Showing papers on "Antibody published in 1977"
TL;DR: FUSION between myeloma cells and spleen cells from immunised donors has been shown to be a successful method of deriving homogeneous anti-SRBC (anti-sheep red blood cell) and anti-TNP antibodies.
Abstract: FUSION between myeloma cells and spleen cells from immunised donors has been shown to be a successful method of deriving homogeneous anti-SRBC (anti-sheep red blood cell) and anti-TNP antibodies1,2. One of the most powerful features of this approach is that, by cloning, one may easily derive cell lines synthesising monoclonal antibodies despite using non-purified immunogens. The multiple components of a heterogeneous population of hybrid cells are resolved by cloning techniques. This feature makes the system a very powerful tool in the study of complex antigenic structures. The established cell lines offer the further advantage of unlimited permanent supply of material, and the possibility of worldwide standardisation.
1,749 citations
TL;DR: In vitro antibody-dependent infection of PBL provides a possible model for study of pathogenetic mechanisms in infants with dengue shock syndrome who passively acquire maternal anti-dengue IgG.
Abstract: Cultured mononuclear peripheral blood leukocytes (PBL) from nonimmune human beings and monkeys are nonpermissive to dengue 2 virus (D2V) infection at multiplicities of infection of 0.001-0.1, but become permissive when non-neutralizing dengue antibody is added to medium. D2V infection occurred in PBL prepared from anti-coagulated but not from defibrinated plasma. Infection enhancement was produced by multiple lots of heterotypic anti-dengue raised in several mammalian species. Homotypic anti-dengue neutralized D2V at high concentrations but enhanced at low concentrations; enhancement end point in one serum was 1:320,000. The infection-enhancing factor was a noncytophilic antibody of the IgG class. D2V infection occurred in the absence of heat-labile complement components but did not occur when complexes were prepared with anti- dengue F(ab)(2). Treatment of PBL with several proteases increased permissiveness to D2V infection by immune complexes but not by virus alone. Two rhesus monkey serums collected 14 days after D2V infection contained an IgG antibody with high-titered enhancing activity but with no hemagglutination-inhibition or neutralizing activity. Virus-antibody complexes are irreversibly attached to PBL within 15 min and completely internalized in 60 min. There was considerable variation in cellular infection in different experiments, however, maximum virus yields usually exceeded 1,000 plaque-forming units per 1 x 10(6) PBL occurring between 2 and 4 days in culture. In vitro antibody-dependent infection of PBL provides a possible model for study of pathogenetic mechanisms in infants with dengue shock syndrome who passively acquire maternal anti-dengue IgG.
760 citations
TL;DR: A new approach to study differentiation antigens by means of monoclonal xenogeneic antibodies produced by myeloma-hybrid lines in culture is described, which allows identification down to minor membrane molecules and also of antigen on small subpopulations of a heterogeneous mixture of cells.
709 citations
TL;DR: Mouse spleen cells could be preparatively separated into immunoglobulin positive (Ig+) and immunoglobeulin-netative (IG-)populations by incubating as many as 2 X 10(8) cells per 100 mm diameter petri plate coated with specifically purified goat anti-mouse immunoglOBulin.
531 citations
TL;DR: An in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B)-cell neoplasia and systematic and predictive studies of anticancer drug effects on myeloma stem cells should now be feasible.
Abstract: The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 10(5)-10(6) and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B)-cell neoplasia. In addition, systematic and predictive studies of anticancer drug effects on myeloma stem cells should now be feasible.
496 citations
TL;DR: The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 percent (23 of 939) as mentioned in this paper.
Abstract: The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception.
468 citations
TL;DR: During fetal life, lower concentrations of anti‐y antibodies were required for modulation of sIgM from B lymphocytes of fetal liver and adult bone marrow than for equivalent removal from circulating B cells of mature individuals.
Abstract: Immunofluorescent techniques were used to examine several aspects of B cell ontogeny in humans. Large lymphoid cells containing intracytoplasmic IgM (pre-B cells) were present in fetal liver as early as 7 weeks of gestation, approximately 2 weeks prior to the appearance of surface IgM positive (sIgM+) B lymphocytes. Pre-B cells outnumbered sIgM+ B lymphocytes in fetal liver up until the 13th week of gestation. In fetuses older than 13 weeks, pre-B cells and sIgM+ B lymphocytes were present in approximately equal proportions in liver and bone marrow. Pre-B cells in fetal liver, and fetal and adult marrow, were large and small (indicating a heterogeneous population of cytoplasmic IgM+. SIg- cells in these sites), while only the small pre-B cells were present in fetal spleen, blood and lymph node. Lymphocytes bearing sIgG were detected earlier than those bearing sIgD or sIgA, which were present by the 12th gestational week. Using double-staining techniques, we determined that during fetal life, (a) the proportion of B lymphocytes bearing only sIgM, as opposed to those bearing both sIgM and sIgD, was much higher in liver and bone marrow than in spleen, blood and lymph node, and (b) sIgG, sIgA and sIgD appear independently on lymphocytes bearing sIgM. Studies of the frequency of double-stained cells for each combination of the four sIg isotypes indicated that B lymphocytes from neonatal humans may simultaneously bear three or more sIg isotypes, whereas sIgG+ and sIgA+ B lymphocytes in adult blood usually express only the single isotype. Lower concentrations of anti-y antibodies were required for modulation of sIgM from B lymphocytes of fetal liver and adult bone marrow than for equivalent removal of sIgM from circulating B cells of mature individuals.
In conjunction with data obtained in mice, our observations indicate that (a) the presence of large and small pre-B cells, (b) a high ratio of sIgM single to sIgM.sIgD double B lymphocytes, and (c) increased sensitivity to modulation of B cell sIgM by divalent anti-μ antibodies define the fetal liver and adult bone marrow as bursa-equivalent sites in humans. Our results are consistent with a model of isotype diversification in which immature sIgM+ cells give rise to B cell sublines devoted to synthesis of each of the Ig classes, and sIgD is secondarily expressed on unstimulated B cells of all of these sublines.
416 citations
TL;DR: In this paper, the role of humoral factors in the pathogenesis of myasthenia gravis was investigated using passive transfer of human serum fractions to mice, where the active fraction was identified as IgG by three different purification methods.
Abstract: To study the role of humoral factors in the pathogenesis of myasthenia gravis, we employed passive transfer of human serum fractions to mice. Immunoglobulins from 16 patients with myasthenia gravis were injected into mice daily for one to 14 days. Typical myasthenic features of reduction in amplitude of miniature end-plate potentials (mean change more than 50 per cent, P less than 0.005) or reduction in acetylcholine receptors at neuromuscular junctions (mean change more than 50 per cent, P less than 0.005) (or both) were produced by immunoglobulin from 15 of the 16 patients. Some mice showed weakness or decremental responses to repetitive nerve stimulation as well. The active fraction was identified as IgG by three different purification methods. Its effect was enhanced by the third component (C3) of the complement system, but the fifth component (C5) had no effect. These data suggest that the pathogenesis of myasthenia gravis often involves and antibody-mediated autoimmune attack on the acetylcholine receptors of the neuromuscular junction.
395 citations
TL;DR: The intestinal lymphocyte population, in comparison with that of peripheral blood, had greater numbers of bone marrow-derived cells, particularly cells bearing membrane IgA; showed spontaneous association with macrophages; underwent rapid rosette formation with sheep erythrocytes; and demonstrated increased in vitro synthesis of immunoglobulin.
Abstract: Viable suspensions of human colonic mucosal lymphoid cells have been prepared by sequential treatment of tissue with dithiothreitol, EDTA in calcium- and magnesium-free salt solutions, and purified collagenase. The intestinal lymphocyte population, in comparison with that of peripheral blood, had greater numbers of bone marrow-derived cells, particularly cells bearing membrane IgA; showed spontaneous association with macrophages; underwent rapid rosette formation with sheep erythrocytes; and demonstrated increased in vitro synthesis of immunoglobulin. Total thymus-derived cells were equal in the two populations. Decreases were found in "null" cell numbers, in cells bearing membrane IgD and IgM, and in responsiveness to phytohemagglutinin. Macrophage/monocytes in the intestinal population were increased in size, granularity, motility, sustained glass adherence, and phagocytic activity. Human intestinal lymphoid cells appear to constitute a cell population that is more "mature" and/or "activated", in comparison with the lymphoid cells of peripheral blood. The method of preparation should lend itself to the study of inflammatory bowel disease, gastrointestinal cancer, and the intestinal secretory immune system.
391 citations
TL;DR: This study found that resetting with antigen-coupled erythrocytes is one of the conceivable methods for pre-selection of lymphocytes with the appropriate antigen combining site, opening the way to the establishment of cell lines producing specific antibodies of choice.
Abstract: EPSTEIN–BARR virus (EBV) is a lymphotropic herpesvirus that converts normal human B lymphocytes into established lines. This ‘immortalisation’ preserves the characteristics of the original B cell, including EBV receptors, complement receptors, surface immunoglobulin and secretory immunoglobulin. Surface immunoglobulin is most frequently IgM. EBV-immortalised lines carry multiple copies of the viral genome, detected by nucleic acid hybridisation, and regularly express an EBV-specific nuclear antigen, EBNA. It has been suggested1 that all B-cells carry EBV receptors. If so, and if all B cells can be transformed into lines by EBV, it should be feasible to establish permanent lines from B lymphocytes capable of producing specific antibodies against appropriate antigens. Clearly, in view of the polyclonal transformation obtained after infection of B lymphocytes with a transforming virus strain, for example, B95-8, it will be necessary to pre-select lymphocytes with the appropriate antigen combining site. Resetting with antigen-coupled erythrocytes is one of the conceivable methods for such pre-selection. While this will select lymphocytes with the appropriate surface immunoglobulin receptors, it was recently shown that EBV-transformation activates normal lymphocytes and induces the release of secretory immunoglobulin2. If the procedure is successful, the established lines might therefore be expected to carry the appropriate surface receptor and also to secrete the corresponding antibody. This was actually found in this study, opening the way to the establishment of cell lines producing specific antibodies of choice.
382 citations
TL;DR: The hypothesis is that EBV infection in vitro of human blood lymphocytes gives rise to increased DNA synthesis and that lymphoid cell lines carrying the EBV genome shed or release immunoglobulins of various classes fits with a polyclonal B-cell activation of EBV.
Abstract: APART from the specific anti-Epstein-Barr virus (EBV) response in infectious mononucleosis (IM), there is a strong general increase of antibody levels1. The major increase comprises IgM. As EBV has been shown to infect B lymphocytes selectively2 we hypothesised that the virus triggered the infected cells to release immunoglobulin, much like the effect of certain B-cell mitogens3, although the mechanism of activation must be different. It is known that EBV infection in vitro of human blood lymphocytes gives rise to increased DNA synthesis4 and that lymphoid cell lines carrying the EBV genome shed or release immunoglobulins5 of various classes. Furthermore, the IgM increase seen in IM would fit with a polyclonal B-cell activation (PBA) of EBV as PBA usually gives rise to IgM secretion6. To test this hypothesis, we have exposed lymphocytes from cord blood and adult peripheral blood to EBV in vitro and measured the released IgM, by a doubleantibody radioimmunoassay, and individual antibody-forming cells (PFC) against haptenated red blood cells and sheep red blood cells (SRBC).
TL;DR: Investigations showed that the ELISA was as sensitive as electron microscopy or radioimmunoassay for detection of this agent and was simple to perform and, when read visually, did not require sophisticated technical equipment.
TL;DR: The results suggest that the inhibition involved blockade or inactivation of particular cell surface molecules and that the retinal cell antigens capable of neutralizing the antibodies represented these molecules or their fragments.
TL;DR: Exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.
Abstract: Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses However, not all of the virus-immune T-cell clones are cross-reactive Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus Even so, the less specific component is significant Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus
TL;DR: The total protective activity of the virus was recovered in the purified G protein preparation, and it can be considered the ideal human antirabies vaccine.
Abstract: Purified rabies virus glycoprotein (G) was shown by complement fixation and immunodiffusion tests to be a second distinct antigen of the virus. It it the only structural protein of the virus that induces the formation of virus-neutralizing antibodies and which confers immunity to animals. When the G protein is taken as antigen, the complement fixation test can be used for the assay of virus-neutralizing antibodies. The total protective activity of the virus was recovered in the purified G protein preparation. The protective activity of G protein increased with purification: 9 ng of G protein was required to protect 50% of the mice as compared to 1.63 micrograms of the virus. Selective immunofluorescent membrane staining and immunocytolysis of rabies virus-infected cells were shown to be G protein specific. Due to its purity and potency, the G protein preparation can be considered the ideal human antirabies vaccine.
Journal Article•
TL;DR: Macrophage cell types are capable of antibody-dependent tumor lysis, that macrophages are probably heterogeneous in effector cell activities, and that they can be stimulated to increased ADL in the complete absence of other cell types.
Abstract: Five murine macrophage or monocyte-related tumor cell lines in culture were compared for antibody-dependent lysis (ADL) of a tumor target (T lymphoma EL4) and lysis and phagocytosis of sheep erythrocytes (RBC). Some lines were effective only with RBC targets, while others were capable of lysing these and tumor targets. Both murine alloantisera to H-2 and Thy 1.2 antigens on the target cells and rabbit anti-mouse spleen and anti-mouse thymus sera directed target lysis, while normal mouse or rabbit sera were inactive. Preincubation of macrophage line RAW264 with lipopolysaccharide (LPS) or purified protein derivative from Mycobacteria (PPD) for 2 days resulted in an average of 76% or 86% increase, respectively, in ADL of RBC, although there was no stimulation in RBC phagocytosis or in nonspecific or antibody-dependent lysis of tumor targets. These results indicate that macrophage cell types are capable of antibody-dependent tumor lysis, that macrophages are probably heterogeneous in effector cell activities, and that they can be stimulated to increased ADL in the complete absence of other cell types.
TL;DR: The demonstration of HBs antigen and antibody after acid dissociation of PEG precipitates from hepatitis B seronegative sera illustrated the fact that PEG does precipitate and thus concentrates circulating immune complexes.
TL;DR: As judged from the length of the incubation period before appearance of HBS Ag in blood, there seemed to be a remarkable difference in infectivity between the HBe Ag-positive serum and the anti-HBe- positive serum; the former serum was 10(8) times more infectious than the latter.
Abstract: For confirmation of the difference in the infectivity of hepatitis B surface antigen (HBS Ag)-positive serum according to differences in the e antigen system, four chimpanzees were inoculated with serum positive for hepatitis B e antigen (HBe Ag), and three chimpanzees were inoculated with serum positive for antibody to HBe Ag (anti-HBe). Since the infectivity titrations are not yet completed, the end infectivity titer of each serum is not known. All four chimpanzees given injections of 10(-1), 10(-4), or 10(-8) dilutions of HBe Ag-positive serum developed hepatitis B virus infection, whereas the one chimpanzee injected with undiluted anti-HBe-positive serum became infected, and other chimpanzees injected with diluted anti-HBe-positive sera did not. As judged from the length of the incubation period before appearance of HBS Ag in blood, there seemed to be a remarkable difference in infectivity between the HBe Ag-positive serum and the anti-HBe-positive serum; the former serum was 10(8) times more infectious than the latter.
TL;DR: Data indicate that glycosylation of newly synthesized IgA and IgE may be necessary for normal secretion to occur, and tunicamycin had little effect on the secretion of normally nonglycosylated lambda light chains or on cell-free protein synthesis.
TL;DR: In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.
Abstract: Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 mug/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.
TL;DR: These differentiation antigens of the human breast epithelial cell are not only useful as specific cell-type markers, but also can provide a tool to study the role of the cell surface in normal and neoplastic mammary development.
Abstract: Rabbit antibodies against components of the human milk fat globule bind specifically to normal human breast epithelial cells and cell lines derived from breast carcinomas, as well as to the outer surface of the human milk fat globule. Variation in indirect immunofluorescence staining in both intensity per cell and percentage of cells stained is observed for the different brest cell lines. Cells derived from other epithelial and other ectodermal tissues, fetal fibroblasts, cells of the blood buffy coat, and even fibroblasts of the breast itself do not bind the antibodies. This suggests that these antibodies are detecting cell-type-specific antigens. These normal breast epithelial cell antigens are on the cell surface and their expression is stable in long-term cultured cell lines, even after much chromosomal variation in a given line. By affinity chromatography, three distinct antigenic components can be isolated from the milk fat globule, one of which contains carbohydrate. These differentiation antigens of the human breast epithelial cell are not only useful as specific cell-type markers, but also can provide a tool to study the role of the cell surface in normal and neoplastic mammary development.
TL;DR: It is anticipated that the approach described here will be useful in the diagnosis of lymphoma, differentiating it from reactive lymphoid hyperplasia by the demostration of monoclonality, and should provide a sensitive and reliable tool for investigating the immunobiology of human lymphoma.
Abstract: Human tissues involved with lymphoma have been examined in frozen sections for immunoglobulin-bearing cells by a technique involving double-label immunofluorescence with mixed anti-kappa and anti-lambda antibodies. F (ab')2 fragments of purified antibodies were employed to avoid any binding via Fc receptors. B cell lymphomas were shown to be composed of monoclonal populations of Ig bearing cells, whereas normal or reactive lymphoid follicles contained a mosaic of Ig-bearing cells derived from multiple clones. Nodules of lymphoma were often surrounded by normal polyclonal B cell populations. We anticipates that the approach described here will be useful in the diagnosis of lymphoma, differentiating it from reactive lymphoid hyperplasia by the demostration of monoclonality. In addition, it should provide a sensitive and reliable tool for investigating the immunobiology of human lymphoma.
TL;DR: A radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.
Abstract: Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.
TL;DR: The findings indicated that the nature of cellular infiltrates differed in mild gingivitis and periodontitis, which had important implications for the contribution of nonspecific effector mechanisms to the destruction of periodontal tissue.
Abstract: Gingival biopsies from areas characterized as clinically normal, mild gingivitis, or periodontitis were examined. Immunoglobulin (IgG, IgA, IgM, IgE and IgD) bearing cells at the sulcular and oral epithelium - lamina propria junctions as well as the central lamina propria areas were quantitated. Normal gingiva (P. I. = 0-0·2) contained few lymphocytes and plasma cells. Biopsies from areas of mild gingivitis (P. I. = 0·2-1) were infiltrated at the sulcular epithelium - lamina propria junction by lymphocytes lacking membrane associated immunoglobulins (94 %). Few plasma cells were evident. In contrast, tissue associated with periodontitis (P. I. = 4·0–8·0) contained significant numbers of immunoglobulin bearing lymphocytes (78 %, IgG; 9 %, IgM; and 4 % IgA) and plasma cells (67 %, IgG; 24 %, IgM; and 8 % IgA) distributed throughout all three major tissue areas.
These findings indicated that the nature of cellular infiltrates differed in mild gingivitis and periodontitis. The presence of predominantly IgG and IgM containing cells in periodontitis had important implications for the contribution of nonspecific effector mechanisms to the destruction of periodontal tissue.
TL;DR: CTLs are believed to play a uniquely important role in physiological immune tissue destruction (for which serum immunoglobulins are usually insufficient), probably utilizing mononuclear phagocytes as an amplifying mechanism.
Abstract: A cytolytic thymus-derived lymphocyte (CTL)* is a specialized cell the recognized function of which is immune killing. CTLs are generated by a process of antigen-induced clonal selection, proliferation, and differentiation. Each CTL apparently recognizes a single H-2 alloantigen. CTL targets are eukaryotic tissue cells bearing specific membrane-associated antigen, such as virus-infected autologous cells, grafted cells of genetically different origin, tumor cells, or autologous cells made more immunogenic by chemical modification. CTLs are believed to play a uniquely important role in physiological immune tissue destruction (for which serum immunoglobulins are usually insufficient), probably utilizing mononuclear phagocytes as an amplifying mechanism.
Journal Article•
TL;DR: It is suggested that the development of B-memory cells involves the formation of antigen-antibody-C3 complexes on dendritic cells in lymphoid follicles, and C3 may serve to stabilize the antigen bridge between d endritic cells and virgin precursors.
Abstract: Adult thymectomized, repopulated mice were chronically depleted of circulating C3 by treatment with cobra venom factor after primary immunization with dinitrophenylated haemocyanin (DNP-KLH). This treatment totally abrogated the development of B-cell memory in such mice, as assayed by a co-operative lymphocyte transfer. The failure of memory development appeared to involve impaired precursor proliferation following priming. It was further shown that the localization of DNP-KLH in splenic lymphoid follicles is both antibody and C3-dependent; thymus-deprived mice make sufficient antibody to DNP-KLH to effect follicular localization of the antigen. On the basis of these and earlier observations we suggest that the development of B-memory cells involves the formation of antigen-antibody-C3 complexes on dendritic cells in lymphoid follicles. C3 may serve to stabilize the antigen bridge between dendritic cells and virgin precursors. In complete contrast, C3 depletion had little effect on the functional expression of primed B cells, thus suggesting that only the early stages of B-cell triggering are C3 dependent.
Journal Article•
TL;DR: It is concluded that an anatomically intact spleen, i.v. presentation of antigen, and persistence of antigen within the eye are all important to the elicitation of F1 LI-ID.
Abstract: The immunizing abilities of alloantigens placed within the anterior chamber of the eye have been studied in inbred rats. Although intracameral inoculation of F1 hybrid lymphocytes into parental strain recipients elicited both cell- and antibody-mediated immunity, a delimited interval was identified postinoculation during which the systemic cell-mediated immune response was suppressed as indicated by prolonged acceptance of orthotopic skin allografts. The prompt appearance of hemagglutinating antibodies in the serum of immunized rats followed a time course which coincided with the suppression of cell-mediated immunity and suggested that the two events are casually related. Since exposure to allogeneic antigens on lymphoid cells via the anterior chamber elicits a transient suppression in cell-mediated immunity, where humoral immunity is preserved, the phenomenon resembles immune deviation.
TL;DR: It is demonstrated that BP may occur in a transient predominantly localized form that remits spontaneously, and most BP patients after successful therapy remain in prolonged clinical remission, and combined therapy with azathioprine plusprednisone appears to be superior to prednisone alone in the treatment of BP.
Abstract: • Thirty-six patients with bullous pemphigoid (BP) have been periodically evaluated for four years. This study demonstrates that BP may occur in a transient predominantly localized form that remits spontaneously, and most BP patients after successful therapy remain in prolonged clinical remission. In this study, all patients with active or recurrent disease had IgG and/or C3 basement membrane zone (BMZ) deposition. Serum anti-BMZ antibodies was an inconstant feature. In most instances, clinical remission of BP was associated with disappearance of BMZ Ig and C3 deposition and serum BMZ antibodies. Fluorescein-conjugated, antihuman C3 appears to be a more sensitive immunoreagent than antihuman, class specific, immunoglobulin antisera in detecting positive BMZ staining in BP. Combined therapy with azathioprine plus prednisone appears to be superior to prednisone alone in the treatment of BP. ( Arch Dermatol 113:1043-1046, 1977)
TL;DR: Double-isotopic-label difference analysis demonstrated that host and viral proteins were synthesized simultaneously during both phases of cytomegalovirus-infected cells, and viral structural ICS proteins and glycoproteins were identified as infected-cell specific.
Abstract: In cytomegalovirus-infected cells, the rate of protein synthesis was detected as two peaks. One occurred during the early phase of infection, 0 to 36 h postinfection, and the other occurred during the late phase, after the initiation of viral DNA synthesis. Double-isotopic-label difference analysis demonstrated that host and viral proteins were synthesized simultaneously during both phases. In the early phase, approximately 70 to 90% of the total proteins synthesized were host proteins, whereas approximately 10 to 30% were viral, even at a multiplicity of infection of 20 PFU/cell. Virus-related proteins or glycoproteins were referred to as infected-cell specific (ICS). Two ICS glycoproteins (gp145 and 100) were clearly detectable and were synthesized preferentially in the early phase of infection. Their synthesis was concomitant with stimulation of the protein synthesis rate. In the late phase of infection, approximately 50 to 60% of the total protein synthesis was viral and approximately 40 to 50% was host. The ICS proteins and glycoproteins detected during the late phase of infection were viral structural proteins. Infectious virus was not detectable until 48 to 72 h postinfection. An inhibitor of viral DNA synthesis, phosphonoacetic acid, prevented the appearance of the late-phase ICS proteins and glycoproteins, but there was little or no effect on early ICS glycoprotein synthesis. Radiolabeled ICS proteins and glycoproteins were identified by their relative rates of synthesis, by their different electrophoretic mobilities compared with those of host proteins and host glycoproteins, and by their similar electrophoretic mobilities compared to those of proteins and glycoproteins associated with virions and dense bodies of cytomegalovirus. Structural viral antigens in the infected-cell extracts were removed by immunoprecipitation, using F(ab′)2 fragments of cytomegalovirus-specific antibodies, and identified as described above. The last two criteria were used to identify viral structural ICS proteins and glycoproteins. Although approximately 35 structural proteins were found to be associated with purified virions and dense bodies, the continued synthesis of host cell proteins complicated their identification in infected cells. Nevertheless, seven of the nine structural glycoproteins were identified as ICS glycoproteins.