RESUMO
Viable and immunologically competent lymphocytes from unsensitized donors damage allogeneic tissue culture cells in the presence of phytohemagglutinin (PHA). This cytotoxicity is specific since syngeneic tissue culture cells are not at all or only slightly damaged under similar experimental conditions. In this investigation, the relation between the stimulation of human lymphocytes and their cytotoxicity was studied. Chang cells (human liver) served as target cells in all experiments. Cell damage was quantitated by measuring the release of isotope from target cells labeled with chromate-(51)Cr. The cytotoxicity of the lymphocytes was dependent on the concentration of PHA in the incubation medium. Cell damage was maximal at concentrations of 4-8 microl PHA/ml. Higher concentrations were inhibitory although aggregation was increased and no injury of the lymphocytes was noted. Stimulation of DNA and RNA synthesis in PHA-treated lymphocytes each followed dose response curves which were similar to that of cytotoxicity. In order to establish whether stimulation without mixed aggregation of lymphocytes and target cells would suffice for cytotoxicity, a series of nonagglutinating stimulants were investigated. Lymphocytes pretreated with a crude filtrate of Staphylococcus aureus for periods of 0.5-72 hr damaged Chang cells even in the absence of PHA. Lymphocytes from a tuberculin-positive donor were strongly cytotoxic after prestimulation with PPD while those from a negative donor were inactive. Moreover, strong cytotoxic effects were also obtained with lymphocytes which had been stimulated by preincubation with allogeneic lymphocytes in mixed culture. When two stimulants were applied at the same time, additive cytotoxic effects were seen. Addition of PHA to the lymphocyte/Chang cell mixtures potentiated the cytotoxicity of prestimulated lymphocytes. The cytotoxic potential of the lymphocytes was in all cases correlated to the degree of stimulation recorded as transformation into blast cells, and was independent both of the degree of aggregation and of the stimulating factor. These findings are compatible with the assumption that injury of the Chang cells reflected an immunologically nonspecific activity of lymphocytes enhanced by stimulation. The possible importance of this activity for a number of tissue-damaging immune reactions in vivo is pointed out.
Assuntos
Técnicas de Cultura , Lectinas/farmacologia , Linfócitos , Staphylococcus , Extratos de Tecidos/farmacologia , Tuberculina/farmacologia , HumanosRESUMO
When monolayers of bovine erythrocytes (Eb) were exposed to purified human blood lymphocytes and either IgG or IgM fractions of rabbit anti-Eb serum, clear zones (plaques) appeared when Eb had been lysed by antibody-dependent effector cells (K cells). IgG-dependent plaque formation was complete by 20 h of incubation, while the IgM-dependent reaction required 40 h. The estimated minimal numbers of plaque forming cells (PFC) were 5.6% (IgG) and 2.0% (IgM) of the added lymphocytes. Inhibition experiments with human IgG or IgM indicated that different immunoglobulin receptors on the effector cells were involved in the two systems. In the IgG system, approximately 50% of the PFC had complement receptors and approximately 30% receptors for Helix pomatia A hemagglutinin (HP). In the IgM system, less than 10% of the PFC had complement receptors, while approximately 60% had HP receptors. The results suggest that a subset of human T cells had IgM-dependent K-cell potential. These cells are different from the majority of the IgG-dependent K cells.
Assuntos
Imunidade Celular , Imunoglobulina G , Imunoglobulina M , Linfócitos/imunologia , Sítios de Ligação , Testes Imunológicos de Citotoxicidade , Humanos , CinéticaRESUMO
Human blood lymphocytes were fractionated on glass bead columns charged with sheep erythrocyte (Es) membranes-bearing human C3b (7,000-10,000 molecules/Es). In the passaged cells the proportion of C receptor lymphocytes was strongly reduced, in parallel with the capacity to lyse chicken erythrocytes (Ec) in the presence of IgG-rabbit anti-Ec antibody. In other experiments, lymphocytes forming rosettes with Es bearing activated rabbit complement [C(ra)] from C6-deficient rabbits were removed by centrifugation through human serum albumin-gelatine mixtures. This procedure also depleted the lymphocyte preparations of antibody-dependent cytolytic effector cells. The results suggest that rations of antibody-dependent cytolytic effector cells. The result suggest that such effector cells have receptors for human C as well as for C(ra). Lymphocytes were not able to lyse erythrocytes bearing either human C3b (similar to 30,000 molecules/Ec) or activated C(ra) in the absence if IgG antierythrocyte antibodies. Under the same experimental conditions these target cells were efficiently lysed in the presence of small amounts of IgG antitarget cell antibodies. This suggests that the interaction between the cellular Fcreceptors and the Fc part of the inducing antibodies is of special significance for the triggering of the cell-mediated lytic reaction. However, although target cell-bound C did not trigger cytolysis, it seemed to potentiate antibody-dependent cytolysis, probably by enhancing effector cell-target cell contacts.
Assuntos
Reações Antígeno-Anticorpo , Proteínas do Sistema Complemento , Hemólise , Imunoglobulina G , Linfócitos/imunologia , Animais , Sítios de Ligação , Galinhas , Humanos , Reação de Imunoaderência , Imunoglobulinas , Coelhos/imunologiaRESUMO
Neuraminidase treatment of human peripheral blood lymphocytes uncovers cell surface receptors that bind purified A hemagglutinin from the snail Helix pomatia. No hemagglutinin was bound to untreated lymphocytes. Binding studies with (125)I-labeled hemagglutinin suggested that the number of receptors on neuraminidase-treated lymphocytes was approximately 1.10(6)/cell. The apparent association constant for hemagglutinin binding to lymphocytes, as calculated from Scatchard's plots, was 5-7.10(8) liters/mol. Immunofluorescent staining with FITC-conjugated hemagglutinin gave positive reactions with approximately 60% of the lymphocytes from normal donors. Positive staining was inversely related to the number of lymphocytes with Fc or complement receptors or with surface immunoglobulin, thus suggesting that See PDF for Structure the lymphocytes with receptors for Helix pomatia A hemagglutinin are T cells. Cell fractionation on columns charged with hemagglutinin indicate that these receptors may be used for separating subpopulations of human peripheral lymphocytes.
Assuntos
Sítios de Ligação de Anticorpos , Membrana Celular/imunologia , Linfócitos T/imunologia , Animais , Anticorpos/análise , Membrana Celular/efeitos dos fármacos , Separação Celular , Eritrócitos/imunologia , Imunofluorescência , Reação de Imunoaderência , Radioisótopos do Iodo , Neuraminidase/farmacologia , Caramujos/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
Peripheral lymphocytes from patients with urinary bladder carcinoma and controls have been separated on the basis of rosette formation with sheep erythrocytes. The fractions were tested for tumor-specific cytotoxicity. The E rosette-forming cells of purity 90% respond well in PHA-induced cytotoxicity but are totally inactive in the tumor assay. The non-E rosette-forming cells (purity 91%) give enhanced activity in the tumor-specific cytotoxicity as well as in antibody-mediated target cell lysis in a model system. These data support the notion that the effector cells in cell-mediated immunity to carcinoma of the urinary bladder are members of the nonthymus-derived population of peripheral lymphocytes.
Assuntos
Carcinoma de Células de Transição/imunologia , Reação de Imunoaderência , Imunidade Celular , Neoplasias da Bexiga Urinária/imunologia , Linfócitos B/imunologia , Linhagem Celular , Células Cultivadas , Proteínas do Sistema Complemento , Meios de Cultura , Técnicas Citológicas , Testes Imunológicos de Citotoxicidade , Humanos , Lectinas , Linfócitos/imunologia , Melanoma , Bexiga UrináriaRESUMO
T cells from human peripheral blood was purified by fractionation on columns charged with human immunoglobulin and rabbit anti-human immuno-globulin. When assayed with 125I- or fluorescein isothiocyanate-labeled wheat-germ agglutinin (WGA), a weakly binding and a strongly binding subpopulation could be distinguished. These T-cell subpopulations were fractionated on columns charged with WGA, convalently bound to Sepharose 6MB. The cells responding to the mitogens leukoagglutinin from Phaseolus vulgaris and concanavalin A were enriched in the strongly binding subpopulation (approximately 20% of the T cells) while they were depleted from the weakly binding subpopulation.
Assuntos
Lectinas/metabolismo , Linfócitos T/metabolismo , Sítios de Ligação , Células Sanguíneas , Separação Celular , Concanavalina A , Humanos , Ativação Linfocitária/efeitos dos fármacos , Lectinas de Plantas , TriticumRESUMO
Germfree rats monocontaminated with the anaerobic microorganisms Clostridium difficile or another Clostridium species (strain G 62) produce auto-antibodies to colon antigen. The antigen can be extracted with phenol water from the feces of germfree rats. Antibodies, demonstrable by means of passive hemagglutination of antigen sensitized sheep erythrocytes appear after monocontamination for 35 days or longer. The indirect immunofluorescence techniques, applied to sections of germfree rat colon, gave positive mucosal staining. The staining was similar to that obtained with sera from patients with ulcerative colitis or from rats immunized with rabbit colon. No antibodies were found in the sera of germfree rats, germfree rats monocontaminated with various other bacteria, conventional rats of germfree origin, or conventional Sprague-Dawley rats. Although the anti-colon antibodies of the Clostridium infected rats reacted with the same feces extract as the antibodies of ulcerative colitis patients or of rabbit colon immunized rats, their specificity was different. While the latter cross-react with polysaccharide from E. coli O14, those from the Clostridium-infected exgermfree rats did not. Rats monocontaminated with Cl. difficile also developed antibodies to this organism, but no cross-reaction between Cl. difficile antigen and colon antigen could be demonstrated. This speaks against breakage of tolerance by cross-reacting bacterial antigen as the cause of autoimmunity in these rats. Other possible mechanisms for autoantibody production in this model are immunogenic alteration of gastrointestinal mucins by bacterial degradation, adjuvant effects of bacterial products, or both.
Assuntos
Autoanticorpos , Infecções por Clostridium/imunologia , Colo/imunologia , Vida Livre de Germes , Animais , Antígenos/isolamento & purificação , Escherichia coli/imunologia , Fezes/análise , Imunofluorescência , Polissacarídeos Bacterianos , RatosRESUMO
Preparations of E. coli 014 lipopolysaccharide (LPS) contain a common enterobacterial antigen (CA) in large amounts or in an immunogenic form. Chemical analysis revealed, in addition to o-acetyl groups, only those sugars which are present in the basal core structure of the E. coli or Salmonella LPS (e.g., galactose, glucose, glucosamine, heptose, and ketodeoxyoctonate). On treatment with acetic acid (pH 3.2) at 100 degrees C for 1.5 hr, a fragment was liberated which after gel filtration on Sephadex G-50 appeared in the molecular weight range of 2-3 x 10(3). The fragment inhibited precipitation of alkali-treated E. coli 014 LPS by antibodies to CA from anti-E. coli 014 serum. It also inhibited hemagglutination between anti-CA antibodies and red cells coated with E. coli 08 LPS. Chemical analysis of the fragment indicated that it corresponded to the core region of E. coli 014 LPS. It contained a heptose and ketodeoxyoctonate in addition to glucose and galactose. However the fraction lacked glucosamine. Enterobacterial CA has previously been found to cross-react with colon antigen of ulcerative colitis. These results should provide a chemical basis for further studies of this cross-reactivity.
Assuntos
Antígenos/análise , Escherichia coli/imunologia , Lipopolissacarídeos/análise , Acetatos , Antígenos de Bactérias/análise , Precipitação Química , Cromatografia em Gel , Galactose/análise , Glucosamina/análise , Glucose/análise , Hemaglutinação , Heptoses/análise , Hidrólise , Imunoquímica , Cetoácidos/análiseRESUMO
The incidence and height of antibody titers to colon, assayed by indirect hemagglutination with a heat stable colon extract from germ free rats, is significantly higher in sera from patients with ulcerative colitis than in those from healthy controls or from patients with amebic liver abscess or dysentery. While sera from ulcerative colitis patients and controls are indistinguishable in regard to incidence and height of antibody titers to Forsman antigen, Staphylococcus aureus S 209, Clostridium difficile, and several common strains of E. coli, they have elevated titers and increased incidence of antibodies to a heat stable antigen of E. coli O14. Patients with amebic dysentery have normal titers of such antibodies. Absorption of patients' sera with E. coli O14 antigen inhibits the colon directed hemagglutination reaction in approximately 30% of the cases tested. Likewise, the anti-E. coli O14 reaction can sometimes be inhibited with the colon extract. Other E. coli strains and other bacteria are inactive or have only weak inhibitory activity. Hemagglutination inhibition experiments show that germ free rat colon and E. coli O14 contain common structures, depicted by antibodies in the patients' sera. This pattern of reactivity closely resembles that seen in rats made autoimmune to colon by injection of newborn rabbit colon. E. coli O14 is known to carry a heterogenetic antigen present in lower concentration (or activity) in most Enterobacteriaceae. Hemagglutination inhibition experiments with rabbit antisera to E. coli O14 suggest that the antigen common for E. coli O14 and colon is related to this heterogenetic antigen. The findings imply that this antigen, which is constantly present in low concentrations in the human colon, may give rise to anticolon antibody formation in ulcerative colitis through breakage of tolerance. Since this antigen is present in healthy individuals as well, additional factors are required to explain the induction of anti-colon autoimmunity in ulcerative colitis.
Assuntos
Formação de Anticorpos , Autoanticorpos/biossíntese , Colite Ulcerativa/imunologia , Animais , Reações Antígeno-Anticorpo , Povo Asiático , População Negra , Clostridium/imunologia , Colo/imunologia , Disenteria Amebiana/imunologia , Escherichia coli/imunologia , Vida Livre de Germes , Haptenos , Testes de Inibição da Hemaglutinação , Testes de Hemaglutinação , Humanos , Abscesso Hepático Amebiano/imunologia , Coelhos , Ratos , África do Sul , Staphylococcus/imunologia , Suécia , População BrancaRESUMO
The occurrence and distribution of distinct receptors for three C3 fragments on purified human blood lymphocytes were studied by rosette formation. Indicator cells were bovine, chicken, or sheep erythrocytes (E) bearing up to 100,000 molecules of human C3b (EC3b) without antibody. EC3b was converted to C3bi-bearing-E (EC3bi) with purified C3b inactivator (factor I) and beta1H (factor H), and to C3d-bearing E (EC3d) by treatment of EC3bi with trypsin. Using bovine E (Eb) as indicators, approximately 11% of the lymphocytes bound EbC3b, 6% bound EbC3bi and 2% bound EbC3d. Fractionation of the lymphocytes by adsorption to monolayers of C3-fragment-bearing Eb or by rosetting indicated that most of the cells with receptors for C3b were distinct from those having receptors for C3bi and/or C3d. Cells from two lymphoblastoid cell lines (Raji and Daudi) formed strong rosettes with EC3b, which were weak. 51Cr-labeled E was used as a target in antibody, C3-fragment-bearing E was not lysed by the lymphocytes. However, at suboptimal concentrations of IgG enhancing capacity of the fragments occurred in the order of C3bi greater than C3d greater than C3b. In addition, C3-fragment-bearing cells inhibited the lysis of antibody-coated cells not concluded that target cell bound C3 fragments enhance ADCC by improving contact between target cells and those effector cells which have C3 receptors. Cell-bound C3 effector cells. It is proposed that certain lymphocytes are capable of interacting with C3bi in addition to C3b and C3d and that C3bi and C3d have a greater regulatory effect on their cytolytic function than C3b.
Assuntos
Complemento C3/imunologia , Citotoxicidade Imunológica , Imunidade Celular , Linfócitos/imunologia , Receptores de Complemento/fisiologia , Animais , Complemento C3b/imunologia , Camundongos , Fragmentos de Peptídeos , Formação de Roseta , Relação Estrutura-AtividadeRESUMO
Monolayers of human erythrocytes (E) infected with Plasmodium falciparum were briefly fixed with 1% glutaraldehyde and air dried. They were then exposed to sera from patients with P. falciparum malaria or from donors immune to this parasite and tested in an indirect immunofluorescence assay (IFA). Parasites in infected E were made visible by counterstaining with ethidium bromide. Immunofluorescence (IF) was restricted to the surface of infected E. No antibody binding was detected unless the E were dried, suggesting that the relevant antigens were not available on the outer layers of the E surface. Staining over large parts of the E surface was seen already when the merozoite penetrated noninfected cells and was strong in E containing early stages of the parasite (rings, trophozoites). It was weak or absent from E containing schizonts. Antibodies in sera from different parts of Africa, Colombia, or Sweden reacted similarly with E infected with a Tanzanian P. falciparum strain kept in culture for many years and with parasitized E freshly drawn from African, Swedish, or Colombian patients. All sera from residents of a holoendemic area (Liberia) were IFA positive. In contrast, some sera from Colombian or Swedish patients with primary infection gave negative results. The results of the IFA and of an enzyme-linked immunosorbent assay in which fixed and dried E were the targets were well-correlated, suggesting that the same antibodies were detected by these assays. The antigens involved in the IFA were susceptible to pronase but not to trypsin or neuraminidase. E surface IF was inhibited by lysates of infected E, merozoite extracts, or soluble antigens present in P. falciparum culture supernatants but not by lysates of normal E or ghost extracts. The inhibitory antigens were heat stable (100 degrees C, 5 min). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting of either antigen-enriched preparations from culture supernatants or merozoite extracts showed that antibodies eluted from monolayers of infected E reacted consistently with a predominant polypeptide of Mr 155,000 and two to four minor polypeptides of lower molecular weights. Metabolic labeling of the parasites with 75Se-methionine indicated that these antigens were parasite derived. We conclude that the antigens involved in these reactions are released from bursting schizonts or merozoites and are deposited in the E membrane in the course of invasion.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Antígenos de Superfície/imunologia , Membrana Eritrocítica/parasitologia , Malária/imunologia , Plasmodium falciparum/imunologia , Anticorpos/imunologia , Antígenos de Superfície/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Membrana Eritrocítica/imunologia , Imunofluorescência , Humanos , Plasmodium falciparum/crescimento & desenvolvimento , Pronase/farmacologiaRESUMO
Erythrocytes infected with trophozoites or schizonts of Plasmodium falciparum bind uninfected erythrocytes, leading to rosette formation. Both established laboratory strains and fresh isolates from patients form such rosettes, but at widely different frequencies. IgG preparations from the serum of some P. falciparum-immune donors and heparin inhibited rosette formation. The results indicate that cytoadherence of infected erythrocytes to endothelial cells and rosetting represent distinct genetic traits.
Assuntos
Eritrócitos/parasitologia , Plasmodium falciparum/fisiologia , Formação de Roseta , Animais , Adesão Celular , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Heparina/farmacologia , Humanos , Imunoglobulina G/imunologia , Microscopia Eletrônica , Tripsina/farmacologiaRESUMO
Rabbit antiserums were prepared against three submicrosomal fractions from liver of normal or phenobarbital-treated rats. The two membrane fractions originating from the rough- and smooth-surfaced endoplasmic reticulum were characterized by the same soluble antigens, with the exception of a highly basic coinponent present only in extracts of rough membranes. The third fraction, whose subcellular origin is unknown, was different. It contained at least two typical marker antigens not present in the other fractions. Of eight tissue antigens common for the endoplasmic reticulum, five displayed nonspecific esterase activity. Some of these esterases were also found in other organs, but none was seen in rat serum. Phenobarbital treatment of the rats led to a rise in activity and characteristic changes in the esterase patterns of all these submicrosomal liver fractions.
RESUMO
Human lymphocytes treated with the plant protein concanavalin A are stimulated to transform into blasts, without developing cytotoxicity for chicken erythrocytes. Prior treatment of lymphocytes with concanavalin A potentiated phytohemagglutinin-induced blast transformation and DNA synthesis but completely inhibited phytohemagglutinin-induced cytotoxicity. Inhibiton was not due to suppression of the mixed lymphocyte-erythrocyte aggregation normally caused by phytohemagglutinin. Inhibition of cytotoxicity was reversible when concanavalin A was removed from the lymphocytes by treatment with methyl-alpha-D-manno-pyranoside after 1 hour but not after 20 hours. The results indicate that blast transformation and cytotoxicity are separate expressions of lymphocyte stimulation.
Assuntos
Transformação Celular Neoplásica , Linfócitos/efeitos dos fármacos , Proteínas de Plantas/farmacologia , Animais , Galinhas , Isótopos do Cromo , Técnicas de Cultura , Eritrócitos/efeitos dos fármacos , Lectinas/farmacologia , Ativação LinfocitáriaRESUMO
Fowl erythrocytes are lysed when exposed to an excess of fowl blood lymphocytes in the presence of phytohemagglutinin. No significant cell damage is seen in the absence of phytohemagglutinin, or when the lymphocytes are replaced by malignant lymphoid cells, thymus cells, or nonlymphoid cells. The lymphocytes remain viable during the reaction. Differences in histocompatibility between lymphocytes and erythrocytes are not required. Autologous lymphocytes are cytotoxic to the same extent as allogenic lymphocytes over a wide range of experimental conditions.
Assuntos
Eritrócitos , Hemólise , Lectinas/farmacologia , Linfócitos , Alergia e Imunologia , Animais , Isótopos de Carbono , Galinhas , Isótopos do Cromo , Técnicas de Cultura , DNA/biossíntese , Linfócitos/efeitos dos fármacos , Estimulação Química , Timidina/metabolismoRESUMO
Chromium-51-labeled chicken erythrocytes (E), treated with rabbit anti-Forssman antibody (A) and the first four (C1-4) or the first seven (C1-7) components of human complement (C), released isotope upon exposure to human leukocytes. Isotope release from EACJ-7 cells proceeded more rapidly and was more extensive than that from EACI-3 cells. Lysis of these cells was suppressed by pretreatment of leukocytes with antimycinA. Monocyte-enriched leukocyte preparations affected both types of target cell-complement intermediates, whereas purified lymphocytes lysed EACI-7 cells but not EACI-3 cells.
Assuntos
Proteínas do Sistema Complemento/farmacologia , Eritrócitos , Leucócitos , Animais , Anticorpos , Antimicina A/farmacologia , Galinhas , Isótopos do Cromo , Humanos , Linfócitos , Monócitos , CoelhosRESUMO
Pf 155, a protein of the human malaria parasite Plasmodium falciparum, is strongly immunogenic in humans and is believed to be a prime candidate for the preparation of a vaccine. Human monoclonal antibodies to Pf 155 were obtained by cloning B cells that had been prepared from an immune donor and transformed with Epstein-Barr virus. When examined by indirect immunofluorescence, these antibodies stained the surface of infected erythrocytes, free merozoites, segmented schizonts, and gametocytes. They bound to a major polypeptide with a relative molecular weight of 155K and to two minor ones (135K and 120K), all having high affinity for human glycophorin. The antibodies strongly inhibited merozoite reinvasion in vitro, suggesting that they might be appropriate reagents for therapeutic administration in vivo.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Protozoários/imunologia , Plasmodium falciparum/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Antígenos de Protozoários/análise , Humanos , Vacinas/imunologiaRESUMO
Alkaline phosphatase from calf intestinal mucosa has been conjugated to a protein antigen, rabbit IgG. Such conjugates, prepared by glutardialdehyde, have been used in a competitive solid phase immunoassay. In this test native antigen inhibits the binding of the conjugate to homologous antibodies adsorbed to plastic tubes. Using this assay 1-100 ng/ml of the antigen could be determined.
Assuntos
Fosfatase Alcalina/imunologia , Anticorpos/análise , Antígenos/análise , Imunoglobulina G , Adsorção , Animais , Especificidade de Anticorpos , Bovinos , Ensaio de Imunoadsorção Enzimática/métodos , Mucosa Intestinal/enzimologia , Coelhos , OvinosRESUMO
Both antibody-dependent and antibody-independent mechanisms are involved in immune protection against the asexual blood stages of the malaria parasite. It is well established that T cells play a crucial role in both induction and maintenance of this immunity. Of the two T-cell subsets (CD4+, CD8+) carrying alpha/beta T-cell receptors, the CD4+ T cells are of major importance for the development of blood stage immunity in both experimental and human malaria. In mice, CD4+ T cells comprise at least two functionally distinct cell types (TH1, TH2), distinguished on the basis of their lymphokine production. The balance between these subsets is critical for the outcome of an infection. In some rodent malarias, TH1 cells producing IFN-gamma and IL-2 are important for controlling infection in its early phases, while TH2 cells, producing i.a. IL-4 and IL-10, together with antibodies, are important for parasite clearance in later phases of infection. Distinct CD4+ T cells of either TH1 or TH2 type also have regulatory functions in human P. falciparum infection. In contrast to the CD4+ T cells, the role of CD8+ T cells in blood stage infection appears to be limited, but suppression of some CD4+ activities has been reported for both experimental and human malaria. As in other infections, peripheral T cells equipped with gamma/delta receptors are strongly upregulated in malaria and also respond to parasite antigens in vitro by proliferation and lymphokine production. However, the importance of the gamma/delta T cells for protection when compared with pathogenesis is presently unclear. Rapid advances made in recent years in the characterization and cloning of plasmodial antigens eliciting immune protection have made it possible to define some of the antigenic structures involved in T-cell immunity. This, together with an improved understanding of cellular mechanisms, provides some basis for the development of modern malaria vaccines.
Assuntos
Malária Falciparum/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Humanos , Vacinas Antimaláricas/imunologia , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/imunologiaRESUMO
We have established hybridoma lines which secrete mouse monoclonal antibodies (Mabs) to human pituitary growth hormone, hGH. Using indirect competitive ELISA and indirect passive hemagglutination inhibition twelve different Mabs were characterized with regard to cross-reactivity with the hGH-related hormones, human chorionic somatomammotropin, hCS, and human prolactin, hPRL. The reactivity of these Mabs with pituitary hGH was compared to that with either bacterially-produced methionyl-hGH or to that of reduced and S-carboxymethylated hGH, which has an altered conformation. None of the Mabs reacted with hPRL. Four did not react with hCS whereas the others showed varying degree of cross-reactivity with hCS. All Mabs reacted more weakly with reduced and S-carboxymethylated hGH than with the native form of the hormone, which was not seen with conventional rabbit antisera to hGH. Thus in the case of hGH the Mabs are superior to conventional antisera in revealing small conformational differences. However the pituitary and bacterially-derived methionyl-hGH were indistinguishable as determined by the 12 Mabs.