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PubMed1980

Neutralization of the effect of delta 9-tetrahydrocannabinol on barbiturate sleeping time by specific active immunization.

Adult mice were actively immunized with delta 9-tetrahydrocannabinol-bovine serum albumin (delta 9-THC-BSA) conjugate. Control animals were immunized with BSA alone. While the administration of pentobarbital and delta 9-THC to control animals resulted in the well known prolongation of the barbiturate sleeping time, in mice immunized with delta 9-THC-BSA conjugate this effect was almost completely neutralized.

Animals↗
PubMed1985

Active immunization of gilts against gonadotropin-releasing hormone: effects on secretion of gonadotropins, reproductive function, and responses to agonists of gonadotropin-releasing hormone.

Sexually mature gilts were actively immunized against gonadotropin-releasing hormone (GnRH) by conjugating GnRH to bovine serum albumin, emulsifying the conjugate in Freund's adjuvant, and giving the emulsion as a primary immunization at Week 0 and as booster immunizations at Weeks 10 and 14. Antibody titers were evident by 2 wk after primary immunization and increased markedly in response to booster immunizations. Active immunization against GnRH caused gonadotropins to decline to nondetectable levels, gonadal steroids to decline to basal levels, and the gilts to become acyclic. Prolactin concentrations in peripheral circulation were unaffected by immunization against GnRH. The endocrine status of the hypothalamic-pituitary-ovarian axis was examined by giving GnRH and two agonists to GnRH and by ovariectomy. An i.v. injection of 100 micrograms GnRH caused release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in control animals, but not in gilts immunized against GnRH. In contrast, administration of 5 micrograms D-(Ala6, des-Gly-NH2(10] ethylamide or 5 micrograms D-(Ser-t-But6, des-Gly-NH2(10] ethylamide resulted in immediate release of LH and FSH in both control and GnRH-immunized gilts. Circulating concentrations of LH and FSH increased after ovariectomy in the controls, but remained at nondetectable levels in gilts immunized against GnRH. Prolactin concentrations did not change in response to ovariectomy. We conclude that cyclic gilts can be actively immunized against GnRH and that this causes cessation of estrous cycles and inhibits secretion of LH, FSH, and gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Involvement of immunization-certified pharmacists with immunization activities.

BACKGROUND: Immunization certification courses allow pharmacists to directly administer vaccines to their patients. However, the demographics and level of immunization involvement of immunization-certified pharmacists compared with those noncertified are unknown. OBJECTIVE: To document the demographics, professional activities, and job satisfaction of immunization-certified pharmacists compared with pharmacists not certified for immunization. METHODS: In a cross-sectional pilot study, immunization-certified pharmacists were compared with noncertified pharmacists via a postal-mailed questionnaire. The questionnaire consisted of demographic and practice site characteristics, involvement in immunization services, and a job satisfaction survey. RESULTS: Response rates were 48% (n = 101) and 36% (n = 158) for immunization-certified and noncertified pharmacists, respectively. Significantly more certified pharmacists were involved in immunizations (99% vs 24%; p < 0.001). Desire to improve the health care of the public and personal satisfaction were important factors that encouraged pharmacists to become certified to administer vaccines. Seventy-four percent of immunization-certified pharmacists directly administered the vaccines, primarily influenza (96%), pneumococcal (77%), hepatitis (55%), and diphtheria, pertussis, tetanus (19%). Adequate training, time, support from management and staff, and liability coverage were important factors that allowed pharmacists to incorporate immunizations into their practice. No significant differences in job satisfaction were observed between immunization-certified and noncertified pharmacists. CONCLUSIONS: Immunization-certified pharmacists are using their skills to administer vaccines to patients within their communities. Efforts to increase the number of these pharmacists throughout the US should be undertaken.

Certification↗
PubMed2006

Microbial translocation is a cause of systemic immune activation in chronic HIV infection.

Chronic activation of the immune system is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. Here we show that circulating microbial products, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically HIV-infected individuals and in simian immunodeficiency virus (SIV)-infected rhesus macaques (P <or= 0.002). We show that increased lipopolysaccharide is bioactive in vivo and correlates with measures of innate and adaptive immune activation. Effective antiretroviral therapy seemed to reduce microbial translocation partially. Furthermore, in nonpathogenic SIV infection of sooty mangabeys, microbial translocation did not seem to occur. These data establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide new directions for therapeutic interventions that modify the consequences of acute HIV infection.

Animals↗
PubMed2003

Hyperhomocysteinemia and immune activation.

Hyperhomocysteinemia is an established risk factor for atherosclerosis, thrombosis and other vascular diseases. Homocysteine auto-oxidation is considered to be crucially involved in the pathogenesis of these diseases. However, the question remains to be elucidated whether vitamin deficiency and homocysteine accumulation are causal for disease development or rather comprise a secondary phenomenon. Most diseases accompanied by hyperhomocysteinemia are also associated with ongoing activation of the immune system. In vitro experiments show homocysteine to accumulate in stimulated peripheral blood mononuclear cells. In patients with coronary heart disease, with rheumatoid arthritis and in patients with dementia, an association between cellular immune activation and homocysteine metabolism is found. Homocysteine concentrations not only correlate inversely with folate concentrations, they also show a positive relationship with concentrations of immune activation markers like neopterin. Moreover, in patients with various kinds of dementia, increased concentrations of serum peroxides, homocysteine and neopterin correlate with each other. Studies support a role of immune system activation in the development of hyperhomocysteinemia. Stimulation and proliferation of immune cells may lead to the production of reactive oxygen species that may oxidize antioxidants and oxidation-sensitive B-vitamins. An enhanced demand for antioxidants as well as folate and vitamin B12 may develop, together with hyperhomocysteinemia, despite sufficient dietary intake.

Cytokines↗
PubMed1975

Nature of "memory" in T-cell mediated antibacterial immunity: cellular parameters that distinguish between the active immune response and a state of "memory".

Immunizing infection in mice with Listeria monocytogenes resulted in the generation of two distinct states of immunological reactivity. There was generated (i) a short-lived state of active immunity that functioned to urgently eliminate the infection organism from the tissues and (ii) a long-lives state of increased immunological potential that enabled the host to respond to seconday infection in an accelerated manner. Short-lived active immunity was mediated by replicating T cells and expressed by activated macrophages, and it ended when these cell types disappeared from the tissue soon after complete elimination of the parasite. Long-lived immunological protential was associated with a persistent level of delayed sensitivity and with the presence of a small number of nonreplicating protective T cells. It is suggested that the state of delayed sensitivity represents a state of immunological T-cell memory of the cell-mediated type.

Animals↗
PubMed2005

Reciprocal role of cyclins and cyclin kinase inhibitor p21WAF1/CIP1 on lymphocyte proliferation, allo-immune activation and inflammation.

BACKGROUND: Immune activation that results due to the aberrant proliferation of lymphocytes leads to inflammation and graft rejection in organ transplant recipients. We hypothesize that the cell cycle control and inflammation are parallel events, inhibition of cellular proliferation by cyclin kinase inhibitor specifically p21 will limit inflammation and prevent allograft rejection. METHODS: We performed in vitro and in vivo studies using lymphocytes, and rat heart transplant model to understand the role of cyclins and p21 on mitogen and allo-induced lymphocyte activation and inflammation. Lymphocyte proliferation was studied by 3H-thymidine uptake assay and mRNA expression was studied RT-PCR. RESULTS: Activation of allo- and mitogen stimulated lymphocytes resulted in increased expression of cyclins, IL-2 and pro-inflammatory cytokines, which was inhibited by cyclosporine. The over-expression of p21 prolonged graft survival in a completely mismatched rat heart transplant model resulted by inhibiting circulating and intra-graft expression of proinflammatory cytokines. CONCLUSION: Cyclins play a significant role in transplant-induced immune activation and p21 over-expression has potential to inhibit T cell activation and inflammation. The results from this study will permit the design of alternate strategies by controlling cell cycle progression to achieve immunosuppression in transplantation.

Animals↗
PubMed2001

Nonproliferating bystander CD4+ T cells lacking activation markers support HIV replication during immune activation.

HIV replicates primarily in lymphoid tissue and immune activation is a major stimulus in vivo. To determine the cells responsible for HIV replication during Ag-driven T cell activation, we used a novel in vitro model employing dendritic cell presentation of superantigen to CD4(+) T cells. Dendritic cells and CD4(+) T cells are the major constituents of the paracortical region of lymphoid organs, the main site of Ag-specific activation and HIV replication. Unexpectedly, replication occurred in nonproliferating bystander CD4(+) T cells that lacked activation markers. In contrast, activated Ag-specific cells were relatively protected from infection, which was associated with CCR5 and CXC chemokine receptor 4 down-regulation. The finding that HIV replication is not restricted to highly activated Ag-specific CD4(+) T cells has implications for therapy, efforts to eradicate viral reservoirs, immune control of HIV, and Ag-specific immune defects.

Antigen Presentation↗
PubMed2005

Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors.

Activating receptors in cells of hematopoetic origin include members of two unrelated protein families, the immunoglobulin (Ig) and C type lectins, which differ even in the orientation of the transmembrane (TM) domains. We examined assembly of four receptors with diverse function: the NK receptors KIR2DS and NKG2C/CD94, the Fc receptor for IgA, and the GPVI collagen receptor. For each of the four different receptors studied here, assembly results in the formation of a three-helix interface in the membrane involving two acidic TM residues from the signaling dimer and a basic TM residue from the ligand recognition module, an arrangement remarkably similar to the T cell receptor (TCR)-CD3 complex. The fact that the TM domains of Ig family and C type lectins adopt opposite orientations proves that these receptor families independently evolved toward the same structural arrangement of the interacting TM helices. This assembly mechanism is thus widely utilized by receptors in cells of hematopoetic origin.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection.

The life cycle of human immunodeficiency virus type 1 (HIV-1) is intricately related to the activation state of the host cells supporting viral replication. Although cellular activation is essential to mount an effective host immune response to invading pathogens, paradoxically the marked systemic immune activation that accompanies HIV-1 infection in vivo may play an important role in sustaining phenomenal rates of HIV-1 replication in infected persons. Moreover, by inducing CD4+ cell loss by apoptosis, immune activation may further be central to the increased rate of CD4+ cell turnover and eventual development of CD4+ lymphocytopenia. In addition to HIV-1-induced immune activation, exogenous immune stimuli such as opportunistic infections may further impact the rate of HIV-1 replication systemically or at localized anatomical sites. Such stimuli may also lead to genotypic and phenotypic changes in the virus pool. Together, these various immunological effects on the biology of HIV-1 may potentially enhance disease progression in HIV-infected persons and may ultimately outweigh the beneficial aspects of antiviral immune responses. This may be particularly important for those living in developing countries, where there is little or no access to antiretroviral drugs and where frequent exposure to pathogenic organisms sustains a chronically heightened state of immune activation. Moreover, immune activation associated with sexually transmitted diseases, chorioamnionitis, and mastitis may have important local effects on HIV-1 replication that may increase the risk of sexual or mother-to-child transmission of HIV-1. The aim of this paper is to provide a broad review of the interrelationship between immune activation and the immunopathogenesis, transmission, progression, and treatment of HIV-1 infection in vivo.

AIDS-Related Opportunistic Infections↗
PubMed1992

Distribution and phenotype of immune cells in normal human gingiva: active immune response versus unresponsiveness.

The oral cavity, and particularly the gingival mucosa, is continuously exposed to numerous food and bacterial plaque antigens, though evident immunologic reactions are uncommon. It is therefore possible that the mucosal associated lymphoid tissue (MALT) of this region is preferentially biased towards unresponsiveness, rather than immune cell activation. The distribution and phenotype of immune cells in normal human gingiva were examined. Their distribution varied, and high and low cellularity areas could be distinguished in the same specimen. The number of CD3 positive (CD3+) T lymphocytes was more than thrice higher in a high cellularity area. In both types of area, intraepithelial T lymphocytes were not activated. Moreover, they showed chromatin condensation and cell shrinkage characteristic of apoptosis. In the stroma of high cellularity areas, foci of cell activation and numerous B cells were present, suggesting a localized active immune response. The vast majority of intraepithelial and stromal T lymphocytes expressed the "memory" CD45RO+ phenotype. The absence of an immune response within the epithelium and the localized response in the stroma (probably due to the binding of memory T cells to antigens in a low affinity, cross-reactive fashion) may be a part of a protective mechanism against indiscriminate stimulation by a multitude of external antigens.

Adult↗
PubMed1989

Immune, growth and carcass responses of ram lambs to active immunization against desulfated cholecystokinin (CCK-8).

This study explored feed intake and carcass responses to active immunization against desulfated cholecystokinin-octapeptide (CCK-8) in ram lambs. Antibody titers 8 wk following primary immunization and booster immunizations given at 4 and 6 wk averaged greater than 1:1,000. Titers increased to greater than 1:10,000 by 16 wk following a final booster immunization at 11 wk. The antibodies developed against desulfated CCK-8 exhibited 29% and 13% cross-reactivities for sulfated CCK-8 and gastrin-17, respectively. Immunization against desulfated CCK-8 had no effect on feed intake, ADG, carcass weight or carcass quality grade. Backfat thickness and carcass yield grade were reduced (P less than .05) by immunization. Organ weights at slaughter, including those of the pancreas and small intestines, were not affected by CCK-8 immunization, with the exception of the lungs, which were 16% lighter (P less than .01) in immunized lambs. In conclusion, active immunization against desulfated CCK-8 resulted in development of high antibody titers against desulfated and sulfated CCK-8. Immunization against CCK-8 decreased fat content of the carcass but failed to affect feed intake, carcass weight or ADG.

Animals↗
PubMed1976

[Immunity against Erysipelothrix rhusiopathiae infection by means of active immunization using homologous neuraminidase (author's transl)].

Neuraminidase may play a role as a pathogenic factor in Erysipelothrix rhusiopathiae infection. The protective effect of active immunization with purified neuraminidase was therefore tested in an infection experiment in white mice. Mice were immunized 2, 4, 6, 8 or 10 times i.p. with Erysipelothrix neuraminidase. A control group received 10 injections with physiological saline. The infective dose varied between 7 and 7 x 10(7) cells. While all control animals infected with 7 x 10(1) germs died, the lethal effect could be reduced to 50% and 25% in animals immunized twice and 4 times, respectively. Only animals immunized 8 and 10 times were still partly protected against germ numbers of 10(3)-10(4). Germ numbers of 10(5) and more were almost always fatal even in highly immunized animals. Even a high immunization with neuraminidase could only lower the lethal by a maximum factor of 10(4) germs used.

Animals↗
PubMed1994

Immune activation during infancy in healthy humans.

Immune activity during infancy was investigated using blood samples from 30 neonates and 52 healthy infants between 2 and 15 months of age attending for immunization. The purpose of this study was to assess the total immune activity of T cells using soluble interleukin-2 receptor (IL-2R) and interferon-gamma concentrations. These were compared with the proportion of CD4 CD45RO-, IL-2R (CD25)-, and transferrin receptor (CD71)-positive peripheral blood lymphocytes. The median duration of breast-feeding and of introduction of solid feeds was 4.2 and 4.0 months, respectively. Compared to neonates, the mean +/- SE soluble IL-2R concentration peaked at 4 months of age (1670 +/- 94 vs 3060 +/- 252 U/ml; P < 0.0001), as did pooled interferon-gamma levels. The percentage of CD4 CD45RO T cells remained low and the proportion of activated peripheral blood lymphocytes decreased during infancy. We conclude that noncirculatory immune activity is increased during infancy and this is associated with weaning.

Antigens, CD↗
PubMed2002

Attenuated signaling associated with immune activation in HIV-1-infected individuals.

Chronic immune activation is associated with impaired signal transduction. Since such activation is commonly found during HIV-1 infection, we studied cellular responses to non-specific T-cell receptor stimulation of PBMC obtained from 20 HIV-1 non-infected individuals and 23 highly or partially immune activated HIV-1 infected individuals. PBMC proliferation and ERK-1/2 phosphorylation following anti-CD3 stimulation, and constitutive levels of Cbl-b, were determined. Increased levels of Cbl-b, decreased proliferation, and lower ERK-1/2 phosphorylation were found in PBMC of highly immune activated HIV-1 infected individuals. The elevated expression of Cbl-b and impaired phosphorylation of ERK-1/2 associated with immune activation probably contribute to the attenuated proliferative and cellular responses characteristic of HIV-1 infection. Therefore, targeting immune negative modulators, such as Cbl-b, may serve as a novel approach for controlling HIV-1 disease progression.

Antigens, CD↗
PubMed1978

The effects of passive immunization with tumor-specific antiserum on the active immune response of mice to sublines of leukemia L1210.

In vivo, tumor cell killing was monitored with 131I-IUdR-labeled tumor cells and whole-body measurement of retained radioactivity. Treatment with antiserum in quantities that were not sufficient to kill the total leukemia cell inoculum (i.e., antigen excess) caused an immunopotentiation of the active immune responses; this was manifested by an accelerated rate of tumor cell killing beginning between days 10 and 11. The results obtained in vivo were confirmed by in vitro quantitation; both the cytotoxic antibody and cell-mediated immune responses were potentiated by the injection of antiserum. Immunosuppression was also observed in passively immunized mice. Whether potentiation or suppression occurred was dependent on the relative amounts of antiserum and leukemic cells injected and the innate immunogenicity (and/or antigenicity) of the leukemic cells; antibody excess and high immunogenicity favored suppression.

Animals↗
PubMed2005

Effect of active immunization against inhibin on hormonal concentrations and semen characteristics in Shiba bucks.

Active immunization against inhibin increased ovulation rate in females; in males, the effects of active immunization against inhibin on hormonal concentrations and sperm production need more investigation. To test the hypothesis that active immunization against inhibin increases FSH secretion and sperm output, the present study was undertaken to determine the effects of active immunization against inhibin on hormonal profile and sperm production in Shiba bucks. The bucks were actively immunized against inhibin alpha-subunit (immunized group, n=6) or Freund adjuvant (control group, n=5) four times, at 5-weeks intervals. Blood samples were collected twice-weekly and two successive ejaculates of semen were collected (with an artificial vagina) once-weekly. Plasma concentrations of FSH, LH and testosterone were measured by radioimmunoassay (RIA) and sperm motility characteristics were measured by computer-assisted sperm analysis (CASA). All inhibin-immunized bucks produced antibodies against inhibin. Relative to control bucks, in immunized bucks there were significant increases in plasma FSH concentrations and in sperm concentrations from 5 to 9 weeks and from 8 to 11 weeks, respectively, after primary immunization. However, plasma concentrations of LH and testosterone, semen volume, percentage of motile spermatozoa and motility parameters (straight-line velocity, curvilinear velocity and linearity index) were similar in both groups. In conclusion, active immunization against inhibin alpha-subunit increased FSH secretions and enhanced sperm production in bucks, whereas LH and testosterone concentrations, semen volume and sperm motility parameters were unaffected. Active immunization against inhibin could be used to improve fertility in Shiba bucks.

Animals↗