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The infectious diarrhea in AIDS is principaly due to Cryptosporidium. The study of the inflammatory and humoral immunity proteins reveal a high exudative enteropathy associated with an IgA, IgG and IgM intestinal immune response. However, this barrier of defence is not sufficient to eradicate the infectious agent.
An animal model of halothane-induced liver injury has been developed in the rabbit to study the production of humoral immunity towards a biotransformation intermediate of halothane. Rabbits exposed many times to halothane in a 75% O2/25% N2 atmosphere produce an antibody that cross-reacts with the trifluoroacetyl moiety of trifluoroacetylated rabbit serum albumin (TFA-RSA). The generation of this halothane-induced immunogen is dependent upon high oxygen tension as shown by the minimal anti-TFA antibody response seen in rabbits exposed to halothane in a 14% O2/86% N2 atmosphere. In addition, halothane exposure of rabbits specifically immunized with the metabolite-carrier complex, TFA-RSA, induces a secondary antibody response toward the immunogen. In rabbits, either immunized with TFA-RSA or not, multiple halothane exposures induce populations of antibodies with varying specificities. Evidence suggests that predominance of the metabolic intermediate, the ensuing immunogen, and the subsequent antibody response depends upon the oxygen tension during successive exposures to halothane. These successive exposures could potentially generate many different immunogens resulting in varied antibody specificities.
The influence of a phase shift in the light-dark cycle on humoral immune responses against sheep red blood cells (SRBC), a thymus-dependent antigen, and against polyvinylpyrrolidone (PVP), a thymus-independent antigen, was studied by using 180 BALB/c mice and 150 C3H/HeN mice. Significant suppression of the immune response to SRBC and the number of splenic plaque-forming cells (PFC) and hemagglutination (HA) titers was observed on days 5 and 6 after inversion of the light-dark cycle. On the other hand, the number of splenic PFC and HA titers in the blood against PVP were minimally suppressed by the phase shift in C3H/HeN mice, except for distortion of the rhythmicity. Corticosterone levels in the blood on days 5 and 6 after inversion were higher than those under a normal lighting regimen. The appearance of the high corticosterone level in the blood after the inversion almost concurred with the suppression of the immune response to SRBC. A decrease of the proportion of splenic T cells was also observed on day 6 after the inversion. These results show that a phase shift in the light-dark cycle provokes suppression of the immune response to SRBC, possibly through an increase of secretion of corticosterone after light-dark inversion, which induces a decrease of the proportion of T lymphocytes in the spleen.
The paper concerns variations in some parameters of humoral immunity in children with phenylketonuria examined at varying time (in the presence of specific dietetics and after its discontinuation). It is concluded that in children over 5 years of age, the hyperphenylalaninemia newly occurring after discontinuation of dietetics does not exert any material effect on the function of the mature enough immune system.
To define the contribution of aggressive lymphoma treatment to the risk of post-splenectomy septicemia, we investigated the humoral immunity of 44 patients with Hodgkin's disease. Specific antibody against Haemophilus influenzae Type b was significantly reduced (mean, 147 ng per milliliter, P less than 0.01) in patients receiving combined treatment (radiotherapy and chemotherapy), whereas single treatment reduced titers marginally (chemotherapy) or not at all (radiotherapy). Untreated patients had normal values (396 ng per milliliter), and splenectomy was without effect. In some patients who received combined treatment, titers were reduced to levels seen in infants. IgM levels were likewise normal in untreated patients. Chemotherapy, however, significantly reduced IgM levels (P less than 0.025), an effect potentiated by prior splenectomy. IgG, IgA, alternate-pathway activity, C3, C4 and CH50 were all normal or elevated. Aggressive treatment with chemotherapy and radiation impairs humoral defense against encapsulated micro-organisms, and thus magnifies the risk of post-splenectomy septicemia in patients with Hodgkin's disease.
Serum and cerebrospinal fluid were obtained from a 6-year-old male with subacute sclerosing panencephalitis (SSPE). Specimens were collected over a 9-month period beginning in the unusually acute phase and ending in a more quiescent phase of the disease. Immune complexes, auto-antibodies and viral antibodies were measured by radio-immunoassays. Fluctuations in these humoral immune parameters coincided with cessation of the acute phase of this disease. The results show that neurological changes in SSPE patients can be reflected in immune responses within both the peripheral circulation and the central nervous system.
HIV-1 Tat has been identified as an attractive target for vaccine development and is currently under investigation in clinical trials as both a therapeutic and preventative vaccine for HIV-1. It is well known that protein based vaccines produce poor immune responses by themselves and therefore require adjuvants to enhance immune responses. We have previously reported on the use of anionic nanoparticles (NPs) for enhancing cellular and humoral immune responses to Tat (1-72). The purpose of this study was to further evaluate the immune response of HIV-1 Tat (1-72) coated on anionic nanoparticles compared to alum using various doses of Tat (1-72). Nanoparticles were effective at generating comparable antibody titers at both 1 and 5 microg doses of Tat (1-72), whereas the antibody titers significantly decreased at the lower dose of Tat (1-72) using alum. Anti-sera from Tat (1-72) immunized mice reacted greatest to the N-terminal and basic regions of Tat, with the NP groups showing stronger reactivity to these regions compared to alum. Moreover, the anti-sera from all Tat (1-72) immunized groups contained Tat-neutralizing antibodies and were able to significantly inhibit Tat-mediated long terminal repeat (LTR) transactivation.
The ORFs-encoded major envelope glycoprotein (GP5) of porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major structural proteins of this virus. In this report, we described the induction of a PRRSV GP5-specific immune response by oral vaccination of mice with eukaryotic expression vectors containing the GP5 gene of PRRSV (pcDNA3-GP5), delived by attenuated Salmonella typhimurium aroA. It demonstrated that oral administration of the transformants resulted in expression of the GP5 transcript in the intestinal epithelium. The level of serum neutralization antibodies to PRRSV was not significantly different between the mice immunized with the transformants and the naked plasmid DNA. But the neutralizing antibody titres in sera of the mice immunized with SL7207/pcDNA3-GP5' and pcDNA3-GP5' (resides 2-25 deletion mutant of GP5) were significantly lower than those immunized with the complete GP5 gene. These results show that oral inoculation of the transformants can induce humoral immune response to PRRSV. The signal peptide of the GP5 protein of PRRSV is associated with the neutralizing epitope of the protein. The attenuated S. typhimurium may be used as a delivery system for oral DNA vaccines containing PRRSV GP5 glycoprotein.
Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.
Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte numbers all decreased during chemotherapy (120 microg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.
Our previous experiments demonstrated that honeybee venom could induce a specific, adaptive humoral immune response in the American cockroach. Since honeybee venom is a complex substance made up of several proteins, a more defined antigen is needed for future characterization studies. One of the components of bee venom, phospholipase A2 (PA2) was found to be highly lethal and immunogenic in the roach. Roaches injected with PA2 generated a specific primary response that developed over a period of time, peaking within 10 days, and then gradually subsiding by the fifth week. Specificity of this response was demonstrated by the fact that immunized animals were protected against the original immunizing PA2, but not to PA2 from a heterologous source. In addition, a secondary response could be induced with PA2, demonstrating the existence of immunologic memory. Thus, we established that PA2 could induce as good, if not better, humoral responsiveness as whole bee venom, and therefore could be utilized as a more defined antigen in studies designed to characterize the inducible humoral factor in the roach.
Two experiments were conducted in which the effect of carrageenan (CGN) on humoral immune response of chicks selected on either high (H) or low (L) antibody production to sheep red blood cells (SRBC) was determined. H and L line chicks were injected i.p. with different doses of CGN prior to immunization with SRBC or Brucella abortus (BA). Four weeks later chicks were reimmunized with the same antigens. In general, control H and L chicks had significantly higher total anti-SRBC titers than CGN-treated chicks in primary response. Also, total anti-BA titers were significantly higher in control chicks than CGN-treated chicks on days 3 and 5 following primary immunization and on days 0 and 7 of the secondary response. Overall, the 2-mercaptoethanol (2ME)-resistant anti-SRBC titers did not differ significantly among the CGN-treated groups. However, control chicks tended to have higher anti-BA 2ME-resistant titers from day 14 p.i. of primary response on. Regardless of antigen or CGN treatment, the H line chicks had significantly higher titers than L line chicks. However, the CGN treatments did not affect the antibody response to BA nor to SRBC differently between L and H line chicks. It would appear that since CGN is cytotoxic for macrophages, selection for antibody production did not result in different abilities of the macrophages of these chicken lines to respond to an antigenic challenge.
In order to investigate the humoral immune response against Entamoeba histolytica a lambda ZapII cDNA library was constructed from trophozoites of the pathogenic E. histolytica strain SFL-3. The library was screened with serum IgG from a patient with invasive amoebiasis. Forty-nine immunopositive lambda clones were isolated and partial sequences from the inserts were obtained. By comparison of the sequences with the merged database MIPSX from the Martinsried Institute for Protein Sequences we were able to identify homologous proteins for 36 of the clones. Twenty-six of the clones encoded intracellular proteins, among these, the major part (16 clones) were highly homologous to the eukaryotic 70-kDa heat shock proteins (Hsps). The open reading frame of one complete clone encodes a protein of 656 amino acid residues of 71.5 kDa which has 69.8% sequence identity with the human Hsp70 protein. In a larger screening experiment only 3 out of 12 patients detected with their IgG the phage which expressed the 70-kDa heat shock protein(s).
This study explored the effect of hyperthyroid state on humoral immune response and NF-kappaB signaling in lymphocytes. Male Wistar rats were treated with l-thyroxin for four weeks. Animals were immunized with sheep red blood cells (SRBC) after three weeks of l-thyroxin treatment. After one week of immunization, serum anti-SRBC titer was measured and NF-kappaB signaling was studied in lymphocytes by Western blot analysis of p-IKB-alpha, IKB-alpha, and p65. These results were compared with that of control rats. Antibody response and density of p-IKB-alpha and p65 were significantly higher in l-thyroxin treated rats in comparison to controls. The antibody response was found to have significant correlation with density of p-IKB-alpha and p65. Our results indicate that NF-kappaB signaling pathway in lymphocytes is activated in hyperthyroid state which might play a role in potentiation of antibody response.
The association between humoral immunity to unique and conserved epitopes of the Chlamydia trachomatis 60-kDa heat-shock protein (hsp60) and immunity to human hsp60 was examined in 129 women with laparoscopically verified pelvic inflammatory disease. An ELISA was used to detect antichlamydial IgG and IgA antibodies, IgG antibodies to recombinant human hsp60, and antibodies to two synthetic peptides of chlamydial hsp60. Half of the patients had antibodies to human hsp60, which correlated with the presence of antibodies to the chlamydial hsp60 peptide 260-271 homologous to the human hsp60 (P = .01). Antibodies to peptide 260-271 were associated with antichlamydial IgG (P < .0001) and IgA (P < .0001). The results suggest that the autoimmune response to human hsp60 can develop following C. trachomatis upper genital tract infection in women, probably as a consequence of an immune response to an epitope of chlamydial hsp60 cross-reactive with the human hsp60.
Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.
OBJECTIVE: To compare humoral immune response by co-inoculating mice with antigen HPV16L1 virus-like particle (VLP) and HPV16L1 recombinant plasmids and then observing the neutralizing antibody activity in vitro. METHODS: C57BL/6 mice were injected intramuscularly/subcutaneously with pcDNA-L1 plasmids plus HPV16L1 VLP. Serum IgG levels were detected by ELISA, antibody neutralizing protective activities were determined by hemagglutination inhibition and HPV16L1 VLP binding inhibition assay. RESULTS: Serum antibody titers and neutralizing antibody activities were increased in HPV16L1 plasmids plus HPV16L1 VLP proteins in co-immunized mice when compared with controls. CONCLUSION: Co-inoculation of the HPV16L1 VLP protein can enhance production of neutralizing antibody activities against aimed antigen, which should be a more promising strategy for effective HPV16 prophylactic vaccine development.
The present investigation was conducted to study the foot and mouth disease virus (FMDV)-specific humoral immune response (HIR) in pigs, following vaccination with oil adjuvanted foot and mouth disease (FMD) vaccine, upto 90 days post vaccination (dpv). For this, 40 Large White Yorkshire (LWY) pigs (20; one-year old female (gilts) and 20; three-month old piglets) were vaccinated @ 2 ml/animal, subcutaneously. Sera samples were collected at fortnight interval from all the animals. The log10 SN50 antibody titres against all the serotypes (Type O, A and Asia-1) were detected in both gilts and piglets from day 7 to 90 dpv indicating the persistence of HIR up to the last day of sampling. The maximum antibody titres were observed on 28 dpv, thereafter, titres started declining, but were present till 90 dpv against all the three FMDV serotypes. HIR was more pronounced in piglets in comparison to gilts, as group mean SN antibody titres against all the three FMDV serotypes were found to be more maintained and significantly higher in piglets.