Suppression of the intestinal immune response to cholera toxin by specific serum antibody.

The possibility that preexisting specific serum antibody could suppress a defined mucosal immune response to a topically applied antigen was studied in rats. Hyperimmune serum antibody induced by parenteral immunization of rats with cholera toxoid markedly suppressed the mucosal immune response to enterically applied cholera toxin. Such antibody was far more suppressive than antibody induced by primary parenteral immunization, apparently due to its greater avidity. Transfusion of small amounts (25 to 100 microliter) of hyperimmune serum suppressed the primary mucosal antitoxin response, the development of specific memory in the mucosal immune system, and, somewhat less effectively, the secondary mucosal antitoxin response. Suppression was due largely to a direct effect of serum antibody upon the interaction of absorbed enteric antigen with lymphoid tissue in Peyer's patches and, possible, mesenteric lymph nodes; interference with antigen absorption played little or no role in the observed suppression. These results do not explain the previously reported suppressive effect of primary parenteral immunization on the mucosal immune response to cholera toxin. However, they support the notions that repeated parenteral immunization can evoke avid serum antibody without necessarily stimulating mucosa-associated lymphoid tissue and that such antibody can markedly suppress primary and secondary phases of the local immune response to mucosally applied antigen. Thus, a mechanism is demonstrated by which repeated parenteral immunization may adversely affect efforts to initiate or sustain protective mucosal immune responses.     

Characterization of the humoral immune response in Sudanese leishmaniasis: specific antibody detected by class- and subclass-specific reagents

Sera from Sudanese patients with either visceral or mucosal manifestations of infection with Leishmania were investigated to determine the class of antibodies against the causative parasite in an enzyme-linked immunosorbent assay (ELISA) with intact promastigotes as antigen. All patient sera had significantly more IgG and more antiparasite IgG than did control Sudanese or control Dutch sera; little or no IgM or IgA antiparasite antibody activity was detected. When sera specific for the subclasses of IgG were used to detect the anti-promastigote antibodies, these were found in IgG1- and IgG3-specific ELISA but not in those for IgG2 or IgG4.     

Is the antibody response specific?

Introduction of heterologous immunoglobulin (Ig) or red blood cells into mice results in an increased production of Ig and immunogen-reactive antibody. Since the increase in both total Ig and specific antibody is similar, it is concluded that the antibody response is specific. This result, which contrasts with those of previous studies in which the production of large amounts of nonspecific Ig was reported, suggests that in vivo T-dependent B cell activation and differentiation to plasma cells requires the presence of immunogen and linked recognition.     

Analysis of the HIV-1 gp41 specific immune response using a multiplexed antibody detection assay

A fluorescence-based, multiplexed, antibody-binding and mapping assay was developed to characterize antibody responses in HIV-1-infected individuals to the ectodomain of the HIV-1 gp41 envelope glycoprotein. The antigen panel included intact recombinant gp41, the fusion peptide region, the polar region, the N-heptad region, the C-heptad region as well as overlapping epitopes in the 2F5 and 4E10 monoclonal antibody-binding regions. The panel included both native and constrained peptides specifically designed to mimic putative gp41 prefusion and fusion intermediates. The results of these analyses revealed a broad pattern of immune responses against the test antigens, suggesting that none of these gp41 regions are immunologically silent. The HIV-1-positive sera were also evaluated using infectivity inhibition assays. No correlation was evident between the breadth or magnitude of specific anti-gp41 reactivities and virus neutralization potency. These evaluations demonstrated the substantial potential of the multiplexed antibody binding and mapping assay for rapid and sensitive analysis of complex antibody responses.     

免疫应答中非对应性激发现象的研究

目的　观察机体的特异性免疫细胞克隆 ,在受到非对应性抗原刺激后的反应情况。方法　首先用定量的卵白、牛乳和牡蛎提取液 (依次简称为EW、MI、OE抗原 ) ,分别对家兔做基础免疫 ,再分别用EW、MI、OE 3种抗原对家兔做交叉免疫。采用酶联免疫法 ,定量检测各组交叉免疫前、后的基础抗体的变化。结果　采用与基础免疫不同的抗原做交叉免疫的各组家兔 ,其基础抗体均有 10 %～ 2 5 %的提高 ,较对照组有显著差异 (P <0 .0 5 )。结论　免疫特异性反应细胞克隆可被非对应抗原激活     

The immune complex: possible ways of regulating the antibody response

B cells express antigen, Fc and complement receptors on their surfaces and can thus bind all three components of an immune complex. In addition to the direct effects that they exert on cells, immune complexes may affect localization, presentation and digestion of antigen. In this article, Birgitta Heyman discusses recent developments in antibody-mediated regulation of the humoral immune response, with emphasis on in vivo systems where antigens are injected together with highly purified IgM or IgG antibodies in the absence of adjuvants.     

The cost of a specific immune response in young guinea pigs

The specific immune system is a protective mechanism that detects infection and fights it by production of antibodies. Newborns are especially susceptible to infections because their immune system is not yet as fully developed as that of adults. This has been well established in altricial mammals. Fighting infection is associated with costs (metabolic rate, protein synthesis) potentially affecting other developmental processes. We investigated the specific immune response in a precocial mammal, by testing the response of 3 and 7 day old young guinea pigs (Cavia aperea f. porcellus) against a non-pathogenic antigen (KLH) and determined the effect of the immune response on growth and metabolic rate. Challenged young produced a substantial specific immune response (IgG). The efficiency of the immune response was almost identical in 3 and 7 day old young, but lower than in adult females. Antibody titres achieved by actively immunised young pups were as high as titres transferred transplacentally by mothers immunised on day 40 and 47 of pregnancy. In comparison to a control group, the immune response did not influence growth and metabolic rate measured on day 4 after each immune challenge and was not reflected by changes in hematocrit value. We discuss whether the weaker immune response of pups is caused by reduced allocation of limited resources in growing young or by the immature immune system of young animals.     

Quantification of specific antibody response to Cryptosporidium antigens by laser densitometry.

Cryptosporidium spp. is a protozoan parasite with worldwide distribution associated with diarrhea in immunocompromised patients (particularly those with acquired immunodeficiency syndrome [AIDS]) and in immunocompetent humans. Immunoglobulin M (IgM) and IgG antibody responses are readily detected by an enzyme-linked immunosorbent assay. To determine which Cryptosporidium antigens invoke antibody responses in humans, we performed polyacrylamide gel electrophoresis using purified oocysts, followed by Western blots with human sera from various populations. Of 40 sera from persons with cryptosporidiosis (24 AIDS and 16 non-AIDS patients), in 37 (93%) a 23,000-dalton antigen measured quantitatively by laser densitometry was recognized. Of 63 sera from IgM- or IgG-positive individuals, as determined by enzyme-linked immunosorbent assay, in 58 (92%) this same antigen was recognized. Up to three additional bands between 125,000 and 175,000 daltons were identified by some of these sera. These results suggest that most persons infected with Cryptosporidium spp. produce antibodies which recognize at least one common low-molecular-weight antigen. Isolation of this antigen will be useful in development of diagnostic tests and may be important in the study of immunity.     

Class specific antibody response to gonococcal infection.

An enzyme immunoassay was used to determine IgM, IgG, and IgA antibodies to gonococcal pili in 68 patients with uncomplicated gonorrhoea, 35 women with pelvic inflammatory disease, and in 115 normal controls. A clear difference in response rate in all three antibody classes between patients with gonorrhoea and healthy controls was evident. Among women with gonorrhoea, the magnitude of antibody response was higher than among men with gonorrhoea, especially in the IgM class. No major differences were found in the overall distribution of serological findings between women with uncomplicated gonorrhoea and those with gonococcal pelvic inflammatory disease. Among this last group, however, high IgM antibody levels in acute phase sera were significantly associated with the isolation of Neisseria gonorrhoeae in the upper genital tract.     

Regulation of the immune response in neonatal piglets by maternal antibody.

The ability of maternal antibody to regulate the humoral immune response to sheep erythrocytes and the hapten-carrier conjugate trinitrophenylated sheep erythrocytes (TNP-SRBC) was investigated in neonatal piglets. It was found that in this system, passively acquired maternal antibody would completely inhibit the in vitro primary immune response to SRBC while leaving the response the TNP intact. Data suggest that maternal antibody is regulating the in vitro response at the B-cell level since T-cell helper function to SRBC must not have been inhibited in order for an anti-TNP response to have occurred to TNP-SRBC. The regulation of immune responses by maternal antibody is temporary and disappears before 3 months of age.     

Sympathetic control of specific and non-specific immune response

Following antigenic stimulation with specific (alloantigen) and non-specific (sheep red blood cells (SRBC) and lipopolysaccharide (LPS] antigens the expression of beta-adrenergic receptors and the interference of immune sera IgG, on uterine smooth muscle beta-adrenoceptor-specific ligands were studied. The binding of alloimmune IgG to beta-adrenoceptors appeared to be specific, because immunization with SRBC and LPS did not induce anti-beta-adrenoceptors antibodies. On the contrary, the decrease in beta-adrenergic receptor expression was observed even with alloantigens and with the conventional antigenic challenge, suggesting that this phenomenon could be a non-specific immunoregulatory mechanism.     

Antigen-specific detection of soluble immune complexes by a solid phase specific antibody system.

An antigen-specific immune complex assay based on the following principle has been developed: xenogeneic, antigen-specific antibodies are attached to a solid phase. During first incubation with patient's serum, immune complexes in antigen excess are bound to the xenogeneic antibody by their free antigenic determinants. In a second incubation a labeled antibody, specific for human immunoglobulins, is combined with the antibody part of the immune complex. Quantitation of the label allows the determination of the immune complexes. The principle of the method has been varied using artificial soluble immune complexes of tetanus toxoid and human anti-tetanus toxoid antibody, and immune complexes prepared by mixing patient sera containing either HBsAg or anti-HBsAg antibodies. The reliability of the results is shown by their coefficient of variation (2.5%). With the method described soluble immune complexes predominantly in slight antigen excess, which are thought to be responsible for development of immune complex disease, have been detected.     

The human antibody repertoire specific for rabies virus glycoprotein as selected from immune libraries

Antibody phage display technology was used to identify human monoclonal antibodies that neutralize rabies virus (RV). A phage repertoire was constructed using antibody genes harvested from the blood of vaccinated donors. Selections using this repertoire and three different antigen formats of the RV glycoprotein (gp) resulted in the identification of 147 unique antibody fragments specific for the RV gp. Analysis of the DNA sequences of these antibodies demonstrated a large variation in the heavy- and light-chain germ-line gene usage, suggesting that a broad antibody repertoire was selected. The single-chain variable fragment (scFv) antibodies were tested in vitro for RV neutralization, resulting in 39 specificities that neutralize the virus. Of the scFv clones, 21 were converted into full-length human IgG(1) format. Analysis of viral escape variants and binding competition experiments indicated that the majority of the neutralizing antibodies are directed against antigenic site III of the RV gp. The obtained specificities expand the set of human anti-RV antibodies eligible for inclusion in an antibody cocktail aimed for use in rabies post-exposure prophylaxis.     

The ability of maternal antibody to increase the immune response in infants

There is a relationship between the titre of antibody in cord blood to pertussis, diphtheria and tetanus antigens, and the antibody response of the babies to pertussis—diphtheria—tetanus vaccine. The response to this vaccine was greater in babies with antibodies in the cord blood.     

Cells involved in the immune response. XXXV. The antigen-specific antibody response in the rabbit is suppressed by thymocytes of allogeneic immunized rabbits (ITSC) and by the non-toxic suppressor factor (ITSF) secreted by these thymocytes

The antigen-specific suppressor cells (ITSC) detected in the thymus of the rabbit 7 days post-iv immunization with sheep or horse erythrocytes (SRBC and HRBC, respectively), and the antigen-specific suppressor factor (ITSF) which the ITSC secrete in culture, inhibit the antigen-specific primary immune response in vivo when injected iv into SRBC and/or HRBC immunized rabbits on Days 0, 3, and 5 (ITSC) or daily on Days 0 to 5 (ITSF) post-primary immunization. The rabbits recover the ability to synthesize the specific antibodies following reimmunization by day 80 post-primary immunization. The primary immune response toward a non-cross-reacting antigen is not inhibited by the antigen-specific ITSC or ITSF. Neither the thymocytes of unimmunized rabbits nor the secretions of these cells in culture can suppress the primary immune response in vivo to either SRBC or HRBC. It must be emphasized that the suppression of the immune response by ITSC and ITSF in the rabbit is antigen-specific. ITSC and ITSF are not cytotoxic to rabbit lymphocytes in vitro. No gross or microscopic changes were detected in any of the lymphoid and nonlymphoid organs of rabbits sacrificed 2 days following 5 daily iv injections of large doses (10 ml) of ITSF. ITSF causes no adverse reaction in vivo since it did not induce morbidity in the rabbits during the 80 days observation period following its injection iv daily for 5 days commencing with the primary immunization.     

Gender-dependent specific immune response during chronic human Schistosomiasis haematobia

The cellular and humoral acquired immune responses to Schistosoma haematobium 28 kD gluthathione S-Transferase (Sh28GST) antigen were evaluated in a Senegalese population chronically infected with S. haematobium parasite. We show a gender-dependent immune response in adult individuals presenting similar intensities of infection. Indeed, the specific IgA response and production of TGF-beta and IL-10 were found significantly higher in females compared to males. In addition, we showed that this profile was combined with a weak production of Th1-related cytokines (TNFalpha and IFNgamma) and was associated with an absence of proliferation to the antigen. A significantly higher Nuclear Matrix Protein 41/7 secretion, an apoptosis marker, was specifically observed in mononuclear blood cell cultures of females suggesting that a specific cell death process was engaged in a gender-dependent manner. This specific profile could be associated with the so-called T helper type-3 (Th3) immune response specifically promoting the production of IgA and would be developed upon the down-regulation of the specific Type-1 response by a probable cell death mechanism. This gender-dependent immune regulation, which may be under the influence of nonimmunological factors like sexual hormones, may be related to the chronicity of the infection.