Showing papers on "Immune system published in 1968"

Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs.

Abstract: The in vitro cytotoxic effect of spleen cells of mice immunized by tumour allografts was studied by measuring target cell inactivation as a function of release of radioactive label (51Cr) or loss of cloning efficiency. When sensitized lymphoid cells were incubated with target cells at a ratio of 100:1, up to 90 per cent of the incorporated label was released within 6–9 hours, while the number of clone-forming cells was reduced by up to 99 per cent in the same time period. Isoantiserum from the graft recipients, as well as its 19S and 7S fractions, protected target cells against the toxic effect of the spleen cells, but a lipoprotein antigen isolated from the tumour cells failed to inhibit the cytotoxic reaction. Target cell lysis as measured by specific release of 51Cr was partially inhibited by actinomycin-D and by cycloheximide at concentrations which effectively blocked DNA-dependent RNA and protein synthesis.

Regulatory effect of antibody on the immune response.

Abstract: Publisher Summary This chapter deals with the regulatory effect of antibody on antibody formation. It is possible to analyze those factors that influence the process of antibody synthesis. Certainly antibody, the end product of the process, is among the most potent and specific of inhibitors of antibody synthesis. That this inhibition results from the interaction of antibody with antigen neutralizing the immunogenicity of the latter seems likely, and the evidence for this is critically presented. The potential use of this mechanism is suggested by its effectiveness in the enhancement of tissue grafts, its use in the therapeutic prevention of anti-D antibody responses in mothers of Rh-incompatible fetuses, and its possible role in the induction of some types of immunological tolerance. The immune response represents a predictable series of events, characterized by the sequential appearance of several classes of γ-globulin antibody molecules and the expression of various cell-mediated immune reactions. One mechanism is described for regulating the concentration of immunoglobulin (IgG) in the circulation. The mechanism operates by increasing the catabolic rate of IgG when the serum concentration is abnormally increased as, for example, in multiple myeloma. Two mechanisms are described both of which regulate the immune response. These are alteration of antigenic stimulation and suppression of the immune response by passive transfer of specific antibodies prior to or shortly after administration of antigen.

Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes.

Abstract: The number of discrete hemolytic foci and of hemolysin-forming cells arising in the spleens of heavily irradiated mice given sheep erythrocytes and either syngeneic thymus or bone marrow was not significantly greater than that detected in controls given antigen alone. Thoracic duct cells injected with sheep erythrocytes significantly increased the number of hemolytic foci and 10 million cells gave rise to over 1000 hemolysin-forming cells per spleen. A synergistic effect was observed when syngeneic thoracic duct cells were mixed with syngeneic marrow cells: the number of hemolysin-forming cells produced in this case was far greater than could be accounted for by summating the activities of either cell population given alone. The number of hemolytic foci produced by the mixed population was not however greater than that produced by an equivalent number of thoracic duct cells given without bone marrow. Thymus cells given together with syngeneic bone marrow enabled irradiated mice to produce hemolysin-forming cells but were much less effective than the same number of thoracic duct cells. Likewise syngeneic thymus cells were not as effective as thoracic duct cells in enabling thymectomized irradiated bone marrow-protected hosts to produce hemolysin-forming cells in response to sheep erythrocytes. Irradiated recipients of semiallogeneic thoracic duct cells produced hemolysin-forming cells of donor-type as shown by the use of anti-H2 sera. The identity of the hemolysin-forming cells in the spleens of irradiated mice receiving a mixed inoculum of semiallogeneic thoracic duct cells and syngeneic marrow was not determined because no synergistic effect was obtained in these recipients in contrast to the results in the syngeneic situation. Thymectomized irradiated mice protected with bone marrow for a period of 2 wk and injected with semiallogeneic thoracic duct cells together with sheep erythrocytes did however produce a far greater number of hemolysin-forming cells than irradiated mice receiving the same number of thoracic duct cells without bone marrow. Anti-H2 sera revealed that the antibody-forming cells arising in the spleens of these thymectomized irradiated hosts were derived, not from the injected thoracic duct cells, but from bone marrow. It is concluded that thoracic duct lymph contains a mixture of cell types: some are hemolysin-forming cell precursors and others are antigen-reactive cells which can interact with antigen and initiate the differentiation of hemolysin-forming cell precursors to antibody-forming cells. Bone marrow contains only precursors of hemolysin-forming cells and thymus contains only antigen-reactive cells but in a proportion that is far less than in thoracic duct lymph.

Immunologic Factors and Clinical Activity in Systemic Lupus Erythematosus

Abstract: To clarify the association between certain immunologic factors and clinical activity in patients with systemic lupus erythematosus, 96 patients were studied. Those with antibodies to deoxyribonucleic acid (DNA) or heat-denatured DNA, or with serum complement levels of less than 50 C′H50 units per ml, were more likely to have renal involvement. Very low complement levels and high titers of complement-fixing antibodies to DNA were always associated with active disease, especially active renal disease, whereas the absence of these abnormalities usually indicated inactive renal disease. A 50 per cent fall in serum complement levels in 22 patients was accompanied by, or preceded the onset of, active nephritis in 19 patients. These serologic factors may thus reflect the in vivo formation of immune complexes that cause nephritis. Serial immunochemical observations may be useful in the management of patients with systemic lupus erythematosus.

Antigens in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles.

Abstract: This paper describes the trapping of antigen in lymphoid follicles of rat popliteal lymph nodes as revealed by electron microscopic radioautographs following injection of (125)I-labeled Salmonella adelaide flagella and other materials. The antigen was taken up vigorously, and to an approximately equal extent, by both primary and secondary follicles. The rate of uptake was faster in preimmunized than in virgin adult rats. The bulk of the antigen in follicles was extracellular, and persisted in this location for at least 3 wk. Label was most frequently found at or near the surface of fine cell processes. Many of these were branches of dendritic follicular reticular cells. Such processes interdigitated with equally fine processes of lymphocytes, creating an elaborate meshwork. In some cases, antigen was found between lymphocytes which appeared to be in close apposition. Occasionally, a few grains appeared over lymphocyte nuclei and study of serial sections suggested that this probably represented true entry of small amounts of antigen into lymphocytes. The characteristic "tingible body" macrophages (TBM) of germinal centers appeared to play only a secondary role in follicular antigen retention. They showed degrees of labeling over their phagocytic inclusions varying from negligible to moderately heavy. Moreover, follicles lacking or poor in TBM retained antigen just as effectively as those containing numerous TBM. The hypothesis is advanced that TBM may be derived from monocytes that migrate down from the circular sinus. Follicular localization of three other materials was also studied, though not in such detail. These were (125)I-HSA complexed to anti-HSA: (125)I-labeled autologous IgG; and (125)I-monomeric flagellin. All of these showed the basic features of intercellular, membrane-associated deposition noted with (125)I-flagella. The role of follicular antigen depots in immune induction is discussed. The tentative conclusion is reached that follicular antigen in a primary follicle encounters natural antibody on the surface of certain antigen-reactive lymphocytes. The resultant reaction causes blast cell transformation and eventually the genesis of a germinal center.

Competition of 19s and 7s antigen receptors in the regulation of the primary immune response

Abstract: Prior to sheep red cells (SRC) mice were given 7S or 19S anti-SRC antibodies or mixtures of both. All 7S preparations suppressed the immune response. All 19S preparations enhanced the primary response, as measured by an up to 15-fold increase in the number of PFC per spleen. Results obtained with mixtures showed that 7S and 19S antibodies are competitive in their effect. The kinetics of the appearance of PFC in the mouse spleen after injection of SRC suggest that the depressive effect of 7S antibody simulates a reduction in SRC dose, whereas the enhancing effect of 19S antibody appears as a temporary increase in the rate at which PFC appear. Antibodies from one animal species are quite effective in another species.

Lymphocyte in vitro cytotoxicity: mechanisms of immune and non-immune small lymphocyte mediated target L cell destruction.

Abstract: Mutual in vitro cell destruction resulted when nonimmune or immune mouse or rat small lymphocytes were attached to genetically dissimilar target cells with phytohemagglutinin or xenogeneic antibody The ability to induce this reaction resided only with viable cells of lymphoid origin The step(s) leading to aggressor-target cell destruction observed in these studies is suggested by the following sequence: a) attachment of the aggressor cell to the target cell, b) membrane site(s) interaction between the lymphocyte and target cell which serves as a recognition step and if the target cell is not recognized as “self,” d) a “triggering” of aggressor lymphocyte activity which results in enlargement of the lymphocyte and release of a soluble toxic factor termed “lymphocyte cytotoxic factor” (LCF) LCF may be the agent responsible for the death of both cells

Lymphocyte Cytotoxicity in vitro : Activation and Release of a Cytotoxic Factor

Abstract: WE have reported that cell contact per se is not sufficient to explain the rapid and dramatic in vitro destruction of target L cells observed when they are treated with immune lymphocytes or non-immune phytohaemagglutinin (PHA)-stimulated lymphocytes derived from various inbred mice1. Instead, cell contact is apparently involved in the induction of additional steps, which result in the release of a soluble toxic factor(s). The presence of the factor(s) is related to the ability of the aggressor cell to promote the destruction of target L cells. Once released, the factor has a non-specific toxic effect when tested on mammalian cells of many genotypes2. Lymphocyte-induced destruction of target cells seems to be related to the capacity of the aggressor lymphocyte to undergo enlargement and form blast cells. With these observations in mind we decided to treat lymphocytes in vitro by various techniques known to induce blast cells, and to test the culture medium for the presence of cytotoxic material.

Vascular Injury and Lysis of Basement Membrane in vitro by Neutral Protease of Human Leukocytes

Abstract: Frozen and thawed granules of human, peripheral-blood leukocytes rapidly produce hemorrhage when injected into animal tissues. The effect is blocked by inhibitors of proteolysis. The granule extract can digest vascular basement membrane in vitro at neutral pH. In addition, basement membranes of blood vessels damaged in vivo by the leukocyte fraction are found to be attenuated when examined by electron microscopy. The proteases of human leukocyte granules differ in several important respects from known lysosomal cathepsins and trypsin-like esterases. Polymorphonuclear neutrophils are a major source of the neutral proteases present in circulating white cells, and release these enzymes during phagocytosis of immune complexes.

Cell to cell interaction in the immune response iii. chromosomal marker analysis of single antibody-forming cells in reconstituted, irradiated, or thymectomized mice

Abstract: Two new methods are described for making chromosomal spreads of single antibody-forming cells. The first depends on the controlled rupture of cells in small microdroplets through the use of a mild detergent and application of a mechanical stress on the cell. The second is a microadaptation of the conventional Ford technique. Both methods have a success rate of over 50%, though the quality of chromosomal spreads obtained is generally not as good as with conventional methods. These techniques have been applied to an analysis of cell to cell interaction in adoptive immune responses, using the full syngeneic transfer system provided by the use of CBA and CBA/T6T6 donor-recipient combinations. When neonatally thymectomized mice were restored to adequate immune responsiveness to sheep erythrocytes by injections of either thymus cells or thoracic duct lymphocytes, it was shown that all the actual dividing antibody-forming cells were not of donor but of host origin. When lethally irradiated mice were injected with chromosomally marked but syngeneic mixtures of thymus and bone marrow cells, a rather feeble adoptive immune response ensued; all the antibody-forming cells identified were of bone marrow origin. When mixtures of bone marrow cells and thoracic duct lymphocytes were used, immune restoration was much more effective, and over three-quarters of the antibody-forming mitotic figures carried the bone marrow donor chromosomal marker. The results were deemed to be consistent with the conclusions derived in the previous paper of this series, namely that thymus contains some, but a small number only of antigen-reactive cells (ARC), bone marrow contains antibody-forming cell precursors (AFCP) but no ARC, and thoracic duct lymph contains both ARC and AFCP with a probable predominance of the former. A vigorous immune response to sheep erythrocytes probably requires a collaboration between the two cell lineages, involving proliferation first of the ARC and then of the AFCP. The results stressed that the use of large numbers of pure thoracic duct lymphocytes in adoptive transfer work could lead to good adoptive immune responses, but that such results should not be construed as evidence against cell collaboration hypotheses. Some possible further uses of single cell chromosome techniques were briefly discussed.

Autologous immune complex nephritis induced with renal tubular antigen. II. The pathogenetic mechanism.

Abstract: The pathogenetic mechanism involved in a form of experimental allergic glomerulonephritis induced by immunization of rats with renal tubular antigen has been investigated. A single immunization with less than a milligram of a crude renal tubular preparation, probably containing less than 25 µg of the specific nephritogenic antigen, is effective in the induction of this form of chronic membranous glomerulonephritis. In the nephritic kidney autologous nephritogenic tubular antigen is found in the glomerular deposits along with γ-globulin and complement. When large amounts of antigen are injected during induction of the disease the exogenous immunizing antigen can also be detected in the glomerular deposits. It appears that this disease results from the formation of circulating antibodies capable of reacting with autologous renal tubular antigen(s) and the deposition of these antibodies and antigen(s) plus complement apparently as immune complexes in the glomeruli. This pathogenetic system has been termed an autologous immune complex disease and the resultant glomerulonephritis has been similarly designated.

Persistence of immunogenicity of antigen after uptake by macrophages.

Abstract: Peritoneal macrophages were cultured for several hours after uptake of 131I-hemocyanin. The cells degraded most of the 131I-labeled protein within 2–5 hr. Their ability to prime lymphocytes of syngeneic mice for a secondary immune challenge remained unchanged for long periods of time despite the loss of more than 90% of the original content of antigen. The persistence of immunogenicity was associated with a small percentage of antigen retained by the cell in a form which was protected from rapid breakdown and elimination.

Tumor-specific transplantation antigens: G. H. A. Clowes memorial lecture.

Abstract: Summary Tumor-specific transplantation antigens capable of inducing rejection responses of variable strength in genetically compatible (syngeneic) hosts, have been demonstrated in most experimental tumors studied by sensitive assay systems with graded challenge inoculum doses. The reactions are particularly clear-cut in tumors induced by chemical carcinogens and oncogenic viruses, but they could also be demonstrated in a number of “spontaneous” tumors of unknown origin. Antigenic cross-reactivity is the rule for tumors induced by a given virus, whereas chemically induced neoplasms tend to show individually distinct antigenic specificity. This opens new avenues of approach for studies on the phenotype of the neoplastic cell. Provided due regard is given to the passenger virus problem, the demonstration of antigenic cross-reactivity in unknown systems may give new clues with regard to possible etiologic relationships. The existence of tumor-specific transplantation antigens raises the paradoxical question of how antigenic tumor cells can grow out in spite of host responses. Neonatal thymectomy increases the incidence of certain chemically and virally induced tumors, indicating that immunologic surveillance normally eliminates potentially neoplastic cells in a fraction of the cases. Its failure in others may be related to the immune status of the primary autochthonous host. This is quite different for different systems; documented situations include full and apparently specific tolerance (demonstrated for certain vertically transmitted oncogenic RNA viruses in their natural hosts, particularly some murine leukemia agents and the mammary tumor agent); nonspecific immunodepression (shown for certain chemical carcinogens), sometimes with a superimposed component of specific antigenic paralysis (indicated for mouse methylcholanthrene-induced sarcomas); nonspecific immunodepression due to aging; and a curious state of inertia characterized by the absence of both tolerance and sensitization (exemplified by most DNA virus-induced tumors or by the Schmidt-Ruppin variant of the Rous agent). This inertia is most liable to be influenced by immunologic reinforcement, although the risk of enhancement must be taken into consideration. The possible therapeutic significance of tumor-specific immune responses still remains to be clarified, but there is good reason to believe that immune responses may contribute to the inhibition of disseminated tumor cells and thus reduce the risk of recurrence, at least in certain systems.

Strain differences in the immune response of mice: I. The neonatal response to sheep red cells

Abstract: Neonatal mice of the inbred strains NZB, Balb/c and C57B1 were injected with sheep, pig or chicken red cells at various ages and antibody plaque-forming cell (PFC) responses in their spleens measured. Marked strain differences were found, notably a high early response by NZB mice to sheep cells. Hybrid and backcross experiments suggested that this was genetically controlled by at least three genes. C57B1 mice were late in developing a response to all of the antigens tested. The kinetics of the PFC responses were interpreted as favouring an explanation not involving cell division in response to antigen. Thymectomy at birth reduced the PFC responses in 1-month-old mice of all three strains to the same low level, while thymectomy after 7 days left the PFC responses intact. It is argued that the thymus must be present for strain-specific immune responses to develop.

A Quantitative Difference in the Immune Response between Male and Female Mice

Abstract: SummaryThe immune response to a protein antigen (BSA, bovine serum albumin) was compared in male and female mice. It was found that female mice developed a stronger and longer lasting immune response and that female mice were more responsive to small doses of antigen. An explanation based on the effect estrogens have on phagocytosis is discussed.

Effect of Bursectomy and Thymectomy on the Responses of Chicken Peripheral Blood Lymphocytes to Phytohaemagglutinin

Abstract: THE immunological significance of the transformation of lymphocytes by phytohaemagglutinin (PHA) has not been clearly denned. PHA stimulates cells other than lymphocytes1–3 and there is evidence to suggest that the response of lymphocytes is not dependent on earlier sensitization to PHA itself4. None the less, transformation seems to be related to the immunological competence of the responding lymphocytes; thus this response is greatly diminished in children with congenital absence of the thymus gland, associated with impaired immune responses5,6.

Rejection of renal allografts: specific immunologic suppression.

Abstract: Kidneys were transplanted across a major genetic barrier (Ag-B locus), from LewisxBN F 1 hybrid rats into bilaterally nephrectomized Lewis rats. Survival of grafts is prolonged (indefinite?) in rats treated with a combination of (i) intravenous injection of donor spleen cells 1 day before the graft, and (ii) passive immunization with antiserum prepared in rats of the recipient strain against donor spleen and lymph-node cells. The recipient9s immune response to other antigens is not impaired.

The immune response of mice to antigen in macrophages.

Abstract: Peritoneal macrophages obtained following an injection of proteose peptone, and after uptake of Maia squinado haemocyanin were transferred to syngeneic hosts. Immunogenicity was tested by the capacity of macrophages containing the antigen to prime normal or irradiated (660–700 r) recipients for a secondary immune challenge. The immunogenicity of macrophages containing antigen depended on interaction with immunocompetent lymphoid cells since irradiated hosts were unresponsive unless normal lymphoid cells were also supplied. For optimal immune response the live macrophages had to gain access to lymphoid organs. Depending on the amount of antigen transferred with the macrophages, the recipient mice synthesized on secondary challenge 7S and/or 19S antibody. The kinetics of response to the antigen in macrophages were similar to those seen when using free soluble material except for some quantitative differences. Although the immune response was dependent on the total dose of antigen transferred with the macrophages, somewhat higher antibody titres were obtained with macrophages having a high antigen—cell ratio. Antigen in macrophages could elicit a secondary response in primed mice. The immunogenicity of macrophage-held haemocyanin was not impaired by X-irradiation of macrophage donors.

Antigens in immunity. XIV. Electron microscopic radioautographic studies of antigen capture in the lymph node medulla

Abstract: Details of antigen trapping and processing in the rat lymph node have been investigated by the technique of high resolution radioautography. A series of 24 adult rats was injected with 20 microg of (125)I-labeled Salmonella adelaide flagella, given as either a primary or a secondary stimulus into one hind foot-pad. At intervals ranging from 3 min to 3 wk, rats were killed and the popliteal nodes were processed for electron microscopic radioautography using Kodak NTE emulsion. The present paper deals with events in the lymph node medulla, and an accompanying report describes the radically different behavior of antigen in the cortical follicles. In the medulla, lightly labeled granulocytes were transiently encountered, but by far the greatest bulk of antigen was in macrophages. Antigen entered these cells in two ways: by direct penetration of the plasma membrane; and by pinocytosis. In either case, the antigen rapidly became surrounded by tiny vesicles which may have represented Golgi-derived "protolysosomes." Vacuolar fusion ensued and a series of progressively larger and more complex antigen-containing "phagolysosomes" was formed. Substantial amounts of antigen could be detected in such bodies for at least 3 wk. The antigen injection, as expected, caused extensive plasma-cytopoiesis. No evidence of label in plasma cells was obtained. No special anatomic relationship between plasma cells and antigen depot sites was discovered. These results are briefly discussed in relation to current theories of immune induction.

The Immunodepressive Action of Lymphocytic Choriomeningitis Virus in Mice

Abstract: Summary Adult mice infected with LCM virus showed a temporary depression in antibody response to sheep red cells, and fewer antibody-forming cells were present in the spleen. There was also a reduction in antibody response to HSA, and decreased susceptibility to systemic anaphylaxis after immunization with OVA. Infection with either ectromelia or cowpox virus did not lead to immunodepression. Following infection with LCM virus in the neonatal period, mice showed a depressed antibody response to sheep red cells during the first few weeks of life, with recovery to normal responsiveness when they became adult. Mice from carrier colonies, in contrast, had normal immune responses whether immature or adult. Ectromelia virus was much more lethal for mice that had been infected a week earlier with LCM virus, and this was attributed to a reduction in the immune response to ectromelia infection. When mice immune to ectromelia were infected with LCM virus and subsequently challenged in the footpad with a large dose of ectromelia virus they survived, but failed to control the growth of virus at the site of challenge. They also showed reduced immune foot swelling compared with control mice, a finding which suggests impaired expression of delayed hypersensitivity. Mice infected neonatally with LCM virus and then 2 weeks later with cowpox virus showed an increase in survival rate, but a decreased footpad response to infection and decreased ability to withstand later challenge with ectromelia virus.

Cell to cell interaction in the immune response. IV. Site of action of antilymphocyte globulin.

Abstract: In this series of papers it has been shown that the immune response of mice to sheep erythrocytes requires the participation of two classes of lymphoid cells. Thymus-derived cells initially react with antigen and then interact with another class of cells, the antibody-forming cell precursors, to cause their differentiation to antibody-forming cells. Antilymphocyte globulin depressed the ability of mice to respond to sheep erythrocytes. This effect was more marked when the antigen was injected intraperitoneally than intravenously, and occurred only when the antilymphocyte globulin was given before or simultaneously with antigen. Injection of thymus cells restored to near normal the ability to respond to an intravenous injection of sheep erythrocytes. Spleen cells from antilymphocyte globulin-treated mice gave a weak adoptive immune response in irradiated recipients. The addition of thymus cells however enabled a response similar to that given by normal spleen cells. When thymectomized irradiated recipients were used, normal spleen cells continued to give a higher response to a challenge of sheep erythrocytes at 2 and 4 wk postirradiation than did spleen cells from ALG-treated donors. This result is more consistent with the notion that thymus-derived target cells are eliminated, rather than temporarily inactivated, by antilymphocyte globulin. These findings suggest that, in vivo, antilymphocyte globulin acts selectively on the thymus-derived antigen-reactive cells.

Studies on the Ontogeny of the Mouse Immune System: II. Immunoglobulin-Producing Cells

Abstract: Summary It has been shown that cells which have the potential to differentiate into immunoglobulin-producing cells appear in the yolk sac, liver and caudal half of the embryo by the 9th day of gestation. Late in pregnancy these cells are found in the thymus, gut, lung, spleen, femur and peripheral blood. Certain of the data suggest that immunoglobulin-producing cell lines and those cells which mediate cell-bound immune responses arise early in gestation as separate cell populations. It has been shown that immunoglobulin synthesis per se is independent of the thymus.

Phagocytosis in subacute bacterial endocarditis. Localization of the primary opsonic site to Fc fragment.

Abstract: The opsonic properties of immune γG-globulins isolated from patients with chronic septicemic conditions, principally subacute bacterial endocarditis were studied. Opsonic capacity as well as complement-fixing properties of γ-globulins appeared to be closely associated with integrity of Fc structures. Progressive pepsin digestion of immune γG-globulins, as monitored by successive loss of Gm(a) and Gm(b) antigens, abolished opsonic activity. Colostral γA, containing agglutinating antibacterial antibodies but no demonstrable complement-fixing activity, was devoid of opsonic capacity. Reduction of γ-globulin opsonins with 0.01 or 0.1 M mercaptoethanol progressively abolished opsonic activity in parallel with loss of ability of treated γ-globulins to fix complement with bacteria. Treatment of γ-globulin opsonins with 0.01 M sodium metaperiodate also produced complete loss of opsonic capacity in parallel with loss of Gm(b) Fc antigens. These findings, together with antiopsonic effects demonstrable with anti-γ-globulin factors showing primary reactivity with Fc structures, indicate that the opsonic property of immune γ-globulins requires the participation of structures integral to the Fc region of γ-globulin.

Immunosuppression during Acute Murine Cytomegalovirus Infection

Abstract: Summary Murine cytomegalovirus was found to exert a suppressive effect on several components of the primary immune response during acute sublethal infection of 4-week-old mice. Neutralizing antibody against MCMV was delayed in appearance, with only minimal titers as late as 14 days after infection. Primary response to i.p. sheep erythrocytes was profoundly suppressed when antigen was administered during the acute stage of MCMV infection. This suppression affected both serum hemagglutinin levels and 19 S and 7 S hemolytic antibody-forming spleen cells. No splenic cell destruction or deletion could be detected at the dosage of virus used. Maximum suppression of hemolytic plaque formation correlated with peak viral concentration in the spleens of these mice; in the case of serum hemagglutinin, suppression persisted well beyond the time when MCMV had been effectively eliminated from the spleen. Evidence was also obtained to show that delay in processing of antigen could not fully account for the immunosuppression. Thus a nonlethal virus-induced alteration in immune cell competence is postulated. This change may relate antibody and interferon production, inasmuch as both functions are suppressed over the same interval in acute MCMV infection.

Immunity and Intracellular Infection: Resistance to Bacteria in Mice Infected with a Protozoan

Abstract: Mice infected with the intracellular parasite Toxoplasma gondii for periods of as long as 7 months were resistant to challenge with numbers of Listeria monocytogenes and Salmonella typhimurium that were uniformly lethal to normal mice. This resistance did not appear to depend on the strain of toxoplasma employed or the route of inoculation of either toxoplasma or bacteria. Onset of immunity to listeria was demonstrable as early as 1 to 2 days after infection with toxoplasma. Resistance to toxoplasma was not demonstrable in mice immune to listeria. Interferon did not appear to be a mediator of the immunity observed in toxoplasma-infected mice.

Specificity of cellular immune responses. Antigen concentration dependence of stimulation of DNA synthesis in vitro by specifically sensitized cells, as an expression of the binding characteristics of cellular antibody.

Abstract: In vitro antigen stimulation of DNA synthesis in lymph node cultures from immunized guinea pigs can be obtained with very low (10–4 µg/ml) antigen concentrations in the culture fluid. Immunization with low doses of DNP-GPA leads to a cell population capable of being stimulated, on the average, by low concentration of antigen whereas immunization with large antigen doses results in a sensitive cell population requiring, on the average, high antigen concentrations for stimulation. These findings correlate well with the affinity for hapten of the serum antibodies produced by these guinea pigs. Both delayed reactions in vivo and DNA synthesis in vitro can be stimulated by hapten conjugated to proteins different from that used in primary immunization. However the immunizing conjugate is much more effective in terms of antigen concentration required for a given response. These results can be understood in terms of a thermodynamically driven interaction of antigen (or "processed" antigen) with cell-associated antibody.

Cells Involved in the Immune Response

Abstract: The antigen-reactive cells in normal rabbit bone marrow could be isolated from a suspension of marrow cells by passage of the cells through an antigen-sensitized glass bead column. The cells which passed through the column were deficient in antigen-reactive cells directed to the antigen used to sensitize the glass beads, whereas the cells eluted from the column could transfer antibody-forming capacity to irradiated recipients only with respect to the specific sensitizing antigen. Separation of the bone marrow antigen-reactive cells could not be achieved by passage of the cells through nonsensitized glass bead columns or in the presence of excess free antigen in the column. Cells which were retained by, and later eluted from, the antigen-sensitized glass bead columns were mostly small mononuclear cells, whereas cells which passed through the columns were morphologically similar to the original unfractionated bone marrow cell suspension. The data indicate the presence of an antibody or antibody-like structure, with defined immunological specificity, on the surface of the normal bone marrow antigen-reactive cell.