Showing papers on "Immune system published in 1979"

Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.

Abstract: Bronchoalveolar lavage is an invaluable means of accurately evaluating the inflammatory and immune processes of the human lung. Although lavage recovers only those cells and proteins present on the epithelial surface of the lower respiratory tract, comparison with open lung biopsies shows that these constituents are representative of the inflammatory and immune systems of the alveolar structures. With the use of these techniques, sufficient materials are obtained from normal individuals to allow characterization of not only the types of cells and proteins present but their functions as well. Such observations have been useful in defining the inflammatory and immune capabilities of the normal lung and provide a basis for the study of lung disease. Lavage methods have been used to characterize inflammatory and immune processes of the lower respiratory tract in destructive, infectious, neoplastic, and interstitial disorders. From the data already acquired, it is apparent that bronchoalveolar lavage will yield major insights into the pathogenesis, staging, and therapy decisions involved in these disorders. (Am J Pathol 97:149--206, 1979).

Epidermal Langerhans cells are derived from cells originating in bone marrow.

Abstract: Langerhans cells constitute a morphologically well characterised subpopulation (3--8%) of mammalian epidermal cells which, in contrast to the bulk of epidermal cells, bear Fc-IgG and C3 receptors, express immune response-associated (Ia) antigens and function as antigen-presenting cells and allogeneic stimulatory cells to primed T lymphocytes. The ontogeny of Langerhans cells has been a subject of considerable debate since their discovery. Although some studies suggest that Langerhans cells are of mesenchymal as opposed to neural or melanocytic origin, direct evidence for this has not been presented. In this study we demonstrate that, after 3 weeks, most of the Langerhans cells (LC) in parenteral skin which had been transplanted on to F1 hybrids were of recipient origin whereas keratinocytes remained of donor origin; this indicates that the LC are derived from a mobile pool of cells. Furthermore, in studies of skin from radiation-induced bone marrow chimaeric animals we found that, depending on the strain combination, up to 80% of the epidermal LC were derived from the bone marrow of the donor animals.

Immune interferon in the circulation of patients with autoimmune disease.

Abstract: The observation that type II, or immune, interferon could be produced by peripheral-blood leukocytes in vitro on an immune-specific basis suggested that it also might be produced in vivo in various autoimmune disorders. We found immune interferon in the serums of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma and Sjogren's syndrome. Among 28 patients with systemic lupus erythematosus, 71 per cent of those with active and 21 per cent of those with inactive disease showed interferon in their serums. Serial serum samples showed a good correlation between interferon titers and disease activity. Moreover, interferon titers correlated positively with antibodies to DNA and negatively with serum levels of the third component of complement. It is possible that the production of interferon may contribute to immunologic aberrations in auto-immune diseases and also protect the already compromised host from viral infections.

Bacterial endotoxins and host immune responses

Abstract: Publisher Summary This chapter discusses the nature of endotoxins and their interactions with cells of the immune system. The direct interaction of endotoxin with B lymphocytes leading to the formation of antibodies to endotoxin as well as a spectrum of other immunoglobulin molecules is discussed. In addition, the interactions of endotoxins with T cells and macrophages and the associated immunoregulatory effects are discussed. The central role of the lipid A portion of the endotoxin molecule in cellular activation and the molecular events occurring at the cell surface in the course of stimulation are presented. The potential of endotoxins as therapeutic manipulators of the immune response in man is also evaluated. Major direct interactions of endotoxins with B lymphocytes have been documented, leading to synthesis and secretion of antibody directed not only against antigenic determinants on the endotoxin molecules themselves, but also with specificities characteristic of the complete repertoire of variable region gene products. Knowledge of the immunobiology of endotoxins has prompted investigations in their therapeutic uses in man as both antigenically distinct and cross-reactive immunogens in protection against gram-negative infections.

The Biology and Detection of Immune Complexes

Abstract: Publisher Summary This chapter describes the interaction of immune complexes (ICs) with complement and with the cells of the immune system. The effect of immune complexes depends to a great extent on their antigen–antibody ratio so that their influence, either stimulatory or suppressive, is itself modulated by quantitative aspects of the immune response. The development of numerous techniques for the detection and quantitation of immune complexes has stimulated clinically related research and expanded the list of diseases in which immune complexes appear to play an important role. An extension of this diagnostic technology is the ability to isolate immune complexes and, in turn, their antigenic component, thereby making it possible to identify the antigens involved in immune processes of a great many diseases, including those of unknown etiology. In vivo and in vitro experiments have clarified many factors involved in IC formation, removal, and localization as well as the mechanisms of IC-induced inflammatory reactions. An individual can make an immune response to a large number of exogenous and a smaller number of endogenous antigens. Depending upon the availability of antigen, the antibodies so produced form ICs, which for the most part serve the purpose of aiding the host in eliminating potential pathogens.

Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice

Abstract: Several immunologic features were analyzed in mice on a zinc-deficient diet [Zn(-)], in mice pair-fed a diet containing zinc [Zn(+)], in mice fed a Zn(+) diet ad lib, and in mice fed laboratory chow ad lib. When placed on a Zn(-) diet, 6- to 8-week-old A/Jax, C57BL/Ks, and CBA/H mice showed loss of body weight, low lymphoid tissue weight, and profound involution of the thymus within 4-8 weeks after initiation of the regimen. Approximately 50% of the mice on the Zn(-) diet developed severe acrodermatitis enteropathica (lesions on tail and paws) and diarrhea. Pair-fed mice on the Zn(+) diet did not show any of these symptoms. Mice on the Zn(-) diet showed the following immune deficiencies: (i) depressed plaque-forming cells against sheep erythrocytes after in vivo immunization; (ii) depressed T killer cell activity against EL-4 tumor cells after in vivo immunization; and (iii) low natural killer cell activity. However, antibody-dependent cell-mediated cytotoxicity against chicken erythrocytes was normal in the mice on the Zn(-) diet. Deficiency of T killer cell activity was not observed when immunization with EL-4 allogeneic lymphoma cells was carried out in vitro. Progressive loss of relative and absolute number of Thy 1.2+ cells and a proportionate relative increase in cells bearing Fc receptors was seen in spleen and lymph nodes of Zn(-) animals. It appears that zinc is an essential element for maintenance of normal T cell and other immune functions in vivo.

Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines.

Abstract: Murine spleen cells activated by concanavalin A (Con A) in culture produce a class of lymphokine molecules which possess biological activity in a number of lymphocyte response assays. Lymphokines with a mol wt of 30,000, as estimated from gel filtration studies, can be resolved into two components which differ by charge, with isoelectric point (pI) values of 4.3 and 4.9, respectively. Both components stimulate (a) the growth of established T-cell lines in culture, (b) the proliferation of thymocytes in the presence of Con A under culture conditions where Con A alone is nonmitogenic, (c) the induction of antibody responses to heterologous erythrocyte antigens in athymic (nude) spleen cultures, (d) the generation of cytotoxic T lymphocytes (CTL) in thymocyte cultures, and (e) the generation of CTL in nude spleen cultures. In each of these culture systems we suggest that the assays are detecting a single class of lymphokine which acts directly on activated T cells. Nonactivated T cells must be stimulated by either antigen or mitogen before becoming responsive to lymphokine, but do not require antigen or mitogen for continued growth with lymphokine. The two molecular species, separable by isoelectric focusing are referred to as the T-cell growth factor (TCGF). A lymphokine, similar in size (30,000 daltons) to TCGF but heterogeneous in charge (pI 3.0--4.0), stimulates immune responses to erythrocyte antigens in T-cell-depleted spleen cultures but has no stimulatory activity in the other lymphocyte assay systems described. The data have been interpreted as showing the two molecular forms of murine TCGF (pI 4.3 and 4.9) are responsible for many of the lymphokine activities described elsewhere as thymocyte mitogenic factor, nonspecific T-cell-replacing factor and killer helper factor or costimulator. The other lymphokine, separable from TCGF by charge, appears to have true T-cell-replacing activity.

Low natural killer-cell activity and immunoglobulin levels associated with smoking in human subjects

Abstract: Previous studies have shown that smoking is associated with a high incidence of certain malignancies and a high incidence of metastatic spread of melanoma. The purpose of the present study was to examine whether this high incidence of malignancy could be associated with certain aspects of immune function believed to be important in restricting tumour growth. Age-and sex-matched smoking and non-smoking normal subjects and male, smoking and non-smoking melanoma patients, were studied for the natural killing (NK) activity of their blood leukocytes against cultured melanoma and Chang cells. The levels of the various immunoglobulin classes in their sera and the E rosette levels of the normal subjects were also assessed. The results indicate that the NK activity of blood leukocytes from both normal subjects and melanoma patients who smoked was significantly lower against cultured melanoma cells than that of non-smokers. Smokers were also shown to have lower IgG and IgA Immunoglobulin levels in their sera compared to non-smokers but no differences in the percentage of E-rosetting (T) cells was detected. Recent studies provide some basis for the belief that the low NK activity and immunoglobulin levels in smokers may be related. These results further suggest that a closer examination of the effects of this environmental hazard on the immune system and its relation to malignancy is needed.

T-cell regulation of murine IgA synthesis.

Abstract: In studies reported here, the polyclonal activator lipopolysaccharide was used to stimulate the synthesis and secretion of IgM, IgA, and IgG in cultures of mouse lymphoid cells. The total immunoglobulin of each class which resulted was measured by specific double-antibody radioimmunoassays. The effect of Con A-activated T cells from various tissues on such immunoglobulin synthesis was then assessed. Variations in regulatory T-cell activity among the various lymphoid tissues for IgA but not for IgM or IgG was observed. In particular, Peyer's patches T cells were found to contain a high level of IgA T-cell helper activity compared to that of spleen or peripheral lymph node. The independent variation of T-cell regulatory activity for IgA as compared to that for IgM and IgG among the different tissues is most consistent with there being a separate subset of T cells specifically regulating IgA. The significance of these findings for the understanding of the secretory immune system is discussed.

Organ and Isotype Distribution of Plasma Cells Producing Specific Antibody after Oral Immunization: Evidence for A Generalized Secretory Immune System

Abstract: Mice were induced to produce IgA antibodies against ferritin after oral immunization. Such antibodies were detected by immunofluorescence in plasma cells in the intestinal mucosa as well as in secretory sites located elsewhere, such as the lactating mammary gland, salivary gland, and respiratory tract. The observation suggested that cells immunized locally via the gut could home to distant secretory sites. To confirm this hypothesis, lymphocyte transfer studies were done with mesenteric node (MN) versus peripheral node (PN) cells from orally immunized donors into nonimmunized recipients. IgA anti-ferritin cells from MN homed to exocrine targets, whereas IgM and IgG anti-ferritin cells homed to PN. The findings overall support the concept of a generalized and interrelated secretory immune system.

The Role of Antigen-Specific T Cell Factors in the Immune Response

Abstract: Publisher Summary This chapter presents a clear account of antigen-specific T cell regulatory factors. The initial concept of interaction of thymus (T)-derived cells and bone marrow (B)-derived cells has been considerably broadened to incorporate macrophage–T cell, T cell–T cell, and T cell–B cell interactions, which as a whole constitute the network of an immunoregulatory system. The interconnectedness of the immunocompetent cells is discussed. The network concept explains it by idiotype–anti-idiotype interactions among lymphocytes. On the other hand, there is abundant experimental data indicating that cell interactions are governed by genes in the major histocompatibility complex (MHC). Several facets of antigen-specific T cell factors found independently by different investigators are examined. There exist both overt similarities and differences between these T bell factors with respect to their immunochemical properties, genetic control, and roles in the immune response.

Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages.

Abstract: We have examined the Fc- and complement-receptor function of resident and thioglycollate-elicited mouse peritoneal macrophages plated on surfaces coated with rabbit antibody-antigen complexes and with complement. We derive four major conclusions from these studies. (a) The trypsin-resistant Fc receptors of resident and thioglycollate-elicited macrophages are completely modulated when these cells are plated on rabbit antibody-antigen complexes. Residual Fc receptor activity is a result of the incomplete modulation of trypsin-sensitive IgG2a receptors. (b) The complement receptors of thioglycollate-elicited macrophages, but not of resident macrophages, are modulated when these cells are plated on complement-coated surfaces. The capacity of the two cell types to modulate their complement receptors is correlated with their ability to ingest complement-coated erythrocytes. (c) The complement and Fc receptors of both types of macrophages move independently of one another. (d) Complement masks the Fc segments of IgG in immune complexes thereby rendering them ineffective as ligands for macrophage Fc receptors.

Abnormalities of Immunoregulatory T Cells in Disorders of Immune Function

Abstract: We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man.

Hyaluronidase-sensitive halos around adherent cells. Their role in blocking lymphocyte-mediated cytolysis.

Abstract: A variety of adherent sarcoma, carcinoma and normal cells are surrounded in vitro by thick, transparent zones (approximately equal to 9 micron thick) that spleen cells and a variety of other cells and particles cannot penetrate. Seven lymphoblastoid cell lines did not possess such halos. The presence of these halos around adherent fibrosarcoma cells appeared to protect them from lymphocyte-mediated cytolysis. Hyaluronidase treatment, which destroyed the halo and allowed lymphocytes to approach the tumor cell membrane, enhanced the cytotoxic action of immune but not of normal spleen cells. These observations, in addition to highlighting a little-known feature of the cell surface, may also be of general relevance to the in vitro and in vivo killing of tumor cells by immune effector cells.

Mouse epidermal Ia molecules have a bone marrow origin

Abstract: The major histocompatibility or H–2 complex of the mouse is divided into five regions (K, I, S, G and D)1. Genes in the I region regulate immune responses2. The I region has several subregions which are designated I–A, I–B, I–J, I–E and I–C. The I–A and I–E subregions also code for a set of serologically detected cell-surface alloantigens, designated Ia antigens3. The relationship between the genes regulating the immune response and those encoding the serologically detectable alloantigens is still unknown. A number of species including man, rats and guinea pigs contain genetic regions apparently equivalent to the murine I region. Ia molecules are integral cell-surface glycoproteins that consist of two subunits of approximate molecular weights 35,000 (α) and 28,000 (β). Unlike the classical transplantation antigens which are present on almost all cells, the Ia antigens are found primarily on cells of the immune system—lymphocytes and macrophages4–6. A notable exception has been the demonstration of Ia antigens in mice, or Ia-like antigens in other mammals, on epidermal cells6–13. There is controversy about the numbers of Ia-positive cells in the epidermis. Fluorescence studies in humans11,12, guinea pigs14 and mice15 indicate that only about 5% of epidermal cells are Ia positive. These cells were identified by morphological criteria as the macrophage-like Langerhans cells. However, cytotoxicity studies in mice using anti-Ia sera indicate that a majority of epidermal cells (up to 90%) are Ia positive6–8. The reason for this discrepancy is not known. Here we demonstrate that the epidermal Ia molecules are synthesised by bone marrow-derived cells, presumably Langerhans cells.

Familial abnormalities of suppressor-cell function in systemic lupus erythematosus.

Abstract: We tested the hypothesis that abnormalities of central immune function are genetically controlled in patients with systemic lupus erythematosus. We used an in vitro suppressor-cell assay t...

Adherent cell function in murine T-lymphocyte antigen recognition. IV. Enhancement of murine T-cell antigen recognition by human leukocytic pyrogen.

Abstract: A macrophage-dependent, antigen-specific murine T-cell proliferation assay was utilized to examine the role of soluble products of murine and human adherent cells in the activation of T lymphocytes Highly purified human leukocytic pyrogen, and supernates from both murine and human mononuclear phagocytes-macrophages stimulated the immune T-cell proliferative response to the multideterminant antigens dinitrophenyl-ovalbumin and keyhole limpet hemocyanin The implications of these studies and the relationship of leukocytic pyrogen to human lymphocyte-activating factor are discussed

Human lymphocyte antigens: production of a monoclonal antibody that defines functional thymus-derived lymphocyte subsets.

Abstract: A monoclonal mouse antibody (3A1) that specifically bound to 65% of human peripheral blood (PB) thymus-derived (T) cells but did not bind to complement receptor-positive PB bone marrow-derived (B) cells, polymorphonuclear leukocytes, or human erythrocytes has been produced. The 3AI antibody was synthesized by a stable cloned lymphocyte hybrid cell line. This lymphocyte hybrid line (3AI) was derived from fusion of P3 X 63/Ag8 myeloma cells and spleen cells from BALB/c mice immunized with HSB-2 cells, a human T cell line. The 3A1 lymphocyte hybrid line produced mouse ascites fluid containing 3A1 antibody in saturating titers of up to 1:25,600. Purified PB T cells that carried the 3A1 antigen incorporated tritiated thymidine maximally in response to phytohemagglutinin and concanavalin A stimulation, whereas purified PB T cells that lacked the 3A1 antigen responded suboptimally to phytohemagglutinin and minimally to concanavalin A. Thus, the 3A1 antibody can be easily used to study the role of 3A1-positive and negative T cell subsets in the regulation of normal and abnormal human immune responses.

Suppressor cells: permitters and promoters of malignancy?

Abstract: Publisher Summary This chapter discusses the relationships between suppressor cells and tumors. It describes the data that demonstrate the augmentation of antitumor responses in experimental immunocrippled animals (adult thyniectomized, splenectomized, X-irradiated, or antithymocyte serum (ATS)-injected animals). Most of these experiments were performed before the recognition of the function of suppressor cells. The chapter presents the more direct experimental evidence showing the effect of specific and nonspecific suppressor cells on the relationships between the tumor and the host immune system. For the most part, the effects of suppressor cells on syngeneic tumors, and occasionally on the so-called nonspecific tumor cells, are discussed. Nonspecific neoplastic cells cannot stimulate a detectable allogeneic immune response after inoculation into an allogeneic host and they can grow progressively in such an environment. The suppressor cells are classified arbitrarily into permitter suppressor cells—which populate the host before its confrontation with the tumor and promoter suppressor cells—which are induced by the tumor. The chapter also describes the chemical, physical, and biological properties of some of these suppressor cells and offers various means for their selective elimination.

Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli.

Abstract: Intravenously administered antigen-antibody complexes or protein aggregates localize in the glomerular mesangium. The mechanism of removal of these deposited substances has been difficult to study. Based on observations that particulates such as ferritin (1) and silver-protein aggregates (2) were found within lyososomes, mesangial cells were concluded to be phagocytic and therefore to participate in the clearing of immune complexes and aggregated IgG from the mesangium. In studies with injection of preformed immune complexes, some of the complexes deposited in glomeruli appeared to be taken up by monocytes rather than mesangial cells (3, 4). Resolution of this issue is clouded by the fact that differentiation between resident and infiltrating cells on purely morphologic grounds is not possible for the majority of cells in the mesangium. The observation that peripheral monocytes are capable of division in local sites of inflammation (5, 6) suggests that studies utilizing labeled bone marrow cells or cross-transplantation of kidneys shortly after pulse labeling may be difficult to interpret. For these reasons, we chose to study the Chediak-Higashi (CH)1 mouse; and thereby take advantage of their characteristic giant lysosomes as a marker which is visible by both light and electron microscopy. In this study we found that CH mice cleared immune complexes normally and their mesangial cells did not contain large lysosomes in the resting state. By examining glomeruli in marrow cross-transplanted CH and C57BL/6J mice we found that after induction of glomerulonephritis with preformed immune complex administration, many of the cells in the glomeruli were marrow derived. The same marrow derived cells contained morphologically defined immune complexes, whereas resident mesangial cells did not. We therefore conclude that mesangial cells do not make a significant contribution to the phagocytic removal of immune complexes from the mesangial matrix.

Studies of Immune Functions of Patients with Systemic Lupus Erythematosus: COMPLEMENT-DEPENDENT IMMUNOGLOBULIN M ANTI-THYMUS-DERIVED CELL ANTIBODIES PREFERENTIALLY INACTIVATE SUPPRESSOR CELLS

Abstract: Patients with systemic lupus erythematosus (SLE) produce excessive amounts of autoantibodies. It has also been demonstrated in several systems that such patients have a relative loss of suppressor thymus-derived (T) cells that inhibit the immune response. This loss of suppressor cells has been suggested as one of the causes of the excessive production of antibodies in patients with SLE. In the present report we have tested the hypothesis that anti-T-cell antibodies found in the plasma of some patients with SLE preferentially kill suppressor cells. T cells from normal individuals can be activated by concanavalin A to develop suppressor cell activity. We therefore cultured normal T cells together with concanavalin A in the presence of plasma or plasma fractions from patients with SLE. We found that plasma from patients with active SLE, in which anti-T-cell antibodies were present, inhibited the development of suppressor activity in such cultures. In contrast, plasma from other active patients and patients with inactive SLE, in which no anti-T-cell antibodies could be detected, failed to block the development of such suppressor activity. Absorption of the plasma that contained anti-T-cell antibodies with T cell, but not non-T cells, could eliminate the suppressor-inhibiting activity of the SLE plasma that contained anti-T-cell antibodies. The immunoglobulin (Ig)M, but not the IgG, fraction of the plasma was shown to possess the inhibiting property and complement was found to be necessary for the effect of such anti-T-cell antibodies. We also demonstrated that exposure of normal T cells to such anti-T-cell antibodies and complement did not affect another population of T cells that could proliferate in response to mitogens.Thus, certain patients with SLE have in their plasma an antibody of the IgM class that can selectively eliminate a population of T cells capable of developing suppressor function. The loss of suppressor T cells in patients with SLE may be the result of the effects of such antibody activity in vivo.

Antiviral antibody reacting on the plasma membrane alters measles virus expression inside the cell

Abstract: SOME viruses are known to persist despite a functional antiviral immune response by the host. For example, measles or measles-like viruses can cause persistent infection in man leading to a progressive degenerative disease, subacute sclerosing panencephalitis (SSPE), characterised by unusually high titres of measles virus antibodies in serum and cerebral spinal fluids (see refs 1, 2 for reviews). Peripheral blood lymphocytes specifically responsive to measles virus antigens are generated and lyse target cells expressing virus antigens on their surfaces3,4. Sera from SSPE patients enhance rather than block or suppress immunologically mediated killing3−5. But although this antimeasles virus immune response is vigorous, the virus infection does not terminate because one can detect virus antigens and isolate infectious virus from central nervous system and lymphoid tissues1. To explain this we postulated that antibody to measles virus modulates or strips viral antigens off surfaces of virus infected cells6–7. This contention is based on the finding that specific measles antibody added to cultured infected cells modulate viral antigens on the cells' surfaces6. These cells then express less viral antigens on their surfaces and thereby avoid the host's immune assault. Cells denuded of viral antigens on their surfaces resist antibody and complement-mediated or immune lymphocyte-mediated killing6,7 yet retain viral genetic information6. Further, during antibody modulation in vitro, the numbers of viral nucleocapsids accumulated inside the cell dramatically increase and are positioned randomly6. This in vitro picture closely resembles the distribution of nucleocapsids in cells obtained by biopsy from patients with SSPE1,8,9. Quantitatively, about 10- to 50-fold less antibody is needed on the surfaces of infected cells to modulate viral antigens than is needed to activate the complement system leading to immune lysis of infected cells5,10. To clarify the molecular events occurring during antibody-induced antigenic modulation, we have studied measles virus antibody bound to the surfaces of infected cells and ascertained what alterations occur within these cells. Here we report that measles virus antibodies added to virus infected HeLa cells decrease the content of both viral structural polypeptide haemolysin expressed on the cell surface and a structural polypeptide (measles virus phosphoprotein, P) found inside the cell. These observations indicate that antibody directed against an antigen on the cell surface can interfere with viral proteins expressed inside the cell. Because phosphoprotein seems to form complexes with the nucleocapsid, our findings may offer leads towards understanding viral regulation during persistence. We also note that three measles virus polypeptides—P, nucleocapsid (NC) and matrix protein (M)—are phosphorylated.

The Murine Kupffer Cell: I. Characterization of the Cell Serving Accessory Function in Antigen-Specific T Cell Proliferation

Abstract: Murine Kupffer cells, the tissue macrohages of the liver, were isolated by collagenase digestion, differential sedimentation over Metrizamide, and glass adherence. The resultant cell population was more than 86% phagocytic, and 95% of cell stained positively for α-naphtyl butyratc esterase activity. The cells also had cell surface receptors for complement (C) and the Fc portion of IgG. In additon, a large proportion of Kupffer cells was shown to bear Ia antigens: about half of the cells bore I-A subregion-encoded antigens. Kupffer cell populations were capable of reconstituting antigen-stumulated proliferative responses of antigen-primed, macrophage-depleted, lymph node T cells. The ability to reconstitute proliferation was enriched in the adheren population and was resistant to radiation and treatment with an anti-Thy antiserum and C. We conclude that isolated murine Kupffer cells bear the Ia phenotype of accessory cells that function in antigen presentation and that Kupffer cells can paricipate in the induction of antigen-specific immune responses. These data suggest that Kupffer cells may play a role in modulating responses to enterically derived antigens.

Acute and latent infection of sensory ganglia with herpes simplex virus: immune control and virus reactivation.

Abstract: Summary The role of antiviral antibody in controlling the acute and latent phases of herpes simplex virus (HSV) infection in sensory ganglia of mice was studied in vitro and in vivo. Organ cultures of ganglia inoculated in vitro with HSV produced infectious virus for at least 3 weeks. In the presence of antiviral antibody, the titre of virus was markedly reduced, but the infection was not eliminated. Similarly, passive administration of antibody to HSV-infected immunodeficient (nude) mice reduced the virus titre but did not eliminate the acute phase of the ganglionic infection. Suppression of the cell-mediated immune response in latently infected immunocompetent mice by treatment with cyclophosphamide and/or X-irradiation resulted in reactivation of HSV in up to 70% of the animals. Reactivation was demonstrated by recovering infectious virus in cell-free homogenates of ganglia and eye globes and by finding virus antigens in ganglia by immunofluorescent staining. Reactivation occurred both in vitro and in vivo in the presence of high concentrations of neutralizing antibody. It is concluded that antibody alone is not sufficient to eliminate the acute phase of the ganglionic infection and that cytotoxic agents known to suppress the host's cellular immune response can reactivate virus in the presence of neutralizing antibody.

Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon.

Abstract: Mixed preparations of fibroblast and immune interferons interacted with cells synergistically to cause the development of a much greater level of protection than expected on the basis of their separate activities. This increased level of protection was 5- to 20-fold greater than expected on the basis of a simple additive effect of the interferons. The potentiating factor copurified with both fibroblast interferon and immune interferon as they were partially purified. The potentiation was not an artifact of a more rapid development of immune interferon-induced antiviral resistance in the presence of fibroblast interferon. The results were consistent with the hypothesis that fibroblast and immune interferons mutually potentiate each other, thus supporting the supposition that they have different modes of action.

Interactions of nutrition, infection and immune response. Immunocompetence in nutritional deficiency, methodological considerations and intervention strategies.

Abstract: . Clinical and epidemiologic data point to a causal interrelationship between nutritional deficiency and infectious illness. Both are major contributors to childhood morbidity and mortality, particularly in underprivileged population groups. Energy-protein undernutrition and deficiencies of iron, folates and pyridoxine, depress a variety of immunity functions. Delayed hypersensitivity and number of T lymphocytes are consistently reduced. In small-for-gestation low birth weight infants, cell-mediated immunity may remain depressed for several years. B lymphocytes, immunoglobulin levels and antibody responses are generally normal, but secretory IgA-antibody is reduced. Serum complement components are low and there is evidence of in vivo consumption of complement C 3. Neutrophil phagocytosis of bacteria and fungi is intact but the next step of intracellular killing is impaired. There are changes also in the production of lysozyme and interferon. Infection per se results in nutrient losses, either actual or by sequestration, and produces immunosuppression. The correction of postnatal nutritional deficits and/or infection is associated with reversal of immunological functions to normal. The interplay of nutrition, immunity and infection, and its biological implications are described.

Circulating Immune Complexes: Their Immunochemistry, Detection, and Importance

Abstract: The size and molecular composition of circulating immune complexes depend on various factors, including the concentrations and valences of antigens and antibodies and the antigen-antibody ...

A defect in the antigen-presenting function of macrophages from neonatal mice.

Abstract: The newborn mammal has a limited ability to mount an immune response1–5. As the individual matures, the potential for immunological reactivity develops and expands. During the early period of relative immune incompetence, tolerance to some foreign antigens is easily induced6,7. It is thought that the individual may be acquiring tolerance to self antigens during this period, hence its importance for immunological homeostasis. The contribution of mononuclear phagocytes to the initiation of immune responses is now well established. These phagocytes are essential for the development of various lymphocyte functions, in particular, those of the T lymphocytes. Most T-lymphocyte activities require that the macrophage take up and ‘present’ the antigen in a process modulated by the I region of the major histocompatibility gene complex (for review see ref. 8). Although some earlier studies5,9–13 have indicated deficient macrophage function in the neonate, precise definition of the putative deficiency is lacking. We show here that macrophages from neonatal mice present antigen poorly and that this can be correlated with the small number of macrophages that bear Ia antigens.