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.

Antitrinitrophenyl (TNP) Plaque Assay. Primary Response of Balb/c Mice to Soluble and Particulate Immunogen

Abstract: SummaryA technique was developed for the detection of individual cells producing anti-TNP antibody by the hemolytic plaque technique. Conjugation of TNP directly to the erythrocyte surface by use of TNBS resulted in a stable reagent that permitted a study of the antihapten response to TNP-KLH. It was possible to induce a primary anti-TNP response with soluble TNP-KLH but the response was greater when the immunogen was made particulate by coating it onto bentonite. Both primary and secondary responding cells (those brought out by antiglobulin serum) were inhibited by TNP-BSA added to the plating medium but at an equivalent concentration of hapten only the secondary cells were completely inhibited. This was interpreted to indicate the higher binding affinity of secondary antibody.Author's note. As we were in process of submitting this manuscript, we became aware of an abstract which indicated that responses of similar magnitude to those reported here with TNP could be obtained in Balb/c mice to DNP using a ...

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.

Blood group isoantibody stimulation in man by feeding blood group-active bacteria

Abstract: It was investigated whether or not the human blood group isoantibodies A and B could be induced by immunogenic stimuli via natural routes with a kind of antigenic substance to which all humans are commonly exposed, or if the appearance of these antibodies is independent of antigenic stimuli as has long been believed. Escherichia coli O86, which possess high human blood group B and faint A activity in vitro, were fed to healthy humans and those with intestinal disorders. 80% of the sick individuals of blood group O and A responded with a significant rise of anti-B antibodies which was frequently de novo in infants; significant increase of anti-A isoantibodies among blood group O individuals was less frequent. Over one-third of the healthy individuals also had a significant isoantibody increase. Intestinal lesions favor isoantibody stimulation by intestinal bacteria; this view was supported by the study of control infants. Persons of blood group A responded more frequently with anti-B and anti-E. coli O86 antibody production than those of blood group O. Isoantibody increase was accompanied with antibody rise against E. coli O86. Inhalation of E. coli O86 or blood group AH(O)-specific hog mucin also evoked isoantibodies. The induced isoantibodies were specifically inhibited by small amounts of human blood group substances. E. coli O86-induced anti-blood group antibodies in germ-free chickens and preexisting blood group antibodies in ordinary chickens were neutralized by intravenous injection of E. coli O86 lipopolysaccharide. This study demonstrates that human isoantibodies A and B are readily elicited via physiological routes, by blood group-active E. coli, provided the genetically determined apparatus of the host is responsive. Antibodies against a person's own blood group were not formed. Interpretation of these results permits some careful generalizations as to the origin of so-called natural antibodies.

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.

Host Antigens in Schistosomiasis

Abstract: It has previously been shown that adult schistosomes excite an immune response in the rhesus monkey but do not themselves succumb to this response. Furthermore, schistosomes are known to persist in the blood of man and experimental animals for long periods. These findings point to the evolution of a special mechanism for circumventing the immune defences of the host. The present paper sets out evidence which suggests that this mechanism involves the incorporation of host antigens at the surface of the adult worm. When adult worms, which had been grown in mice ('mouse worms'), were transferred into the hepatic portal systems of normal monkeys, a large proportion (84%) were recovered alive 1 to 6 weeks later. Worms recovered after 1 week were pale and shrunken and the females had ceased egg production; worms recovered after 6 weeks were normal and egg production had been resumed. Evidently, the transferred worms find difficulty at first in adapting to their new host species, but in time they are able to adapt fully. In contrast, when mouse worms were transferred to monkeys previously immunized against normal mouse tissues (anti-mouse monkeys), very few of these worms survived. Indeed, when the monkeys were immunized against mouse spleen and liver cells or erythrocytes, combined with Freund's complete adjuvant, the transferred mouse worms were completely destroyed. This result indicates that the worms grown in mice had mouse antigens closely associated with them, and that on transfer to anti-mouse monkeys, the worms were destroyed by the ensuing immunological reaction. This immunity was passively transferred to normal monkeys by means of serum; thus the immunity is largely antibody-mediated. Most of the mouse worms died between 7 and 25 h after transfer. The immune reaction was directed mainly against the tegument of the worm, causing breaks in the plasma membrane and vacuolation and subsequent degeneration of the underlying syncytium. The mixed agglutination reaction and the use of a ferritin-labelled antiserum combined with electron microscopy confirmed that host antigens were located at the surface of the worm. The antigens appear to be host species-specific; worms which were grown in monkeys or libyan jirds survived normally when transferred to anti-mouse monkeys. There is evidence that the antigens may readily be exchanged between host and parasites. Mouse worms which were transferred to a normal monkey and then transferred after 7 days to an anti-mouse monkey survived as well as monkey worms. Evidently the mouse worms had lost their mouse antigens during this period, perhaps exchanging them for monkey antigens. Three days in a normal monkey was not sufficient, however, for all of the mouse worms to lose their mouse antigens. It is suggested that these host antigens are synthesized by the host, but that they become firmly bound to or incorporated inthe tegument. It is conceivable that these antigens serve to disguise the worms as host tissue, thus preventing their rejection by the immune defences of the host. This hypothesis provides an explanation for the apparent anomalies, referred to earlier: the insusceptibility of adult worms to the immune response which they are known to provoke, and their long persistence in the blood, an immunologically hostile environment.

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.

The Attenuation, with Loss of Oncogenicity, of the Herpes-type Virus of Marek's Disease (Strain hprs-16) on Passage in Cell Culture

Abstract: Summary The herpes-type virus of Marek's disease showed a gradual increase in the rate of development of cytopathic effect on passage in cell culture By the 60th passage macroscopic plaques were produced after 6 days under fluid overlay, but no cell-free virus could be recovered after filtration of culture medium A loss of pathogenicity for chicks was noticed in the virus after 33 passages in cell culture Furthermore, an antigenic change occurred between the 20th and 30th passage which was characterized by the loss of an antigen which could normally be found in the supernatant medium of cultures infected with low passage virus The possible origin of the attenuated virus is discussed

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

Standardized viral hemagglutination and hemagglutination-inhibition tests. II. Description and statistical evaluation.

Abstract: Standardized hemagglutination and hemagglutination-inhibition procedures are described and statistically evaluated for all animal viruses where applicable, except for rubella and the arbovirus group. The standardized tests employ a constant phosphate-buffered saline diluent and constant volumes of serum, antigen, and standardized erythrocyte suspension. The standardized hemagglutination test has a reproducibility of 84 to 96% with adenoviruses, rubeola, and the myxoviruses, and 78 to 93% with reoviruses; the standardized hemagglutination-inhibition test has a reproducibility of 95 to 100% with all viruses tested.

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.