Showing papers on "Immune system published in 1970"

The relative importance of blood monocytes and fixed macrophages to the expression of cell-mediated immunity to infection.

Abstract: Infection in mice with Listeria monocytogenes results in a substantial accumulation of migrant macrophages in the liver. The immigrant cells populate both the infective foci and intervening sinusoids. They have the labeling characteristics of blood monocytes, and their appearance in infective foci in the liver corresponds to the expression of a high level of antimicrobial immunity in this organ. The infected liver acquires additional new macrophages by Kupffer-cell division. The proliferation of these cells, however, is not essential for the expression of immunity in the liver. The results indicate that the macrophages which express immunity to a primary infection with L. monocytogenes are those derived from circulating monocytes. Most of these cells are quickly lost once the parasite is eliminated from the tissues.

Specific in vitro Cytotoxicity of Thymus-derived Lymphocytes sensitized to Alloantigens

Abstract: THE immune response to a specific antigen is characterized by the development of antibody-producing cells and of sensitized lymphocytes active in cell-mediated immunity. Although there is good evidence that antibody-producing cells are bone marrow-derived cells1–2, the role of thymus-derived cells is less well understood. Development of cell-mediated immunity is impaired in neonatally thymectomized animals3, and it is therefore likely that sensitized lymphocytes are thymus-derived cells. Spleen cell populations of mice immunized with allogeneic cells contain lymphocytes able to destroy in vitro appropriate target cells bearing the sensitizing alloantigens4–5. Earlier studies demonstrating the in vitro cytotoxic activity of sensitized thymus cells6 suggested that cytotoxic cells found in immune spleen cell populations were thymus-derived. As shown recently7–8 mouse thymus-derived cells in the peripheral lymphoid organs carry a surface marker, the θ alloantigen9, and are lysed when incubated in the presence of anti-θ serum and complement. This study was undertaken to test the effect of anti-θ serum on the cytotoxic activity of spleen cells sensitized to alloantigens. Its effect on alloantibody-producing cells present in the same spleen cell populations was tested in parallel.

Cooperation of Immune Lymphoid Cells with Macrophages in Tumour Immunity

Abstract: An immunologically specific cellular cooperation may resolve the paradox that immune spleen cells injected into normal mice prevent the growth of lymphoma cells in vivo but fail to do so in vitro.

Cellular and humoral immune responses to human urinary bladder carcinomas.

Abstract: Leukocytes from 17 of 19 patients with urinary bladder carcinomas were cytotoxic for autochthonous as well as allogeneic bladder carcinoma cells in vitro. The cells from all 11 individual bladder carcinomas studied were susceptible to this cytotoxic action of patients' leukocytes. In contrast, no cytotoxicity was observed when cells from unrelated tumours or various normal tissues were used as target cells. Purified blood lymphocytes from patients whose leukocytes were active, were also cytotoxic. Sera of 8 out of 13 patients with bladder carcinomas contained complement-dependent antibodies which were cytotoxic for autochthonous and allogeneic bladder tumour cells. When serum was taken from the same patient on different occasions over a period of 8 months cytotoxicity was found in some samples but not in others. Sera from 4 out of 9 patients exhibited a blocking activity, which completely abolished the cytotoxic effects of patients' leukocytes. The serum of one out of 9 patients contained antibodies which were not cytotoxic without leukocytes but which conferred a cytotoxic activity onto leukocytes from control subjects. This opsonizing antibody was complement-dependent and probably of IgM nature. The effect of hydrostatic pressure therapy on the immune state of the patients was followed by examination of the leukocytes from 16 patients with bladder carcinoma. Leukocytes from 10 patients were cytotoxic before as well as after the pressure treatment. Leukocytes from six patients did not react before the treatment while those from four became active after treatment. A more detailed study of three individual cases indicated that cytotoxicity of the leukocytes appeared after pressure treatment and was of relatively short duration (approximately 1 month). In one case, the development of cytotoxic antibodies was similar. The patient who had opsonizing antibodies had no cytotoxic antibodies. The opsonizing antibodies appeared when the cytotoxicity of the leukocytes decreased.

Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity.

Abstract: Cellular immunity induced by tumour allografts in inbred mice was studied with the help of an in vitro assay system measuring the cytotoxic effect of sensitized lymphocytes on 51Cr-labelled target cells. It is shown that lymphoid cells from spleen, lymph nodes and blood of the allograft recipients reach a peak of cytotoxic activity on days 10–11 after immunization. Incubated with labelled target cells at a ratio of 100:1, the sensitized lymphocytes caused the specific release of up to 70 per cent of the radioactivity within 1 hour. A second population of target cells added to the same cell suspension was destroyed at a slightly accelerated rate, suggesting stimulation of the effector cells by the first interaction. The cytotoxic activity of circulating lymphocytes was found to reach a plateau between days 20 and 60 after immunization, while the activity of spleen cells dropped to low levels in the same time period. The specificity of target cell destruction by sensitized lymphocytes is demonstrated by the lack of lytic activity for syngeneic target cells, and by the selective destruction of target cells carrying a tumour specific antigen. Tumour cells, lymphocytes and embryonic fibroblasts of the donor strain are shown to differ considerably in their sensitivity to lysis by immune lymphocytes.

Role of thymus-derived lymphocytes in the secondary humoral immune response in mice.

Abstract: THERE is now good evidence that the theta (θ) isoantigen of mice1 is carried only by those peripheral lymphocytes which are thymus-derived2–4, so that anti-θ antiserum should be useful in elucidating the role of these cells in immunity. In experiments reported here, anti-θ has been used in vitro in an adoptive transfer system5 to study the function of thymus-derived lymphocytes in the secondary humoral immune response to hapten–protein conjugates, particularly in terms of cellular cooperation and carrier effects.

Mixed Lymphocyte Cultures Produce Effector Cells: Model in vitro for Allograft Rejection

Abstract: Mouse peripheral lymphocytes sensitized in vitro by culturing with allogeneic lymphocytes produced immunospecific destruction of target cells, as measured by release of chromium-51. Thus the sensitizing and effector phases of the cell-bound immune response can both be studied in an in vitro system.

Cellular sites of immunologic unresponsiveness.

Abstract: The reconstitution of the immune response of lethally irradiated mice to human γ-globulin is dependent on the synergistic action of bone marrow with thymus cells. Immunologic unresponsiveness appears to involve a functional defect at each of these cellular levels, inasmuch as neither bone marrow nor thymus cells from unresponsive donors are capable of demonstrating synergism in combination with their normal counterpart.

Mechanisms of recovery from a generalized viral infection: mousepox. I. The effects of anti-thymocyte serum.

Abstract: Agglutination and immunofluorescence tests in vitro showed that the ATS used in these experiments cross-reacted with macrophages and RBC. However, ATS was not toxic in vivo, and small doses given subcutaneously depleted thymus-dependent areas of lymphoid tissues and selectively depressed blood lymphocyte counts without affecting other cell types in the blood. Furthermore, the function of littoral macrophages as indicated by the clearance of blood-borne virus and its subsequent behavior over a 48 hr period in the liver and spleen was not changed by ATS. Thus, the innate resistance of these vital target organs was not depressed. A similar regimen of subcutaneous ATS caused a highly significant increase in mortality from mousepox with an associated failure to control virus growth in the liver and spleen which was manifest by 6 days after infection. The interferon and neutralizing antibody responses were not impaired in ATS-treated mice, but the cell-mediated immune response was significantly suppressed. This evidence, and consideration of the timing of these host responses during the course of infection in relation to the control of virus growth in the liver and spleen, led to the conclusion that cell-mediated immunity probably contributed an essential acquired recovery mechanism. However, no evidence was obtained concerning the nature of this antiviral mechanism.

Synergistic interaction of macrophages and lymphocytes in antigen-induced transformation of lymphocytes.

Abstract: The role of macrophages and lymphocytes in antigen-induced transformation of lymphocytes has been investigated. Lymphocytes and macrophages were obtained from inbred strain 13 guinea pigs which were either unimmunized or immunized with complete Freund's adjuvant (CFA) or tetanus toxoid in CFA. The transformation response to PPD or tetanus toxoid was assayed by tritiated thymidine incorporation. Addition of macrophages to immune lymphocytes significantly increased their response to purified protein derivative (PPD) or tetanus toxoid. This was observed if the macrophages were (a) "immune" or "nonimmune", (b) unirradiated or irradiated (3000 R), (c) 99% pure, and (d) peritoneal or alveolar in origin. Neither immune nor nonimmune macrophages were able to induce nonimmune lymphocytes to respond to PPD or tetanus toxoid. When macrophages were incubated with PPD or tetanus toxoid and then washed, they stimulated immune lymphocytes to transform. An incubation time of ½ hr was adequate, however, 2–4: hr was optimal. These studies indicate (a) that antigen-induced transformation of lymphocytes is greatly enhanced by macrophages; (b) that macrophage-antigen interaction can antecede lymphocyte-antigen interaction and results in macrophages which are able to stimulate lymphocyte transformation; and (c) that the immunological memory requisite to elicit specific transformation responses is a property of the lymphocyte and not the macrophage.

The Effect of Cyclophosphamide on the Ontogeny of the Humoral Immune Response in Chickens

Abstract: Antibody formation and immunoglobulin synthesis were severely depressed in adolescent chickens treated daily with the alkylating agent, cyclophosphamide (Cy), for the first 3 days of extraembryonic life. Most birds failed to produce significant levels of antibodies to three test antigens injected at 7 and 11 weeks of age. Moreover, IgM and IgG levels in the sera of 5 out of 13 Cy-treated birds were less than 0.5% of the immunoglobulin levels found in untreated birds of the same age. The selective nature of Cy suppression on the ontogeny of the humoral immune response was evidenced by the intact graft- vs -host reactivity of peripheral blood cells derived from Cy-treated birds.

Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection : ii. relationship of the anti-lymphocytic choriomeningitis immune response to tissue injury in chronic lymphocytic choriomeningitis disease

Abstract: Tissue injury (chronic disease) associated with persistent LCM infection is apparently caused by the host immune response to the virus. Employing parabiosis or cell transfer from hyperimmune donors to isologous virus carriers, the tissue injury of chronic disease could be initiated and/or intensified. Furthermore, the transfer of anti-LCM antibody to SWR/J carrier mice results in acute necrotizing inflammatory lesions in regions of viral persistence, followed by chronic mononuclear infiltrates quite similar to those seen after the transfer of immune cells. The pathogenesis of the nonglomerular tissue injury of chronic LCM disease is apparently at least in part related to the interaction of circulating anti-LCM antibody with viral antigen at the tissue site. Trapping of circulating virus-antibody complexes in the glomerular filter is apparently the major cause of the glomerulonephritis.

Cellular recognition by mouse lymphocytes in vitro i. definition of a new technique and results of stimulation by phytohemagglutinin and specific antigens

Abstract: The media and culture conditions required for in vitro stimulation of mouse lymphoid cells are described. The medium was arginine-rich and contained heat-inactivated human serum. A component of the human sera necessary for stimulation of the cells was a natural mouse cell agglutinin, which affected both background stimulation and the degree of induced stimulation with phytohemagglutinin (PHA). Absorption of the agglutinin from the human serum rendered the medium incapable of sustaining DNA synthesis in the presence of PHA. The response to PHA of mouse spleen and thymus cells was age-dependent and, although this response was not present at birth, it rapidly rose to adult levels. Spleen cells from mice immunized with bacillus Calmette-Guerin (BCG) or sheep erythrocytes (SRBC) showed increased in vitro reactivity to added purified protein derivative (PPD) or SRBC stroma, dependent on the time of immunization. The dose response curve for the SRBC stroma stimulated, immune spleen cells is compatible with a theory of cell to cell interaction being necessary for an in vitro reaction to antigen. The possible role of the mouse cell agglutinin (AMLG) is discussed.

The role of nonlymphoid accessory cells in the immune response to different antigens.

Abstract: Tissue culture techniques were combined with cell separation procedures to investigate the cellular requirements for a response to antigen, leading to the production of antibody-forming cells. Mouse spleen was dissociated, and the cells were separated into various groups on the basis of density, size, and active adherence. The ability of fractions to initiate a response in vivo, on transfer to an irradiated recipient, was compared to the response in vitro; and this ability was correlated with the presence or absence of phagocytic cells. Two different antigens were studied, sheep erythrocytes (SRC) and polymerized bacterial flagellin (POL). Density distribution analysis of spleen showed a wide density range of cells responding to both antigens in vivo. The same fractions responded to POL in vitro as in vivo. By contrast, only the light density regions responded in vitro to SRC. Response occurred in regions of overlap between lymphocytes and phagocytic macrophages. Separation by active adherence on columns of large glass beads gave a preparation containing large, medium, and small lymphocytes but no detectable phagocytic macrophages and very low levels of phagocytic polymorphs. This lymphocyte preparation responded to both antigens in vivo. In vitro it gave a full response to POL, but no response to SRC. Addition of a small quantity of the adherent fraction, enriched for phagocytic cells, restored response to SRC. The use of strain-specific antisera in a mixed culture containing a C57 phagocytic fraction and CBA lymphocytes showed that the lymphocyte fraction contributed the precursors of the final antibody-forming cells. The accessory cells from C57 spleen banded in the light regions of the density gradient where phagocytic macrophages were found. Irradiated spleen cells also activated the lymphocyte preparation, suggesting that the irradiated host provided the accessory cells for the in vivo response to SRC. Small lymphocytes were purified from spleen by the small glass bead size filtration technique. This sample of small lymphocytes responded less well to POL than the total lymphocyte population, but it responded as well in vitro as in vivo. The small lymphocyte preparation responded in vivo to SRC but not in vitro. Addition of a small quantity of the phagocyte-rich fraction from adherence columns restored the in vitro response to SRC. The results indicated that phagocytic cells are not required in the initiation of an immune response to POL. By contrast some accessory cell, possibly a phagocytic macrophage, is required for a response to SRC. The basis for this marked difference is discussed.

Antibody-mediated suppression of the immune response in vitro. II. A new approach to the phenomenon of immunological tolerance.

Abstract: Immunological tolerance to H antigens of Salmonella adelaide may be induced in vitro by the exposure of mouse spleen cells for 6 hr to an immunogenic dose of polymerized flagellin in the presence of low concentrations of specific antibody. Such antibody-mediated tolerance requires an optimal antigen: antibody ratio for its induction. A shift in this ratio in favor of the antibody concentration results in failure of tolerance induction and leads to immune suppression commonly known as antibody-mediated feedback inhibition which is not analogous to immunological tolerance. Fragment A of flagellin fails to induce immunological tolerance in vitro. Tolerance to polymerized flagellin may however be induced in vitro, provided the spleen cells are exposed to fragment A in the presence of specific antibody for 6 hr. The results are discussed in the light of current theories of the mechanism of tolerance induction.

Linkage between the Poly-L-Lysine Gene and the Locus Controlling the Major Histocompatibility Antigens in Strain 2 Guinea Pigs

Abstract: The data presented demonstrate linkage between the major histocompatibility locus of inbred strain 2 guinea pigs and a „specific immune response gene,” the PLL gene, which controls responsiveness to poly-L-lysine and hapten conjugates of this polypeptide in these animals. This finding extends to another species and to a different immune system the linkage observed in mice between the H2 locus and specific immune response genes at the Ir-1 locus. The general significance of the linkage of specific immune response genes to histocompatibility loci is discussed.

Induction of a hemolysin response in vitro. Interaction of cells of bone marrow origin and thymic origin.

Abstract: The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.

Antibody-mediated suppression of the immune response in vitro. I. Evidence for a central effect.

Abstract: Antibody-mediated suppression of the in vitro immune response to polymerized flagellin of Salmonella adelaide and to sheep erythrocytes was studied at the cellular level. Normal mouse spleen cells, preincubated in vitro with mixtures of antigen and antibody for short periods of time before being washed, did not respond to an optimal antigenic challenge in vitro, whereas similar cells treated with antibody alone gave a normal response. The degree of immune suppression was found to depend on the time of preincubation. Significant immune suppression could be induced in as short a time as 15 min, whereas profound suppression (90%) required the incubation of cells with mixtures of antigen and antibody for 4–6 hr. Mouse spleen cells treated similarly were also unable to respond subsequently to the antigen upon transfer to lethally irradiated hosts, as measured at both the level of the antigen-reactive cell and that of serum antibody production. These results were taken as evidence that in vitro an effect of antibody-mediated suppression occurred at the level of the immunocompetent cell. Similarities between immune tolerance and antibody-mediated suppression in vitro were described, and the significance of the findings discussed in the light of current concepts of the mechanism of antibody-mediated suppression.

Cell to cell interaction in the immune response. V. Target cells for tolerance induction.

Abstract: Collaboration between thymus-derived lymphocytes, and nonthymus-derived antibody-forming cell precursors occurs during the immune response of mice to sheep erythrocytes (SRBC). The aim of the experiments reported here was to attempt to induce tolerance in each of the two cell populations to determine which cell type dictates the specificity of the response. Adult mice were rendered specifically tolerant to SRBC by treatment with one large dose of SRBC followed by cyclophosphamide. Attempts to restore to normal their anti-SRBC response by injecting lymphoid cells from various sources were unsuccessful. A slight increase in the response was, however, obtained in recipients of thymus or thoracic duct lymphocytes and a more substantial increase in recipients of spleen cells or of a mixture of thymus or thoracic duct cells and normal marrow or spleen cells from thymectomized donors. Thymus cells from tolerant mice were as effective as thymus cells from normal or cyclophosphamide-treated controls in enabling neonatally thymectomized recipients to respond to SRBC and in collaborating with normal marrow cells to allow a response to SRBC in irradiated mice. Tolerance was thus not achieved at the level of thelymphocyte population within the thymus, perhaps because of insufficient penetration of the thymus by the antigens concerned. By contrast, thoracic duct lymphocytes from tolerant mice failed to restore to normal the response of neonatally thymectomized recipients to SRBC. Tolerance is thus a property that can be linked specifically to thymus-derived cells as they exist in the mobile pool of recirculating lymphocytes outside the thymus. Thymus-derived cells are thus considered capable of recognizing and specifically reacting with antigenic determinants. Marrow cells from tolerant mice were as effective as marrow cells from cyclophosphamide-treated or normal controls in collaborating with normal thymus cells to allow a response to SRBC in irradiated recipients. When a mixture of thymus or thoracic duct cells and lymph node cells was given to irradiated mice, the response to SRBC was essentially the same whether the lymph node cells were derived from tolerant donors or from thymectomized irradiated, marrow-protected donors. Attempts to induce tolerance to SRBC in adult thymectomized, irradiated mice 3–4 wk after marrow protection, by treatment with SRBC and cyclophosphamide, were unsuccessful: after injection of thoracic duct cells, a vigorous response to SRBC occurred. The magnitude of the response was the same whether or not thymus cells had been given prior to the tolerization regime. The various experimental designs have thus failed to demonstrate specific tolerance in the nonthymus-derived lymphocyte population. Several alternative possibilities were discussed. Perhaps such a population does not contain cells capable of dictating the specificity of the response. This was considered unlikely. Alternatively, tolerance may have been achieved but soon masked by a rapid, thymus-independent, differentiation of marrow-derived lymphoid stem cells. On the other hand, tolerance may not have occurred simply because the induction of tolerance, like the induction of antibody formation, requires the collaboration of thymus-derived cells. Finally, tolerance in the nonthymus-derived cell population may never be achieved because the SRBC-cyclophosphamide regime specifically eliminates thymus-derived cells leaving the antibody-forming cell precursors intact but unable to react with antigen as there are no thymus-derived cells with which to interact.

Separation of normal and immune lymphoid cells by antigen-coated columns : antigen-binding characteristics of membrane antibodies as analyzed by hapten-protein antigens

Abstract: Specific fractionation of immunologically competent cells derived from normal or immune animals was achieved by filtration through antigen-coated bead columns. This selective retention of the relevant reactive cells could be shown to produce a cell population, which after passage through the column would behave like a suspension rendered immunologically tolerant by "classical" means. The immunologically specific elimination of potential antibody-forming capacity of the filtered cells could be shown to affect the IgM and the IgG system to a similar extent. Analysis of the binding characteristics of the membrane antibodies responsible for this selective retention indicate striking similarities to those of the humoral antibodies produced against the antigen. Thus, the surface receptor could distinguish isolated haptenic groups on a "foreign" carrier background and the receptor of the hapten-reactive cells in the present system (high-rate antibody-forming cells against NIP) failed to combine with carrier specific determinants in analogy with the binding behavior of the serum anti-hapten antibodies. The binding of anti-hapten reactive cells to bead-attached haptens could be specifically inhibited by the presence of free hapten in the columnar fluid during cellular filtration. The results strongly suggest that the potential humoral antibody-forming cell has preformed receptors on its outer surface with binding characteristics, indicating similarity, if not identity, to those of the eventual product of the cell, the humoral antibody.

Immunity in cutaneous leishmaniasis of the guinea-pig.

Abstract: This paper describes the course of infection and development of immunity in guinea-pigs after intradermal inoculation of Leishmania enriettii, and the use of in vivo and in vitro techniques to characterize the immunological response to infection and artificial immunization. Inoculation of 106 amastigotes into the ear produced a nodule which ulcerated in 2–3 weeks and healed in 8–16 weeks. 8% of animals developed cutaneous metastases which healed with the original lesions. Histology of the primary lesions showed epidermal necrosis overlying a mass of parasitized macrophages which, after 4–6 weeks, became surrounded and infiltrated by lymphocytes. Histological changes in the draining lymph node began after 3 days and proceeded for 6 weeks; both germinal centres and paracortical areas were hyperplastic and the medulla contained many plasma cells. Superinfection produced an `isophasic' lesion, but reinfection after healing elicited only a delayed hypersensitivity response. Artificial immunization with soluble and insoluble antigenic extracts of L. enriettii in Freund's complete adjuvant partially protected against infection; extracts of other leishmanial species failed to protect. Immunological paralysis, attempted with intravenous injections of soluble antigen, increased the severity of subsequent infection. Both infection and immunization were accompanied by delayed hypersensitivity which could be transferred passively by lymphoid cells. Cell-mediated immunity was studied in vitro by the ability of soluble leishmanial antigens to transform lymphocytes, to inhibit macrophage migration, and to induce the production of lymphokine factors from lymphocytes of sensitized animals. A target cell system was devised in which sensitized lymphocytes destroyed monolayers of parasitized macrophages. Cross reactivity of leishmanial with mycobacterial antigens was shown in skin tests and in target cell destruction, but not in cell transfer or in the other cell culture systems. The phagocytic activity of peritoneal macrophages from recovered animals was increased for homologous but not for heterologous species of Leishmania; the growth of ingested organisms was not however reduced. Circulating antibodies were not demonstrated by passive cutaneous anaphylaxis, or by agglutination of antigen coated sheep erythrocytes, in the sera of infected or convalescent animals, although some convalescent animals showed active cutaneous anaphylaxis. However, antibodies were demonstrated by both these techniques in immunized animals, which also showed anaphylactic and Arthus hypersensitivity when skin tested with the soluble antigens. The results are taken to indicate that cellular mechanisms are prominent in the development of immunity of the guinea-pig against L. enriettii, and ways in which the host may eliminate the parasite are discussed. It is concluded that this model provides an experimental counterpart of human cutaneous leishmaniasis and that it is suitable for the analysis of the role of cell-mediated specific immunity in resistance to intracellular infection.

A Certain Symmetry : Histocompatibility Antigens compared with Immunocyte Receptors

Abstract: Recent work on cancer immunity suggests that the character and diversity of cell membrane antigens may be controlled by processes similar to those concerned with the origin of specific patterns in the immune system.

The role of immunoglobulins in lymphocyte-mediated cell damage, in vitro. I. Comparison of the effects of target cell specific antibody and normal serum factors on cellular damage by immune and non-immune lymphocytes.

Abstract: Rats were immunized by intraperitoneal injection of target cells (Chang cells). Five days after immunization antibody, lytic to Chang cells in the presence of complement, which separated in Peak I on Sephadex G-150 was detectable. At the same time antibody lytic to Chang cells in the presence of lymphoid cells from unimmunized animals and separating in Peak II on Sephadex G-150 was found. Both antibodies reached a maximum titre between 2 and 4 weeks after immunization. At that time the antibody dependent upon normal lymphoid effector cells was active at more than 1000 times the maximal dilution of complement dependent antibody activity. The Peak II antibody affected both im-immune and non-immune Black Hooded (BH) rat spleen cells in a similar way. Normal rat serum markedly enhanced target cell survival. This effect did not require heat labile components of complement. The enhancing capacity of immune serum appears to be greater than that of normal serum; the reason for this is discussed, but the problem is not resolved.

The Role Of Immunoblasts In Host Resistance And Immunotherapy Of Primary Sarcomata

Abstract: Publisher Summary This chapter focuses on the central role of immunoblasts in host resistance and immunotherapy of primary sarcomata. The demonstration that nearly all neoplastic cells in experimental animals, however induced, contain antigens absent from normal adult cells in their plasma membrane has focused attention on the mechanisms that allow tumor cells to escape immunological destruction by the host. The discussion is restricted to tumors that are demonstrably antigenic in the host in which they are growing. Even within this restricted field, the suppression of an established malignant process by natural immune reaction is only observed in experimental animals under special circumstances such as in tumors resulting from the exposure of adult animals to an oncogenic virus. The effector mechanisms of immune response are confined by the limits imposed by the physiological properties of different anatomical sites, as well as by the amounts of cytotoxic cells and antibodies that are potentially available. Most of the experimental tumor immunology, which is presented in the chapter, is based on the study of primary fibrosarcomata induced in rats by the subcutaneous implantation of a pellet of 3:4 benzpyrene. Immunoblasts are responsible for propagating and disseminating the immune response throughout the body and can, thus, generate high titers of specific antibody in the blood serum when transferred to an unimmunized, syngeneic recipient.

Some biochemical aspects of the immune macrophage.

Abstract: Some of the biochemical properties of mouse peritoneal macrophages immune to Corynebacterium ovis were characterised. Total cellular protein of immune cells exceeded that of normal phagocytes by 1·85 times. The activities of 7 hydrolytic enzymes, acid phosphatase, β-glucuronidase, Cathepsin D, lysozyme, BPN-ase, MN esterase and aryl sulphatase were measured in lysed cell suspensions and monolayer cultures. Immune macrophages possessed substantially higher levels of these enzymes than did normal cells. No one enzyme was significantly more associated with the development of cellular immunity than another. Resting immune macrophages consumed significantly less oxygen than normal cells required but were twice as active in glycolysis. ATP levels, in agreement, were 5 times higher in normal macrophages whereas ATP-ase activities were equivalent. Normal macrophages were approximately twice as active in protein synthesis measured by the in vitro incorporation of 14C L-glycine by monolayer cultures than were immune cells. These results were considered in the light of known morphological differences between the 2 cells noted at the ultrastructural level.

The role of lysosomes in immune responses.

Abstract: Publisher Summary This chapter discusses the role of lysosomes in immune responses. Lysosomes are the central part of many studies related to the tissue injury, inflammation, and immunity. Lysosomes can also be considered as the important part of a vacuolar system or an “exoplasmic reticulum” concerned with the digestion of heterologous and autologous material. Although there is a considerable body of evidence implicating macrophages in the afferent limb of the immune response, their exact role is not clear. Macrophages may prevent excess antigen from paralyzing lymphocytes that act as convenient carriers of antigen throughout the body, concentrate and retain antigen over longer periods of time, present antigen to responsive cells, degrade antigen into active subunits, convert crude antigen into a better immunogen, translate antigen into specific information, or exert some nonspecific effect on antigen-reactive cells that allow them to perform properly. Trapping of antigens by reticular cells may not be the only mechanism responsible for their localization in follicles. Recently, there is a new subpopulation of lymphocytes that binds antigen–antibody complexes in the presence of modified complement. Because the bulk of this subpopulation, termed “complement receptor lymphocytes,” resides in the follicular areas of peripheral lymphoid tissue, it may seem that the lymphocytes contribute to antibody mediated retention of antigens by lymphoid follicles.

Studies on the immune response to a characterized antigenic determinant of the tobacco mosaic virus protein

Abstract: The following peptides have previously been shown to bind specifically with antibodies to TMVP: ( a ) An eicosapeptide representing residues 93–112 of TMVP and having the sequence Ileu-Ileu-Glu-Val-Glu-AspNH2-GluNH2-Ala-AspNH2-Pro-Thr-Thr-Ala-Glu-Thr-Leu-Asp-Ala-Thr-Arg. ( b ) Its C-terminal decapeptide. ( c ) Its C-terminal pentapeptide. ( d ) N -octanoyl-C-terminal-tripeptide. ( e ) (Lys)4-C-terminal-pentapeptide. ( f ) (Lys)7 C-terminal-pentapeptide. The present communication deals with the investigation of several parameters of the immunological activity of the peptides. The results show that none of the peptides tested were immunogenic in guinea pigs, nor did they stimulate the incorporation of 14C-thymidine by spleen cells derived from TMVP-primed animals. Results also showed that all of the peptides tested could elicit specific delayed and immediate skin reactions in TMVP-sensitized guinea pigs, and furthermore, that the peptides could specifically inhibit the migration of peritoneal exudate cells derived from these animals. The elicitation of delayed skin reactions and the ability to inhibit migration of peritoneal exudate cells were independent of carrier specificity.