promoting cellular differentiation, as well as by promoting cellular function via hormonal effects.

Activation of T and B Lymphocytes by Insoluble Phytomitogens

Abstract: Although insoluble phytomitogens are probably not taken within cells, they are shown here to activate both T and B cells. It is conceivable therefore that antigens also stimulate lymphocytes through a similar membrane event.

Myeloma Proteins as Tumor-Specific Transplantation Antigens

Abstract: BALB/c mice immunized with myeloma proteins 315 or 460 made antibodies to the individually specific (“idiotypic”) determinants of these proteins and suppressed growth of the corresponding transplanted tumor cells (MOPC-315 or MOPC-460). Stable, variant MOPC-315 tumors that produce only the light chain of protein 315 grew in several of the mice immunized with this protein, probably because the anti-idiotypic immune response selects against those myeloma cells that form the intact myeloma protein.

Evidence for a receptor recognizing antigen complexed immunoglobulin on the surface of activated mouse thymus lymphocytes.

Abstract: The distribution in the mouse of lymphoid cells carrying receptors for IgG or IgG-Ag was investigated. B lymphocytes were found to have receptors reacting with both IgG and IgG-Ag. Resting T lymphocytes did not react with IgG-Ag. T lymphocytes activated by passage through irradiated, allogeneic mice had a receptor reacting with IgG-Ag, but not with IgG.

Ragweed Hay Fever: Genetic Control and Linkage to HL-A Haplotypes

Abstract: Clinical ragweed pollenosis (hay fever) and IgE antibody production specific for antigen E (the major purified protein antigen from ragweed pollen extract) correlated closely with HL-A haplotypes in successive generations of seven families. HL-A associated IgE antibody responsiveness was antigen specific and extended also to IgE antibody production. These data indicate an immune response (Ir) gene specific for antigen E necessary but not sufficient for the development of hay fever. This appears to be the first documentation of an Ir gene in man.

Serologically defined and lymphocyte-defined components of the major histocompatibility complex in the mouse

Abstract: The mixed leukocyte culture (MLC) test is an in vitro model of the recognition phase of the homograft response. For the most part, activation in MLC is dependent on differences of the major histocompatibility complex (MHC). Our present studies in the mouse suggest that activation is primarily associated with differences of genetic regions of the MHC other than those which control the serologically defined (H-2) antigens. These differences do not lead to cytotoxic or agglutinating antibody formation despite extensive immunization; we have called these differences lymphocyte-defined (LD) differences. The strongest stimulation in MLC is associated with differences of the Ir region. It is possible that the Ir product is the T cell receptor and that it is this same molecule which can act as the stimulatory agent in MLC. Other possibilities are discussed.

Human Serum Activities against Hemophilus influenzae, Type b

Abstract: Humoral immunity to Hemophilus influenzae, type b was studied in normal human adults by means of assays for serum bactericidal and opsonizing activities against the organism and for passive hemagglutinating activity using erythrocytes sensitized with polyribophosphate, the type-specific capsular antigen. Hemagglutinating activity was detectable in about 60% of the 114 sera tested. Serum bactericidal and opsonizing activities were found in all sera tested; the levels in some sera, however, were quite low. The antibacterial activities were due not only to antibodies directed against the polyribophosphate capsule but also to antibodies that appear to be directed against somatic antigens. Type b strains differed in their susceptibility to the antisomatic antibodies of particular sera but were uniformly sensitive to anticapsular antibody.