scispace - formally typeset
Search or ask a question

Showing papers on "Antibody published in 1973"


Journal ArticleDOI
TL;DR: The ACIF test was used as a tool to trace the Epstein‐Barr virus genome at the cellular level to study the complementfixing antigens of human lymphoblastoid cell lines.
Abstract: Anti-complement immunofluorescence (ACIF) was used to study the complementfixing antigens of human lymphoblastoid cell lines. These cell lines carry the Epstein-Barr virus (EBV) genome although only producer cultures synthetize EBV-specific antigens (virus capsid antigen, VCA and early antigen, EA) detectable by direct and indirect immunofluorescence, usually in less than 5% of the cells. The ACIF test revealed an antigen localized in the nucleus of the lymphoblastoid cells. In contrast to EA and VCA, this antigen was present in over 90% of the cells of both producer and non-producer cultures. The antigen was shown to be specific for EBV by comparing the reactions of 52 sera in the ACIF test. Sera giving the nuclear reaction contained antibodies to VCA, EA or antigens detectable by complement fixation tests on cell extracts, but sera without EBV antibodies failed to give the reaction. Weak, equivocal or discordant reactions occurred with six sera with low titres in VCA, EA or complement fixation tests. Cell lines derived by transformation of human and primate lymphocytes by EBV gave the nuclear reaction. Control cells with no known association with EBV were non-reactive. These included foetal lymphocytes transformed by phytohaemagglutinin, cell lines derived from breast cancer, glioma, normal glia, pleuritis maligna and myeloma, and two marmoset lymphoid lines carrying Herpesvirus saimiri (HVS). In preliminary experiments, the ACIF test was used as a tool to trace the EBV genome at the cellular level. Cells from two Burkitt lymphoma biopsies, one tested after biopsy and one after passaging in nude mice, contained an EBV-specific antigen. Three clones of cells derived from hybrids of mouse somatic cells and a human lymphoblastoid cell line also contained such an antigen, but the number of reactive cells varied from clone to clone. A fourth clone was non-reactive.

1,632 citations


Journal ArticleDOI
TL;DR: The data demonstrate that efficient presentation of macrophage-associated antigen to the lymphocyte requires identity between macrophages and lymphocyte at some portion of the major histocompatibility complex.
Abstract: Antigen activation of DNA synthesis in immune thymus-derived lymphocytes of guinea pigs requires the cooperation of macrophages and lymphocytes. We have investigated the role of histocompatibility determinants in this macrophage-lymphocyte interaction using cells from inbred strain 2 and 13 guinea pigs. The data demonstrate that efficient presentation of macrophage-associated antigen to the lymphocyte requires identity between macrophage and lymphocyte at some portion of the major histocompatibility complex. The failure of allogeneic macrophages to effectively initiate immune lymphocyte proliferation was not the result of the presence of an inhibitor of blastogenesis released in mixtures of allogeneic cells, peculiarities of the antigen or lymphoid cells employed, nor differing kinetics of activation by allogeneic macrophages. In addition, data were presented that demonstrated that alloantisera inhibit lymphocyte DNA synthesis by functional interference with macrophage-lymphocyte interaction.

939 citations


Patent
17 Dec 1973
TL;DR: In this paper, a novel immunoassay is provided, as well as particular reagents, for determining the presence of a ligand, where a Reagent is employed having at least two epitopes, one of the epitopes being common with the ligand and the other epitope being a foreign epitope.
Abstract: A novel immunoassay is provided, as well as particular reagents, for determining the presence of a ligand. A Reagent is employed having at least two epitopes, one of the epitopes being common with the ligand, and the other epitopes being foreign to the ligand. The two epitopes are positioned in the Reagent so that antibody bound to one of the epitopes sterically inhibits the binding of antibody to the second epitope. In carrying out the assay, the sample, the Reagent, and antibodies to the two epitopes are combined. Because of the steric inhibition to the simultaneous binding of the two antibodies to the Reagent, the amount of antibody bound to the epitope of the Reagent foreign to the ligand will be related to the amount of ligand present in the assay medium. By analyzing directly or indirectly for the antibody bound to the epitope foreign to the ligand, and comparing the results to known standards, qualitative or quantitative determinations of the amount of ligand may be made. Various detector systems may be employed for determining the amount of antibody to the foreign epitope which is unbound or bound. These systems include stable free radicals, enzymes, radioactive labels, fluorescers, and the like.

789 citations


Journal ArticleDOI
07 Dec 1973-Science
TL;DR: Spherical 27-nanometer particles were visualized in stools obtained from hepatitis A patients in the acute phase of the disease and suggest that it is the etiologic agent of hepatitis A.
Abstract: Spherical 27-nanometer particles were visualized in stools obtained from hepatitis A patients in the acute phase of the disease. The particle was serologically specific for this disease, and every hepatitis A patient tested demonstrated a serologic response to this antigen. The findings suggest that it is the etiologic agent of hepatitis A.

774 citations


Journal ArticleDOI
TL;DR: Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma and it was concluded that B lymphocytes, in contrast to T lymphocyte, have receptors for EBV.
Abstract: Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus (EBV) because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma. This was done by a cytoadherence technique where virus-producing cells, displaying fresh viral determinants in their cytoplasmatic membrane, were mixed with lymphocytes. Unfractionated lymphocytes were found to adhere to these cells in contrast to column-purified T lymphocytes. The specificity of the binding was confirmed by blocking experiments that showed that sera containing high titers of antibodies directed against the virus could partially inhibit the adherence in contrast to low-titer sera. It is concluded that B lymphocytes, in contrast to T lymphocytes, have receptors for EBV. In a second line of experiments it was found that established human lymphoblastoid lines that carry the EBV genome had receptors characteristic for B lymphocytes and did not form T-lymphocyte rosettes. In contrast, a line of known T-lymphocyte origin that did not carry the EBV genome had receptors characteristic for T lymphocytes. EBV-transformed simian lymphoblastoid lines had surface markers indicating a B-lymphocyte origin in contrast to HVS-transformed simian lines that lacked surface immunoglobulin but carried receptors for sheep red blood cells.

498 citations


Journal ArticleDOI
TL;DR: The finding that JC virus agglutinates human type O erythrocytes permitted the rapid assaying of human sera for antibodies against this virus to give an indication of the incidence of infection by JC virus.
Abstract: JC virus is a papova-like virus that was isolated recently from the brain tissue of a patient with progressive multifocal leukoencephalopathy (PML) [1]. Our initial studies indicated that JC virus is a new virus that probably belongs in the polyoma-SV40 subgroup of papova viruses. PML is a rare demyelinating disease that usually occurs in people with an immunologic deficiency due to a preexisting chronic disease [2]. It is not known whether such people are more easily infected or whether a latent virus becomes activated in such cases. The finding that JC virus agglutinates human type O erythrocytes permitted the rapid assaying of human sera for antibodies against this virus. The results presented here give an indication of the incidence of infection by JC virus.

451 citations


Journal ArticleDOI
TL;DR: Through the use of absorbed idiotypic antisera prepared against single isolated monoclonal IgM anti-γ-globulins, partial cross-idiotypic specificity was demonstrated, indicating basic similarities between proteins of a given activity even in unrelated individuals.
Abstract: Through the use of absorbed idiotypic antisera prepared against single isolated monoclonal IgM anti-γ-globulins, partial cross-idiotypic specificity was demonstrated with other IgM anti-γ-globulins. Such antisera classified these proteins into at least three groups. The major group which included 60% of the anti-γ-globulins was particularly homogeneous. The anti-γ-globulin specific antigens were detected best in hemagglutination and hemagglutination inhibition systems. They were not found in monoclonal IgM proteins that lacked anti-γ-globulin activity although related antigens were detected at low concentrations in pooled immunoglobulin preparations as well as in heterogeneous anti-Rh antibodies. Several lines of evidence were obtained indicating that the antibody combining site was involved in the specific determinants. Attempts were made to analyze the fine specificity of each anti-γ-globulin for the Fc fragment of different subclasses of human immunoglobulins as well as those of other species. Differences were observed but these were not readily related to the cross-specificity antigens. The anti-γ-globulin specific antigens were very analogous to those previously described for monoclonal IgM cold agglutinins. Although each protein could be distinguished from all the others on the basis of individual idiotypic antigens, the antigens common to the specific groups of proteins with each of these activities were prominent and readily detected with multiple antisera. The results indicate basic similarities between proteins of a given activity even in unrelated individuals.

381 citations


Journal ArticleDOI
TL;DR: The finding of lymphocytes with only one of the two B cell markers suggests that these markers are not uniformly present on all B cells and that depending on the source, one or the other may be deficient.
Abstract: Human lymphocytes from normal peripheral blood, thymus, spleen, thoracic duct, and peripheral lymphocytes from patients with chronic lymphatic leukemia were studied for complement receptor sites (CRL), surface immunoglobulin (SIg), and for the ability to form rosettes with sheep erythrocytes (TRFC). The two B cell markers (CRL and SIg) were found to be in overlapping, but not totally identical populations, whereas cells that were able to form rosettes were found in a totally unrelated population of lymphocytes; TRFC is therefore probably a reliable marker for T cells. In peripheral blood 24% of lymphocytes had SIg, but only half of these were also CRL. Almost all of the non-SIg peripheral blood lymphocytes were TRFC. In the spleen and thoracic duct only a few lymphocytes were observed that had SIg and were not CRL. On the other hand, in two of three spleens studied 10-20% of cells were CRL that did not have SIg. In the thoracic duct all non-CRL that did not have SIg. In the thoracic duct all non-CRL, non-SIg cells were TRFC. In chronic lymphatic leukemia three findings were made: (a) The presence or absence of CRL was independent of the presence or absence of SIg so that in individuals whose cells were non-SIg. CRL were usually plentiful. (b) Leukemic cells were essentially negative for TRFC. (c) Leukemic cells reacted poorly with human C3 compared to mouse C3, EACmo detecting up to 20-fold more CRL than EAChu. This latter finding was in sharp contrast to normal CRL that reacted somewhat preferentially with EAChu. These data suggest that altered surface Ig receptors and complement receptors are present in chronic lymphatic leukemic cells. Since the cells obtained from all leukemic patients tested in this study had either the complement receptor or surface immunoglobulin in a high percentage of their cells and were essentially negative for TRFC, it is strongly suggested that leukemic lymphocytes are of B cell origin. The finding of lymphocytes with only one of the two B cell markers suggests that these markers are not uniformly present on all B cells and that depending on the source, one or the other may be deficient.

360 citations


Journal ArticleDOI
TL;DR: A new slide-agglutination method was developed for the serological typing of pneumococci, where type-specific antibodies were bound to stabilised, protein-A containing staphylococci through theri Fc fragments.
Abstract: Summary A new slide-agglutination method was developed for the serological typing of pneumococci. Type-specific antibodies were bound to stabilised, protein-A containing staphylococci through theri Fc fragments. The combining sites of the antibodies remained available to the corresponding type-specific antigen; when pneumococci were mixed with a suspension of the stabilised staphylococci coated with homologous antibody, strong agglutination occurred rapidly. Eighty-nine pneumococcal strains were typed by this agglutination method. The results obtained were in complete agreement with those of typing by Neufeld's capsule-“ swelling” method.

340 citations


Journal ArticleDOI
TL;DR: IgE antibody measurements may be useful in the assessment of the severity of reaginic allergy in highly sensitive patients and the inverse association between IgE and IgG antiragweed antibodies requires further study.
Abstract: Specific IgE anti-ragweed antibodies (IgEAR) were measured over two years in two groups of highly sensitive patients treated (immunized) with either ragweed extract or placebo and in a third group of placebo-treated, relatively insensitive patients. The IgEAR on the patients' basophils were assessed by ragweed antigen E (AgE)-induced histamine release; blocking (IgG) antibodies were measured by their ability to inhibit AgE induced histamine release. These data were evaluated against the clinical severity of ragweed hay fever in each patient. We found that: (a) In placebo treated patients IgEAR usually declined gradually prior to the ragweed season and were boosted by environmental exposure to ragweed pollen. (b) In immunized patients the IgEAR rose at the beginning of treatment, but fell as immunotherapy proceeded; by the end of the second year the levels had decreased in 18/19 patients. (c) The increase in blocking antibody during immunotherapy correlated significantly (P < 0.05) with the decrease in serum IgEAR. (d) Judged by their sensitivity to AgE induced histamine release, IgEAR on basophils correlated significantly with IgEAR in the serum of untreated patients (P < 0.01). (e) The highly sensitive placebo treated patients' symptom scores were significantly correlated with their IgEAR in serum (P < 0.01) and with the sensitivity of their basophils to AgE-induced histamine release (P < 0.01). Neither correlation was observed in the relatively insensitive patients. (f) In the treated group the IgEAR measurements predicted neither the degree of their illness nor their clinical improvement We conclude tha IgE antibody measurements may be useful in the assessment of the severity of reaginic allergy in highly sensitive patients. Its use in modestly sensitive patients requires patients requires further study, as does the inverse association between IgE and IgG antiragweed antibodies.

332 citations


Journal ArticleDOI
TL;DR: In 15 patients, antibodies to core appeared in acute viral hepatitis, type B, twelve to twenty weeks after exposure, usually during antigenaemia and well before the appearance of anti-HBAg, and anti-core antibodies were found in all chronic HBAg carriers tested.

Journal ArticleDOI
TL;DR: The “protective” level of serum anti-type b antibodies, estimated by two methods, was achieved by immunization of infants, which suggests that this procedure may confer protective immunity.
Abstract: Extract: Haemophilus influenzae type b antibodies were measured quantitatively in normal and immunized humans and in commercially available pooled immunoglobulin. A “protective” serum level was estimated to be 0.06 to 0.1 $mUg antibody/ml based upon the anti-type b concentration in normal adult sera and pooled immunoglobulin. An age-related difference characterized the adult and infant serum antibody response to injection of the purified type b capsular polysaccharide. The adults responded with higher and sustained antibody levels than the infants and children. An immunized infant reacted with type b antibody formation after nasopharyngeal carriage of H. influenzae type b and two infants reacted with type b antibodies after enteric carriage of Escherichia coli with a cross-reacting antigen. Speculation: Qualitative and quantitative differences characterize the adult versus the infant re-response to the capsular polysaccharide of H. influenzae type b. This age-related difference in the serum anti-type b antibody response may be due to the development of differentiated cells induced by whole bacteria, either as H. influenzae type b or by other organisms with cross-reacting antigens. The “protective” level of serum anti-type b antibodies, estimated by two methods, was achieved by immunization of infants, which suggests that this procedure may confer protective immunity.

Journal ArticleDOI
TL;DR: The results imply that Epstein-Barr virus is capable of inducing malignant lymphoma in at least one primate species, and additional evidence is required before its oncogenic capacity in this host can be accepted without reservation.
Abstract: Neoplasia resembling human malignant lymphoma, reticulum cell sarcoma type, occurred in cottontop marmosets inoculated with materials containing Epstein-Barr virus. One of four monkeys that received autologous cells transformed in vitro by Epstein-Barr virus developed lymphoma in mesenteric lymph nodes 7.5 months after inoculation. Three of four marmosets inoculated with cell-free Epstein-Barr virus developed lymphoma. The latent period for detectable tumor formation after addition of virus was 31-46 days. Immunosuppressive drugs given with the virus accelerated the course of disease. Nevertheless, malignant lymphoma occurred in an animal given only cell-free virus. Six of eight marmosets inoculated with the virus demonstrated antibodies to the virus. Four marmosets not exposed to the virus, including two that received immunosuppressive drugs, developed neither tumors nor antibodies to Epstein-Barr virus. Virus antigen detectable by immunofluorescence was found in 5% of cells shed from one tumor maintained in organ culture. These results imply that Epstein-Barr virus is capable of inducing malignant lymphoma in at least one primate species. Additional evidence is required before its oncogenic capacity in this host can be accepted without reservation.

Journal Article
TL;DR: The envelope glycoprotein of rabies virus was shown to be the antigen responsible for the induction of virus neutralizing (VN) antibody formation and for the protection of animals against subsequent challenge with rabies, which could be explained by the amount of residual glycop protein present in these preparations.
Abstract: The envelope glycoprotein of rabies virus was shown to be the antigen responsible for the induction of virus neutralizing (VN) antibody formation and for the protection of animals against subsequent challenge with rabies virus. Preparation of two other envelope proteins and of the nucleocapsid protein, derived from disrupted virions, induced the formation of only low levels of VN antibody and protection of animals against rabies, which could be explained by the amount of residual glycoprotein present in these preparations. Purified preparations of free viral nucleocapsid, isolated from infected cells, did not induce VN antibody formation, but elicited, in immunized animals, the formation of antibodies demonstrable by complement fixation or fluorescent antibody tests.

Journal ArticleDOI
TL;DR: Findings indicate that circulating abnormal cells are related to thymus-derived lymphocytes, and were killed by a specific rabbit antihuman T-cell antiserum.
Abstract: The Sezary syndrome consists of erythroderma, lymphadenopathy and abnormal mononuclear leukocytes. In four of six patients with this syndrome, the abnormal cells were smaller than the classic large Sezary cell. The membrane properties of circulating abnormal cells, studied by conventional stains, electron microscopy, cytogenetic analysis, immunofluorescence, and rosette formation, manifested similar ultrastructural and chromosomal characteristics whether the cells were large or small. The abnormal cells were devoid of membrane-bound immunoglobulin detectable by immunofluorescence, did not bind aggregated human IgG, were able to form spontaneous rosettes with sheep erythrocytes and, in the three patients studied, were killed by a specific rabbit antihuman T-cell antiserum. These findings indicate that these cells are related to thymus-derived lymphocytes. (N Engl J Med 289:341–344, 1973)

Journal ArticleDOI
TL;DR: The response of adult rabbit small intestine to the heat-stable (ST) and heat-labile (LT) enterotoxins of Escherichia coli has been investigated by employing the ligated loop technique, finding a sharp increase in the proportion of the cumulative net secretory response attributable to LT with time.
Abstract: The response of adult rabbit small intestine to the heat-stable (ST) and heat-labile (LT) enterotoxins of Escherichia coli has been investigated by employing the ligated loop technique. Fluid accumulation was determined in relation to enterotoxin dose and duration of gut exposure. The individual responses to ST and LT differed in a characteristic manner. Onset of net fluid accumulation in response to ST appeared to be immediate even at the lowest dose tested. Onset of net fluid accumulation in response to LT was rapid at high doses but delayed at low doses. Maximum volume per length ratios elicited by ST occurred between 4 and 6 h after injection of loops over the entire range of doses tested. However, maximum ratios elicited by LT occurred no less than 10 h after injection even at low doses. Fluid accumulation elicited by LT increased in duration with increasing dose; high doses of LT producing a response which was sustained for at least 18 h. The net effect of these differences in reaction characteristics is a sharp increase in the proportion of the cumulative net secretory response attributable to LT with time. Therefore, a 6-h assay time is appropriate for the titration of ST, whereas an 18-h assay is not. The 18-h assay was found more appropriate for toxin-antitoxin neutralization studies since only LT was neutralized by anti-enterotoxin serum. LT of E. coli (swine) strain P-263 and (human) strain 334 was neutralized by antibody stimulated by enterotoxin from E. coli (human) strain H-10407. LT was labile to mild acid conditions, whereas ST was not.

Journal ArticleDOI
TL;DR: It seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes, as reactions with recombinant strains of mice indicate that the cell-surface antigen responsible for this specificity is determined by gene in or to the left of the Ir-1 region of the major histocompatibility complex.
Abstract: Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.

Journal ArticleDOI
TL;DR: A new system of lymphocyte alloantigens in mice is described and may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.
Abstract: A new system of lymphocyte alloantigens in mice is described. This Lna (lymph-node antigen) system is associated with the Ir region of the H-2 (histocompatibility-2) gene complex. It has the following distinctive characteristics: (1) The gene or genes controlling these antigens has been mapped in the Ir (immune response) region between H-2K and Ss-Slp. (2) The antigens are most readily detectable on lymph-node cells, although they are also expressed on peripheral blood lymphocytes, splenic lymphocytes, and thymocytes. (3) Cytotoxicity against only about half of lymph-node cells is consistently observed. (4) Cytotoxic antibody titers against these antigens are strikingly high—more than 2000 by 51Cr-release and up to 100,000 in the microcytotoxic test. (5) At least two, probably allelic, forms of the antigen(s) have been defined, one associated with the H-2k haplotype and one with the H-2a haplotype. (6) Antisera against Lna contain multiple antibody specificities that can be fractionated by absorption either with certain recombinants or with other H-2 halotypes that have crossreactive antigens. The antisera against Lna may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.

Journal ArticleDOI
TL;DR: A factor that transforms human and simian blood leukocytes into continuous cell lines was found in throat washes from 23 of 25 patients with the infectious-mononucleosis syndrome.
Abstract: A factor that transforms human and simian blood leukocytes into continuous cell lines was present in throat washes from 23 of 25 patients with the infectious-mononucleosis syndrome. The factor was not detected in similar materials obtained from 17 control subjects. The factor was found eight days to 16 months after onset of the syndrome. Transformation of umbilical-cord leukocytes by this factor allowed detection by complement fixation of Epstein-Barr viral antigens; however, such antigens detectable by immunofluorescence were found in transformed cells derived only from adult human beings or marmosets. The transforming capacity of three throat washes was neutralized by reference serums with Epstein-Barr virus antibody but was unaffected by serums without the antibody. The results suggest that the transforming factor present in throat washes of patients with infectious mononucleosis is the Epstein-Barr virus. This agent is present in the oropharynx long after the appearance of serum antibodies an...

Journal ArticleDOI
TL;DR: In this article, the effect of opsonin deficiency on phagocytosis of pneumococci was studied in patients with sickle-cell disease, and it was found that opsonins did not fully activate and fix the essential Opsonin C3 to the microorganism by the alternate pathway.
Abstract: Enhancement of phagocytosis by serum from patients with sickle-cell disease was studied in an attempt to define further the opsonin deficiency present in the disorder and its role in the increased susceptibility of these patients to infection. Serums from 28 patients promoted phagocytosis of pneumococci normally if the bacteria had previously been sensitized with an excess of antibody, but a deficiency emerged when the amount of antibody added to the system was decreased. The abnormality could not be attributed to a deficiency of antibody or complement components. However, under conditions that prevented activation of C1 and the classic complement sequence, the serums did not fully activate and fix the essential opsonin C3 to the micro-organism by the alternate pathway. When specific antibody is deficient, such patients may be unable to phagocytize invading pneumococci normally because of an inability to utilize fully the alternate pathway as a mediator of natural immunity. (N Engl J Med 288:803–...

Journal ArticleDOI
13 Jan 1973-BMJ
TL;DR: Tests showed that antibody to this virus was very common in the population and began to be acquired after the age of 1 year, and no clinical illness has so far been associated with the development of this antibody in a series of paired sera from children.
Abstract: Over 500 human sera were tested by complement fixation and haemagglutination inhibition tests for antibody to the human polyomavirus (B.K.). Both tests showed that antibody to this virus was very common in the population and began to be acquired after the age of 1 year. No clinical illness has so far been associated with the development of this antibody in a series of paired sera from children.

Journal Article
TL;DR: Rises in serum bactericidal activity against H. influenzae type b generally accompanied rises in antibody concentration as measured by the antigen-binding assay, which was not related to the preimmunization antibody concentration.
Abstract: One hundred forty-one children of 5 to 59 months of age were immunized with a single intramuscular dose of 0.67, 3.3, 17, or 67µg polyribophosphate (PRP), the capsular antigen of Hemophilus influenzae, type b. The immunizations were well tolerated, particularly at doses of .67 to 17µg. Antibody activity was measured by radioactive antigen binding, using 3H-labelled PRP. Doses of 3.3 and 17µg produced significant antibody rises in nearly 90% of recipients; 0.67 and 67µg in approximately half. The geometric mean titers were similar at three and six weeks after immunization and were greater with the middle doses. The net antibody increase in responding children was strongly age dependent, but was not related to the preimmunization antibody concentration. Rises in serum bactericidal activity against H. influenzae type b generally accompanied rises in antibody concentration as measured by the antigen-binding assay.

Journal Article
TL;DR: These antibodies, although rare, may provide a serological marker for a small proportion of active chronic hepatitis cases differing in several respects from other recognized subgroups in this disease.
Abstract: An autoantibody reacting with microsomal membranes has been characterized by a distinctive immunofluorescence pattern on proximal renal tubules and hepatocytes. The microsomal nature of the antigen was demonstrated by absorption and quantitative complement fixation studies. These results showed the antibodies to be quite distinct from the mitochondrial antibodies found in primary biliary cirrhosis. Microsomal antibodies have so far been detected in sixteen cases, of whom twelve had liver disorders. These antibodies, although rare, may provide a serological marker for a small proportion of active chronic hepatitis cases differing in several respects from other recognized subgroups in this disease.

Journal ArticleDOI
TL;DR: The conclusion is allowed that the cellular mediators of anti-Listeria immunity belong to an expanded population of rapidly dividing, short-lived T cells, suggested that they have the same properties as the T cell effectors of allograft immunity.
Abstract: An intravenous immunizing infection with the facultative, intracellular parasite, Listeria monocytogenes results in the production in the spleen of a population of immunologically-committed lymphocytes which can adoptively immunize normal recipients against a lethal challenge infection. These cellular mediators of immunity are first produced in the spleen between days 2 and 4 of infection and reach peak production on day 6. Their production then progressively decreases until about day 20 when their presence can no longer be detected. Increased production of cellular mediators is coincident with major increases in cell division, cellularity, and spleen weight. Decreased production of cellular mediators, on the other hand, is associated with decreases in cell division, cellularity, and spleen weight. Again, the level of delayed sensitivity to Listeria antigens expressed by the host at any one time is proportional to the number of cellular mediators in the spleen. Increased production of cellular mediators is also associated with major increases in the total numbers of replicating T cells and B cells in the spleen. That the cellular mediators of immunity are part of the replicating T cell population, rather than the B cell population, is evidenced by their susceptibility to anti-θ serum and by their resistance to anti-Ig serum. Furthermore, they can be completely eliminated from the spleen by a brief pulse of the antimitotic drug, vinblastine. This study allows the conclusion that the cellular mediators of anti-Listeria immunity belong to an expanded population of rapidly dividing, short-lived T cells. It is suggested that they have the same properties as the T cell effectors of allograft immunity.

Journal Article
TL;DR: Observations provide evidence for local synthesis of poliovirus antibody in the genital tract, and its implication may be applicable to other genital infections.
Abstract: Antibody response to poliovirus type I in serum, the nasopharynx, and the secretions of the genital tract was studied in human volunteers after intravaginal, intrauterine, nasopharyngeal, or intramuscular immunization with inactivated poliovaccine The techniques of radioimmunodiffusion and autoradiography with P32 labeled poliovirus as the antigen were employed to determine antibody activity in the major classes of immunoglobulin in serum and secretions Intravaginal and intrauterine immunization consistently resulted in the appearance of secretory antibody to poliovirus in the genital tract The vaginal response was predominantly of γA immunoglobulin, while the response in the uterus was essentially limited to γG immunoglobulin Intramuscular immunization resulted in a delayed appearance of γG response in the genital tract, which could be correlated with the highest γG antibody titers in the serum No genital γA response was observed, however, after such immunization These observations provide evidence for local synthesis of poliovirus antibody in the genital tract, and its implication may be applicable to other genital infections

Journal ArticleDOI
TL;DR: The antigenic system thus identified has been named X.1.1 and is ascribed tentatively to a sub-type of MuLV that is not passage A Gross virus and is probably not the dominant sub- type in strains with a high incidence of leukemia.
Abstract: Two BALB radiation leukemias are strongly rejected by hybrids of BALB with certain other mouse strains, although BALB mice themselves exhibit no detectable resistance whatever. Hybrids immunized with progressively increased inocula are resistant to 200 x 106 or more leukemia cells; their serum is cytotoxic for the leukemia cells in vitro and protects BALB mice against challenge with these BALB leukemias. The antigenic system thus identified has been named X.1. In (BALB x B6) hybrids the major determinant of resistance was shown to be a B6 gene in the K region of H-2 . This is likely to be the Rgv-1 ( Resistance to gross virus ) locus of Lilly, which may thus be identified in this case as an Ir ( Immune response ) allele conferring ability to respond to X.1 antigen on MuLV and leukemia cells, and so responsible for production of X.1 antibody and the rejection of X.1+ leukemia cells by hybrid mice. Immunoelectron microscopy with X.1 antiserum (from immunized hybrids) shows labeling both on the cell surface and on virions produced by the leukemia cells. It is not known whether X.1 comprises only one or more than one antigen. Three radiation-induced BALB leukemias, one A strain radiation-induced leukemia, and 15/15 AKR primary spontaneous leukemias were typed X.1+ by the cytotoxicity test. Several other leukemias, including one induced by passage A Gross virus and one long-transplanted AKR ascites leukemia carried in (B6 x AKR)F1 hybrids, were X.1-. Normal mice of strains with a high incidence of leukemia and one other strain (129) express X.1 antigen, but evidently in amounts too small for certain detection in vitro; by the method of absorption in vivo, however, these strains could be typed X.1+ and other strains X.1-. We ascribe the X.1 antigen system tentatively to a sub-type of MuLV that is not passage A Gross virus and is probably not the dominant sub-type in strains with a high incidence of leukemia. After repeated passage in hybrids, one of the BALB leukemias became relatively resistant to rejection by the hybrid, partially lost its sensitivity to X.1 antiserum in vitro, and in electron micrographs was seen to produce fewer virions. The serum of untreated (BALB x B6) hybrids often contains cytotoxic antibody against leukemia cells, some of it probably anti-X.1. But another commonly occurring antibody, which is cytotoxic for C57BL leukemia EL4, appears to belong to another (undefined) system.

Journal ArticleDOI
28 Mar 1973-Nature
TL;DR: The cytotoxic effector cell is described as a non-Ig-bearing lymphoid cell which is not of T cell origin, and some investigators have suggested that this cell is a B lymphocyte.
Abstract: ANTIBODY-COATED target cells may be killed by suspensions of lymphoid cells after depletion of active phagocytes1–4. Harding et al.5 and Van Boxel et al.6 also report that a non-thymus-derived lymphocyte is responsible for this antibody-dependent cell-mediated cytotoxicity in both the rat and mouse. The further observations that the cytotoxic cell acts through an Fc receptor4 similar to that found on most immunoglobulin (Ig)-bearing cells7,8 and that it can be inhibited by pretreatment with anti-Ig sera6, have led some investigators6 to suggest that this cell is a B lymphocyte. The following experiments, however, describe the cytotoxic effector cell as a non-Ig-bearing lymphoid cell which is not of T cell origin.

Journal ArticleDOI
20 Apr 1973-Nature
TL;DR: New knowledge of the specific determinants of microbial pathogenicity provides a sounder basis for the development of effective vaccines and the following report is an example of this approach to disease control.
Abstract: ALTHOUGH vaccination has assisted the control of many bacterial diseases, parenteral vaccination against enteric disease is not as satisfactory as we could wish1. This is attributable to incomplete knowledge of both the pathogenesis of intestinal infections and the protective immune responses of the alimentary tract, with the result that vaccine development has been largely empirical. New knowledge of the specific determinants of microbial pathogenicity2 provides a sounder basis for the development of effective vaccines and the following report is an example of this approach to disease control.

Journal Article
TL;DR: It was considered that WEHI-22 cells either possess a mixture of T and B cell characteristics or are neoplastic variants of T cells possessing surface IgM with antiglobulin activity.
Abstract: Nineteen different radiation-induced thymomas originating in BALB/c, NZB and NZW mouse strains were tested for Ig synthesis by short-term culture with 14 C-amino acids followed by radioimmunoelectrophoresis. Twelve were negative, six produced light (L) chains and one synthesized a protein similar to IgM. The IgM producer, WEHI-22, and one of the L chain producers, WEHI-105, were established as cloned cultured cell lines and shown to possess the lymphoid cell characteristics of susceptibility to inhibition by low concentrations of thymidine and of cortisol. Both were also shown to bear the θ antigen, a thymus-derived (T) lymphocyte marker. Cells of the WEHI-22 line also possessed surface immunoglobulin readily detectable by binding of labeled anti-Ig antibody and were able to bind mouse antibody-coated sheep erythrocytes forming rosettes, while WEHI-105 did neither. The specificity of the Ig receptor mediating rosette formation appeared from myeloma protein competition experiments to be very similar to that of the receptor described for non-thymus-derived (B) cells. It was considered that WEHI-22 cells either possess a mixture of T and B cell characteristics or are neoplastic variants of T cells possessing surface IgM with antiglobulin activity.

Journal ArticleDOI
TL;DR: It is concluded that antibody against the neuraminidase of the influenza virus prevented or modified infection in a situation in which haemagglutinin antibody had no effect.