Showing papers on "Antibody published in 1970"

A Theory of Self- Nonself Discrimination.

Abstract: 1) Induction of humoral antibody formation involves the obligatory recognition of two determinants on an antigen, one by the receptor antibody of the antigen-sensitive cell and the other by carrier antibody (associative interaction). 2) Paralysis of antibody formation involves the obligatory recognition of only one determinant by the receptor antibody of the antigen-sensitive cell; that is, a nonimmunogenic molecule (a hapten) can paralyze antigen-sensitive cells. 3) There is competition between paralysis and induction at the level of the antigen-sensitive cell. 4) The mechanisms of low- and high-zone paralysis, and maintenance of the unresponsive state, are identical. 5) High-zone paralysis occurs when both the carrier antibody and the receptor antibody are saturated, so that associated interactions cannot take place. 6) The mechanisms of paralysis and induction for the carrier-antigen-sensitive cell are identical to those for the humoral-antigen-sensitive cell. 7) The formation of carrier-antigen-sensitive cells is thymus-dependent, whereas humoral-antigen-sensitive cells are derived from bone marrow. Since carrier antibody is required for induction, all antigens are thymus-dependent. 8) The interaction of antigen with the receptor antibody on an antigen-sensitive cell results in a conformational change in an invariant region of the receptor and consequently paralyzes the cell. As the receptor is probably identical to the induced antibody, all antibody molecules are expected to be able to undergo a conformational change on binding a hapten. The obligatory associated recognition by way of carrier antibody (inductive signal) involves a conformational change in the carrier antibody, leading to a second signal to the antigen-sensitive cell. 9) The foregoing requirements provide an explanation for self-nonself discrimination. Tolerance to self-antigens involves a specific deletion in the activity of both the humoral- and the carrier-antigen-sensitive cells.

A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization.

Abstract: A population of lymphoid cells from several animal species, including man, was identified through a membrane receptor which binds sheep red blood cells treated with antibody and complement. When cells from different lymphoid organs were incubated with EAC at 37°C, only part of the lymphocytes (named CRL) bound EAC and formed rosettes, and this interaction was shown to be C3-dependent. Mouse lymphoid cells could be specifically depleted of CRL by allowing them first to interact with EAC and then submitting the mixture to ultracentrifugation in a gradient of BSA. After ultracentrifugation, a population of cells containing 95% or more of non-CRL were recovered from the upper layers of the gradient. In addition to their different abilities to bind EAC, CRL and non-CRL from mouse lymphoid organs could be distinguished by the following properties: (a) CRL adhered preferentially to nylon wool at 37°C in the presence of mouse serum. (b) After differential flotation in a gradient of BSA, a significantly higher proportion of CRL were recovered from the upper layers of the gradient. (c) The population of CRL contained most of the lymphocytes bearing immunoglobulin determinants on their membranes. (d) The distribution of CRL was quite different among lymphocytes obtained from various lymphoid organs, and they were never found in the thymus. (e) The membrane receptor for EAC was not detected in plaque-forming cells of mice which had been previously immunized with burro red cells. CRL and non-CRL could not be distinguished by their life span, as they were found in similar proportions among long-lived and short-lived lymphocytes from mouse peripheral lymph nodes. The function of this receptor on the membrane of certain lymphoid cells may be related to (a) the trapping and localization of antigen in lymphoid organs or (b) the localization of lymphoid cells in inflammatory sites.

Differential Reactivity of Human Serums with Early Antigens Induced by Epstein-Barr Virus

Abstract: Inoculation of 64-10 or Raji cultures with Epstein-Barr virus derived from the HRI-K clone of the P3J Burkitt's lymphoma line caused abortive infections in most of the lymphoblastoid cells with synthesis of "early antigens" but few, if any, capsids. Antibodies to early antigens were detected by indirect immunofluorescence in serums of many patients with infectious mononucleosis, Burkitt's lymphoma, or nasopharyngeal carcinoma. These antibodies were rarely present in other serums even though some of them showed high titers of antibodies to Epstein-Barr virus when assayed on EB3 Burkitt tumor cells; they also prevented synthesis of early antigens, provided the serums were mixed with the virus prior to inoculation. Antibodies to early antigens possibly reflect current or recent disease processes that are associated with the virus.

Immunoglobulin spots on the surface of rabbit lymphocytes.

Abstract: Small and medium lymphocytes from the peripheral blood and lymphoid tissues of the rabbit react in suspension with antibodies directed against different immunoglobulin determinants. Through immunofluorescence, it was possible to show that numerous discrete spots on the surface of the positive lymphocytes carry immunoglobulin molecules. The positive lymphocytes are about one-half of all lymphocytes in the different preparations; thymus lymphocytes are all negative. With antisera specific for rabbit IgM as well as with antisera directed against allotypic determinants specific for IgM or IgG, it was possible to show that about nine-tenths of the immunoglobulin-positive lymphocytes carry IgM molecules on their surface. With antisera directed against a - and b -locus determinants, it was also possible to demonstrate that both heavy and light chains were present in the surface immunoglobulins. Furthermore, in animals which were heterozygous at the a or the b locus, it was found that each lymphocyte had immunoglobulins synthesized under the influence of only one of two alleles. A very small proportion of lymphocytes could be shown to have a specific surface reaction with one antigen (horse ferritin); the proportion of these cells increased very much after immunization.

Hemagglutination Assay for Antigen and Antibody Associated with Viral Hepatitis

Abstract: Hemagglutination assays are described for measuring hepatitis-associated Australia antigen and antibody. Red cells coated with isolated antigen, with chromic chloride as a coupling agent, are used for detection of antibodies. Detection of the antigen in serums depends on inhibition of hemagglutination. The test has the sensitivity and rapidity of the best tests available, is simpler to perform, and lends itself to large-scale screening of blood donors.

Established immunoglobulin producing myeloma (IgE) and lymphoblastoid (IgG) cell lines from an IgE myeloma patient

Abstract: Two IgEL and one IgGK producing cell lines have been established in vitro from peripheral blood and bone marrow of an E myeloma patient. Morphologic and immunologic studies indicate that cells of the IgE producing lines are derived from the same clone of myeloma cells which grew in vivo. They have remained essentially unaltered with a stable near-diploid karyotype and continuous production of intact IgE molecules during 18 months in culture. The IgGK producing line has all the characteristics ascribed to permanent lymphoblastoid lines and is considered to be of non-malignant lymphoid origin. The process of establishment is described and it is suggested that lymphoblastoid cells have a selective advantage over myeloma cells. Permanent myeloma cell lines can therefore probably be obtained only if cells capable of forming established lymphoblastoid lines are very few or absent in the original biopsy. The establishment of a permanent cell line continuously producing intact molecules of IgE should permit further studies on the biological role of this class of immunoglobulins.

Immunoglobulin determinants on the surface of mouse lymphoid cells.

Abstract: THERE is increasing evidence that lymphocytes have antigen-specific receptors on their surface1–3 and it seems reasonable to suppose that the receptors are immunoglobulins (Ig)1. The existence of Ig on the surface of lymphocytes has also been inferred from the transforming effect of anti-Ig sera4 and the opsonic adherence to macrophages of lymphocytes treated with anti-Ig5. We report here the demonstration of Ig determinants on the surface of living mouse lymphocytes by the use of immunofluorescence and immunoautoradiography.

Cytotoxins in disease. Autocytotoxins in lupus.

Abstract: Lymphocytotoxic antibodies were found in 56 of 64 serum specimens from patients with systemic lupus erythematosus and 30 of 53 patients with rheumatoid arthritis. These cytotoxic antibodies characteristically reacted with a temperature optimum of 15°C as was found earlier with serums from patients with infectious mononucleosis, rubella and rubeola. The lymphotoxin found in systemic lupus was cytotoxic to autologous lymphocytes in 24 of 32 specimens tested. No correlation was found to the antibodies detected by radioactive labeled deoxyribonucleic acid (DNA) immunoelectrophoresis, antibodies against single-strand DNA and DNA. However, a definite association with antinuclear-factor activity and a weak association with latex-fixation tests were found. Association of specificity was tested against 18 different HL-A specificities, and antibodies against HL-A11, Te54, Te56 and Te59 were frequently observed.

Cellular and humoral immune responses to human urinary bladder carcinomas.

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

Surface alloantigens of plasma cells

Abstract: A serological study of immunoglobulin-forming cells of the mouse, normal and malignant, shows that they lack all known surface differentiation antigens of the thymocyte-lymphocyte axis: TL, theta, Ly-A, Ly-B, and MSLA. Two systems of normal alloantigens are expressed on these cells, H-2 and a new system named PC. The gene Pca (Plasma cell antigen) which specifies PC.1 alloantigen segregates as a mendelian dominant not closely linked with H-2. This cell surface antigen is absent from thymocytes, leukemias, and very probably from thymus-derived lymphocytes also; it is present on cells of the liver, kidney, brain, and lymph nodes as well as on hemolytic plaque-forming cells of the spleen, and on myelomas. So PC.1 is properly classified as a differentiation alloantigen. The strain distribution of PC.1 does not conform to that of any known immunoglobulin allotype or cell surface alloantigen previously described. Thus the cell surface antigens of immunoglobulin-producing cells are clearly different from those of cells belonging to the thymocyte-lymphocyte axis. Each family of cells has distinctive alloantigens, and the two families share alloantigens of only one known system, H-2. This implies that either immunoglobulin-producing cells are not derived from thymic lymphocytes, or if they are, the program responsible for the transition must include extensive revision of cell surface structure.

Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization.

Abstract: Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 µg of BGG is more effective than a dose of 50 µg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for ϵ-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization. These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.

Distribution of gamma E-forming cells in lymphoid tissues of the human and monkey.

Abstract: The sites of synthesis of immunoglobulin E were studied by the fluorescent antibody technique. Frozen sections of human and monkey tissues were treated with guinea pig anti-γE and stained by fluorescent antibody against guinea pig immunoglobuins. The results showed that γE-forming plasma cells were predominant in the respiratory and gastrointestinal mucosa and in the regional lymph nodes. In addition to the plasma cells, the tonsils, adenoids, and broncheal and mesenteric lymph nodes contained germinal centers stained by anti-γE. In contrast, γE plasma cells were scarce in the spleen and subcutaneous lymph nodes. A possible role of locally synthesized γE immunoglobulin in respiratory allergy was discussed.

Mechanisms of passive sensitization. I. Presence of IgE and IgG molecules on human leukocytes.

Abstract: Immunoglobulins E and G were detected on human leukocytes by autoradiography. Evidence was obtained that specifically purified anti-human γE antibody combined with basophilic leukocytes from both normal and atopic individuals, and that anti-γG antibody bound with neutrophils and monocytes. Upon passive sensitization, E myeloma protein bound with basophils and normal γG bound with neutrophils and monocytes. The results show that basophils have receptor sites for γE, and that both neutrophils and monocytes have receptor sites for γG. Binding of the Fc fragments, but not the F(ab′) 2 fragments, of E myeloma protein with basophils indicated that γE combines with basophils through the Fc portion of the molecules. The binding of γE with basophils appears to be a process of passive sensitization for both antigen-induced and antibody-induced histamine release from leukocytes.

Rosette formation by peripheral lymphocytes.

Abstract: In preparations of human peripheral lymphocytes suspended in serum absorbed with sheep red cells, up to 30% of the lymphocytes may make rosettes with sheep erythrocytes. Washed lymphocytes suspended in Hanks' solution make many rosettes if tested without delay. Such lymphocytes rapidly lose their capacity to make rosettes, but it can be restored by adding the serum of man or of the horse, rabbit or guinea-pig. The lymphocytes of three newborn babies, and of one adult who had no detectable antisheep agglutinin in the serum, made rosettes with sheep cells. Rosette formation is uncorrelated with serum agglutinin levels. Many normal adults have far higher titres of agglutinins against the red cells of other animals than against sheep cells; yet their lymphocytes do not make rosettes with the cells of these other animals. Sodium cyanide (0·01 M) abolished rosette formation, and horse antihuman lymphocyte globulin inhibits it. It is concluded that sheep cell rosette formation by human peripheral lymphocytes is not due to humoral antibody or delayed hypersensitivity, because of the great proportion of lymphocytes that are capable of it. Its nature is obscure, but it is suggested that it may be due to a substance, not primarily an antibody, that is elaborated by a large proportion of circulating lymphocytes and cross-reacts with some red cell antigens as plant lectins do. Caution is advised in using the system to test antihuman lymphocyte serum until more is known about it.

Receptors for human gamma G globulin on human neutrophils.

Abstract: Cell surface receptors for human gammaG antibodies directed against bacterial antigens were demonstrated on human neutrophils using an in vitro bacteriocidal-phagocytic assay. These results were confirmed by adherence of sensitized erythrocytes to monolayers of neutrophils or monocytes. Erythrocytes sensitized indirectly with antibacterial gammaG antibodies after passive sensitization with bacterial antigens adhered to both neutrophils and monocytes. Erythrocytes sensitized directly with conventional anti-D gammaG antibodies adhered only to monocytes, while those sensitized with the hyperimmune anti-CD gammaG antibody Ripley adhered to both monocytes and neutrophils. Adherence of anti-Rh or antibacterial gammaG antibodies to monocytes and neutrophils could be inhibited by whole gammaG, myeloma globulins of the gamma(1) or gamma(3) subclasses, or Fc fragments, but not by Fab fragment. These results indicate that receptors for the Fc portion of human gammaG antibodies exist on both neutrophils and monocytes, and that gammaG antibodies differ in their ability to attach to these two cell types. Differences in the behavior of the gammaG antibodies studied may be related to differences in the density of antibodies on the erythrocyte surface and receptors on the phagocytic cells.

Common individual antigenic determinants in five of eight BALB-c IgA myeloma proteins that bind phosphoryl choline.

Abstract: Eight IgA myeloma proteins derived from independently induced plasma-cytomas in genetically similar inbred BALB/c mice are functionally related by their binding of phosphoryl choline-containing antigens (Pneumococcus C polysaccharide or Lactobacillus antigen) Each protein resembles a single species of immunoglobulin in antibody The proteins are characterized by highly sensitive myeloma-specific antisera prepared by immunizing mice of other inbred strains with the BALB/c myeloma proteins Individual or myeloma-specific determinants located on Fab fragments were found on three of the proteins that were unique for that protein and did not react with any other IgA protein among over 70 tested Remarkably, five of the proteins shared two common myeloma-specific determinants which were specific for this group of five proteins These results suggest that the five functionally and genetically related proteins sharing the same myeloma-specific determinants might also be structurally similar

Suppression of Immunoglobulin G Synthesis as a Result of Antibody-Mediated Suppression of Immunoglobulin M Synthesis in Chickens

Abstract: Development of heterogeneity of immunoglobulin classes has been investigated in the chicken by studying the effects of antibody-mediated suppression of IgM synthesis. Treatment of 13-day embryos with purified goat antibodies to IgM resulted in the elimination of IgM-containing cells from the bursa of Fabricius of 16- and 19-day embryos. When combined with bursectomy at hatching, administration of anti-IgM in ovo suppressed the synthesis not only of IgM but also of IgG. A number of experimental birds lacked detectable circulating immunoglobulins, plasma cells, and germinal centers when killed at 10 weeks of age. Contrasting results were obtained when IgM synthesis was suppressed after bursectomy at hatching. Birds so treated produced little or no IgM but synthesized normal amounts of IgG. The results suggest that, within the bursal environment, IgG-producing cells arise exclusively from cells that previously synthesized IgM. A model for generation of antibody variability is presented.

Epstein-Barr virus (EBV)-associated antibody patterns in malignant lymphoma and leukemia. I. Hodgkin's disease.

Abstract: Sera from Swedish patients with Hodgkin's disease as well as control sera from donors without known disease were titrated for antibodies to the Epstein-Barr virus (EBV) by the indirect immunofluorescence technique. In the same sera antibodies capable of blocking the direct membrane immunofluorescence reaction obtained between Epstein-Barr virus carrying lymphoblastoid cell lines and a fluorescein-conjugated reference serum from a patient with Burkitt's lymphoma (F-Mutua conjugate) were tested. The serological reactivity of the control sera was very similar to that described in previous reports. In contrast, sera from Hodgkin's disease patients showed an increased reactivity in both tests. When the donors were grouped in relation to clinical and histological data of prognostic importance, an inverse relationship was found between the frequency of lymphoid cells and EBV-associated serological reactivity. Whereas paragranuloma cases did not exceed the reactivity level of the controls, patients with Hodgkin's sarcoma were highly reactive in both tests, reaching levels comparable to those seen in Burkitt's lymphoma and nasopharyngeal carcinoma. The granuloma group was intermediate with regard to serological reactivity. CARACTERISTIQUES DES ANTICORPS ASSOCIES AU VIRUS ET LA LEUCEMIE. I. MALADIE DE HODGKIN D'EPSTEIN-BARR (VEB) DANS LE LYMPHOME MALIN Des serums de Sutdois atteints de la maladie de Hodgkin et des serums de ttmoins apparemment sains ont btk titrts par la technique d'immunofluorescence indirecte pour la recherche d'anticorps au virus d'Epstein-Barr ( VEB). On a analyst dans les m strums Its anticorps capables de bloquer la rtaction d'immunofluorescence directe de la membrane obtenue entre les ligntes cellulaires lymphoblastoides contenant le virus d'Epstein-Barr et Im strum de rkftrence conjuguk a la fluoresctine provenant d'un malade porteur d'un lymphome de Burkitt (ensemble F-Mutua) . La rkactivite strologique des strums ttmoins est tr semblable ci celle qui a dtja fait l'objet de plusieurs rapports. Par contre, le serum de sujets atteints de la maladie de Hodgkin a fait preuve d'une reactivite accrue lors des deux tests. Lorsque les donneurs sont groupes selon des donnees cliniques et histologiques importantes du point de vue du pronostic, on observe une relation inverse entre la frequence des cellules lymphoides et la reactivite serologique associee au VEB. Alors que, dans les cas de paragranulome, la reactivite n'est pas superieure a celle des temoins, les malades atteints de sarcomes de Hodgkin reagissent fortement aux deux tests, et les niveaux atteints sont comparables a ceux que l'on observe pour le lymphome de Burkitt et l'epithelioma du rhinopharynx. Le groupe des granulomes fait preuve d'une reactivite serologique moyenne.

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

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

The reaction mechanism of human c5 in immune hemolysis

Abstract: The data presented here indicate that the C5 reaction step may proceed via the specific attachment of C5 to EAC1,4,2,3 and the formation of a hemolytically active C5 intermediate complex. During this process only a minor proportion (less than 4%) of C5 offered to EAC1,4,2,3 becomes bound, although the remaining C5 also participates in the reaction as evidenced by its inactivation in the fluid phase. Once bound, C5 is exceptionally efficient in producing hemolysis, requiring less than seven specifically bound molecules per cell for the production of a hemolytic lesion. The extent of formation of the C5 intermediate complex is primarily dependent on the number of molecules of C4, 2 and C3 present on the cells employed for its generation. In these respects, the mode of action of C5 is completely analogous to that of the other components of complement thus far investigated. The C5 step differs, however, in other aspects. The binding of C5 is influenced by C6 and C7, components which are thought to act subsequent to it in the complement sequence. In addition, the hemolytic activity of the isolated C5 intermediate complex is exceedingly labile, having an average half-life at 30°C of only 9 min. This characteristic distinguishes the C5 step, along with the C2 step, as potentially rate-limiting in the complement reaction. However, unlike C2, C5 remains firmly cell-bound during the decay process and apparently undergoes an alteration in situ which renders it hemolytically unreactive. Finally, C5 is unique in that it readily adsorbs in native form to unsensitized erythrocytes. This nonspecifically bound C5 remains firmly attached, although it may be specifically utilized as a source of C5 by an ongoing complement reaction. The significance of the marked affinity of native C5 for cell-surface receptors remains to be determined.

Immunology for students of medicine

Abstract: Sommaire : 1- Introduction /2- Innate immunity /3- Antibodies and complement /4- The production of antibodies /5- Antigens /6- Serological aspects of the antigens-antibody reaction : the detection and measurement of antigen and antibody /7- The protective effects of antibody /8- Prophylactic immunization and serotherapy /9- Hypersensitivity mediated by antibodies /10- Delayed-types hypersensitivity /11- Immunilogical tolerance /12- Auto-immunity and its relation to human disease

Recovery and characterization of a minute virus of canines.

Abstract: Four antigenically related transmissible agents were recovered from canine fecal specimens. The agents produced cytopathic effects in a continuous dog cell line developed in this laboratory. Increased antibody titers were demonstrated in three of the four dogs which provided the isolates. The virus did not produce cytopathic effects in primary canine kidney or thymus cell cultures, or in cell cultures of human, simian, porcine, bovine, feline, and murine origin. The agent is resistant to ether, chloroform, and heat treatment, and the growth of the virus is inhibited by 5-iodo-2-deoxyuridine. After acridine orange staining, green fluorescent intranuclear inclusions are seen in infected cell cultures. By electron microscopy, the virions measure approximately 20 to 21 nm in overall diameter and are present in the nuclei of infected cells. These properties are consistent with membership in the parvovirus or picodnavirus group. The agent hemagglutinates rhesus red blood cells at 5 C and by hemagglutination-inhibition tests could be readily distinguished from H-1, rat virus, and the minute virus of mice. Canine gamma globulin contains high titers of neutralizing antibody and neutralizing antibody was found in a high percentage of military dogs and in beagles of a breeding colony.

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

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

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

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