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PubMed2005

[C3d enhances the immune response against HBV-preS2/S following gene immunization in mice].

OBJECTIVE: To investigate whether C3d can enhance the immune response to HBV-preS2/S induced by direct injecting naked plasmid containing three copies of C3d and HBV-preS2/S in fusion form. METHODS: HBV-preS2/S coding sequence was introduced into the eukaryotic expression vectors TR421 and TR421-C3d3 containing 3 copies of C3d respectively. PCR was used to identify the direction of insertion, DNA sequencing analysis was used on the positive clones. The recombinant plasmids TR421-preS2/S and TR421-preS2/S-C3d3 were transfected into the human breast cancer cells of the line 4T1 as a transient expression system. Semi-quantitative RT-PCR was used to detect the expression of HBV-preS2/S protein. TR421-preS2/S and TR421-preS2/S-C3d3 were injected into the anterior tibial muscles of female BALB/c mice, 6 in each group, 3 times at an interval of 3 weeks. Six mice were injected with blank plasmid TR421 as controls. The total blood was collected from the mice. ELISA was used to detect the level of specific anti-HBs antibody. The splenocytes of the immunized mice were collected and stimulated with HbsAg protein and then harvested to analyze the specific lympho-proliferative response by (3)H-thymidine incorporation assay. CR2 positive Raji cells were added with plasmid transfected and mouse anti-HBs serum. Flow cytometry was used to detect the integration of preS2/S-C3d3 fusion protein. RESULTS: The 4T1 cells transfected with TR421-preS2/S and TR421-preS2/S-C3d3 effectively expressed HBV-preS2/S, with the expression level of TR421-preS2/S-C3d3 lower by 15.25% than that of TR421-preS2/S. Twelve weeks after immunization, the specific anti-HBs-IgG level (A(490nm)) was 0.81 +/- 0.09 in the TR421-preS2/S primed mice, significantly higher than that in the blank plasmid injected mice (0.49 +/- 0.02, P < 0.05); and the specific anti-HBs-IgG level (A(490nm)) was 1.24 +/- 0.29 in the TR421-preS2/S-C3d3 immunized mice, significantly higher than that of the TR421-preS2/S primed mice (P < 0.001). The lympho-proliferative response of the TR421-preS2/S primed mice was significantly stronger than that of the blank plasmid injected mice (P < 0.05) and the lympho-proliferative response of the TR421-preS2/S-C3d3 primed mice was significantly stronger than that of the TR421-preS2/S primed mice (P < 0.05). Surface binding of protein could be detected only in the TR421-preS2/S-C3d3 transfected supernatant. About 43.19% of the CR2 positive Raji cells integrated C3d fusion protein. TR421-preS2/S transfected supernatant and negative control did not show obvious integration. CONCLUSION: C3d enhances the humoral and cell-mediated immune responses against HBV induced by gene immunization.

Animals↗

PubMed1991

The effect of some drugs on in vitro cellular immune reactions and on circulating immune complexes in patients with myocardial infarction.

The immunomodulatory effect of the lipid-reducing etofibrate, the calcium antagonist nifedipine and the immunosuppressive cyclosporine A was studied on in vitro cellular immune response in the presence of human aortic extract and of human LDL in 56 patients with acute myocardial infarction. 50 sex- and age-matched healthy persons were used as controls. Leukocyte migration test, level of C1q and of immune complexes and serum lipid parameters were measured. Leukocyte migration inhibition was observed against aorta in 68%, against LDL in only 23% of patients, which were significantly reduced by etofibrate and nifedipine and a similar, but not significant tendency was found using cyclosporine A against aorta. Leukocyte migration stimulation was observed in 9.0% and in 27% of patients against aorta and LDL, respectively. They were also considerably decreased by etofibrate and nifedipine. A high level of circulating immune complexes was found in hyperlipemic younger patients together with lower migration inhibition against LDL, which may be explained by authors' hypothesis: LDL is a component of circulating immune complexes, so there are few free LDL for lymphokines in the circulation. A correlation between specific (anti-aorta, anti-LDL) and nonspecific (PHA) immune responses was also detected in patients. The use of these drugs may be useful in the therapy of patients with myocardial infarction in order to modulate cellular immune reactions against vascular wall and LDL.

Aged↗

PubMed2006

[Immunization with dendritic cells infected with human AFP adenovirus vector effectively elicits immunity against mouse hepatocellular carcinomas].

OBJECTIVE: To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding xenogeneic alpha-fetoprotein (AFP) on breaking the immune tolerance and induction of immunity against hepatocellular carcinomas. METHODS: Human and mouse alpha-fetoprotein full-length cDNA were cloned from human HepG2 and mouse Hepa 1 - 6 hepatoma cell lines, respectively, using RT-PCR, and then inserted into adenoviral shuttle vectors to construct Ad hAFP and Ad mAFP. Mice were immunized with Ad hAFP-infected DC and in vitro CTL activity against Hepa 1 - 6 cells was examined by standard (51)Cr release assay. Survival was studied of the immunized mice, with or without depletion of CD8+ or CD4+ T cells, inoculated with Hepa 1 - 6 mouse hepatoma cells. RESULTS: The lytic activity of CTL elicited by the Ad hAFP-infected DCs were much stronger than that by Ad mAFP-infected DCs. 80% of the Ad hAFP/DCs-immunized mice of the inoculated with 5 x 10(6) Hepa 1 - 6 hepatoma cells were still alive two months after inoculation. However, the Ad mAFP/DCs-immunized mice inoculated with 1 x 10(6) Hepa 1 - 6 cells were just 20% surviving two months later. Depletion of CD8+ or CD4+ T cells abolished such an antigen-specific immunity elicited by the DCs infected with Ad hAFP. CONCLUSION: Adenovirus vector-mediated xenogeneic AFP-infected DCs can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce strong antigen-specific T cell response, which are dependent on CD8+ and CD4+ T cells.

Adenoviridae↗

PubMed1976

Non-specific immunity after local immunization.

The most important advantage of local immunization is the non-specific effect. The active protection test in mice shows an immunity against oral infection with virulent Salmonella typhimurium bacteria after oral immunization with heterologous inactivated enterobacteria. We observed the same non-specific protection in a viral model. After oral immunization with inactivated S. typhimurium bacteria, the mice are protected against oral infection with a virulent parapoliomyelitis virus. In the phagocytosis test after local immunization a non-specific effect is also demonstrated. The rate of phagocytosis of macrophages against streptococci rises significantly after oral immunization or after inhalation with heat-killed S. typhimurium bacteria.

Administration, Oral↗

PubMed1990

Cellular and humoral immune responses to a recombinant P. falciparum CS protein in sporozoite-immunized rodents and human volunteers.

The immune responses of sporozoite-immunized rodents and of human volunteers exposed to multiple bites of irradiated Plasmodium falciparum infected mosquitos have been investigated using a yeast-derived recombinant P. falciparum circumsporozoite (rPfCS) protein. The murine immune response to immunization with rPfCS was not genetically restricted. Nine different murine haplotypes, when immunized with rPfCS, developed high levels of antisporozoite antibodies detectable by IFA and RIA. In addition, injection of rPfCS induced a secondary antibody response in P. falciparum sporozoite-primed mice. Murine T-cell epitopes were mapped in the C terminus of the rPfCS protein using overlapping synthetic peptides. The human T-cell response was investigated using T-cell clones derived from peripheral blood lymphocytes (PBL) of a P. falciparum sporozoite-immunized volunteer. A total of 40 CD4+ T-cell clones were obtained. Stimulation indices ranged from 2.5 to 103.4 following challenge with rPfCS in the presence, but not in the absence, of antigen-presenting cells. The clones were specific for rPfCs and did not proliferate or secrete lymphokines when challenged with yeast-derived recombinant P. vivax or P. berghei CS protein or with a yeast-extract control. The clones also recognized the native CS protein in extracts of P. falciparum, but not P. berghei or P. cynomolgi, sporozoites.

Animals↗

PubMed1989

[Cell-mediated immunity in calves immunized against or infected with the bovine rhinotracheitis virus].

Simple and expeditious methods--leucocyte adherence inhibition LAI and leucocyte migration inhibition LMI--are described in the present paper; these methods enable to investigate cell-mediated immunity of animals. The two tests, along with serological and virological methods, were used to study changes in the immunity of calves after experimental infection by IBRV and after immunization by inactivated oil vaccine against IBRV. The results have indicated that the changes in cell-mediated immunity after experimental infection and vaccination of calves assumed courses independent of the changes in humoral reaction. Total cell-mediated immunity reaction started earlier in experimentally infected calves than in vaccinated ones. In some vaccinated calves a modified course of cellular immunity reactions was observed, characterized also by elimination of IBR virus on the nasal mucous membrane after challenge infection. The LAI and LMI test can be recommended for immunological monitoring in clinical laboratories and in research.

Animals↗

PubMed1989

[The immune structure of the population of the Bashkir ASSR in connection with hemorrhagic fever with renal syndrome and the relation of indices of collective immunity to morbidity and the nature of the landscape].

The study of 9,176 serum samples obtained from all regions and 15 cities of Bashkiria, carried out by the method of radioimmunoassay with the use of the antigen of hemorrhagic fever with the renal syndrome (HFRS), has revealed considerable differences in the size of the natural immune stratum of the population (43.9-0.8%). The size of such immune stratum characterizes the activity of natural foci: the largest immune stratum (25.4%) exists among the population of regions with broad-leaved forests, this stratum is somewhat less (12.2-13.2%) in regions with combined coniferous and broad-leaved forest, in regions with different combinations of broad-leaved forests and steppes, as well as mountain forests. On the Aĭsko-Kungurskaia forest-steppe territory and in regions characterized by a combination of steppe areas with mountain forests the immune stratum has been found to be even lesser (7.3-8.4%). The least immune stratum (3.4%) exists in steppe regions. By comparing the percentage of the population immune to HFRS and having had the diagnosis of HFRS over the period of 30 years the quality of the clinical diagnosis of this infection on the given territory may be determined.

Antibodies, Viral↗

PubMed1989

General recommendations on immunization. Immunization Practices Advisory Committee.

This revision of the "General Recommendations on Immunization" updates the 1982 statement. Changes or new sections include (1) listing of vaccines available in the United States by type and recommended routes, (2) updated schedules for immunizing infants and children, (3) clarification of the guidelines for spacing administration of immune globulin preparations and different vaccines, (4) an updated table of recommendations for routine immunization of children infected with human immunodeficiency virus, (5) listing of conditions that are often inappropriately considered contraindications to immunization, and (6) addition of information on the National Childhood Vaccine Injury Act of 1986 and the National Vaccine Injury Compensation Program. These recommendations are not comprehensive for each vaccine; Immunization Practices Advisory Committee (ACIP) recommendations on each vaccine should be consulted for more details.

Adjuvants, Immunologic↗

PubMed1987

[Immune response of calves following vaccination with Paramyxovirus parainfluenzae-3 and adenovirus-1 under different colostral immunity stresses].

Studied was the immune response of calves, with colostrum antibodies and without colostrum antibodies, immunised with different dosages of live bivalent vaccine against P. parainfluenzae-3 and Adenovirus-1. For the group of calves with colostrum immunity, after single hypodermic immunisation with doses from 10(4) till 10(5) CPE50/cm3 for adenovirus, was not proved immune response, as a result of blocking of the vaccinal antigen of colostrum antibodies. For calves which missed these antibodies, the immune response was determined at the 15th day after the first vaccination with the lesser dose of bivaccine. Regardless of the degree of the antibodies of the calves, after the second vaccination (with the big and the little dose) was proved immune response, which does not differ considerably for the separated groups of calves. It was established, that the optimal dose, necessary for the calves to build an immunity at an early age (from 1 to 3 months), when immunised with bivaccine, was 10(4) CPE50/cm3 for the P. parainfluenzae-3 and 10(3) CPE50/cm3 for the Adenovirus-1. The bigger dose is useless not only from the economic point of view, but from the danger of provoking an unwanted shock of the vaccinated calves.

Adenoviridae↗

PubMed1986

Lymphotropic viruses, Epstein-Barr virus (EBV) and human T-cell lymphotropic virus-I (HTLV-I)/adult T-cell leukemia virus (ATLV), and HTLV-III/human immune deficiency virus (HIV) as etiological agents of malignant lymphoma and immune deficiency.

The ubiquitous, DNA herpesvirus, EBV, has B cell tropism and the geographically restricted RNA retrovirus, ATLV/HTLV-I has T cell tropism. Clinical descriptions by Burkitt and Takatsuki led to discovery of these viruses which infect silently early in life; however, ATLV is also transmitted to a spouse or by blood transfusion. In normal seropositive persons both viruses infect only 1 in about 10,000 B or T cells, respectively. EBV is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. ATLV is associated with adult T cell leukemia/lymphoma and smoldering T cell lymphoma. EBV infects polyclonally and is controlled by multiple cellular and humoral control mechanisms. Escape from immune surveillance as in immune deficient African children with malaria, males with x-linked lymphoproliferative syndrome, organ transplant recipients, and AIDS patients permits conversion from polyclonal to oligoclonal and finally, monoclonal malignancy. T cell immune defects permit proliferation of cells which undergo molecular and/or cytogenetic alterations. In contrast to EBV, which is integrated and nonintegrated in B cells, ATLV is monoclonally integrated. Viral transforming proteins and immune suppressive substances are produced. Immune deficiency in silent carriers of ATLV and in those with smoldering ATL suggest that immune surveillance deters emergence of ATL. Prevention of primary infection by vaccination against these lymphotropic viruses, and use of immunotherapy and antiviral drugs may potentially retard conversion of infected B or T cells to monoclonal malignancy.

Acquired Immunodeficiency Syndrome↗

PubMed1986

[Effect of the heterogeneity of persons vaccinated, with respect to the state of their immune system, on the intensity of the immune response].

Prior to the immunization of children aged 3-7 years with parotitis vaccine the state of their immune system was evaluated by the determination of the concentration of IgM, IgG and IgA, the ratio and absolute numbers of T- and B-lymphocytes, the intensity of the blast transformation of lymphocytes. This study revealed that the group of immunized children was essentially heterogeneous with respect to the state of their immune system: in 79.9% of the children all immunological characteristics were normal, in 20.1% of the children some deviations from the characteristics considered to be normal for their age (gammopathy, eosinophilia, the deficiency of T- and B-lymphocytes, a decrease in the intensity of their blast transformation, the leftward shift of the leukocytic formula) were noted. The intensity of humoral immune response in children with deviations from normal characteristics peculiar to their age was significantly lower than in children with normal immunological characteristics. On the basis of these results, the immunological rehabilitation of the risk group among the children to be immunized is recommended.

Antibodies, Viral↗

PubMed1985

Transfer of immunity by means of spleen cells from mice immunized with outer membrane proteins of Shigella flexneri.

Intraperitoneal immunization of mice with a single dose (5 micrograms) of outer membrane proteins (OMP) of Shigella flexneri was found to evoke in the spleen the appearance of cells by means of which immunity to lethal dose of Shigella could be transferred into other mice. Active cells capable of transferring immunity appeared in the spleen of the animals as early as on day 3, reached the strongest protective activity on day 4 and disappeared on day 8 after immunization. Active cells from animals immunized with two doses of OMP maintained in the spleens for 19 days. The experiments revealed that immunity to Shigella could be transferred only with lymphocytes; macrophages were found to be inactive.

Animals↗

PubMed1968

Studies on heterologous immunity in schistosomiasis. 2. Heterologous schistosome immunity in rhesus monkeys.

Previous studies on heterologous immunity in mice have indicated that Schistosoma bovis and S. mattheei could be used to limit the severity of infection resulting from subsequent challenge by S. mansoni. These observations have now been extended to study the immunizing effect in rhesus monkeys of both S. mattheei and S. bovis.The bovine schistosomes were shown to be relatively non-pathogenic in rhesus monkeys. Immunization with 1000-2000 cercariae resulted in a marked reduction in the pathogenic effect of subsequent challenge with S. mansoni. This effect was demonstrated by a decrease in the worm load and tissue egg densities in 10 immunized monkeys as compared with 5 control animals.There was no correlation between fluorescent antibody titres and the intensity of infection or the degree of acquired immunity. There was a cross-reaction between S. mansoni and the bovine schistosomes.It is suggested that natural heterologous immunity (zooprophylaxis) may be of considerable epidemiological importance in determining the severity of schistosomiasis in man.

Animals↗

PubMed1980

Cytomegalovirus-specific immune response and the cellular immune status of malignant lymphoma.

Cytomegalovirus (CMV)-specific immune responses and the general cellular immune status of 24 untreated patients with Hodgkin's disease (HD) and 22 with non-Hodgkin lymphoma (NHL) were evaluated in comparison with matched controls. The incidence of antibodies against CMV-induced early (EA) or late (LA) antigens was not different between patients and controls. LA antibody titres were markedly lower in the lymphoma patients (p = 0.01), especially in the NHL subgroup (p = 0.008), but not in HD patients. EA antibody titre levels were not significantly different between patients and controls. CMV-specific lymphocyte reactivity (LR) was impaired in LA seropositive--and even more so in EA seropositive--lymphoma patients. General cellular immunity tested with LR to mitogens and an antigen cocktail was more disturbed in HD patients (only PWM-LR normal) than in NHL patients (only Con A-LR disturbed). The percentage of circulating T lymphocytes was markedly lowered (less than 60%) in only 2 HD and 4 NHL patients. The impairment of CMV-LR was not directly related to the general cellular immune status of the patients. It appeared furthermore to be virus-specific when it was compared with LR to Epstein-Barr virus antigen. The impairment of CMV-specific immunity in lymphoma patients probably reflects a defect of the immunological defence against endogenous CMV. This defect apparently, occurs early in the course of illness before the general cellular immune status has deteriorated and it may have a pathogenetic significance for lymphoid malignancies.

Adolescent↗

PubMed1984

Induction of "latent a2" allotype in a1a1 homozygous rabbits as the major part of a bidirectional immune response to immunization with anti-a2 antibody.

Previously, we induced Ab to a common idiotypic specificity (IdC) of rabbit anti-a2 VH Ab. We observed then that some of the putative anti-IdC Ab molecules induced by immunizing a1a1 rabbits with anti-a2 Ab did not have the expected nominal allotypic markers (a1, x32, or y33) characteristic of the genotype of the immunized rabbits. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab induced population of molecules that reacted with anti-a2 Ab but bore an unidentified (unknown) VH region marker. The following observations indicate that these molecules bear a "latent a2" allotypic marker: (a) when the unknown VH molecules were used to immunize a1 a1 and a3 a3 rabbits, anti-a2 Ab was produced; (b) when an a2 a2 rabbit was immunized with the same preparation of unknown VH molecules, an anti-idiotypic Ab was produced; and (c) when the unknown VH molecules were used to inhibit the binding of labeled a2 IgG to anti-a2 Ab, the inhibition curve obtained was essentially the same as that obtained by using normal a2 IgG. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab provided a bidirectional stimulus to produce both nominal "a1" anti-IdC Ab and a "latent a2" allotype. The distribution of nominal to latent allotypes induced ranged from 3% nominal/92% latent to 57% nominal/23% latent. In absolute terms, the maximum amount of "latent a2" molecules was 1.18 mg/ml of serum, which far exceeds the amount of latent allotype described by others (0.3 mg/ml of serum). The effective induction of large amounts of "latent a2" allotype may have resulted from a simultaneous stimulation of an idiotope and a paratope on the surface of the "latent a2"-producing cells.

Animals↗

PubMed1980

Host immune status in uraemia. I. Cell-mediated immune mechanisms.

An experimental model of stable uraemia has been used to determine the effect of uraemia on cell-mediated immune mechanisms in the rat. Controlled resection of renal tissue allowed the establishment of a 'moderate' (blood urea 100-200 mg/100 ml) and 'severe' grade of uraemia (BU > 200 mg/100 ml). The immune responsiveness of isolated lymphocyte suspensions from uraemic animals was similar to that of sham-operated animals but lymphocyte function in both groups was suppressed compared with control non-manipulated animals. This was particularly evident in the graft vs host reaction. The host vs graft which assumes the cell-mediated immune status in the live animals, was also depressed in the uraemic animals but in contrast to the previous results sham-operated animals exhibited normal responses. The results underscore the importance of surgically induced anergy as a factor complicating the assessment of immune function in uraemia and may explain some of the inconsistencies observed in the evaluation of cell-mediated immunity by in vitro analysis of lymphocyte suspensions and tests of immune function in the intact host.

Animals↗

PubMed1984

Contribution of intraperitoneal immunization to the local immune response in the respiratory tract of sheep.

The contribution of gut-associated lymphoid tissue (GALT) to the local immune response in the respiratory mucosa of sheep has been investigated. Sheep were primed intraperitoneally (i.p.) with antigen in Freund's complete adjuvant, a procedure known to produce a large IgA-specific antibody-containing cell (ACC) response in intestinal lymph. ACC and their class specificity were then enumerated by double fluorochrome immunofluorescence in respiratory tissues after intratracheal (i.t.) antigen administration. This immunization procedure produced an enhanced IgA-specific ACC response in the upper respiratory tract mucosa compared with either i.t. or i.p. immunization alone and this was not reflected in the regional lymph nodes. Furthermore, chronic drainage of the intestinal efferent lymphatic duct for the duration of the immunization period abrogated the enhanced response in the respiratory mucosa. These data are consistent with the concept of an intermucosal cell circuit with respect to IgA cell precursors, and provide indirect evidence that IgA responses in the respiratory tract can be enhanced by harnessing the immune potential of GALT as a source of IgA precursors by appropriate immunization strategies.

Animals↗

PubMed1983

Conjunctival immunity: compared effects of ocular or intestinal immunization in rats.

The ability to induce a conjunctival antitoxin response by conjunctival or enteric administration of cholera toxin antigen was studied in rats. Repeated enteric immunization caused a vigorous jejunal antitoxin response, but none in the conjunctiva. Enteric immunization did, however, prime for a conjunctival antitoxin response to locally applied antigen, as did direct ocular administration of cholera toxin. Vigorous conjunctival antitoxin responses occurred only after ocular challenge, and were localized to the challenged eye. These results agree with the notions that (1) specific memory cells migrate to the conjunctiva after enteric immunization, or arise locally after ocular immunization; and (2) specific antibody-producing plasma cells arise almost entirely within the immunized conjunctiva, and few if any migrate to the conjunctiva from distant mucosae or from the conjunctiva of the immunized eye to that of the nonimmunized eye.

Animals↗