Showing papers on "Immune system published in 1974"

Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis.

Abstract: THE cytotoxic activity1,2 of immune thymus-derived lymphocytes (T cells) for 51Cr-labelled fibroblasts, or macrophages infected with lymphocytic choriomeningitis (LCM) virus is restricted by the H-2 gene complex3,4. Specific lysis of LCM-infected monolayer cultures occurs only when targets and overlaying, sensitised T cells share at least one set of H-2 antigenic specificities.

Generation of cytotoxic t lymphocytes in vitro : i. response of normal and immune mouse spleen cells in mixed leukocyte cultures

Abstract: Mouse cytotoxic T lymphocytes (CTL) were generated in mixed leukocyte cultures (MLC) using spleen cells as responding cells and irradiated allogeneic spleen cells as stimulating cells. Cytotoxicity was assessed by a quantitative 51Cr assay system and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Inclusion of 2-mercaptoethanol in the MLC medium resulted in a 20–40-fold increase in the relative number of CTL generated at the peak of the response. Under these culture conditions, cell-mediated cytotoxic activity was detectable in MLC populations as early as 48 h after the onset of the cultures. When spleen cells from mice immunized with allogeneic tumor cells 2–4 mo previously were cultured with irradiated spleen cells of the same alloantigenic specificity (MLC-Imm), it was found that the cell-mediated cytotoxic response was detectable earlier and reached higher levels than that observed in a primary MLC. At the peak of the response, MLC-Imm populations were observed to lyse up to 50% of the target cells within 3 h at a lymphocyte: target cell ratio of 0.3:1. Immunological and physical characterization of the effector cells generated in MLC-Imm indicated that they were medium to large-sized T lymphocytes. Altogether, these studies suggested the existence of an anamnestic cell-mediated cytotoxic response in MLC-Imm.

Circulating Immune Complexes in the Serum in Systemic Lupus Erythematosus and in Carriers of Hepatitis B Antigen QUANTITATION BY BINDING TO RADIOLABELED Clq

Abstract: A sensitive and reproducible procedure for the detection of soluble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled C1q is reacted with sera containing immune complexes. Separation of free from complex bound [(125)I]C1q is achieved by selective precipitation with polyethylene glycol (PEG). The method is based on both the large molecular size and the C1q-binding property characterizing immune complexes. The minimal amount of aggregated immunoglobulins thus detected is about 10 mug and that of soluble human IgG-anti-IgG complexes is about 3 mug of complexed antibody. Some immune complexes formed in large antigen excess (Ag(2)Ab) can still be detected by this radiolabeled C1q binding assay. The specificity of the radiolabeled C1q binding test was documented by the inability of antigen-F(ab')(2) antibody complexes to lead to a precipitation of [(125)I]C1q in PEG. In a second step, this radiolabeled C1q binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes.Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the hepatitis B antigen (HB-Ag). Significantly increased [(125)I]-C1q binding values were observed in 52 sera from SLE patients when compared to values obtained with healthy blood donors (P<0.001). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [(125)I]C1q binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [(125)I]C1q percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [(125)I]C1q. The results were also used for a correlative study of [(125)I]C1q binding to IgG levels in the sera but increased [(125)I]C1q binding could not be attributed to high serum IgG levels which are likely to account for gammaglobulin aggregates. These examples suggest the utility of the radiolabeled C1q binding assay for the evaluation of immune complex diseases in human pathology.

GENETIC CONTROL OF RESPONSES TO BACTERIAL LIPOPOLYSACCHARIDES IN MICE I. Evidence for a Single Gene that Influences Mitogenic and Immunogenic Respones to Lipopolysaccharides

Abstract: In vivo immune responses and in vitro mitogenic responses to bacterial lipopolysaccharides (LPS) have been compared in strains of C3H mice. C3H/HeJ spleen cultures did not support mitogenic responses to LPS and in vivo these mice produce low IgM responses to LPS. On the basis of these two responses, C3H/HeJ mice have been termed low LPS responders. All other strains of C3H mice tested (C3HeB/FeJ, C3H/DiSn, C3H/Str, CWB, CSW, and C3H/Sf and its H-2 congenics) are high LPS responders supporting large in vitro mitogenic and in vivo immune responses to LPS. The immune response difference between low and high LPS responders is a quantitative one. IgM responses are observed in C3H/HeJ mice in the range of 1.0–10 µg LPS. At lower and higher LPS concentrations, immune responses are not observed. In contrast, high LPS responders elicit LPS immune responses over a much wider dose range (0.1–200 µg). The ability to respond well to LPS is dominant as shown by the response of F1 hybrid mice of low responder and high responder strains. The linkage relationships of mitogenic and immune responsiveness to LPS have been investigated in backcross (C3H/HeJ x CWB)F1 x CWB mice. All mice that gave in vivo immune responses to LPS also supported mitogenic responses to LPS. The defect in C3H/HeJ mice that limits mitogenic and immune responsiveness to be due to a single autosomal gene which is not linked to the H-2 histocompatibility or heavy-chain allotype loci.

Evidence of suppressor cell activity in spleens of mice bearing primary tumors induced by moloney sarcoma virus

Abstract: Spleens from Moloney sarcoma virus (MSV) tumor-bearing C57BL/6N mice contained four times the normal number of mononuclear cells and displayed a markedly elevated "spontaneous" (mitogen-independent) DNA synthesis on a per cell basis. The number of macrophages were increased three-fold while there was a slight reduction in the percentage of T lymphocytes. The phytohemagglutinin (PHA) response on a per cell basis of spleens from tumor-bearing mice was decreased about 90% when compared with normal control mice. The primary in vitro immune response to sheep red blood cells was also suppressed to levels of less than 10% of normals. The PHA response could be restored by purification of MSV spleen cells by rayon adherence columns and by removal of phagocytic cells by an iron/magnet technique. The activity of suppressor cells in MSV spleens was demonstrated in mixtures with syngeneic normal spleen cells where a marked impairment of the PHA response was observed. Spleen cells from tumor-free nude mice and normal spleen cells treated by anti-theta serum plus guinea pig complement (C'), both totally unreactive to PHA, had no such effect. The inhibitor cell in MSV spleens was shown to be insensitive to inactivation by anti-theta plus C', but could be removed by the adherence columns and the iron/magnet technique. These data suggest that this suppressor cell is a cell of the monocyte/macrophage series. Suggestive evidence was also presented that the suppressor cells belong to a proliferating population in MSV spleens. Similar suppressor cells have been previously demonstrated in spleens of mice during a variety of immune responses. Our data show, that a tumor, although stimulating the immune system, nevertheless may be suppressive on certain immune functions through the activation of suppressor cells.

Cell-Mediated Immunity to Tumor Cells

Abstract: Publisher Summary An individual's immunological response to some of the antigens can result in protection against tumor growth. However, it has been found that the generation of antitumor immunity is not always effective and may at times even lead to the acceleration of tumor growth. This chapter reviews the information on the role of the immune system in limiting tumor growth and discusses the concept of immunological surveillance. It discusses the types of antigens that have been associated with tumors, their specificity, and their potential significance. It also presents the evidence for the existence of specific, cell-mediated immunity, both in vivo and in vitro , against tumor-associated cell surface antigens. There is considerable evidence for the role of immune cells in the resistance of the host to tumor growth. The chapter discusses the possible role of assays in the diagnosis, prognosis, and therapy of cancer.

The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of new zealand mice

Abstract: The use of monospecific antisera for the analysis by radioimmunoassay and immunofluorescence study of two major viral proteins, gp69/71 and p30 of murine leukemia virus, that could be of significance in the pathogenesis of immune complex glomerulonephritis of mice, particularly NZB and B/WF1 hybrid mice, yielded the following conclusions. A remarkably high concentration of viral envelope glycoprotein, gp69/71, was detected in the spleen and serum of New Zealand mice (NZB, NZW, B/WF1, and W/BF1); the concentration in the spleen was 10-fold greater than that found in AKR mice and 30-fold greater than that present in C57BL/6 mice. The gp69/71 was deposited along with bound immunoglobulins, apparently as an immune complex, in the diseased kidneys of mice, and the glomerular site and extent of deposition of gp69/71 was related to the severity of the glomerulonephritis. This study suggests that the pathogenesis of immune complex glomerulonephritis (and vasculitis) in mice is related to the expression of this specific viral envelope glycoprotein and to the host immune response to this protein.

Suppression of Cellular Immunity in Rats and Mice by Maternal Treatment with 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxin

Abstract: Treatment of female F-344 rats and C57B1/6 mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the latter half of gestation and in the postnatal period resulted in a severe depletion of lymphocytes in the thymic cortex of the offspring. Cellular immunity was impaired in these animals. Allograft rejection times were prolonged in rats and mice. Graft-versus-host (GVH) activity of spleen cells as well as the response of rat thymus and spleen cells to phytohemagglutinin (PHA) was reduced on a cell-for-cell basis. No reduction occurred in the response of thymus cells to concanavalin A (Con A). Maternal treatment postnatally on day 0, 7 and 14 with 5 μg TCDD/kg of body weight reduced total PHA and Con A response recoverable from the thymus by 91 and 74%, respectively. Histologically, depletion of thymic cortex was not due to lymphocyte destruction. There was no adrenal hypertrophy. Stress-induced release of glucocorticoids is not considered responsible for the immune suppression observed. In contrast to the marked effects in early life, reduced responsiveness of spleen cells to PHA in mice treated with TCDD when 1 month old was only seen at a dose level that was clearly toxic. In 4-month-old mice, PHA responsiveness as well as GVH activity were not decreased. Response of unstimulated and stimulated thymus and spleen cell cultures was not reduced by adding TCDD in vitro. In TCDD-exposed rats, decreased eosinophilia was observed in acidophilic cells in the adenohypophysis. This finding is discussed in view of the effect of TCDD on the thymus, and a possible mode of action of TCDD is proposed.

Mechanism of thymus-independent immunocyte triggering : mitogenic activation of b cells results in specific immune responses

Abstract: The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP. The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.

The B-Lymphocyte Nature of the Hairy Cell of Leukaemic Reticuloendotheliosis

Abstract: Summary. Functional studies were performed on the ‘hairy’ cells of five cases of leukaemic reticuloendotheliosis (LRE) to see whether they behaved as histiocytes or lymphocytes. The ‘hairy’ cells were less active than normal or leukaemic monocytes in respect of adhesion to glass, transformation to macrophages and phagocytosis and killing of Candida; they also lacked IgG and C3 receptors for immune phagocytosis. Surface-bound immunoglobulins were demonstrated in a high proportion of ‘hairy’ cells; and they did not form rosettes with sheep red cells. Similar results were obtained with the lymphocytes of chronic lymphocytic and prolymphocytic leukaemia. In addition, the majority of the ‘hairy’ cells in one case were found to have C3 receptors for immune complexes. The ‘hairy’ cells of three patients did not respond to phytohaemagglutinin (PHA) or to pokeweed mitogen (PWM) but, in another case, half the cells transformed normally with PHA. It is concluded that the ‘hairy’ cell is of lymphocytic origin (resembling B lymphocytes) and that LRE should be included within the lymphoproliferative disorders and differentiated from histiocytic-cell disorders.

Genetic control of immune responses in vitro v. stimulation of suppressor t cells in nonresponder mice by the terpolymer l-glutamic acid60-l-alanine30-l-tyrosine10 (gat)

Abstract: In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-theta serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained theta-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

Reversal of immunological tolerance by cyclophosphamide through inhibition of suppressor cell activity.

Abstract: IT has been shown in mice that specific immunological unresponsiveness to contact sensitisation with picryl chloride induced by pretreatment with picryl sulphonic acid is a positive phenomenon rather than an absence of specific immunocompetent cells1. In this system it was shown that transfer of lymph node cells from unresponsive to normal mice would limit the recipients' contact sensitivity response to picryl chloride and that these cells had characteristics suggesting that they were T as opposed to B cells2. We should like to report that a similar state of unresponsiveness to the dinitrophenyl group in guinea pigs can be broken by treatment with cyclophosphamide (CY) just before sensitisation and this is associated with the return of the ability of T cells to proliferate in the draining lymph node as part of the immune response.

Decline in Suppressor T Cell Function with Age in Female NZB Mice

Abstract: Type III pneumococcal polysaccharide (SSSIII) did not cross-react with the nucleic acid antigen polyinosinic · polycytidylic acid when tested in NZB or CBA mice. Neither antigen requires thymic helper cells for the induction of an antibody response. The antibody response to each antigen, given alone or together, was increased by simultaneous administration of antithymocyte serum. Studies of the immune response to SSSIII were conducted in NZB mice since it was felt that this autoimmune strain might represent a natural model for the loss of suppressor T cells. The number of plaque-forming cells to SSSIII following immunization increased with age in female NZB mice. No such age-associated increase was observed in non-autoimmune BALB/c mice, suggesting that NZB mice might have a loss of suppressor function with age. This was supported by the reduction in the high PFC response to SSSIII of 10-month-old NZB mice by transfer of thymocytes from 4-week-old NZB mice.

Immunological Resistance to Pulmonary Metastases in C3Hf/Bu Mice Bearing Syngeneic Fibrosarcoma of Different Sizes

Abstract: Summary Immunological resistance to pulmonary metastases of a syngeneic methylcholanthrene-induced fibrosarcoma (FSA) was studied in C3Hf/Bu mice that were actively immunized against or that had borne that tumor for varying times. Tumor metastases were induced by i.v. inoculation of FSA cells, and their number was determined 14 to 17 days later. The number of metastases was greatly reduced in mice that previously had been immunized against the same tumor but not in those immunized against syngeneic mammary carcinoma. This reduction was mediated through the activity of immune spleen and lymph node cells and was related to the number of immune cells transferred into the recipient mice. Spleen cells were found to be more effective than lymph node cells. The presence of the s.c.-growing tumor reduced the number of pulmonary metastases. This was noted when s.c. implantation of FSA preceded the i.v. inoculation of the tumor cells by 3 hr and 3, 7, and particularly 14 days. Spleen cells from mice bearing s.c.-growing FSA for 3, 8, 12, 20, and 27 days were able to transfer immunity to pulmonary metastases of FSA in sublethally irradiated syngeneic recipients. Immunity was transferred most effectively by spleen cells from mice bearing the tumor for 12 days; this activity of the spleen cells markedly decreased in mice bearing the tumor for 27 days. Lymph node cells, however, were able to transfer antitumor immunity only if taken from mice bearing the tumors for 12 or 20 days. Serum from mice bearing FSA given i.v. to the tumor cell recipient mice as a single injection or in multiple doses did not prevent the reduction of pulmonary metastases by immune spleen and lymph node cells.

Analyses of Lymphocytes from Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus OCCURRENCE OF INTERFERING COLD-REACTIVE ANTILYMPHOCYTE ANTIBODIES

Abstract: Large percentages of the lymphocytes from some patients with rheumatoid arthritis and systemic lupus erythematosus were densely covered with Ig demonstrable by immunofluorescence, which was occasionally present in the form of caps. The amount and character of the Ig staining depended largely on the procedures used in the isolation and washing of the lymphocytes. Cold-reactive antilymphocyte antibodies present in many sera wre primarily responsible for these variations. Overnight culture of the lymphocytes proved to be an efficient procedure for the removal of adsorbed antibody. Some evidence was also obtained for the presence of circulating immune complexes and exogenous rheumatoid factor molecules on the lymphocyte surface. Thus on freshly isolated cells the demonstration of surface Ig proved to an unreliable marker of bone marrow-derived (B) cells in these disease: the actual percent of B cells with intrinsic surface Ig was often markedly decreased. In patients with systemic lupus erythematosus, this reduction was in agreement with the low numbers of cells that had a receptor for aggregated IgG. The mean percentage of thymus-derived (T) cells in both diseases was slightly greater than the normal level. The concentrations of lymphocytes in joint fluids from patients with rheumatoid arthritis were often greater than levels found in blood. T cells primarily accounted for this increase. The T cells typically formed unusually dense rosettes with sheep erythrocytes. B lymphocytes were proportionally much diminished. Evidence was obtained for the existence of a major joint fluid lymphocyte population that lacked all assayed surface markers.

Release of dna in circulating blood and induction of anti-dna antibodies after injection of bacterial lipopolysaccharides

Abstract: The present data demonstrate the induction of antisingle-stranded (SS) DNA and antidouble-stranded DNA antibodies in various strains of mice, including athymic C57BL/6 nude mice, after the injection of bacterial lipopolysaccharide (LPS). This anti-DNA response is dose dependent and varies quantitatively according to the strain of the injected mice. It is not correlated to the H-2 histocompatibility locus nor to the immune response to LPS. The lipid A fraction appears to be the active part of the LPS molecule for this particular effect. In addition, it was found that DNA is released in circulating blood a few hours after the injection of LPS. Most of the DNA released has physicochemical and immunochemical characteristics of SS DNA. Therefore, the anti-DNA response induced by injections of LPS may be the result of a release of DNA in a particularly immunogenic form at a time when the immune system, in particular the B lymphocytes, is rendered capable by LPS of developing an immune response to such a soluble antigen. These effects of LPS may account for the triggering or the exacerbation of ante-DNA antibodies during infections with gram-negative bacteria, and a similar mechanism may be involved in the pathogenesis of systemic lupus erythematosus.

Immune Complexes induce Selective Release of Lysosomal Hydrolases from Macrophages

Abstract: IMMUNE complexes contribute to tissue damage in a variety of experimental and human diseases. Immune complexes induce arthritis1 and nephritis2,3 in laboratory animals while lupus glomerulonephritis4 and possibly rheumatoid arthritis5 are examples of their effects in man. The mechanisms by which damage is initiated and perpetuated are poorly understood. In the acute stage of inflammation resulting from immune complexes many granulocytes are present. These cells have abundant lysosomes rich in acid hydrolases which when released can degrade various tissue components. Enzyme release may result from cell death or exocytosis of granules from viable cells. Henson6 and others7,8 have shown that granulocytes exposed to immune complexes in vitro release lysosomal enzymes while remaining viable, and presumably the same happens in Arthus reactions in vivo.

Escape from Immune Destruction by the Host through Shedding of Surface Antigens: Is This a Characteristic Shared by Malignant and Embryonic Cells?

Abstract: Summary The hypothesis is advanced that macromolecules normally found only in embryonic and fetal cells are also found in tumors because malignant cells, like the fetus, must develop mechanisms to avoid immunological destruction by the host. While anatomical factors play an important role in the “escape” of the fetus as well as the tumor, they are not by themselves adequate. In tumors, the shedding of antigens in a soluble form provides powerful protection because such antigens compete with the tumor for the effector processes of the immune response. Soluble antigens form adducts with antibodies as well as cytotoxic cells, which are then no longer capable of killing the tumor cells. Evidence is presented that the rate of spontaneous shedding of antigen may determine in part the growth pattern of the tumor in vivo. Sarcoma cells, which shed antigen rapidly, metastasize more readily than those with a slow spontaneous release of antigen. It is proposed that rapid shedding of transplantation antigens is a characteristic of embryonic cells and tumors.

Role of Macrophages in Resistance to Murine Cytomegalovirus

Abstract: The role of macrophages in protecting mice from murine cytomegalovirus (MCMV) was studied in Swiss, CBA/J, and C57BL/6J mice. CBA/J mice were more resistant to virus than were C57BL/6J mice at all ages tested. Prior treatment of adult Swiss mice with 60 mg of silica, a dose selectively toxic to macrophages, increased mortality due to MCMV infection. Transfer of syngeneic adult macrophages to suckling mice significantly increased their resistance to subsequent MCMV infection. Transfer of syngeneic, nonimmune adult lymphocytes to suckling mice also had a lesser but significant protective effect against subsequent MCMV challenge. In vitro infection of adult CBA/J and C57BL/6J macrophages with virulent and attenuated MCMV resulted in productive infection in only a small percentage of cells and recovery of very little virus from the extracellular fluid. Infection of CBA macrophages was no less productive than C57BL/6J nor was infection with virulent virus more productive than with attenuated virus. Histological examination of the livers of MCMV-infected CBA/J and C57BL/6J mice suggested that divergent cellular immune responses to infection might account for differences in susceptibility. It is postulated that the macrophage may facilitate the inductive phase of cellular immunity, one possible explanation for its demonstrated importance in host defenses against MCMV. Images

Natural resistance to Salmonella infection, delayed hypersensitivity and Ir genes in different strains of mice.

Abstract: THE development of immunity to an intracellular bacterial infection such as that produced by Salmonella typhimurium in mice can be followed by the fall in the numbers of living bacteria in the liver and spleen. Resistance to infection appears at about the same time as delayed hypersensitivity to appropriate antigens of the infecting organisms and both may be taken as indicators of a cell-mediated immune response1. Inbred mouse strains differ widely in their resistance to salmonella infections and one possible explanation is that they differ in their ability to produce cell-mediated immune responses in general. This has been tested by comparing the degrees of delayed hypersensitivity detectable in different strains of mice sensitised with a number of unrelated antigens. The results discussed here disprove the hypothesis but suggest a more interesting one.

The role of macrophages in defense against neoplastic disease.

Abstract: Publisher Summary This chapter reviews the role of macrophages in defense against neoplastic disease. Macrophages do exert both natural and adjuvant-stimulated, afferent and efferent antineoplastic activities. Macrophages appear to be essential for the uptake and processing of tumor antigens preceding the initiation of an effective immune response. Additionally, the macrophage alteration of antigen may promote successful immunization as opposed to the induction of tolerance or production of enhancing or blocking factors. The macrophage might further enhance the immune response by stimulating the proliferation of immunocompetent cells through the production of lymphocyte-activating factor (LAF) or the delivery of macrophage-contained adjuvant. Aided by cytophilic antibody, specific macrophage arming factor (SMAF), macrophage migration inhibitory factor (MIF), interferon, nonspecific opsonins, or nonspecific activation, macrophages, either alone or in concert with other immune cells, can exert both immune and nonimmune cytotoxicity toward neoplastic cells. This antitumor activity is most likely mediated through a nonphagocytic, contact-dependent mechanism, associated in only a few systems with the release of soluble toxic substances. Such direct macrophage-mediated antitumor activity, as well as macrophage-mediated induction and the amplification of antitumor immune responses, appear to contribute significantly to host survival and deserve careful consideration in both the experimental and clinical study of animal and human neoplastic disease.

Regulatory mechanisms in cell-mediated immune responses. I. Regulation of mixed lymphocyte reactions by alloantigen-activated thymus-derived lymphocytes.

Abstract: Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

Receptors for Immune Complexes on Lymphocytes

Abstract: Publisher Summary This chapter discusses receptors for immune complexes on lymphocytes. The discovery that lymphocytes can be grouped into subpopulations (B and T lymphocytes) with specific properties and functions has been firmly established, and has opened the way to new investigations. Membrane receptors for complement have been detected through the binding of sheep erythrocytes sensitized with antibody and complement, leading to the formation of rosettes that can be seen and counted under the microscope. This chapter also discusses some aspects of the interaction between lymphocytes and immune complexes, the use of membrane receptors for complexes in the detection, identification, and isolation of B lymphocytes, and the possible participation of the cell receptors in the induction of the immune response in vivo . Finally, the study of the mechanism of interaction of immune complexes with lymphocytes may be of relevance to several important areas of immunological research as well as to the understanding of mechanisms of disease. Further insights may derive from the experiments that test directly the hypothesis, that immune complexes of certain structural composition play a central role in the triggering of diverse cell functions.

BINDING OF SOLUBLE IMMUNE COMPLEXES TO HUMAN LYMPHOBLASTOID CELLS : II. Use of Raji Cells to Detect Circulating Immune Complexes in Animal and Human Sera

Abstract: Cells from a human lymphoblastoid cell line (Raji), with B-cell characteristics, and having receptors for human IgG Fc, C3b, and C3d, were used in an immunofluorescence test as in vitro detectors of immune complexes in animal and human sera. By this test, as little as 200-300 ng aggregated human gamma globulin or immune complexes per ml serum could be detected. The receptors for IgG Fc on the Raji cells were shown to be inefficient in detecting aggregated human gamma globulin and binding of aggregates to these receptors was inhibited by physiologic concentrations of 7S human IgG. Enhancement of aggregated human gamma globulin binding and binding of immune complexes formed in vitro to Raji cells was observed when the receptors for complement on these cells were used. By using the receptors for complement on Raji cells, circulating immune complexes were detected in rabbits with acute serum sickness, in mice with acute lymphocytic choriomeningitis virus infection, and in humans with immune complex type glomerulonephritis. The Raji cell test may be useful in detecting complement fixing immune complexes in different disease states, in monitoring circulating complexes in patients with immune complex diseases and in identifying the antigen(s) responsible for the induction of pathogenic immune complexes in humans and animals.