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PubMed2004

Identification of HER2/ neu-derived peptides capable of inducing both cellular and humoral immune responses in HLA-A24 positive breast cancer patients.

HRE2/neu-specific cellular and humoral immune responses are often detected in breast cancer patients, but identification of more immunogenic CTL epitope peptides is necessary prior to development of a cancer vaccine. There is accumulating evidence of strong immunogenicity of peptides capable of inducing both cellular and humoral immune responses. To identify such peptides, this study intended to determine HER2/neu-derived peptides capable of inducing both cellular and humoral immunity in HLA-A24(+) breast cancer patients. IgGs reactive to the HER2(342-350), HER2(485-493), and HER2(553-561) peptides were detected in the sera of these patients with the frequency of 47, 24, and 24%, respectively. These peptides also induced peptide-specific and tumor-reactive CTL activity in the peripheral blood mononuclear cells of HLA-A24(+) breast cancer patients with the frequency of 50, 63, and 25%, respectively, but such activity was not induced from any HLA-A24(-) patients. Cellular and humoral responses to each of these three peptides were also observed in PBMCs and sera from the other epithelial cancer patients. These results may provide a scientific basis for new clinical trials of HER2/neu-peptide-based immunotherapy for breast cancer and also other epithelial cancer patients.

Antibody Formation↗
PubMed1994

Specific cellular and humoral immune responses induced by different antigen preparations of Echinococcus multilocularis metacestodes in patients with alveolar echinococcosis.

A specific proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by antigens of Echinococcus sp. has been shown in patients with cystic as well as alveolar echinococcosis. However, the development of a major granulomatous reaction around the parasitic larvae is a characteristic feature of the local immune response to E. multilocularis while humoral immune responses seem to predominate in E. granulosus infection. The aim of this study was to analyse the specific proliferation of the PBMC from 36 patients with alveolar echinococcosis, and 23 controls, induced by a crude preparation of E. multilocularis (EmcAg) as well as by two E. multilocularis specific antigen preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant correlation observed between the proliferation index either by Em2 and ES or by Emc suggests that both antigens account for an important part of the lymphocyte proliferative response. The strong effect of these species specific antigens on lymphocyte proliferation is confirmed by the comparison of the results obtained in this study to those obtained in a previous study of specific cellular immunity to E. granulosus antigens in patients with cystic echinococcosis. The proliferation indices were significantly elevated in all those 7 patients with a proven AE who were sero-negative using the Emc ELISA as well as in the 12 patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients who had had a complete resection of the parasitic lesions two years before the lymphocyte proliferation evaluation, the PI was above the threshold value for two dilutions of EmcAg. PI under the threshold values were obtained only in patients with residual lesions. These results suggest that E. multilocularis specific antigens promote the proliferation of lymphocytes which could be TH1 cells, responsible for the intense periparasitic granulomatous reaction characteristic of alveolar echinococcosis.

Adult↗
PubMedDate not supplied

HIV specific humoral immune response in Rio de Janeiro, Brazil. The HEC/Fiocruz AIDS Clinical Research Group.

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals residents in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analyses of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studies analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable for neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successful: while the Brazilian B clade B " variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.

Antibody Formation↗
PubMed2001

The humoral immune response to influenza vaccination in lung transplant patients.

The purpose of this study was to evaluate the humoral immune response to influenza vaccination in lung transplant recipients. Antibody levels to the three viral antigens included in the 1999-2000 trivalent influenza vaccine (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/ 98) were measured before and 4 weeks postvaccination in 43 lung transplant recipients and 21 healthy adult controls. The ability to develop protective antibody levels, a serological response, and the magnitude of change in levels were assessed. The humoral immune response to influenza vaccination was significantly lower in the transplant group for all three viral antigens. To A/Sydney, 95% of the control group and 40% of the transplant group developed protective levels (p=0.0009); to A/Beijing, 71% of the control group and 30% of the transplant group developed protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19% of the transplant group developed protective levels (p=0.02). Those receiving cyclosporine had lower antibody responses when compared to those receiving tacrolimus (r=-0.3056, p=0.0463). The humoral immune response to influenza vaccination in lung transplant recipients is poor. Lung transplant recipients receiving cyclosporine may have a lower antibody response than those receiving tacrolimus. Alternative prevention strategies may be needed.

Adult↗
PubMed2001

Humoral immune response to cruzipain and cardiac dysfunction in chronic Chagas disease.

The humoral immune response to epitopes expressed on cruzipain was evaluated in 31 Chagas disease patients (CDP) with different degrees of cardiac dysfunction. We took advantage of the availability of anti-Trypanosoma cruzi microsomal fraction monoclonal antibodies (MoAbs) reactive with epitopes that are recognized (5A9B11) or not recognized (1A10C11) by CDP sera. The 5A9B11- and 1A10C11-like epitopes are expressed on cruzipain. The reactivity of 5A9B11 against cruzipain was completely inhibited by sera of severe cardiopathy patients while a partial inhibition was found with sera from chagasic patients with mild disease. CDP sera did not block cruzipain recognition by 1A10C11. The antigenic determinants recognized by CDP sera appeared to be linear and carbohydrate free. When the overall anti-cruzipain immune response was evaluated, 70% of CDP with severe disease showed cruzipain titers higher than 1/800 while none of them displayed titers lower that 1/400. This report shows for the first time that the humoral immune response against epitopes expressed on cruzipain appeared to be related with the severity of chronic Chagas disease.

Adult↗
PubMed1997

Predominance of detrimental humoral immune responses to HIV-1 in AIDS patients with CD4 lymphocyte counts less than 400/mm3.

The humoral immune response to human immunodeficiency virus type 1 (HIV-1) was studied in 25 AIDS patients with CD4 lymphocyte counts of less than 400/mm3. Humoral immune responses against tissue culture adapted strains of HIV-1, and two limited-passage patient isolates were investigated. Total anti-HIV antibody levels were not significantly different between different individuals. Neutralizing titres against HIVLA1 and HIVSF2 were 10- to 100-fold higher than against clinical isolates. The complement-mediated, antibody-dependent enhancement of HIV-1 infection titre was high (mean 1:14,000). Antibody-complement mediated cytotoxicity of both HIVLA1 and HIVSF2 was ineffective using human complement as a complement source. The antibody-dependent, cell-mediated cytotoxicity (ADCC) activity varied against the four isolates with tissue culture-adapted strains being more susceptible than clinical isolates. Finally, an ADCC effector cell function, natural killer or NK activity, was measured for all 25 patients, and NK activity of patients was decreased by nearly 75% compared to uninfected individuals. In summary, beneficial humoral immune responses are low in HIV-1 infected individuals with CD4 counts of less than 400/mm3 if the in vitro assay system is constructed to best mimic the in vivo situation. These results suggest that the lack of functional antibody responses to HIV may play an important role in viral pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[The role of T-lymphocytes in the development of a humoral immune response to the corpuscular antigen of Staphylococcus aureus].

The dependence of humoral immune response and the formation of immunological memory to corpuscular staphylococcal antigen (CSA) on the T-system of immunity was studied in experiments on B-mice and on mice with the congenital absence of the thymus (nude). Primary and secondary immune response to CSA in athymic mice was found to be considerably less than in normal animals. After the repeated immunization of genetically athymic mice the pronounced secondary reaction of the formation of antibodies to CSA was observed. As shown in this investigation carried out with the use of adoptive transfer techniques, the induction of memory B-cells to CSA may occur in animals with congenital or experimentally induced T-immunodeficiency. The conclusion was made on the T-dependence of humoral immune response to CSA, the formation of immunological memory to this antigen being relatively T-independent.

Animals↗
PubMed1977

Schistosomiasis mansoni in the hamster: cellular and humoral immune responses to soluble egg antigens (SEA).

Cellular and humoral immune responses to soluble egg antigens (SEA) were studied in the course of Schistosoma mansoni infection in the hamster. No immune response to SEA could be detected before the parasite had started oviposition. The liver granuloma size reached a maximum 6 weeks after infection and decreased rapidly thereafter. The in vitro cell-mediated immune response to SEA (lymphocyte blast transformation) showed a maximum reaction 12 to 16 weeks after infection (depending on the infection rate) and also declined later. Parallel to the lowered reactivity of the lymphocytes to SEA in vitro, responsiveness to the nonspecific T-cell mitogen, phytohemagglutinin M, was also reduced in chronic infections. Humoral anti-SEA antibodies could be detected in increasing amounts up to 10 weeks after exposure.

Animals↗
PubMed1986

Humoral immune response of asymptomatic cats naturally infected with feline leukemia virus.

The humoral immune response of cats that were naturally infected with the feline leukemia virus (FeLV) was examined after antigenic stimulation with the synthetic antigen poly(L-Tyr, L-Glu)-poly(DL-Ala)-poly(L-Lys). The primary humoral antibody response in FeLV-infected cats was both delayed and greatly reduced, compared with that seen in uninfected control cats. A similar discordance was observed after secondary stimulation with the antigen, in the FeLV-infected cats had both a delayed response and a reduced response, compared with uninfected cats. The levels of total immunoglobulins of the immunoglobulin G and immunoglobulin M classes in the sera of FeLV-infected cats were significantly higher (two- and threefold, respectively) than were those of the uninfected control animals. The presence of an impaired humoral immune response to newly presented antigens in the presence of elevated immunoglobulin levels has been thoroughly documented in the case of people with the acquired immunodeficiency syndrome. This further emphasizes the potential value of FeLV-infected cats as a model for human acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Study of the phases of development of humoral immune response].

In previously performed investigations to make clinical immunological diagnosis the principle of humoral immune response division into phases was put forward. The phases of humoral immune response were determined with lower content of immunoglobulins.

Antigen-Antibody Complex↗
PubMed1985

Cell-mediated and humoral immune response to Mycoplasma hyopneumoniae in pigs enhanced by dextran sulfate.

The effect of dextran sulfate (DS), known to be cytotoxic to macrophages, on the cell-mediated and humoral immune response to nonviable Mycoplasma hyopneumoniae in pigs was investigated. The cell-mediated immune response was determined by means of lymphocyte transformation a test, using uptake of [3H]thymidine in a microculture system and the humoral immune response by means of a microplate complement-fixation test. Peripheral blood lymphocytes from pigs vaccinated with nonviable M hyopneumoniae and DS incorporated substantially more [3H]thymidine than did those from pigs given Mycoplasma or DS alone. The transformation of lymphocytes from M hyopneumoniae-DS vaccinated pigs was enhanced when M hyopneumoniae cells used in the assay system were heated at 60 C for 30 minutes. Similarly prepared M flocculare and M hyorhinis cells also stimulated lymphocytes from M hyopneumoniae-DS vaccinated pigs, but not nearly as great as when M hyopneumoniae cells were used. The humoral antibody response and the cell-mediated immune response to nonviable M hyopneumoniae was markedly enhanced by DS. Pigs were vaccinated with nonviable M hyopneumoniae and/or DS 4 times and challenge exposed intratracheally with viable M hyopneumoniae. Pigs vaccinated with M hyopneumoniae and DS had less severe pneumonia than did nonvaccinated pigs.

Animals↗
PubMed1992

[Effects of substance P in rat spinal cord on the humoral immune response to SRBC].

The effects of substance P (SP) in rat spinal cord on the humoral immune response to sheep red blood cells (SRBC) were investigated by the hemolytic plaque-forming cell (PFC) technique. Radioimmunoassay was used for assessing SP content. Catecholamines contents were measured by high performance liquid chromatography (HPLC) with electrochemical-detection. The results suggest that SP in the spinal dorsal horn, but not in the lateral horn, could inhibit the thymus-dependent humoral immune response to SRBC, and this inhibitory effect might be related to the influence of dorsal horn SP on thymic activity. Increased SP content in the spinal dorsal horn at the peak of a humoral immune response might suppress the immune response and play a negative feedback role, preventing excessive immune response.

Animals↗
PubMed2000

Humoral immune responses to adenovirus vectors in the brain.

We have investigated the humoral immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of mice. Injection of these non-replicating vectors into the brain induced systemic antibody production to adenovirus vectors in dose dependent manner. Apparent antibody production to beta-galactosidase, the product of the lacZ gene, was detected later than anti-adenovirus antibody. Neutralizing antibody was not detected. This study demonstrates that E1-deleted adenovirus vectors injected into the brain trigger humoral immune responses to the adenovirus and its gene products, but they are not sufficient to block the infection of cells by adenovirus upon repeat injection.

Adenoviridae↗
PubMed1999

Longitudinal humoral immune responses of Indian leaf monkey (Presbytis entellus) to Brugia malayi infection.

Humoral immune responses of the Indian leaf monkey (Presbytis entellus) experimentally infected with Brugia malayi and exhibiting disease manifestations were studied. Microfilaraemia, filaria-specific IgG and circulating immune complexes (CICs) were determined in the monkeys at different time-points after inoculation of B. malayi 3rd-stage larvae. Sera were analysed for recognition pattern of adult parasite antigen molecules by immunoblotting. More than 60% of the infected monkeys developed episodic or persistent limb oedema with or without fever and with low or no microfilaraemia. While both CIC and filaria specific IgG levels were comparable in animals showing no disease symptoms (asymptomatics) and some animals showing symptoms (symptomatics), IgG levels peaked during pre-patent stage in symptomatics and during latent stage in asymptomatic animals. However, some of the symptomatic animals showed a low level of filaria-specific IgG as compared to asymptomatic and other symptomatic animals. The immunoblot analysis showed non-reactivity of 17 and 55 kDa antigens with sera of symptomatic animals. The results thus suggest that humoral immune responses as measured in the present study do not precede the development of the manifestations. However, 2 non-reactive antigen molecules identified by symptomatic sera need further study to establish their possible involvement, if any, in the development of acute disease manifestations in this model.

Animals↗
PubMed2003

Co-immunization with plasmids coding the full length and a soluble form of glycoprotein D of HSV-2 induces protective cellular and humoral immune response in mice.

At present, the significance of antibody for protection of the female genital tract against infection with HSV-2 remains controversial. In the present study, the ability of a DNA vaccine encoding different forms of glycoprotein D (gD) of herpes simplex virus-2 (HSV-2) to induce simultaneously cellular and humoral responses was evaluated. Mice immunized with a plasmid encoding full length gD (pgD) developed a strong cellular immune response but weak antibody titers in serum and vaginal washings. On the other hand, mice immunized with a plasmid encoding soluble form of gD (pdeltagD) showed high titers of antibodies but a very weak cell-mediated immune response. When mice were immunized simultaneously with both plasmids, cellular and humoral immune responses were elicited. This mice showed neutralizing antibodies in serum and vaginal washings as well as a high number of IFN-gamma secreting cells in spleen. When challenged with 50 lethal doses of virus, mice immunized with pgD along with pdeltagD showed a more complete protection than mice immunized with pgD alone. Collectively these results suggest that neutralizing antibodies help cell-mediated immune response for the protection against HSV-2 infection.

Animals↗
PubMedDate not supplied

Humoral immune responses during acute rejection in rat lung transplantation.

The detailed responses of humoral immunity during acute rejection remain obscure in lung transplantation (LTx). In order to clarify the reactions of alloantibodies (allo-Abs) during acute rejection, we demonstrated the time-course of changes in anti-donor Ab reaction in the peripheral blood and deposition in the grafts using a rat LTx model. Lewis (LEW) rats served as recipients for Brown Norway (BN) lung allografts (MHC fully incompatible combination). The left lung was transplanted orthotopically using a cuff technique. Syngeneic transplants (LEW to LEW) served as control. No immunosuppression therapy was administered in this model. We evaluated the alloreactivity against donor in rat recipients by detecting allo-Abs with a flow cytometric cross-match (FCXM) technique. Recipient serum samples were incubated with donor lymphocytes and stained with anti-rat immunoglobulin (Ig), to determine the titers of circulating allo-Abs in the peripheral blood with a three-color FCXM technique. We also examined the deposition of anti-donor Abs (IgG and IgM) in the grafts with an immunofluorescent method. All allografts were completely rejected and lost their aeration within 6 days after LTx. Strong allo-Abs responses of both IgG and IgM were observed in the peripheral blood during acute rejection. The level of IgM allo-Abs had already significantly increased on day 2 at the time of mild rejection; however, IgG Abs did not elevate until day 6, when the grade of rejection was severe. Circulating IgM levels started decreasing on day 8, whereas IgG Abs continued elevating. On the other hand, no evident deposition of allo-Abs in the grafts was observed until day 6. We have shown in this study that circulating IgM allo-Abs was detected at the time of mild allograft rejection, interestingly, before evident deposition in the graft. It might be suggested that allograft rejection progressed without antibody deposition until severe rejection.

Animals↗
PubMed1989

Humoral immune response in patients with cerebral parenchymal cysticercosis treated with praziquantel.

The humoral immune response to treatment with praziquantel (PZQ) was studied in eight patients with parenchymal cerebral cysticercosis (CC). In the serum and in the cerebrospinal fluid (CSF) before, during and after the administration of the drug, the following were quantitated (a) levels of specific anticysticercous antibodies measured in optical densities by the ELISA method; (b) levels of IgG, IgM, IgA and IgE; (c) levels of complement fraction C3, C4; (d) presence of immune complexes; (e) total number of white blood cells in the CSF. It was found that after treatment with PZQ, the level of specific anticysticercous antibodies and the level of IgG rose significantly in the CSF but not in the blood. The levels of the fractions of the complement and the immunoglobulins IgM, IgA and IgE did not change significantly either in the serum or in the CSF. The blood-brain barrier was found ruptured in three patients before therapy and in five patients after the therapy as measured by the albumin index. Nevertheless, the IgG index showed that there was local production of IgG in five patients before treatment and in seven after the end of it. The relative specific antibody index was greater than 1.0 in five patients before therapy and in seven after therapy. This data strongly supports the idea that the specific antibodies are produced intrathecally and are not derived from the serum pool through a ruptured blood-brain barrier. It was concluded that patients with parenchymal CC have an elevation of specific anticysticercous probably due to a combination of a ruptured blood-brain barrier and intrathecal synthesis. The relatively small rupture of the blood-brain barrier and the high IgG and relative specific antibody index suggest that intrathecal synthesis is the most important mechanism. The humoral immune response may be of importance not only in the elimination of the parasite but also in the genesis of the illness.

Adult↗