Showing papers on "Immune system published in 1980"

Current concepts in immunology: Regulation of the immune response--inducer and suppressor T-lymphocyte subsets in human beings.

Abstract: HUMAN T lymphocytes are endowed with the capacity to recognize specific antigens, execute effector functions, and regulate the type and intensity of virtually all cellular and humoral immune responses.1 Two major functionally distinct subsets of T cells have been defined with heteroantiserums, autoantibodies, and monoclonal antibodies directed at stable cell-surface antigens.2 3 4 5 6 7 8 Both have been independently programmed for their respective inducer (helper) and cytotoxic/suppressor functions during intrathymic differentiation. This review focuses on the biology of human regulatory T-cell subpopulations in health and disease. Development of T Lymphocytes A thymic microenvironment is necessary for the differentiation of T cells in all species. . . .

Age influence on the immune system.

Abstract: Publisher Summary This chapter discusses many observations indicating a decline in immune function with aging both in experimental animals and in humans. It is evident that a decline in T cell function gradually occurs and this affects the entire immune system. Antibody formation and B cell function appear to be secondarily altered. Various autoantibodies are increased in older experimental animals and humans that may relate to the observed decrease in suppressor cells. Cell-mediated immunity has been analyzed in vivo and in vitro. Various T cell-dependent functions decline with age. Normal immune functions can begin to decline as early as when an individual reaches sexual maturity. The decline is due to changes in the immune cells and their milieu. Cell loss, shift in the proportion of subpopulations, and qualitative cellular changes, the three possible types of changes that can cause the decline, have all been detected.

Sjögren's Syndrome (Sicca Syndrome): Current Issues

Abstract: This paper outlines the clinical, serologic, and immunogenetic differences and similarities of Sjogren's syndrome alone (primary) and Sjogren's syndrome associated with rheumatoid arthritis and systemic lupus erythematosus (secondary). The immunoregulation in Sjogren's syndrome is discussed and the incidence of immune complex-like material, its nature, pathophysiology, and clearance by the Fc recptor of the reticuloendothelial system presented.

Immunological Aspects of Cancer Chemotherapy

Abstract: The immune response may be related to cancer chemotherapy in several ways. First, the patient with advanced cancer may have depressed immunological responsiveness prior to commencement of chemotherapy. Secondly, chemotherapy itself may markedly influence the immune response. Finally, chemotherapy and immunotherapy may be used together in the treatment of specific neoplasms. Before discussing these in detail, it is pertinent to review the immune response and the techniques by which it can be assessed.

T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor.

Abstract: The results of this paper are consistent with the hypothesis that progressive growth of the Meth A fibrosarcoma evokes the generation of a T-cell-mediated mechanism of immunosuppression that prevents this highly immunogenic tumor from being rejected by its immunocompetent host. It was shown that it is possible to cause the regression of large, established Meth A tumors by intravenous infusion of tumor-sensitized T cells from immune donors, but only if the tumors are growing in T-cell-deficient recipients. It was also shown that the adoptive T-cell-mediated regression of tumors in such recipients can be prevented by prior infusion of splenic T cells from T-cell-intact, tumor-bearing donors. The results leave little doubt that the presence of suppressor T cells in T-cell-intact, tumor-bearing mice is responsible for the loss of an earlier generated state of concomitant immunity, and for the inability of intravenously infused, sensitized T cells to cause tumor regression. Because the presence of suppressor T cells generated in response to the Meth A did not suppress the capacity of Meth A-bearing mice to generate and express immunity against a tumor allograft, it is obvious that they were not in a state of generalized immunosuppression.

The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies.

Abstract: Viral infections are often associated with immunodeficiency states. Although T lymphocytes have been thought to suppress the host's response, the precise etiology remains unclear. Therefore, we characterized T lymphocytes from six patients during both acute and convalescent phases of infectious mononucleosis (IM) with monoclonal antibodies (titer, 10(-5) to 10(-7) to antigens restricted to the TH2- helper (T4) and TH2 suppressor (T5) T cell subsets as well as to a common T cell antigen (T3) and HLA-D related Ia antigens. It was found that during acute infectious mononucleosis, there is both activation and increase of suppressor T cells (T5+, Ia+ phenotype). Fuctionally, the acute IM lymphocytes suppress autologous T cell proliferation to antigens as well as pokeweed mitogen driven B cell immunoglobulin production. In contrast, convalescence is associated with a return to normal of T cell subsets and immune function. These results demonstrate that viral infections can preferentially activate a specific T cell subset and suppress the overall human immune response.

The maintenance and regulation of the humoral immune response: persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells.

Abstract: The evidence indicating that antigen can persist for months or years in the spleens and draining lymph nodes of immunized animals is persuasive. This retained antigen Is almost exclusively, if not exclusively, associated with processes of dendritic cells in the follicles of these lymphoid organs (reviewed in this volume by Mandel et al. 1980), However, the role persisting antigen plays, once an immune response has been initiated, is open to question. It has been suggested that persisting antigen and specific antibody are the major components in an antibody feedback system which maintains and regulates antibody levels in vivo (Richter et al. 1965, Britton & MoUer 1968, Bystryn et at, 1971, Weigle 1975). It is well known that no additional antigen is required to maintain circulating antibody levels in hyperimmunized animals. Even when large volumes of blood are removed, antibody levels soon return to their previous levels. TTiis phenomenon might be explained by assuming that persisting antigen is unable to stimulate antibody synthesis

Duck influenza lacking evidence of disease signs and immune response.

Abstract: Influenza viruses A/duck/Hokkaido/5/77 (Hav7N2), A/budgerigar/Hokkaido/1/77 (Hav4Nav1), A/Kumamoto/22/76 (H3N2), A/Aichi/2/68 (H3N2), and A/New Jersey/8/76 (Hsw1N1) were experimentally inoculated into Pekin ducks. Of these, the influenza viruses of duck and budgerigar origin replicated in the intestinal tract of the ducks. The infected ducks shed the virus in the feces to high titers, but did not show clinical signs of disease and scarcely produced detectable serum antibodies. Using immunofluorescent staining, we demonstrated that the target cells of the duck virus in ducks were the simple columnar epithelial cells which form crypts in the large intestines, especially in the colon. After primary infection, the birds resisted reinfection with the duck virus at least for 28 days, but from 46 days onward they were susceptible to reinfection. These infections were quickly restricted by a brisk secondary immune response, reflected in the rapid appearance of high titers of antibody after reinoculation. In contrat to the avian influenza viruses, the remaining three influenza viruses of human origin did not replicate in the intestinal tract but did cause a serum antibody response.

Thymic nurse cells—Ia-bearing epithelium involved in T-lymphocyte differentiation?

Abstract: The vertebrate thymus has a crucial role in the development and organisation of the immune system. Physiologically, maturation of primitive incompetent precursor cells to immunocompetent T lymphocytes takes place in the thymus1. Recently, evidence has been presented suggesting that the capacity to recognise determinants of the self major histocompatibility complex (MHC), which underlies MHC restriction of T-lymphocyte recognition, is also acquired within the thymus2. Pathologically, T-cell lymphomas are known to arise within the thymus3. In all three cases, it is probable that at least some developmental events require close spatial interactions, if not direct contact, between migrating lymphoid cells and sessile stromal thymus elements. We describe here a state of maximal contact between both thymic cell partners, which might represent certain contact-dependent stages of T-cell development. We found that in all normal mouse and rat strains tested so far, the thymuses contain a sizeable number of huge cells of epithelial origin, which engulf and release up to 50 thymic lymphocytes. As the epithelial cells do not degrade the invading lymphocytes, but may rather provide microenvironmental requirements necessary for lymphocyte proliferation and differentiation, we call them ‘thymic nurse cells’ (TNCs). These TNCs express all the MHC determinants required by a cell involved in the establishment of T-lymphocyte MHC restriction. They express high doses of K/D antigens of the H-2 complex, and equally high doses of I–A region determinants. However, TNCs lack surface immunoglobulin and T-lymphocyte-specific Thy-1 antigen.

A new immunodeficiency disorder in humans involving NK cells.

Abstract: Immunodeficiency disorders have provided much information on the development and interaction of the various B and T lymphoid components in the immune system of man. As the lymphoid system becomes increasingly divided into functional subsets of cells it will be important to find immunodeficiencies affecting newly discovered cell types. Natural killer (NK) cells are a recently described but ill-defined subpopulation of lymphocytes which is thought to play an important part in surveillance against tumour development. Mice homozygous for the beige gene were found to have a selective deficiency in NK function and were more susceptible to transplantation of syngeneic tumours as predicted. We report here that patients carrying the analogous, autosomal recessive Chediak-Higashi (CH) gene have a profound defect in their ability to spontaneously lyse various tumour cells in vitro by either antibody-dependent or independent mechanisms. Since other cell-mediated cytolytic functions were relatively normal, these results suggest that the beige or Chediak-Higashi gene in both man and mouse controls NK function.

Immunity to ticks.

Abstract: Publisher Summary The investigation of acquired immunity to ticks has a long history. It was observed early this century that different breeds of cattle tend to carry different numbers of the tick Boophilus microplus and the first laboratory investigations of immunity were made in the 1930s. These early reports were sporadic and often inconclusive in their results. The chapter discusses the ways in which immunity is expressed and explains the various types of immune responses: antibody formation and complement activation; delayed hypersensitivity; immediate hypersensitivity; and cellular reactions. It also focuses on the nature of the antigens involved and the possibility of artificial immunization. The chapter discusses that “immunity” is used to denote any immunologically mediated response that is disadvantageous to the parasite. Frequently, this immunity is partial in that a proportion of parasites complete their life cycle successfully.

The somatic generation of immune recognition

Abstract: Antibody specificity is determined by structural v-genes that code for the amino acid sequences of the variable regions of antibody polypeptide chains. The present hypothesis proposes that the germ-cells of an animal carry a set of v-genes determining the combining sites of antibodies directed against a complete set of a certain class of histocompatibility antigens of the species to which this animal belongs. The evolutionary development of this set of v-genes in phylogeny is traced back to the requirements for cell to cell recognition in all metazoa. The hypothesis leads to a distinction between two populations of antigen-sensitive cells. One population consists of cells forming antibodies against foreign antigens; these lymphocytes have arisen as mutants in clones descending from lymphocytic stem cells which expressed v-genes belonging to the subset (subset S) coding for antibody against histocompatibility antigens that the individual happens to possess. The other population consists of allograft rejecting lymphocytes that express v-genes of the remaining subset (subset A) coding for antibody against histocompatibility antigens of the species that the individual does not possess. The primary lymphoid organs are viewed as mutant-breeding organs. In these organs (e. g. in the thymus), the proliferation of lymphocytes expressing the v-genes of subset S and the subsequent suppression of the cells of these “forbidden” clones, leads to the selection of mutant cells expressing v-genes that have been modified by spontaneous random somatic mutation. This process generates self-tolerance as well as a diverse population of antigen-sensitive cells that reflects antibody diversity. The proliferation in the primary lymphoid organs of lymphocytes expressing v-genes of subset A generates the antigen-sensitive cell population that is responsible for allo-aggression. The theory explains how a functional immune system can develop through a selection pressure exerted by self-antigens, starting during a period in early ontogeny that precedes clonal selection by foreign antigens. The hypothesis provides explanations for the variability of the N-terminal regions of antibody polypeptide chains, for the dominant genetic control of specific immune responsiveness by histocompatibility alleles, for the relative preponderance of antigen-sensitive cells directed against allogeneic histocompatibility antigens, for antibody-idiotypes, for allelic exclusion, for the precommitment of any given antigen-sensitive lymphocyte to form antibodies of only one molecular species and for the cellular dynamics in the primary lymphoid tissues.

Analysis of autoimmunity through experimental models of thyroiditis and allergic encephalomyelitis.

Abstract: Publisher Summary This chapter presents the relationship between the normal state of self-tolerance and its abnormal corollary, autoimmunity. The several possible bases for loss of self-tolerance, including failure of immune regulation and abnormal presentation of potential self-antigens, are considered in terms of current understanding of cellular and humoral immune processes. A particularly thorough evaluation of suppressor cells and their possible role in self-tolerance and autoimmunity is presented. The pathogenic mechanisms that may be involved in autoimmune disease are examined in the light of two familiar experimental models, allergic encephalomyelitis and autoimmune thyroiditis. The pathogenic potential of cellular autoimmune responses in encephalomyelitis, on the one hand, and of autoantibody responses in thyroiditis, on the other, indicates the very different pathogeneses, which may operate in autoimmunity. The various mechanisms that are responsible for the loss of tolerance to self antigens can be divided into three general categories. First, abnormalities may occur in the regulatory mechanisms that control the normal immune response. Second, a component of self that was once sequestered and nonimmunogenic may become exposed and presented in an antigenic form to the immune system. Third, a normally tolerated self component may for some reason circumvent the prevailing regulatory mechanisms and activate one or more arms of a normal immune system. Numerous factors are involved in autoimmune diseases including genetic control at major histocompatibility complex (MHC) and non-MHC loci, immunologic regulatory mechanisms, self-nonself recognition, and logistics and/or nature of the target autoantigens.

Alteration of T and null lymphocyte frequencies in the peripheral blood of human opiate addicts: in vivo evidence for opiate receptor sites on T lymphocytes.

Abstract: Street opiate addiction produces a significant depression in the absolute number of total T lymphocytes in peripheral blood as measured by the ability of the lymphocytes to rosette sheep red blood cells (SRBC). Associated with the decrease in T cells, there is an increase in the absolute number of null lymphocytes but no significant changes in B lymphocytes or total white blood cell count. The T cell values for 2 different populations of addicts (n = 12 and 32) are 31.8% and 23.1%, whereas the null cell values are 51.1% and 57.6%, respectively. The values for comparable control populations (n = 18 and 10) are: T% = 70.7% and 67.4%, and null % = 9.2% and 14.5%. Self-reported use of marihuana does not significantly alter the distribution of cell populations. A 1- to 3-hr incubation of addicted-derived lymphocytes with 10(-6) to 10(-7) M Naloxone reverses both T cell depression and null cell increase by allowing the null cells to express SRBC receptors. Cyclic AMP and dibutyryl cyclic AMP can also convert the null cells to T cells. The conversion of null to T lymphocytes has additionally been measured by monitoring the increase in PHA-stimulated growth in 72-hr cultures as determined by tritiated thymidine incorporation into DNA. These results support the hypothesis that opiates can alter T lymphocyte number and function in vivo, and that this alteration may produce a significant degeneration in the immune competence of street opiate addicts.

Relapses in Wegener's granulomatosis: the role of infection.

Abstract: Out of 20 relapses that occurred in patients with Wegener's granulomatosis, nine were provoked by bacterial or viral infection. Seven of these occurred during maintenance treatment in response to infection with common pathogens, and treatment of the infection alone was insufficient to produce remission. Circulating immune complexes were seen only in relapses due to infection and rarely in infections that occurred without relapse. A possible mechanism for infection-provoked relapses is that infection-derived complexes reactivate disease; alternatively, the acute-phase or cellular response to infection may enhance quiescent disease. Infection may exacerbate Wegener's granulomatosis and other autoallergic diseases, but whether it does so by a common mechanism is not known and further study is required.

The experimental foundations of modern immunology

Abstract: The Concept of Immunization Structure of the Immune System Resolution of the Basic Structure of Immunoglobulins The Properties and Fine Structure of Immunoglobulins Genetic Basis of Immunoglobulin Structure Structure - Function Relationships in Antibody Molecules Complement Historical Development of the Concept of Major Histocompatibility Gene Complexes Genetic Organization of the Major Histocompatibility Complexes of Mice and Humans Biochemistry and Molecular Genetics of Major Histocompatibility Gene Complexes Lymphocyte Subpopulations The Basic Biology of T Cells and B Cells The Humoral Immune Response Cell-Mediated Cytotoxicity The Role of the Thymus in Development of the T-Cell Receptor Repertoire Immunity to Infection Reactions of Immunological Injury: Hypersensitivity and Inflammation Autoimmunity Clinical Organ Transplantation Immunity and Cancer Index.

Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages.

Abstract: Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (M phi). Acquisition of Ia paralleled M phi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal M phi was lost during the 1st d of culture. In the continued presence of immune LK, Ia was re-expressed on virtually all M phi by the 2nd and 3rd d. Alternatively, > 95% Ia negative populations were obtained by culturing the cells 3 d; then, addition of LK induced Ia on most cells within 1 d. Once induced, Ia persisted on the M phi surface for at least 2 d. [35S]methionine radiolabeling indicated that immune LK selectively increased radiolabeling of M phi Ia, again with other non-MHC-linked plasma membrane polypeptides as controls. LK-induced Ia-bearing M phi were tested as primary mixed leukocyte reaction stimulators. 1 x 10(5)-2 x 10(5) M phi did not stimulate 4.5 x 10(6) responding T cells, whereas 10(4) dendritic cells induced strong responses, as previously described. Because Ia-positive M phi do not actively sensitize T cells in a model immune response, we propose that M phi MHC products serve primarily as recognition sites for previously sensitized T cells, thereby enhancing T cell-mediated M phi activation.

Immunologic Abnormalities in Sarcoidosis

Abstract: Patients with active sarcoidosis (acute and chronic) have a depression in systemic cell-mediated immunity manifested by a reduction in the number of circulating T cells and impaired responses of these cells to polyclonal mitogens and recall antigens These abnormalities are absent in patients with resolved disease and contrast with heightened B-cell activity The latter includes elevated serum immunoglobulins and the presence of autoantibodies and circulating immune complexes Similarly, many humoral abnormalities (for example, immune complexes) are absent in patients with resolved disease Studies of bronchoalveolar cells have revealed changes that are opposite to what is found in peripheral blood The number of lymphocytes recovered by bronchoalveolar lavage is increased This is mainly due to an increase in the number of T cells and a subpopulation of activated T cells These findings suggest that the lung (when involved) is the site of an immune inflammatory response

T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice.

Abstract: T-cell immunocompetence and diversity are thought to be generated in the thymus1,2. This view is based on the findings that (1) T-cell ontogeny is thymus dependent3,4, (2) the major histocompatibility restrictions of T-cell interactions are phenotypically related to the H–2 type of the thymus5–9, and (3) the phenotypic manifestation of H–2-linked immune responsiveness parallels the restriction elements selected in thymus10–12. However, it is unclear whether pre-thymic cells programmed to develop into T cells do already express a receptor diversity, also whether pre-thymic cells have the potential to react against self-antigens, and whether the mechanism of self-tolerance is initiated in the thymus by either elimination or suppression of self-reactive clones. If it were possible to confer on pre-thymic cells antigen-specific effector functions, the impact of the thymus on the generation of T-cell diversity and function could be analysed in more detail. In mice, the nude mutation lacks a functioning thymus13,14; nu/nu mice possess a thymic rudiment which is epithelial in the embryo15 and a fibrous, cystic remnant in adult15,16; this remnant is not populated by lymphoid cells15–17. At present, the absence of immunocompetent T cells in nu/nu mice is explained by a lack of thymic differentiation and maturation of pre-thymic cells (reviewed in ref. 13). Here we report that injection of allogeneic stimulator cells plus a Lyt 1 T-cell-derived helper factor18,19, termed interleukin 2 (for the system of nomenclature, see ref. 20) allows lymphocytes of nu/nu mice to differentiate in vivo into alloreactive cytotoxic T lymphocytes (CTLs).

The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxim

Abstract: Mice that are unresponsive to lipopolysaccharide (LPS) (strain C3H/HeJ) can be rendered LPS-sensitive by the adoptive transfer of bone marrow cells from LPS-sensitive mice (strain C3H/HeN). This model of adoptive transfer was used to evaluate the contribution of lymphoreticular cells to five effects of endotoxin on the host: immunogenicity, adjuvanticity, lethality, induction of interferon, and induction of colony-stimulated factor. C3H//HeJ mice became sensitive to each of these effects after adoptive transfer of bone marrow cells from C3H/HeN mice. The efficacy of transfer was directly proportional to the dose of X-irradiation and inversely proportional to the number of surviving host stem cells. The most effective dose of radiation was 850 rad, and C3H/HeN leads to C3H/HeJx chimeras prepared at this dose were as sensitive to LPS for each parameter tested as were the C3H/HeN donors except for a threefold greater resistance to lethality than LPS-responsive C3H/HeN mice. C3H/HeN mice could also be rendered unresponsive to LPS by the adoptive transfer of C3H/HeJ bone marrow cells. C3H/HeN chimeras were resistant to all of the effects of LPS studied except for the induction of colony-stimulating factor. These results demonstrate that lymphocytes and/or macrophages play a primary role in mediating a number of diverse and seemingly unrelated host responses to endotoxin.

Regulation of macrophage populations. I. Preferential induction of Ia-rich peritoneal exudates by immunologic stimuli.

Abstract: The amounts of Ia-positive and -negative macrophages were studied in peritoneal exudates of normal mice or of mice injected with various inflammatory materials, infected with Listeria monocytogenes, or injected with hemocyanin. Ia-negative macrophages predominated in exudates from normal mice or from mice given mineral oil, peptone, thioglycollate, culture media, or endotoxin. Infection with Listeria caused a very marked increase in Ia-positive macrophages. The induction of Ia-positive macrophages by Listeria inoculation resulted in great part from an immune process. The Ia-positive exudates were more readily generated in immune mice given a secondary challenge with heat-killed organisms. Furthermore, immune T cells transplanted together with heat-killed organisms into normal mice resulted in Ia-rich exudates. Injection of hemocyanin also induced Ia-rich exudates involving an immune process. We conclude that an immune reaction involving T cells regulates the Ia phenotype of the exudate macrophage population. The Ia-positive macrophages were Fc and C3 receptor positive and phagocytized latex particles.

Immunity to Trypanosoma cruzi.

Abstract: Publisher Summary Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, is a digenetic trypanosomatid, which circulates in the bloodstream of the vertebrate host as trypomastigotes and has an obligatory intracellular phase in which the parasite multiplies as amastigotes, which differentiate into trypomastigotes. From an immunological point of view, therefore, the parasite presents stages that are directly exposed to the effector elements of the immune response, such as antibodies and macrophages, as well as stages that are sequestrated within host cells. T. cruzi infection is characterized by an acute phase with large numbers of parasites and by a sub-patent chronic phase in which circulating and tissue stages are difficult to detect. The mechanisms involved in the resistance to the parasite and in the control of parasitism during the chronic phase are not known. Chagas disease is life-long and spontaneous cures do not occur. There is increasing evidence that auto-immune processes participate in the pathogenesis of the cardiac and digestive forms of the disease. These many obscure aspects and challenging problems explain the increasing use of T. cruzi as a model for the study of humoral and cellular immunity in both basic and applied immunology.

Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation.

Abstract: The capacity of 15 separate populations of mouse peritoneal macrophages to generate and release H2O2 (an index of oxidative metabolism) was compared with their ability to inhibit the intracellular replication of virulent Toxoplasma gondii. Resident macrophages and those elicited by inflammatory agents readily supported toxoplasma multiplication and released 4-20X less H2O2 than macrophages activated in vivo by systemic infection with Bacille Calmette-Guerin or T. gondii, or by immunization with Corynebacterium parvum. Immunologically activated cells consistently displayed both enhanced H2O2 production and antitoxoplasma activity. Exposure to lymphokines generated from cultures of spleen cells from T. gondii immune mice and toxoplasma antigen preserved both the antitoxoplasma activity and the heightened H2O2 release of toxoplasma immune and immune-boosted macrophages, which otherwise were lost after 48-72 h of cultivation. In vitro activation of resident and chemically-elicited cells by 72 h of exposure to mitogen- and antigen-prepared lymphokines, conditions that induce trypanocidal (5) and leishmanicidal activity (14), stimulated O2- and H2O2 release, and enhanced nitroblue tetrazolium reduction in response to toxoplasma ingestion. Such treatment, however, failed to confer any antitoxoplasma activity, indicating that intracellular pathogens may vary in their susceptibility to macrophage microbicidal mechanisms, including specific oxygen intermediates. In contrast, cocultivating normal macrophages with lymphokine plus heart infusion broth for 18H rendered these cells toxoplasmastatic. This in vitro-acquired activity was inhibited by scavengers of O2-, H2O2, OH., and 1O2, demonstrating a role for oxidative metabolites in lymphokine-induced enhancement of macrophage antimicrobial activity. These findings indicate that augmented oxidative metabolism is an consistent marker of macrophage activation, and that oxygen intermediates participate in the resistance of both in vivo- and vitro-activated macrophages toward the intracellular parasite, T. gondii.

An immunological suppressor cell inactivating cytotoxic T-lymphocyte precursor cells recognizing it.

Abstract: The immune system does not normally react against self components. Originally, it was postulated that self-reactive cells were somehow deleted or blocked1. More recent thinking2,3 is that such cells are suppressed by regulatory networks similar to those limiting the immune response against non-self determinants. Both mechanisms may exist4,5. I describe here a type of suppression more closely related to the first postulate. In the in vitro, one-way, mixed lymphocyte reaction (MLR), cytotoxic T-lymphocyte precursor cells (CLP) from the responder population give rise to cytotoxic T-lymphocytes (CL) capable of lysing target cells from the stimulator population6–8. A sub-population of cells in the spleen of athymic nude mice can, when added to such cultures, inactivate CLP capable of recognizing either the H–2 antigens or TNP modifications of the nude spleen. Regarding the nude spleen cells, activation of self-react ve cells is being prevented.