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PubMed1987

Secondary immune amplification following live poliovirus immunization in humans.

Eight subjects inoculated orally with live attenuated poliovirus were investigated to study the effects of live virus infection on human T-cell responses. Proliferation to poliovirus and unrelated recall antigens were measured serially over a 3-week period. Five of eight subjects inoculated demonstrated a clear anamnestic response to poliovirus, but three did not. Only the five subjects demonstrating an anamnestic response to poliovirus were found to have augmented secondary immune responses to two unrelated recall antigens (tetanus toxoid and reovirus) and in the autologous mixed lymphocyte response (AMLR). No consistent changes were found in circulating T-cell surface activation antigens whether or not the subjects responded to poliovirus. These studies suggest that an asymptomatic poliovirus infection associated with immunization in humans can induce nonspecific secondary immune amplification as measured by in vitro T-cell proliferative response. This amplification pathway is a potential mechanism for immune responses against antigens other than those of the infecting virus.

Administration, Oral↗
PubMed1991

Embryo losses in Rasa Aragonesa ewes actively immunized against androstenedione or passively immunized against testosterone.

Two-day-old embryos from untreated ewes were transferred to the oviducts of ewes actively immunized against androstenedione (n=26, Group A), passively immunized against testosterone (n=19, Group B) or left untreated (n=25, Group C). Donor ewes superovulated after treatment with follicle-stimulating hormone and fluorogestone acetate (FGA). Recipient ewes were treated with FGA and pregnant mare serum gonadotropin (PMSG, 300 I.U.). Group A received two injections of Fecundin at a 4-wk interval. FGA sponges were inserted when the second injection was given. Group B was treated with antitestosterone antiserum (35 ml) at sponge withdrawal. Each recipient received two morphologically viable embryos 52 to 62 h after the onset of estrus. Antibody titre at embryo transfer and progesterone concentration on Days 2, 4, 6, and 12 after estrus were determined. Fertility was lower in Group A when compared to Group C (42.3 vs 84.1%; P<0.01) while that of Group B (63.2%) did not differ from those of Groups A and C. In immunized groups, most of the embryo losses occurring were complete (both embryos were lost), resulting in a decreased fertility, while in the untreated group embryo losses were mainly partial (only one embryo was lost), hence lowering prolificacy. Fertility in immunized groups changed according to the antibody titre reached. Ewes from Groups A and B with higher antibody titres displayed lower fertility than control ewes. On Days 4 and 12 of the cycle, Group A plasma progesterone concentrations positively correlated with antibody titres and were higher with respect to those of Group C (P<0.05). Progesterone levels in Group B were similar to those of Group C. These results indicate that ewes reaching higher antibody levels had more embryo losses, attributable to the adverse influences of the oviductal and/or uterine environment on embryo development.

Journal Article↗
PubMed1992

Immune dysfunction following infection with chicken anemia agent and infectious bursal disease virus. II. Alterations of in vitro lymphoproliferation and in vivo immune responses.

To determine the functional impact of alterations in lymphocyte concentrations and ratios following infection with chicken anemia agent (CAA) alone or in combination with infectious bursal disease virus (IBDV) on the immune system of young chickens, in vitro lymphoproliferation assays and in vivo responses to vaccination with several common viral agents were assessed at various time intervals post-inoculation (PI). Concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) stimulation of splenic lymphocytes (SPL) collected from control birds could not be detected until 10-14 days PI. Infection with CAA was characterized by significantly higher PWM stimulation of SPL at 17 days PI and significantly lower PWM stimulation of peripheral blood lymphocytes (PBL) at 14 days PI, compared with uninfected controls. Concanavalin A and PWM stimulation of SPL was significantly increased in birds inoculated with IBDV alone. Lymphocytes harvested from birds inoculated simultaneously with CAA and IBDV had significantly lower responses. Effects on humoral and cell-mediated immunity following CAA and/or IBDV were determined by evaluating vaccination responses to Newcastle disease virus (NDV), fowl pox virus (FPV) and infectious laryngotracheitis virus (ILTV) during the acute phase of CAA infection (2 weeks PI). Vaccination of birds 2 weeks following CAA infection at 1 day of age resulted in decreased protection against NDV (85.7%) and ILTV (7.1%) challenge compared with protection rates in control birds (100% and 53.3% respectively). Infectious bursal disease virus infection was associated with decreased protection against NDV (60%) only. Concomitant infection at 1 day of age resulted in a greater reduction in NDV challenge protection (33.3%), slightly decreased FPV protection (87.5%), increased numbers of persistent FPV vaccination lesions and increased protection against ILTV challenge (71.4%). Vaccination of birds 2 weeks following CAA infection at 2 weeks of age resulted in slightly decreased NDV humoral antibody, development of persistent FPV vaccination lesions (17%) and increased immunity to ILTV challenge compared with control birds (83.3% vs. 66.7%). Chickens inoculated with IBDV alone displayed a more severe depression in NDV antibody titers and only a slight decrease in ILTV protection. Vaccination following concomitant infection at 2 weeks of age resulted in a higher percentage of FPV persistent vaccination lesions (39%) and greatly enhanced immunity to ILTV challenge (100%).

Animals↗
PubMed1986

Relationship between immune system and gram-negative bacteria. Acid-treated Salmonella minnesota R595 (Re) enhances immune responsiveness in patients with gynecologic malignancies.

Nine patients with gynecologic malignancies (six cervix, two endometrium and one ovary) were injected with acid-treated Salmonella minnesota R595 (Re). Patients received a total of four injections (at increasing doses from 0.5 to 3 micrograms) every 2 weeks. All patients, before treatment, had a severe impairment of their immune system either of cell-mediated immunity (leukocyte inhibiting factor activity) or non-specific immunity (polymorphonuclear cell and/or monocyte-mediated phagocytosis and killing). In contrast, the same patients displayed a normal Natural Killer cell frequency in their peripheral blood as evaluated in an agarose-single cell cytotoxic assay. At the end of the immunotherapeutic regimen, all the above immune functions significantly augmented likely via an immunomodulating effect exerted by the lipid A portion of Salmonella minnesota Re which represents the lipopolysaccharide molecule in these bacteria. This suggests a potential role for lipid A in the treatment of cancer-related immunodeficiency.

Cytotoxicity, Immunologic↗
PubMed1984

Cytomegalovirus vaccine: persistence of humoral immunity following immunization of renal transplant candidates.

A randomized, placebo-controlled, double-blind trial of Towne live, attenuated cytomegalovirus (CMV) vaccine in renal transplant candidates underway since January 1979 has enabled us to assess the durability of humoral immunity after immunization. Among 53 seronegative subjects, Towne vaccine elicited a geometric mean indirect immunofluorescent (IF) antibody titre of 72.3, but titres in patients either not transplanted or given kidneys from seronegative donors declined substantially by one year postimmunization. Vaccine boosted the geometric mean IF antibody titre in 21 seropositive untransplanted subjects from 66.5 pre-immunization to 91.0 approximately three months later. Seventeen seronegative subjects given a seropositive kidney and 27 subjects seropositive before immunization experienced a sharp boost in geometric mean antibody titre posttransplant signifying reactivation of their own CMV strain or acquisition of virus from the donor kidney. These data indicate that Towne vaccine is immunogenic in renal transplant candidates but does not completely prevent posttransplant infections.

Antibodies, Viral↗
PubMed1991

Immunization of monkeys with rabies ribonucleoprotein (RNP) confers protective immunity against rabies.

The ability of rabies virus ribonucleoprotein (RNP) to induce protective immunity against rabies and to prime for production of virus-neutralizing antibodies (VNA) was studied in monkeys. Following two immunizations with RNP, monkeys developed a strong anti-RNP response and were protected against a challenge infection with a lethal dose of street rabies virus. Monkeys that were primed with RNP and then immunized with a single dose of human diploid cell vaccine (HDCV) developed VNA titres comparable to the VNA titres in non-primed monkeys after a second HDCV immunization. The utility of rabies RNP for the pre-exposure prophylaxis of human rabies is discussed.

Animals↗
PubMed1995

Immunotoxicological investigation using pharmaceutical drugs. In vitro evaluation of immune effects using rodent or human immune cells.

In order to evaluate the relevance of in vitro methods for immunotoxicity assessment, the effects of pharmaceutical drugs on lymphoproliferative and cytotoxic functions of mouse splenocytes and human peripheral blood mononuclear cells (hPBMC) were studied. A comparison of sensitivity of immune cells from different origins to an in vitro exposure to different xenobiotics was performed using non-immunosuppressive (cimetidine and furosemide) and immunosuppressive (azathioprine (AZA), cyclosporine A (CSA), and dexamethasone (DEX)) drugs. For CSA, sensitivity of both rat and mouse splenocytes following in vitro exposure was compared to the one of hPBMC. Immune function tests included lymphoproliferative response to mitogenic lectins (concanavalin A (Con A) and phytohemagglutinin (PHA-P)) or to allogeneic cells (mixed leukocyte response (MLR)) and cytotoxicity assays (cytotoxic-T lymphocyte (CTL) and natural killer (NK) cell-mediated cytolysis). Additionally, to evaluate how well in vitro assays represent the in vivo situation, a comparison of the effect of cyclosporine A on the same immune function tests following in vivo or in vitro exposure was performed. The data obtained show numerous similarities in the effects observed following in vitro exposure of rodent or human cells to the drugs and a very similar sensitivity of rat and mouse cells to CSA in vitro. Discrepancies between human and rodent cells such as lymphoproliferative response to PHA-P following exposure to DEX or sensitivity of CTL-mediated cytolysis to CSA do exist. In vitro assays were very representative of the in vivo situation, both in the rat and in the mouse, following CSA exposure, except for NK cell activity in the rat. These data show the usefulness of in vitro systems for immunotoxicity assessment. They allow direct comparison of rodent and human systems, and could be representative, for drugs altering specifically the immune system like CSA does, of the in vivo situation.

Animals↗
PubMed2005

Immune surveillance and anti-tumor immune responses: an anatomical perspective.

The development of adaptive immune responses against infectious agents relies on the initiation of antigen specific immune responses in secondary lymphoid organs and on the migration of effector cells at the site of infection. Similarly, the development of anti-tumor immunity depends on the recognition of tumor-derived antigens by specific lymphocytes in the context of the lymphoid tissues and on the re-localisation of the cells to the site of cell transformation. Here, we will review the preclinical studies, which have defined the spatial and temporal organisation of anti-tumor immunity, and discuss the implications of these findings in active immunotherapy.

Animals↗
PubMed2004

On the origins of adaptive immunity: innate immune receptors join the tale.

Among members of the Ig superfamily (IgSF), antigen receptors have the unique capacity to rearrange their variable domains, thereby creating an extensive repertoire for antigen recognition. It is assumed that antigen receptors evolved from a non-rearranging IgSF member by insertion of a transposable element. Although the nature of this predecessor is unknown, two multigene families of innate immune receptors that bear a close structural resemblance to antigen receptor chains have been identified in mammals and bony fish, respectively: signal-regulatory proteins (SIRPs) and novel immune-type receptors (NITRs). Members of both families encode V-set Ig domains with a typical antigen receptor-like joining (J) motif and possess the potential to signal through immunoreceptor tyrosine-based inhibition motifs (ITIMs) or immunoreceptor tyrosine-based activation motifs (ITAMs). By analogy to the T-cell receptor (TCR) and certain innate receptors [e.g. killer cell inhibitory receptors (KIRs)] that recognize MHC molecules, SIRP members regulate immune function by interaction with broadly expressed 'self' ligands. We propose the existence of an evolutionary and functional link between innate and adaptive immune receptors that sheds light on the nature of the antigen receptor predecessor(s).

Amino Acid Sequence↗
PubMed2005

Reversion of immune escape HIV variants upon transmission: insights into effective viral immunity.

Many viruses that cause chronic viremic infections, such as human immunodeficiency virus type 1 (HIV-1), mutate extensively to avoid effective control by the host immune system. However, each immune escape mutation probably results in some fitness cost to the virus. The most effective immune responses might be those that target the regions of the virus where escape mutation inflicts the largest fitness cost to the virus. A virus crippled by immune escape mutations would result in reduced viral load and delayed disease. Such knowledge could be used to rationally design more effective vaccines.

Animals↗
PubMed2005

Intranasal immunization with a replication-deficient adenovirus vector expressing glycoprotein H of murine cytomegalovirus induces mucosal and systemic immunity.

A vaccine vector, designated AdV-gH, was constructed by inserting the complete open reading frame of MCMV gH under control of the human CMV IE-1 promoter into the E-1 region of a replication-deficient adenovirus 5. In vitro infection of QB1-293 cells and mouse embryo cells with AdV-gH resulted in expression of MCMV gH detected by IFA. Immunization of BALB/c mice with AdV-gH (1 x 10(7) PFU) given by the intranasal route induced a humoral response with antibody detected in serum of 100% of vaccines. Antibody to MCMV gH was also detected in the bronchoalveolar lavage, fecal suspensions and vaginal washings. The viral titer of lung and salivary gland of immunized mice 10 days after intranasal challenge with MCMV (1 x 10(5) PFU) were significantly reduced compared to controls, but virus infection was not prevented. Re-exposure of mice to AdV-gH 30 days after primary immunization induced a significant boost of serum antibody response. When rechallenged with MCMV intranasally, these mice had further reduction of MCMV titers in the lung and salivary glands. Such a strategy may be important in reducing horizontal transmission of CMV infections across mucosal surfaces and in altering host immunity to CMV.

Adenoviridae↗
PubMed2006

'Combined vaccines are like a sudden onslaught to the body's immune system': parental concerns about vaccine 'overload' and 'immune-vulnerability'.

The recent controversy surrounding the safety of the measles, mumps, and rubella vaccine (MMR) has heightened parents' concerns about the safety of vaccines, and led some to believe that giving vaccines in a combined form may 'overload' children's immune systems. However, to date no studies have been published examining how British parents conceptualise the notion of 'immune-overload' or how they relate this concept to their own children. Eighteen focus groups were conducted with parents between November 2002 and March 2003. The literature on vaccine decision-making suggests that parents base their immunisation decisions on two key risks: those posed by the diseases, and those associated with the vaccines aimed at preventing those diseases. Our study suggested that for some parents a third factor plays an important role, namely their assessment of the ability of their child's immune system to 'cope' with the challenge of combined vaccines, or to fight the disease. We conclude that although there is no scientific evidence that supports parents' fears about combined vaccines causing 'immune-overload', policy makers need to recognise these concerns if they are to successfully persuade parents that combined vaccines are safe.

Child↗
PubMed2006

L-Arginine stimulates intestinal intraepithelial lymphocyte functions and immune response in chickens orally immunized with live intermediate plus strain of infectious bursal disease vaccine.

Infectious bursal disease (IBD) continues to pose potential threat to poultry industry all over the world. The disease can spell disaster not only through its infection but also by break of immunity in chickens vaccinated for other diseases. l-Arginine, a ubiquitous, semi-essential amino acid has emerged as an imunostimulant from variety of human and animal studies. In the present study, we demonstrate the stimulatory effects of l-arginine on intestinal intraepithelial lymphocyte (iIELs) functions as well as on systemic immune response in chickens orally vaccinated with live intermediate plus (IP) strain of IBD vaccine. Challenge studies with virulent IBDV revealed complete (100%) protection in IP+l-arginine group compared with 80% protection recorded in IP strain vaccinated chickens. Functional activities of iIELs evaluated by cytotoxicity assay demonstrated significantly high percentage cytotoxicity in IP+l-arginine groups compared with IP group (P<0.05). Proliferative response of iIELs against IBDV antigen and Con-A was also significantly higher in IP+l-arginine group. Similar results were obtained with peripheral blood mononuclear cell blastogenic response to IBDV and Con-A analyzed as an indicator of systemic cell-mediated immune response. Orally administered IP strain vaccine elicited good antibody titres in both the groups, IP and IP+l-arginine, however, the antibody titres were significantly higher in IP+l-arginine group compared with IP vaccinated group (P<0.05). These results clearly demonstrate that l-arginine stimulates intestinal and systemic immune response against IBDV.

Administration, Oral↗
PubMed2003

A novel tumour model system for the study of long-term protective immunity and immune T cell memory.

We present a novel non-transgenic system to be used for studies on anti-tumour adoptive immunotherapy (ADI) and long-term T cell memory. Tumour-reactive donor immune cells against lacZ-transfected syngeneic tumour cells (ESbL-Gal) were generated from a naíve T cell repertoire in DBA/2 mice by a well-established priming/restimulation protocol, and transferred to tumour-inoculated athymic nu/nu mice. The donor immune cells efficiently mediated protective anti-tumour immunity involving both CD4(+) and CD8(+) T cells, and anti-metastatic effects were stronger in 4.5 Gy pre-irradiated than in non-irradiated tumour-inoculated hosts. Long-term persistence of beta-galactosidase (Gal)-specific T cells was shown ex vivo by tetramer staining of CD8(+) T cells specific for an immunodominant Gal epitope. Resistance of treated nu/nu mice against tumour rechallenge revealed the existence of long-term protective immune memory.

Animals↗
PubMed1993

A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura.

Fifty-three children, aged 7 months to 14.4 years and with typical acute immune thrombocytopenic purpura and platelet counts < or = 20 10(9)/L, were randomly assigned to receive intravenously administered immune globulin G (IVIG), 1 gm/kg per day for 2 consecutive days (n = 19); orally administered prednisone, starting at a dose of 4 mg/kg per day, with tapering and discontinuation of corticosteroids by day 21 (n = 18); or no therapy (n = 16). Both IVIG and prednisone resulted in significantly fewer days with platelet counts < or = 20 x 10(9)/L in comparison with no therapy (median, 1 and 2 days vs 4 days; corresponding ranges, 1 to 20 and 1 to 11 days vs 1 to 132 days; p < 0.01). Reversal of clinically important thrombocytopenia assessed by the number of days taken to achieve a platelet count of > or = 50 x 10(9)/L was significantly faster in children randomly assigned to receive IVIG (median, 2 days; range, 1 to 34 days) than in those receiving prednisone (median, 4 days; range, 2 to 13 days; p < 0.001) or no therapy (median, 16 days; range, 2 to 132 days; p < 0.001). Because the risk of intracranial hemorrhage in children with acute immune thrombocytopenic purpura is highest in the group with severe thrombocytopenia, and appears to be restricted to children with platelet counts < or = 20 x 10(9)/L, these results support the use of IVIG or high doses of prednisone as initial therapy in children with acute immune thrombocytopenic purpura and severe thrombocytopenia (platelet counts < or = 20 x 10(9)/L).

Administration, Oral↗
PubMed1998

Inhibition of immune cell proliferation with haloperidol and relationship of tyrosine hydroxylase expression to immune cell growth.

Previous studies indicated that exogenous dopamine and its agonists directly regulated mitogen-induced immune cell proliferation. In this study, we further investigated role of endogenous dopamine in immune cell growth. Haloperidol, a general antagonist for dopamine receptors, could reduce the cell growth rate of T cell hybridoma (10I) and rat nervous pheochromocytoma cells (PC12). Tyrosine hydroxylase (TH) catalyzes the initial rate-limiting step of catecholamine biosynthesis in the nervous system. Flow cytometric analysis indicated the expression of TH in various immune cells. The presence of TH in PC12 cells was used as a control. Temporal studies indicated that the expression of TH increased during 10I cell growth. Both alpha-methyl-p-tyrosine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine reduced TH expression and cell growth in a dose-dependent manner. These results suggest that immune T cells express TH which is correlated to cell growth, and that dopamine released from these cells may bind to the receptors to act in an autocrine or paracrine way.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

Adjuvanticity of pGPL-Mc and LRS in the immune responses of monkeys to oral immunization with diphtheria and tetanus toxoids.

Experiments were carried out to examine the adjuvanticity of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) or the London rocket seed (LRS) when combined with diphtheria and tetanus toxoids in an oral immunization of the African green monkey. The results showed that none of the monkeys receiving diphtheria and tetanus toxoids combined with 25 mg/kg of pGPL-Mc showed an increase in the the level of diphtheria antitoxin (DA) on the third and sixth weeks following the first and the second immunizations. One monkey from this group responded with increased seroneutralizing antibodies 3 weeks after the third feeding. On the other hand, one monkey, 3 weeks after the first immunization, and three monkeys, 3 weeks after the second and third oral vaccinations, showed an increase in specific anti-diphtheria antibody responses when the toxoids were combined with 25 mg/kg of LRS. The anti-diphtheria antitoxin responses of monkeys receiving diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc or 50 mg/kg of LRS were significantly enhanced compared to the groups administered 25 mg/kg of the two adjuvants. The increase was observed in four out of five pGPL-Mc administered and in three out of five LRS-receiving monkeys. The results show that pGPL-Mc induced the highest titres of anti-diphtheria antitoxin compared to LRS, whereas the level of anti-diphtheria antitoxin titre of the two monkeys receiving the toxoids alone was less than 0.1 i.u./ml of serum throughout the experiment. According to the statistical analyses, no significant differences were recorded between the diphtheria antitoxin responses of monkeys following the first, second or third administration of LRS-adjuvated diphtheria and tetanus toxoids. However, a significant difference (P < or = 0.05) was observed in the diphtheria antitoxin response between the first and the second immunization of monkeys administered with toxoids adjuvated with 50 mg/kg of pGPL-Mc. The tetanus antitoxin responses of all monkeys were less than 0.1 i.u. of antitoxin per millilitre of serum throughout the study, which is considered not to be protective. However, we have recorded an anti-tetanus antitoxin titre of more than 0.2 i.u./ml of serum in one monkey that received diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc.

Adjuvants, Immunologic↗
PubMed1999

Immune responses to P. falciparum-MSP1 antigen: lack of correlation between antibody responses and the capacity of peripheral cellular immune effectors to respond to this antigen in vitro.

Protective immunity to P. falciparum blood stage infection is thought to be dependent on IgG antibodies, although the mechanisms that underlie such immunity are not clearly understood. One of the antigens thought to be involved in this protective response is MSP1. The present study has examined the levels and distribution of IgG (and IgM) antibodies to the C-terminal 19 kDa fragment of MSP1 in plasma from P. falciparum immune adult Senegalese and the capacity of the peripheral blood mononuclear cells from these patients to either proliferate or secrete IFN-gamma, IL-10 or IL-4 in vitro in response to this antigen. Specific antibodies were found in 74% of individuals' plasma; 44% of mononuclear cells proved capable of proliferating in vitro and IFN-gamma, IL-10 and IL-4 were detected in 37, 23 and 0% of culture supernatants, respectively. No significant association was found between the presence of antibodies and immune cell reactivity under the culture conditions used. This study emphasizes the complexity of the mechanisms responsible for the sustained production of potentially protective antibodies in response to proposed T-cell dependent P. falciparum blood stage antigens.

Adult↗

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