Showing papers on "Antigen published in 1969"

The influence of immunologically committed lymphoid cells on macrophage activity in vivo

Abstract: It has been shown that the immune response of mice to infection with L. monocytogenes gives rise to a population of immunologically committed lymphoid cells which have the capacity to confer protection and a proportionate level of delayed-type hypersensitivity upon normal recipients. The cells were most numerous in the spleen on the 6th or 7th day of infection, but persisted for at least 20 days. Further study revealed that the immune cells must be alive in order to confer protection, and free to multiply in the tissues of the recipient if they are to provide maximum resistance to a challenge infection. The antibacterial resistance conferred with immune lymphoid cells is not due to antibacterial antibody; it is mediated indirectly through the macrophages of the recipient. These become activated by a process which appears to depend upon some form of specific interaction between the immune lymphoid cells and the infecting organism. This was deduced from the finding that immune lymphoid cells from BCG-immunized donors, which were highly but nonspecifically resistant to Listeria, failed to protect normal recipients against a Listeria challenge unless the recipients were also injected with an eliciting dose of BCG. The peritoneal macrophages of animals so treated developed the morphology and microbicidal features of activated macrophages. It is inferred that acquired resistance depends upon the activation of host macrophages through a product resulting from specific interaction between sensitized lymphoid cells and the organism or or its antigenic products. Discussion is also made of the possibility that activation of macrophages could be dependent upon antigenic stimulation of macrophages sensitized by a cytophilic antibody.

The radioimmunoassay of circulating carcinoembryonic antigen of the human digestive system

Abstract: A radioimmunoassay has been developed for determining the serum levels of carcinoembryonic antigen of the human digestive system in patients with cancer of the colon and rectum The assay is simple to perform and has a high degree of reproducibility and specificity The test detects a concentration of 25 ng of carcinoembryonic antigen per ml of serum and this has provided the first demonstration of a circulating tumor-specific antigen in the sera of cancer patients

Genetic control of specific immune responses.

Abstract: Publisher Summary This chapter discusses the genetic control of specific immune responses. The chapter reviews the recent important findings concerning “immune response genes” to antigenic determinants of different amino acids. The immune response to a specific antigen is a complex process that must involve genetic control at various levels. The fact that genetic factors are involved in the response to antigenic stimulus has long been known. The use of synthetic polypeptide antigens played a major role in elucidating the multiple genes that are described in the chapter. The intriguing question of at what level in the immune response these genes act remain to be determined. Genetic and structural analysis of normal immunoglobulins, myeloma proteins, and antibodies has produced a great deal of information about the genetic basis of antibody structure but has not yet given a clear picture of the genetic basis of antibody specificity. Structural analysis of myeloma proteins has led to a similar conclusion for the human and mouse light chain. The chapter summarizes the characteristic features common to the various genetic systems and analyzes the functions controlled by “immune response genes.”

Cytotoxic effects of lymphoid cells in vitro.

Abstract: Publisher Summary This chapter discusses the cytotoxic effects of lymphoid cells in vitro. The chapter discusses the complex problem of different types of cytotoxic effects of lymphoid cells. These outstanding workers in the field have managed to present a cohesive picture of the various effects on the target cells. The role of “nonspecific” factors is particularly well clarified. The interrelationships among contact lysis, release of pharmacologically active substances, and the terminal components of the complement system are given in the chapter for special consideration. In an in vitro model, it is shown that lymphoid cells from sensitized donors destroy tissue culture cells carrying the antigen to which the cell donor is sensitized. This type of cytolytic reactions is encountered in a great variety of immune situations, comprising all those mentioned in the chapter. The cell that initiates in vitro cytotoxic reaction is assumed to be the sensitized lymphocyte, equipped with its own recognition sites for antigen on the cells that are destroyed. Although this may be true in many situations, it now seems clear that “normal” lymphoid cells can become cytotoxic to other cells by a variety of pathways. The study of the various pathways by which lymphoid cells can become cytotoxic has been helpful for the understanding of effector role of these cells in cell-destructive reactions in general.

Cell selection by antigen in the immune response.

Abstract: Publisher Summary This chapter discusses the essential features of the antibody with respect to the interaction of antigen with preformed, cell-bound, antibody-like receptors. The effect of this interaction on individual cells is determined by the affinity of the antigen cell-bound antibody combination and results in the recruitment or selection of cells and their activation. The chapter also describes certain basic phenomena that are characteristic of the immune response and analyzes their mechanism at both the cellular and the molecular levels. These phenomena are an attempt to formulate a unified concept of the immune response as an antigen-driven proliferation and selection of specific cells that are committed to the synthesis of specific immunoglobulin molecules prior to the contact with antigen. This process, describable in thermodynamic terms, is the central biological event that can explain or predict such features of the antibody response as the progressive increase in average binding affinity of antibody produced, the effect of antigen dose on amount and affinity of antibody, the mechanism of action of adjuvants, the essential role of specific cell proliferation stimulated by antigen, the interference of humoral antibody with antigenic selection of cells, the phenomenon of “original antigenic sin,” and the induction of tolerance.

Characterization of a Soluble Cytoplasmic Antigen Reactive with Sera from Patients with Systemic Lupus Erythmatosus

Abstract: Summary A tissue antigen reactive with sera from SLE patients has been partially characterized. The antigen is a soluble cytoplasmic component which is present in a variety of human tissues and is distinct from known nuclear antigens. It is an acidic macromolecule which has the electrophoretic mobility of an α 1 globulin and is resistant to most proteolytic enzymes including trypsin, pepsin and chymotrypsin. Antigenicity is destroyed by 0.02 M periodate and by 0.001 M parahydroxy mercuribenzoate. Antibodies to this antigen have been found in 40% of unselected LE sera and were absent from a large number of sera from normal persons and from the sera of patients with other connective tissue disorders.

Cellular immunity against tumor antigens.

Abstract: Publisher Summary This chapter summarizes the evidence that tumors possess tumor-specific transplantation antigens (TSTA). Virtually all animal neoplasms contain TSTA. Immune reactions against the specific antigens of syngeneic tumors are similar to allograft reactions by which transplanted normal and tumor cells are rejected if they contain isoantigens that are foreign to the recipients. They are to a large extent mediated by immunologically competent cells—that is, lymphocytes and macrophages. The chapter describes several techniques by which cellular immunity to transplantation antigens can be demonstrated, along with a review of different systems in which such techniques were used to detect lymphocyte-mediated immune reactions to TSTA. TSTA are macromolecules present in tumor cells and absent in the normal cells of the same individual and against which immune reactions can be demonstrated with transplantation techniques. The transplantation methods used to demonstrate TSTA can involve the immunization of recipient animals with tumor cells that have been rendered incapable of multiplication (X-irradiation) or that are inoculated in subthreshold doses. Immunization can be also achieved by the inoculation of living tumor cells and excision of the subsequent tumor nodule. The possible role of cellular immunity to TSTA is also discussed in the chapter. The demonstration of cellular immunity to TSTA implies that autochthonous neoplasms appear in the presence of immune lymph node cells, which can destroy their cells at least in vitro . The chapter reviews the phenomenon of allogeneic inhibition. This phenomenon has been postulated to operate in parallel to the immunological mechanisms as part of the organism's defense against antigenic neoplastic cells.

An immunoglobulin-enzyme bridge method for localizing tissue antigens.

Abstract: An immunohistochemical method not requiring conjugation of a label to antibody is described for visualizing tissue antigens. The method depends on binding of an enzyme label to the tissue antigen t...

Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type.

Abstract: The immune responses of inbred mice to a related series of three synthetic polypeptide antigens are genetically controlled traits which are closely correlated with the genotype for the major histocompatibility (H-2) locus. All strains of the same H-2 type exhibit the same pattern of immune response, independent of the remainder of a given strain's genetic background. There is marked antigen-specific polymorphism between strains of different H-2 types with respect to their patterns of response.

Tumour-specific Antibodies in Human Malignant Melanoma and their Relationship to the Extent of the Disease

Abstract: Biopsy specimens and sera were obtained from 103 melanoma patients. Autoantibodies were demonstrated by (1) complement-dependent cytotoxicity of autologous melanoma cells in short-term culture; (2) complement-dependent inhibition of ribonucleic acid synthesis; (3) immunofluorescent staining of the cytoplasm of killed melanoma cells and of the surface membrane of viable melanoma cells. Over one-third of the sera studied had antibodies to autologous melanoma cells. Although for technical reasons all three tests could not be performed with the cells from every melanoma, whenever multiple testing was possible there was complete concordance. The autoantibodies were virtually confined to patients in whom the disease was not widely disseminated, and over 80% of such patients had positive sera. In a limited number of patients who have been followed autoantibodies disappeared as the disease progressed to become widely disseminated. Two patients with generalized disease developed autoantibodies following inoculation by their own irradiated tumour cells. Two types of autoantibodies were recognized: one, active against antigen(s) in the cell surface membrane, was specific for each tumour—that is, only the autologous serum reacted—and was concerned in the cytotoxic activity; the other reacted with cytoplasmic antigens which appeared to be present in most or all melanoma cells.

Theta isoantigen as a marker of thymus-derived lymphocytes in mice.

Abstract: THERE is an obvious need for a marker that will differentiate one type of lymphocyte from another. The need has become urgent in view of recent evidence suggesting that there are at least two populations of lymphocytes, one thymus-derived and one bone marrow-derived, which participate in different ways in the immune response1. The theta (θ) isoantigen (θ is determined by a single locus with two alleles: θAKR found in AKR and RF mice and θC3H present in most other inbred strains of mice tested), described by Reif and Allen2,3, which is found chiefly in thymus lymphocytes and brain, and to a lesser extent in peripheral lymphocytes in mice, seemed a possible antigenic marker of thymus-derived lymphocytes. To establish that θ is such a marker, it is necessary to demonstrate that there is a discrete population of peripheral lymphocytes which carry the antigen and that these cells are thymus-dependent.

Regulation of the immune response i. reduction in ability of specific antibody to inhibit long-lasting igg immunological priming after removal of the fc fragment

Abstract: The ability of 7S and F(ab')2 antibody fragments to suppress priming with low doses of antigen was compared. The 7S preparation was approximately 100–1000 times more potent than the F(ab')2 preparation when the agglutinin titers of the two preparations were the same. The presence of any ability to suppress priming in the F(ab')2 preparation may reflect an inherent capacity of the F(ab')2 antibody or contamination with small amounts of 7S antibody. The difference between 7S and F(ab')2 antibody in ability to suppress priming is attributed to the lack of the Fc portion on the F(ab')2 antibody. The Fc portion may be needed to prevent rapid excretion of antibody from the body, to induce rapid phagocytosis of antigen-antibody complexes with consequent breakdown and elimination of antigen, or to inactivate or suppress the antigen-sensitive cells from reacting to antigenic determinants. More detailed studies will permit a better assessment of the importance of these three possible regulatory roles of the Fc portion of the immunoglobulin in the immune response.

Cell separation on antigen-coated columns. Elimination of high rate antibody-forming cells and immunological memory cells.

Abstract: Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells.

Immune specific induction of interferon production in cultures of human blood lymphocytes.

Abstract: Human blood lymphocytes stimulated with nonviral antigens in vitro produce an antiviral substance with the biological and biochemical characteristics of interferon. The induced response was specific for cells obtained from immune donors. Cells from nonimmune donors did not produce interferon on exposure to these substances. The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased. Interferon production was maximum during days 4 to 7 in culture. In contrast, phytohemagglutinin-induced interferon was primarily produced during the first 4 days in culture.

Thymus and Antigen‐Reactive Cells

Abstract: Neonatal thymectomy severely limits the ability of some rodents to engage in certain immune responses, particularly cell-mediated immunities such as delayed hypersensitivity and the homograft reaction (reviewed in Miller & Osoba 1967). Many antigens apparently elicit normal humoral antibody responses in thymectomized animals but some, such as heterologous erythrocytes and serum proteins, do not. To account for the immune defects following thymectomy, it was originally postulated that the thymus produced 'the originators of immunologically competent cells' which migrate to other sites (Miller 1961). The simplest relationship between the thymus and the cells taking part in immunity would be that, in response to antigenic stimulation, thymus-derived immunologically competent cells generate the effector cells which actually carry out the response. Recent experiments in our laboratory have attempted to examine this hypothesis in order to define more precisely the cellular basis of the immune defects in thymectomized mice. The purpose of this article is to summarize this work without reviewing the entire literature in the field.

Serum-mediated protection of neoplastic cells from inhibition by lymphocytes immune to their tumor-specific antigens

Abstract: The combined effect of immune lymphocytes (lymphnode cells or blood lymphocytes) and serum from tumor-bearing donors was assessed in four tumor systems with the use of the colony inhibition assay: (a) Moloney virus-induced sarcomas in mice, (b) Shope papillomas in rabbits, (c) spontaneous mammary carcinomas in mice, and (d) two adenocarcinomas of the colon and two adenocarcinomas of the lung in humans. The neoplasms studied had previously been shown to possess tumor-specific antigens, against which cellular immunity could be detected in vitro. In all four systems, it was found that sera from hosts with progressively growing neoplasms could abrogate the inhibitory effect of lymphocytes which were immune to the specific antigens of the corresponding tumor type. Studies with Moloney sarcomas, in particular, showed that the serum effect had at least some degree of specificity.

Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation.

Abstract: Complement fixation techniques are described for measuring a virus-like antigen associated with viral hepatitis Antigen was found in the blood of 98 percent of 130 patients, with the serum form of hepatitis, from whom multiple samples were obtained Antibodies arising during hepatitis are usually combined with antigen and cause anticomplementary activity in the serum, which is reversible with excess antigen or antibody Tests for antigen and specific anticomplementary activity can be used diagnostically and to screen blood donors for hepatitis carriers

The pathogenesis of aleutian disease of mink i. in vivo viral replication and the host antibody response to viral antigen

Abstract: Mink inoculated with 1 x 10(5)ID(50) of Aleutian disease virus revealed very high virus titers in the tissues 8-18 days later. The highest virus titers observed were 5 x 10(8)ID(50) per g of spleen and 1 x 10(9)ID(50) per g of liver 10 days after inoculation. Concomitant with the increase in infectious virus titers, viral antigen(s) was found in the cytoplasm of macrophages in the spleen and lymph nodes and in Kupffer cells in the liver. Antiviral antibody was assayed by indirect immunofluorescence, using sections of infected liver as the source of antigen. A few mink infected for 9 days and all those infected 10 days or more developed antibody to Aleutian disease virus antigen(s). By 60 days after infection, when hypergammaglobulinemia was marked, the mink had an exceptionally high mean antibody titer of 100,000. The pathogenesis of the glomerulonephritis of Aleutian disease is apparently related to formation of viral antigen-antibody-complement complexes which lodge in glomerular capillaries. No evidence was found that viral infection of the kidney took place, and no autoimmune responses were found. In this "slow-virus" disease the virus replicates rapidly and the morphologic and biochemical manifestations of disease are apparently due to the continuing interplay between a replicating antigen and the host immune response.

An in vitro reaction between labelled flagellin or haemocyanin and lymphocyte-like cells from normal animals.

Abstract: Labelled bacterial flagellin and haemocyanin reacted with lymphocyte-like cells from several rat and mouse tissues. This reaction occurred at low temperatures and in the presence of sodium azide, conditions which inhibited uptake of labelled proteins by phagocytic cells. The reactive cells took up at least 40,000 molecules of labelled flagellin, and appeared to have a much greater capacity, since pretreatment with 10,000 times this amount of flagellin was required to inhibit the reaction. The flagellin and haemocyanin were firmly bound to the cells, possibly to immunoglobulin at the cell surface, since prior treatment with antisera directed against mouse immunoglobulin inhibited the reaction with lymphocytes from mouse spleen and peritoneal exudate. The number of reactive cells in spleen was proportional to the concentration of labelled protein. At a given concentration of labelled protein, however, the number of reactive lymphocytes was characteristic of each tissue. Spleen, lymph node and thoracic duct lymph contained a similar proportion of reactive lymphocyte-like cells, peritoneal exudate contained more, and thymus contained few if any such cells. Bone marrow contained a high proportion of reactive lymphoid cells which apparently reacted in a non-specific manner, since the uptake of labelled protein by these cells was not inhibited by anti-immunoglobulin serum.

The distribution of large dividing lymph node cells in syngeneic recipient rats after intravenous injection

Abstract: The distribution of large dividing lymph node or thoracic duct lymph cells, labeled in vitro with (3)H-thymidine, was studied in syngeneic recipient rats after intravenous injection. In most experiments the donor rats had been immunized with Bacillus pertussis 4 days earlier, but in some instances cells from nonimmunized donors were used. In smears, the labeled donor cells had the appearance of large lymphocytes or large pyroninophilic cells. By electronmicroscopy, the majority of labeled donor cells were seen to have only scanty endoplasmic reticulum. It was found that the labeled cells rapidly "homed" to lymphoid tissue and recirculated in the recipient, in a fashion resembling that of small lymphocytes. However, the distribution of labeled cells was found to depend upon the source of the donor cells. Cells from mesenteric lymph nodes or thoracic duct lymph showed a marked preferential accumulation in lymphoid tissue within or adjacent to the intestine, whereas cells from peripheral nodes accumulated preferentially in peripheral lymph nodes. Cells from any of these sources showed an equal tendency to accumulate in the white pulp of the spleen. Suspensions of small lymphocytes, labeled in vitro with (3)H-uridine, did not display a similar tendency to localize preferentially in lymphoid tissue in certain regions. It was also found that large dividing lymph node cells from donors immunized with an antigen (2,4-dinitrophenyl-bovine gamma globulin (DNP-BGG) or B. pertussis) showed a greater tendency to accumulate in a recipient lymph node containing that antigen than in the contralateral node. It was not determined whether the selective accumulation of large dividing lymphoid cells from different sources in lymphoid tissue of different regions in recipients was due to an antigen recognition mechansim or was the result of two different populations of cells with different "homing" mechanisms.

Specific Inactivation of Antigen-reactive Cells with 125I-Labelled Antigen

Abstract: A QUESTION of current interest is whether the initial stages of an immune response—either the induction of antibody formation or of specific tolerance—may involve the reaction of an antigen with a specific lymphocyte. Naor and Sulitzeanu1 have demonstrated, both in vivo and in vitro, a reaction of 125I-labelled bovine serum albumin with a small proportion (about 1/5,000) of mouse spleen lymphocytes. We have since shown2 that both flagellin and polymerized flagellin (Salmonella adelaide) and haemocyanin (Jasus lalandii) labelled with 125I or 131I react in vitro with certain cells from spleens of rats and mice. Of the strongly reactive cells, almost all are mononuclear with a high nuclear/cytoplasmic ratio and 7–12 microns in diameter and, for any one antigen, comprise about 1/5,000 of the total cell population. These reactive cells adsorb between 4,000–40,000 molecules of labelled protein when allowed to react at 0° C with labelled protein (about 3 × 1012 molecules/ml.) in 10 per cent foetal calf serum. A similar proportion of such reactive cells was observed in cell suspensions from lymph nodes and thoracic duct lymph, while peritoneal exudate contained a higher proportion and thymus a lower proportion of these cells2. The reaction was not inhibited by concentrations of sodium azide which restricted the uptake of labelled antigen by macrophages but was inhibited, using mouse cells, by rabbit anti-mouse globulin serum. Spleen cells from germ-free and conventional mice reacted equally well with 131I-labelled flagellin2. We wished to know whether the ability of these cells to react with antigen was immunologically significant. Experiments were devised to distinguish between the following possibilities: that the reactive cells were (1) cells present because of a prior experience of the animal with a related antigen, (2) antigen-reactive cells3,4 which had not had prior antigenic experience but which were capable of contributing to a specific immune response such as formation and secretion of antibody, and (3) cells coated non-specifically with cytophilic antibody.

Use of erythrocytes sensitized with purified pneumococcal polysaccharides for the assay of antibody and antibody-producing cells.

Abstract: A method was described for the sensitization of erythrocytes with purified type-specific pneumococcal polysaccharide antigens using chromium chloride as a coupling agent. Erythrocytes so sensitized can be used in routine passive hemagglutination and hemolysis tests as well as in the technique of localized hemolysis-in-gel for the detection of specific antibody and specific antibody-producing cells, respectively.

Cell interactions in the primary immune response in vitro: a requirement for specific cell clusters

Abstract: Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro. About 10% of the cell clusters had the following unique properties; (a) they contained most, if not all, antibody-forming cells, (b) they contained only cells forming antibody to one antigen when cell cultures were immunized with two antigens, (c) the cells in clusters reaggregated specifically after dispersion, and (d) the specific reaggregation of clusters appeared to be blocked by antibody to the antigen. The integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clustering by mechanical means or by excess antibody blocked the immune response. Antibody and antigenic determinants on the surfaces of cells probably provide the basis for interaction. The unique microenvironment of cell clusters was essential for the primary immune response in vitro.

A complement-fixation test for measuring Australia antigen and antibody.

Abstract: The role of Australia antigen (Au) in serum hepatitis is ill-defined, but there is growing evidence that the antigen may be the virus of serum hepatitis or a virus-associated protein [1-3]. Au antigen has been measured in the sera of persons with acute or chronic hepatitis; antibody to Au antigen (anti-Au) has been studied less well but is known to occur in sera from a proportion of hemophiliacs [3] and other persons receiving multiple transfusions [4]. Until now Au and anti-Au have been detected primarily by agar gel diffusion (AGD) techniques. In only a few reported studies has the antigen or the antibody been quantitated. The present study describes a complement-fixation (CF) test for the measurement of Au and anti-Au, the relative sensitivity and specificity of the test, and its use in detecting, quantitating, and serologically comparing Au and anti-Au.