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PubMed1985

[Failure of immunization with Naegleria fowleri in mice born to immune mothers]

Female BALB/c mice weighing 18-20 g were immunized by three injections of 1 x 10(6) Naegleria fowleri trophozoites intraperitoneally at the interval of one week 6 times for the pregnant mice and 3 times for the offspring mice. One week after immunization the mice were challenged intranasally with N. fowleri trophozoites 5 x 10(4) under secobarbital anesthesia. Experimental primary amoebic meningoencephalitis developed between day 7 and 16 after infection. All mice were dead due to amoebic meningoencephalitis in all experimental groups except in the offspring born to non-immune mothers. Mean of survival time, which is the duration of survival of mice from infection to death, was delayed in the groups of mice born to immune mothers, immune mice born to immune mothers. Active or passive protective immunity against N. fowleri infection was demonstrated in the immunized mice and mice born to immune mothers. But the effectiveness of immunization was greatly impaired in terms of mortality in the immune mice born to immune mothers when N. fowleri was infected intranasally.

Journal Article↗

PubMed1986

Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. II. Response of mouse strains with selective immune defects.

The efficacy of a new vaccination procedure against Schistosoma mansoni, involving intradermal injection of nonliving antigen combined with the bacterial adjuvant Mycobacterium bovis strain bacillus Calmette Guérin, was tested in several strains of mice. Development of protection against subsequent infection was compared with in vivo skin test reactivity and in vitro humoral reactivity to soluble and surface-associated schistosome antigens. Significant levels of resistance and immune response were displayed by many inbred mouse strains, including C57BL/6J, C3H/HeN, and CBA/J, as well as outbred Swiss-Webster mice. However, no definite correlation was observed between the level of any particular immune response and the level of resistance to challenge S. mansoni infection. Development of protective immunity was also examined in mice with various immune defects, to determine whether these responses are relevant to resistance in this model. Animals with defective specific immediate hypersensitivity response due to deficiencies in IgE (SJL/J) or mast cell (W/Wv) production displayed strong resistance as a result of immunization. Likewise, mice bearing the lpsd (C3H/HeJ) or xid (CBA/N) mutations, affecting cellular or humoral response to certain thymus-independent antigens, developed significant levels of resistance after immunization. A/J mice, with defects in cellular recognition of bacterial endotoxin as well as deficiencies in natural killer cell activity and complement function, also showed significant protective immunity. Thus, these reactivities do not appear to be essential to the resistance against S. mansoni induced by the nonliving vaccine. Two nonresponder strains were identified, P and BALB/c. P mice were defective in specific delayed hypersensitivity response as well as resistance to infection. However, BALB/c mice showed no obvious immune deficiencies at the time of challenge. These results agreed with previous findings in mice immunized by exposure to radiation-attenuated cercariae with one exception; BALB/c mice were protected by vaccination with irradiated cercariae but not by the nonliving vaccine. Thus, further examination of immune response in mice identified in this study as high and low responder strains should allow characterization of critical immune resistance mechanisms induced by the nonliving vaccine, as well as immune mechanisms operating in common between these two models of resistance to S. mansoni.

Animals↗

PubMed1995

Long-term humoral and cellular immunity induced by a single immunization with replication-defective adenovirus recombinant vector.

This study examines the suitability of replication-defective adenovirus vectors for engineering recombinant vaccines. The immunological abilities and limitations of E1-deleted adenoviruses containing the lacZ gene (Ad-beta-gal) were investigated by examining the humoral and cellular immune responses to the beta-galactosidase protein. BALB/c mice (H-2d) were given in a single injection of recombinant adenovirus. The cytotoxic T lymphocyte (CTL) response of spleen cells was evaluated. Recognized target cells were H-2d-derived tumor cells transfected by the lac Z gene, or incubated with the 876-884 beta-galactosidase peptide known to be restricted by the Ld molecule of the major histocompatibility complex. A long-lasting beta-galactosidase-specific cytotoxic T cell response was obtained. By contrast, CTL from mice immunized with the Ld-restricted peptide were less specific for the endogenous epitope presented by the transfectants expressing beta-galactosidase. Ad-beta-gal-immunized mice were also protected against an intra-cerebral challenge with a recombinant vaccinia virus expressing the lac-Z gene. These results suggest that Ad-beta-gal-induced CTL have protective abilities in vivo. The induction of beta-galactosidase-specific T helper lymphocytes and humoral IgG responses were also examined. A proliferative response occurred only late after immunization and the primed T lymphocytes produced interleukin-2, but no interleukin-4. A humoral IgG response to the beta-galactosidase protein was detected 15-30 days after a single immunization and remained stable for 6 months without boosting. Lastly, we followed the evolution of the immune response over the course of successive immunizations. The magnitude and kinetics of the cellular and humoral responses were similar to those obtained after a single immunization. Consistent with these observations, an adenovirus-specific neutralizing antibody response was detected as early as the second immunization. Thus, a single immunization with a replication-defective adenovirus recombinant vector induces long-lasting humoral and cellular immune responses specific to the transgene product.

Adenoviridae↗

PubMed1982

Antigenic variation in cancer metastasis: immune escape versus immune control.

Antigenic variation in cancer metastasis was observed in a syngeneic murine tumor system consisting of a low metastatic parental tumor line (derived from a methylcholanthrene-induced DBA/2 T lymphoma, Eb), a high metastatic spontaneous variant thereof (ESb), and a low metastatic 'revertant' from ESb (ESb-M). All three lines expressed tumor-associated transplantation antigens (TATA) which elicited specific T cell-mediated antitumor immune reactions in the host. The strongest host response was elicited upon intradermal inoculation. It could be followed by (a) the infiltration of the locally growing tumor by host cells, such as lymphocytes and macrophages, (b) the establishment of specific systemic antitumor immunity, (c) the generation of immune cells capable of transferring protective antitumor immunity into a normal syngeneic recipient, and (d) the generation of tumor specific cytotoxic T lymphocytes (CTL). Anti-TATA CTL were used as typing reagents to investigate the stability or variability in the TATA expression by cloned tumor cell lines. Antigenic variability in the TATA expression was seen under various conditions: (a) clone-dependent variation in the sensitivity to anti-TATA CTL lysis upon prolonged growth in tissue culture, (b) qualitative change in the TATA (TATA1 leads to TATA2) upon successive i.p. transplantation of the parental Eb tumor line and, (c) generation of TATA negative immune escape variants (TATA2 leads to TATA-) during metastasis formation from a s.c. site. The relative inefficiency of specific immunization procedures against ESb was found to be due to the effective generation of TATA negative variants by this highly metastatic tumor. The balance between immune control and immune escape could be influenced to the advantage of the host by some means, for instance optimizing the route of antitumor-immune sensitization or by infusion of allogeneic but H-2 identical antitumor-immune T cells. Such immune cells recognized the tumor via minor histocompatibility antigens and thus circumvented the need of TATA recognition. Finally, manipulations at the cell surface of the highly malignant ESb tumor such as those introduced in the ESb-M variant were found to dramatically effect its metastatic potential.

Animals↗

PubMed1993

Oral immunization with recombinant BCG induces cellular and humoral immune responses against the foreign antigen.

It has been shown recently that BCG can be used as a live recombinant vaccine to stimulate immune responses. Proliferative or cytotoxic T-cell responses against several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral immunization with BCG expressing these proteins. Antibody responses were also obtained after immunization of mice with recombinant BCG strain which expressed lac Z under the control of a promoter sequence isolated from Mycobacterium paratuberculosis. We have used this recombinant vaccine in guinea-pigs to investigate the influence of various routes of immunization on the immunogenicity of a foreign antigen expressed by recombinant BCG. Guinea-pigs were immunized by oral, respiratory or intradermal routes and proliferative responses, delayed-type hypersensitivity and antibody responses specific for beta-galactosidase were followed for 16 weeks. Results demonstrated that humoral and cellular immune responses specific for beta-galactosidase can be produced in all groups of guinea-pigs. However, the respiratory and especially the oral route of administration induced higher local and systemic immune responses than the intradermal route of immunization. Moreover, the oral immunization of mice with this recombinant BCG induced IgA responses which could be detected in both sera and intestinal secretions. Therefore, this study demonstrates for the first time that oral immunization with recombinant BCG can induce strong cellular and humoral immune responses.

Administration, Inhalation↗

PubMed2004

Intranasal immunization with liposome-encapsulated plasmid DNA encoding influenza virus hemagglutinin elicits mucosal, cellular and humoral immune responses.

BACKGROUND: Influenza viral infections are a significant global public health concern due to the morbidity and mortality associated with acute respiratory disease, associated secondary complications and pandemic threat. Currently, the most effective preventative measure is an annual intramuscular (i.m.) injection of a trivalent vaccine. Intramuscular immunization induces strong systemic humoral responses but not mucosal immune responses which are important in the first line of defense against influenza. OBJECTIVES: A plasmid encoding influenza A/PR/8/34 (H1N1) hemagglutinin (HA; pCI-HA10) was evaluated with respect to the mucosal, cellular and humoral immune responses generated and to its efficacy in protection against a challenge with a lethal dose of influenza. STUDY DESIGN: BALB/c mice were immunized with pCI-HA10 DNA or liposome-encapsulated pCI-HA10 by either an intranasal (i.n.) or i.m. route. Sera and bronchoalveolar lavage (BAL) fluid were collected at various times and evaluated for HA-specific IgG and IgA antibodies and T cells, isolated from draining lymph nodes and spleens, were analyzed for their proliferative ability. Immunized mice were challenged with a lethal dose (5LD(50)) of influenza and monitored for survival. RESULTS AND CONCLUSIONS: Intranasal immunization with liposome-encapsulated pCI-HA10 stimulated both IgG and IgA humoral responses and increased IgA titers in BAL fluid, whereas immunization with naked pCI-HA10 had no effect on the antibody response. Intramuscular immunization with both naked and liposome-encapsulated pCI-HA10 elevated serum IgG levels, but had no effect on IgA levels in either the serum or BAL fluid. Both i.n. and i.m. administration of HA vaccine (naked and liposome-encapsulated) elicited T cell proliferative responses. These results suggest that i.n. administration of liposome-encapsulated HA-encoding DNA is effective at eliciting mucosal, cellular and humoral immune responses. Mice immunized i.n. were able to withstand a lethal challenge of influenza virus, confirming that the immune responses mediated by the vaccine were protective.

Administration, Intranasal↗

PubMed2005

Mucosal immune responses are related to reduction of bacterial colonization in the stomach after therapeutic Helicobacter pylori immunization in mice.

The aim of this study was to investigate the capacity of oral and parenteral therapeutic immunization to reduce the bacterial colonization in the stomach after experimental Helicobacter pylori infection, and to evaluate whether any specific immune responses are related to such reduction. C57BL/6 mice were infected with H. pylori and thereafter immunized with H. pylori lysate either orally together with cholera toxin or intraperitoneally (i.p.) together with alum using immunization protocols that previously have provided prophylactic protection. The effect of the immunizations on H. pylori infection was determined by quantitative culture of H. pylori from the mouse stomach. Mucosal and systemic antibody responses were analyzed by ELISA in saponin extracted gastric tissue and serum, respectively, and mucosal CD4+ T cell responses by an antigen specific proliferation assay. Supernatants from the proliferating CD4+ T cells were analyzed for Th1 and Th2 cytokines. The oral, but not the parenteral therapeutic immunization induced significant decrease in H. pylori colonization compared to control infected mice. The oral immunization resulted in markedly elevated levels of serum IgG+M as well as gastric IgA antibodies against H. pylori antigen and also increased H. pylori specific mucosal CD4+ T cell proliferation with a Th1 cytokine profile. Although the parenteral immunization induced dramatic increases in H. pylori specific serum antibody titers, no increases in mucosal antibody or cellular immune responses were observed after the i.p. immunization compared to control infected mice. These findings suggest that H. pylori specific mucosal immune responses with a Th1 profile may provide therapeutic protection against H. pylori.

Animals↗

PubMed1993

Interference of immune globulin with measles and rubella immunization.

Passively acquired antibody may interfere with the active antibody response to live viral vaccines such as measles and rubella. To evaluate the duration of this inhibitory effect, we measured the measles and rubella antibody responses of Apache children immunized with measles, mumps, and rubella vaccine at varying intervals after administration of an immune globulin termed bacterial polysaccharide immune globulin (BPIG). This specific immune globulin contained measles and rubella antibody titers similar to those in standard intramuscularly and intravenously administered immune globulins. Antibody responses to measles vaccine were inhibited for up to 5 months after a BPIG dose of 80 mg IgG per kilogram of body weight, but responses to rubella vaccine were inhibited for only 2 months. Most children who had a decreased measles antibody response to primary measles, mumps, and rubella immunization given 1 1/2 to 4 months after BPIG administration responded to a booster immunization given 6 months after their last BPIG dose. We conclude that high doses of immune globulin (> 10 mg/kg) may inhibit the antibody response to measles for more than 3 months. We propose that the interval between administration of immune globulin and measles and rubella immunization be adjusted on the basis of the dose of immune globulin.

Antibodies, Viral↗

PubMed2003

Passive immunization of mice pups through oral immunization of dams with a plant-derived vaccine.

Passive immunization plays an important role in protecting young mammals against pathogens before the maturation of their own immune systems. Although many reports have shown active immunization of animals and human through the use of plant-derived vaccines, only one report has given evidence of passive immunization of offspring through oral immunization of parents using plant-derived vaccines. In this case, a challenge alone provided the evidence of passive immunization and the mechanism through which this occurred was not investigated. This report describes the first step in elucidating the mechanism of passive immunization of offspring through actively immunizing the female parent through an orally delivered, plant-derived vaccine. The authors found passive immunization of offspring was caused by transfer of antigen-specific IgG through either transplacental transfer or ingesting colostrum. Future studies will investigate the roles of transplacental antibody transfer and ingesting colostrum in passive immunization and the possible involvement of IgA in this immunization route.

Administration, Oral↗

PubMed1978

Protective antitoxic cholera immunity in mice: influence of route and number of immunizations and mode of action of protective antibodies.

An adult mouse model has been elaborated for studies of experimental cholera (Vibrio cholerae enterotoxin-induced intestinal secretion) and protective antitoxic immunity in either ligated small bowel loops or intact small intestine. Mice of different inbred strains varied markedly in intestinal susceptibility to toxin, C57B1 being the most sensitive strain tested. Fluid accumulation started within 1 h after the inoculation of toxin and was maximal after 5 h, whereafter recovery gradually ensued. The dose-response curve was sigmoid, the ED50 of crude toxin being equivalent to about 0.1 microgram purified toxin/cm in the loops and 0.3 microgram/cm in the nonligated intestine. Two peroral (p.o.) immunizations induced significant protective immunity which increased markedly after two further immunizations by the same route. Additional p.o. immunizations did not appreciably enhance the protective immunity any further. Intravenous (i.v.) vaccination had to be repeated more than 5 times before intestinal immunity could be observed. No correlation between serum antitoxin titers and protective immunity was found. Electron microscopic examination revealed that whereas peroxidase-coupled cholera toxin bound tightly to intestinal microvilli from unimmunized or 5-times i.v. immunized mice it did not bind to the microvilli of p.o. immunized animals. The data thus suggest that the protective immunity is mediated exclusively by locally produced antibodies which prevent the binding to toxin to the gut epithelium.

Administration, Oral↗

PubMed2005

Effectiveness of intragastric immunization with protein and oligodeoxynucleotides containing a CpG motif for inducing a gastrointestinal mucosal immune response in mice.

PURPOSE: To investigate a new modality of mucosal vaccines, we evaluated the effectiveness of intragastric immunization for inducing a mucosal immune response in the gastrointestinal tract. METHODS: Mice were immunized with beta-galactosidase (beta-gal) and synthesized oligodeoxynucleotides containing a CpG motif (CpG-DNA) by intragastric injection, and the immune response was compared with those induced by 3 other immunization forms: intranasal, oral, and intradermal. RESULTS: Intragastric immunization with beta-gal and CpG-DNA induced significant anti-beta-gal fecal IgA production at 2 weeks; however, at 4 weeks the response was lacking. In contrast, intranasal immunization with beta-gal and CpG-DNA induced the highest anti-beta-gal fecal IgA production at 4 weeks. CONCLUSION: Although intragastric immunization with protein and CpG-DNA induces a mucosal immune response in the gastrointestinal tract, intranasal immunization is the most effective to induce both mucosal and systemic immune responses. This finding may increase the possibility for developing vaccines against mucosal pathogens, especially Helicobacter pylori.

Animals↗

PubMed1989

[Humoral and cellular immunity in mice immunized with mutagenic NTG-attenuated cercariae of Schistosoma japonicum].

Observation was made on humoral and cellular immunity in mice immunized with NTG-attenuated cercariae. Results showed that the specific antibody in serum of immunized mice increased gradually. The titer by ELISA and IFA were more than 1:1,280 respectively at week 7 post-immunization with NTG-attenuated cercariae (15 min. pc or 60 min. ip). SDS-PAGE electrophoresis showed that there was an extra-band of IgG with MW, between 50,000 and 40,000 in the serum of immunized mice and there was no obvious difference in IgM bands. It suggested that there were differences in not only the increase of antibody titre, but also the composition of antibody post-immunization. The results also indicated that there were differences in levels of lymphocyte proliferative response to schistosome antigens at different weeks post-immunization. The proliferative response to SEA was greater in immunized mice than in infected mice, especially in lymph node lymphocytes. It suggested that NTG-attenuated cercariae did stimulate mice to produce immunity. The dynamic characteristics of humoral and cellular immunity may play roles in the induction of protective immunity against S. japonicum.

Animals↗

PubMed1981

Acceleration of allogeneic antitumor immunity with immune RNA in vitro and T-cell suppression by L1210 tumor bearer spleen cells.

RNA fractions extracted from the spleens of immunized animals prepared against L1210 leukemia cells can transfer allospecific cell-mediated immunity both in vitro and in vivo. Both preculture of nonsensitized lymphocytes prior to the treatment with immune RNA and additional culture of lymphocytes after 1-hr treatment with immune RNA enhance the growth-inhibitory activity of immune RNA-treated lymphocytes. Preculture for 5 hr and additional culture for 24 hr are sufficient for maximal enhancement of the growth-inhibitory activity. There is no significant difference in inhibition between lymphocytes treated with immune RNA for 1 hr and 24 hr. The growth inhibition by lymphocytes is augmented proportionally to the increase in the dose of immune RNA in vitro but not in vivo. In mice given i.p. injections of immune RNA-treated syngeneic spleen cells (before or after inoculation with L1210 cells), a significant prolongation of the mean survival time [27.0 +/- 5.4 (S.D.) days, 0.05 < p < 0.1] was not achieved when compared with control mice (21.4 +/- 1.6 days). Evidence is presented that suppressor cells in the spleens of L1210-bearing mice are involved in preventing effector cell function in vivo. The present study revealed that 8 X 10(3) and 5 X 10(5) suppressor cells were sufficient to inhibit completely the activity of immune RNA-treated effector cells in vitro and in vivo, respectively. Suppressive activity was abolished by treatment with anti-Thy 1.2 serum and complement and partially abolished with irradiation (1500 R). The suppressor cells belonged to a radiation-sensitive T-cell population. The limited activity of immune RNA in vivo is probably due to the destruction of immune RNA by RNase present in the host plasma and tissues and the acquisition of suppressor cells which inhibits nonadherent peritoneal exudate cell activity in the animal.

Animals↗

PubMed2000

Enhancing influenza immunization. Postcard and telephone reminders and the challenge of immunization site shift.

OBJECTIVE: To determine if postcard and telephone reminders increased the rate of influenza immunization of Medicare beneficiaries. DESIGN: Before and after trial (postcard reminders) with systematically allocated control group (telephone reminder intervention). SETTING: A semirural family practice residency program. PATIENTS AND OTHER PARTICIPANTS: All 475 noninstitutionalized persons older than 65 years who had received at least 1 office service in the previous 2 years. INTERVENTION: In September 1996, each of 475 patients received a postcard urging prompt influenza immunization. Those not responding within 1 month were systematically allocated either to a group receiving further telephone contact or to a control group. At the time of telephone contact, any offered information about influenza immunization received outside the Smoky Hill Family Practice Center, Salina, Kan, was recorded. MAIN OUTCOME MEASURES: We measured the percentage of change in practice-administered influenza immunizations compared with the baseline rate of the preceding 2 years; the difference in immunization rates between the telephone intervention group and controls; and the number of patients contacted by telephone who reported receiving influenza immunization at a site other than the Family Practice Center. RESULTS: Twenty-eight percent of patients who received a postcard obtained office influenza immunizations within 1 month, but no additional immunizations could be attributed to the telephone intervention. Thirty-five percent of patients contacted by telephone reported receiving influenza immunization at a site other than the Family Practice Center. CONCLUSIONS: The postcard intervention was associated with a significant increase in the office immunization rate. This increase may have been confounded by "site shift" in which individuals came to the office for an immunization that they might otherwise have received at other community sites.

Aged↗

PubMed2006

Gene conjugation of molecular adjuvant C3d3 to hCGbeta increased the anti-hCGbeta Th2 and humoral immune response in DNA immunization.

Human chorionic gonadotropin (hCG) has been used as an anti-fertility vaccine and as a target for cancer immunotherapy. We have explored the use of three copies of C3d in DNA vaccine as molecular adjuvant to improve the immunogenicity of this hormone in previous work and found that the immune response induced by pcDNA3-hCGbeta-C3d3 has been enhanced 243-fold compared with pcDNA3-hCGbeta following DNA immunization in BALB/c mice. In the present study, a new functionally active DNA vaccine of hCGbeta-C3d3 chimera based on pCMV4 vector has been described. We compared the expression efficiency of pCMV4 and pcDNA3 eukaryotic vectors for hCGbeta and hCGbeta-C3d3 fusion protein and the immune response of mice immunized with pcDNA3-hCGbeta, pCMV4-hCGbeta, pcDNA3-hCGbeta-C3d3 and pCMV4-hCGbeta-C3d3, respectively, at 25, 50 and 100 pmol dose, and further analyzed the levels of Th1 and Th2 cytokines produced by spleen lymphocytes of the immunized mice upon hCG restimulation in vitro. It was found that pCMV4 vector achieved 1.3-1.5-fold higher protein expression and raised 1.1-1.2 (primary) and 1.2-1.3 (booster) logs higher titer of anti-hCGbeta IgG than pcDNA3. Mice vaccinated with 50 pmol of hCGbeta-C3d3-DNAs elicited the highest titer of hCGbeta-specific antibody among the serial doses and the immune response induced by pCMV4-hCGbeta-C3d3 were, respectively, 1.3, 1.3 and 1.2 logs higher than that of pcDNA3-hCGbeta-C3d3 and 2.2, 2.9 and 2.4 logs higher than that of pCMV4-hCGbeta at week 2 following the booster immunization. Moreover, we observed that the production of IL-4 and IL-10 increased in mice vaccinated with hCGbeta-C3d3-DNAs and the ratio of IL-4/IFN-(gamma) showed a Th2 bias of immune response in the mice immunized with hCGbeta-C3d3-DNAs. These findings indicated that gene fusion of C3d3 to hCGbeta, as a means of harnessing the adjuvant potential of the innate immune system, may improve the antigen-specific Th2 humoral immune response of the hCGbeta DNA vaccine and the pCMV4 vector is a more ideal eukaryotic vector for DNA vaccine than pcDNA3.

Animals↗

PubMed2004

Effective induction of antitumor immunity by immunization with plasmid DNA encoding TRP-2 plus neutralization of TGF-beta.

Plasmid DNA vaccine is an appealing cancer immunotherapy. However, it is a weak immunogen and immunization with plasmid DNA encoding self-antigens, such as melanoma-associated antigens, could not induce antitumor immunity because of tolerance. In this study, we investigated the feasibility of using a plasmid DNA encoding Xenopus laevis transforming growth factor-beta 5 (aTGF-beta5) as an immunogen to induce neutralizing antibodies against murine TGF-beta1 (mTGF-beta1) and thus enhance the efficacy of plasmid DNA vaccine encoding murine tyrosinase-related protein 2 (mTRP-2) through neutralization of TGF-beta. The results showed that immunization with aTGF-beta5 resulted in the generation of mTGF-beta1-neutralizing antibodies, and immunization with a combination of aTGF-beta5 and mTRP-2 induced specific cytotoxic T lymphocytes (CTLs). On the contrary, immunization with mTRP-2 alone could not elicit the CTL response. Moreover, immunization of C57BL/6 wild-type mice with a combination of aTGF-beta5 and mTRP-2 induced the protective and therapeutic antitumor immunity to B16F10 melanoma, whereas the antitumor activity was abrogated in both CD4-deficient mice and CD8-deficient mice on the C57BL/6 background. Our results indicate that immunization with aTGF-beta5 is capable of breaking immune tolerance and induces mTGF-beta1-neutralizing antibodies. Neutralization of TGF-beta can enhance the efficacy of DNA vaccine encoding mTRP-2 and the induction of antitumor immunity by this immunization strategy is associated with CD4+ and CD8+ T cells.

Animals↗

PubMed1984

Immunoglobulin G-induced experimental chronic immune synovitis: cell-mediated immunity to native interstitial collagen molecules and their constituent polypeptide chains.

In vitro cell-mediated immune responses to homologous rabbit immunoglobulin G (IgG), purified protein derivative (PPD), native Type I, II, and III collagen, and denatured Type I, II, and III collagen were studied in an IgG-induced animal model of immune synovitis. Immune response was measured as augmented [3H]thymidine incorporation by spleen cells on exposure to antigen. Immune responses were observed in vitro after 72 hr of culture with antigen, while a majority of responses to antigens occurred after 96 hr of incubation. Separation of spleen cell subpopulations showed that measured immune responses were of T-cell origin. In vitro cell-mediated immune responses were observed for native and denatured collagen in splenic cell cultures from six of seven synovitic rabbits (P less than 0.01) but not in control spleen cell cultures derived from normal, adjuvant-primed or IgG-immune nonsynovitic rabbits. The incidence of cellular reactivity to incubation with native interstitial collagens was as follows: Type I, 43%; Type II, 43%; Type III, 57%. The incidence of in vitro immune responses to denatured collagens in cultures derived from rabbits with synovitis was: Type I, 50%; Type II, 50%; Type III, 67%. The relatively high incidence of immune response to both native and denatured collagens suggests that immunity to structural components of the synovial membrane and the adjacent surface of articular cartilage may play a role in the inflammation observed in immune synovitis.

Animals↗

PubMed1989

Modulation of Fc receptor clearance and antiplatelet antibodies as a consequence of intravenous immune globulin infusion in patients with immune thrombocytopenic purpura.

In 1981 Paul Imbach first reported the usefulness of intravenous immune globulin infusions in the treatment of children with immune thrombocytopenic purpura. Other studies have shown that intravenous immune globulin was associated with the fastest platelet increase of any therapy, confirming the initial observation in children and adults. We and other investigators have used intravenous immune globulin as a maintenance therapy and speculated that repeated single infusions might have a curative value, in addition to an acute effect. The best-defined mechanism of intravenous immune globulin in this model autoimmune disease is Fc receptor blockade. This was first demonstrated by a slowing of antibody-coated, chromium-labeled red blood cell survival. Subsequent confirmation has come from the use of intravenous anti-D and a monoclonal anti-FcRIII that has been used in patients refractory to treatment. In vitro studies have demonstrated alteration in Fc receptor expression on circulating cells, and this mechanism is presumed to be related intimately to the acute platelet increase seen after intravenous immune globulin. Studies with the latest platelet antibody methodology do not support interference with binding of antiplatelet antibodies as an important mechanism, but there are in vitro data to support this hypothesis. Another leading hypothesis is that intravenous immune globulin decreases the production of autoantibodies. Clinically, this has been suspected in immune thrombocytopenic purpura in which there are apparent improvements in patients with chronic disease, but no controlled studies have been performed to verify this. In acquired hemophilia and von Willebrand's disease, however, it seems quite clear that there is direct neutralization of autoanti-factor VIII antibodies by intravenous immune globulin by a presumed Fab-mediated anti-idiotype mechanism. This hypothesis has appeal and has been postulated on the basis of in vitro studies, as well as looking directly at the B cell. Another study supporting this mechanism showed that intravenous immune globulin preparations with altered Fc portions still mediate some platelet increase, even if not as much as intact IgG molecules. It remains unclear whether any effects that are the result of a lower level of autoantibody could be mediated through T cells or macrophages, rather than having direct action on the B cell. In any event, these findings strongly support the hypothesis that decreased levels of autoantibody lead to intermediate (weeks) and long-term (months to years) responses after intravenous immune globulin treatment.

Autoantibodies↗