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PubMedDate not supplied

Analyses of the primary in vitro responsiveness of non-immune porcine peripheral blood mononuclear cells with reference to immunization by African swine fever virus antigen and treatment with leucine methyl ester.

Peripheral blood mononuclear cells (PBMC) from non-immune pigs were immunized in vitro using African swine fever (ASF) virus antigen with concomitant mitogenic stimulations known to have varying effects on B and T lymphocyte activity. None of these conditions, including those previously reported as being successful for the in vitro immunization of non-immune porcine PBMC with ASF virus antigen, supported the induction of specific antibody. Due to the reports on in vitro immunization of human PBMC, attempts were made to control suppressor cell activity in the porcine PBMC from non-immune pigs through L-leucine methyl ester (Leu-OMe) treatment. Upon immunization of the Leu-OMe treated PBMC with ASF virus antigen, concomitant with mitogen or cytokine stimulations, no specific antibody production was detected. Nevertheless, aspecific porcine immunoglobulin secretion was observed. Further analysis of the PBMC responsiveness demonstrated that 2.5 mM Leu-OMe (the dose recommended for use with human PBMC) suppressed mitogen-induced porcine lymphocyte proliferation, but in the absence of any detectable cytotoxicity. In fact, both anti-ASF virus antigen specific immunization and stimulation with "T-lymphocyte" mitogens were suppressed, whereas pokeweed mitogen stimulation of B lymphocyte aspecific immunoglobulin secretion was unaffected. Consequently, it was not possible to immunize in vitro non-immune porcine PBMC with ASF virus antigen as had been previously reported, nor was it possible to transfer the technology successfully used with non-immune human PBMC to the in vitro stimulation/immunization of non-immune porcine PBMC. The furtherance of this work will require greater insight into the immunobiological parameters and dynamics of the stimulation of non-immune porcine peripheral blood leukocytes, which are not as simple as previously reported, nor the same as identified with human PBMC.

African Swine Fever↗

PubMed1995

Immune responses in sheep after immunization with Toxoplasma gondii antigens incorporated into iscoms.

An immunization and infection experiment using 12 sheep was conducted to study the immune responses elicited by an experimental vaccine consisting of Toxoplasma gondii antigens incorporated into immunostimulating complexes (iscoms). Five sheep were immunized subcutaneously with Toxoplasma iscoms. Two doses were given, with a 6 week interval, and 22 days after the second immunization, these five sheep and five non-immunized sheep were inoculated orally with T. gondii oocysts. The two remaining animals served as non-immunized, uninfected controls. The antibody response was analysed by an indirect fluorescent antibody test detecting IgM and an enzyme-linked immunosorbent assay detecting IgG. The first immunization induced low levels of both IgM and IgG, and the second resulted in high levels of IgG but no marked IgM response. After infection, a further increase in IgG was observed in the immunized animals. In the non-immunized sheep, substantial IgM and IgG levels were detected following infection. Immunoblotting analysis indicated that the antibody response to immunization was directed against the same T. gondii antigen as the early antibody response after infection in the non-immunized sheep. Antibodies recognizing the P30 antigen appeared first, followed by antibodies to P22 and other antigens which were probably also of membrane origin. Lymphocyte stimulation tests were performed 15 and 21 days after the last immunization and 105 days after infection. Significant antigen-induced proliferative responses were observed after immunization as well as after infection.

Animals↗

PubMed2004

Intravaginal immunization with viral subunit protein plus CpG oligodeoxynucleotides induces protective immunity against HSV-2.

Although the genital tract has been considered a poor inductive site for immunization with non-replicating antigens, genital immunization may be important for protection against sexually transmitted infections. Recently, we and others showed that CpG oligodeoxynucleotides (ODNs) serve as potent adjuvants for mucosal immunization. The purpose of this study was to determine whether intravaginal (IVAG) immunization with recombinant glycoprotein B (rgB) of herpes simplex virus type 2 (HSV-2) plus CpG ODN can induce specific immunity and protect against genital HSV-2 challenge. C57BL/6 mice were immunized IVAG with rgB plus CpG ODN, rgB plus non-CpG ODN, or rgB alone and challenged IVAG with HSV-2. Mice immunized with rgB + CpG had higher levels of anti-gB IgA and IgG in the vaginal washes and serum compared to mice immunized with rgB alone. Mice immunized with rgB + CpG also had the highest levels of gB-specific IgG in the nasal washes, however no specific IgA was detected in the nasal washes of any group. Mice immunized IVAG with rgB + CpG showed higher survival and lower pathology scores following genital HSV-2 challenge than mice immunized with rgB + non-CpG ODN or rgB alone. Additionally, vaginal viral titers were lower in the rgB + CpG group after infection. These results clearly show that the genital tract is capable of generating a protective immune response after local intravaginal immunization and that a non-replicating antigen is able to induce such a response when administered with an appropriate adjuvant.

Administration, Intranasal↗

PubMed2005

Induction of protective immunity against toxoplasmosis in mice by immunization with Toxoplasma gondii RNA.

Toxoplasma gondii enters the mucosal surfaces of the host, and so immunity at these sites is of major interest. Due to the compartmentalization of the immune response, systemic immunization does not induce high levels of immunity at mucosal surfaces. Intranasal immunization has been shown to be very effective in inducing both systemic and mucosal immune responses. Immunization with mRNA can induce both humoral and cell-mediated immune responses, both of which are important in conferring immunity to T. gondii. The efficacy of RNA vaccination by the nasal route with T. gondii RNA was evaluated. We assessed the percentage of cumulative survival after an oral challenge with a lethal dose of T. gondii cysts (40 cysts), and the number of brain cysts following a challenge with a sublethal dose of T. gondii 76 K cysts (15 cysts). Vaccinated mice were found to be significantly better protected than non-immunized mice after a challenge with a lethal dose of cysts; and a challenge with a sublethal dose also resulted in fewer brain cysts than in non-immunized mice. Sera and intestinal secretions of immunized mice recognized T. gondii antigens, suggesting that a specific humoral immune response may occur. Moreover, a specific lymphoproliferative response observed in cervical lymph nodes may confer protection. These preliminary findings suggest that RNA vaccination by a mucosal route could be feasible.

Animals↗

PubMed2006

Immunization with autologous T cells enhances in vivo anti-tumor immune responses accompanied by up-regulation of GADD45beta.

Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57Bl/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P<0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD45b was measured by real-time PCR. The results indicated that GADD45beta transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/Bl mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P<0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.

Animals↗

PubMed1997

Immune responses in mice after gastric and subcutaneous immunization with BCG.

Mucosal immunization can induce immune responses different from those induced by systemic immunization. In this study, murine immune responses were analysed after immunization through gastric and subcutaneous routes with Mycobacterium bovis BCG. The number of circulating cells secreting antigen-specific immunoglobulins (Ig), and the number of gamma interferon (IFN-gamma) secreting cells in spleen-cell cultures after in vitro stimulation with mycobacterial antigens were analysed at the single cell level by the ELISPOT method. Levels of antigen-specific antibodies in sera were determined by ELISA. In the subcutaneously immunized mice the authors found approximately 100 times more splenic cells secreting antigen-specific IgG than in gastrically immunized mice or control mice. Their levels of antigen-specific IgG in sera were 66-6700 times higher than in sera from gastrically immunized mice or control mice. In contrast, the numbers of IFN-gamma producing cells in spleen-cell cultures after in vitro activation with BCG were equally high in the immunized groups of mice, and for both groups higher than in non-immunized controls. Furthermore, IFN-gamma producing cells could be demonstrated in gastrically immunized animals even without in vitro activation. The results demonstrate that gastric immunization with the BCG vaccine can induce a systemic T cell-mediated immune response against mycobacterial antigens.

Animals↗

PubMed1976

Mediation of cytotoxic immune responses against human tumor-associated antigens by xenogeneic immune RNA.

Xenogeneic immune RNA (I-RNA), extracted from the lymphoid organs of sheep or guinea pigs immunized with human tumor cells, mediated in vitro cytotoxic immune responses that were directed specifically against tumor-associated antigens of human tumor target cells. Normal human peripheral blood lymphocytes from healthy donors became markedly more cytotoxic for human tumor target cells after being incubated with I-RNA extracted from the lymphoid organs of animals that had been immunized with that particular tumor. Gastric carcinoma, malignant melanoma, and carcinoma of the breast were studied. Lymphocytes incubated with RNA from animals immunized with only complete Freund's adjuvant evidenced no increased cytotoxic activity. RNA extracted from the lymphoid organs of animals immunized with normal skin fibroblasts that were autologous to the immunizing tumor, when incubated with normal allogeneic lymphocytes, also mediated cytotoxic immune reactions against tumor target cells. These immune responses probably were directed principally against normal transplantation antigens. However, when lymphocytes that were autologous to the immunizing tumor and/or the tumor target cells were incubated with RNA from animals immunized with autologous normal fibroblasts, cytotoxicity did not increase. Only I-RNA extracted from donor animals specifically immunized with tumor cells mediated cytotoxic antitumor immune responses when incubated with autologous lymphocytes.

Animals↗

PubMed2001

Genetic immunization with the region encoding the alpha-helical domain of PspA elicits protective immunity against Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) is a pneumococcal virulence factor capable of eliciting protection against pneumococcal infection in mice. Previous studies have demonstrated that the protection is antibody mediated. Here we examined the ability of pspA to elicit a protective immune response following genetic immunization of mice. Mice were immunized by intramuscular injections with a eukaryotic expression vector encoding the alpha-helical domain of PspA/Rx1. Immunization induced a PspA-specific serum antibody response, and immunized mice survived pneumococcal challenge. Survival and antibody responses occurred in a dose-dependent manner, the highest survival rates being seen with doses of 10 microg or greater. The ability of genetic immunization to elicit cross-protection was demonstrated by the survival of immunized mice challenged with pneumococcal strains differing in capsule and PspA types. Also, immunized mice were protected from intravenous and intratracheal challenges with pneumococci. Similar to the results seen with immunization with PspA, the survival of mice genetically immunized with pspA was antibody mediated. There was no decline in the level of protection 7 months after immunization. These results support the use of genetic immunization to elicit protective immune responses against extracellular pathogens.

Animals↗

PubMed2000

Gene gun-mediated DNA immunization primes development of mucosal immunity against bovine herpesvirus 1 in cattle.

Vaccination by a mucosal route is an excellent approach to the control of mucosally acquired infections. Several reports on rodents suggest that DNA vaccines can be used to achieve mucosal immunity when applied to mucosal tissues. However, with the exception of one study with pigs and another with horses, there is no information on mucosal DNA immunization of the natural host. In this study, the potential of inducing mucosal immunity in cattle by immunization with a DNA vaccine was demonstrated. Cattle were immunized with a plasmid encoding bovine herpesvirus 1 (BHV-1) glycoprotein B, which was delivered with a gene gun either intradermally or intravulvomucosally. Intravulvomucosal DNA immunization induced strong cellular immune responses and primed humoral immune responses. This was evident after BHV-1 challenge when high levels of both immunoglobulin G (IgG) and IgA were detected. Intradermal delivery resulted in lower levels of immunity than mucosal immunization. To determine whether the differences between the immune responses induced by intravulvomucosal and intradermal immunizations might be due to the efficacy of antigen presentation, the distributions of antigen and Langerhans cells in the skin and mucosa were compared. After intravulvomucosal delivery, antigen was expressed early and throughout the mucosa, but after intradermal administration, antigen expression occurred later and superficially in the skin. Furthermore, Langerhans cells were widely distributed in the mucosal epithelium but found primarily in the basal layers of the epidermis of the skin. Collectively, these observations may account for the stronger immune response induced by mucosal administration.

Animals↗

PubMed2001

Genetic immunization of wild-type and hepatitis C virus transgenic mice reveals a hierarchy of cellular immune response and tolerance induction against hepatitis C virus structural proteins.

To study the effect of genetic immunization on transgenic expression of hepatitis C virus (HCV) proteins, we evaluated the immunological response of HCV transgenic mice to HCV expression plasmids. FVB/n transgenic mice expressing HCV structural proteins (core, E1, and E2) and wild-type (WT) FVB/n mice were immunized intramuscularly with plasmids expressing core (pHCVcore) or core/E1/E2 (pHCVSt). After immunization, HCV-specific humoral and cellular immune response was studied. Both WT and transgenic mice immunized with either HCV construct produced antibodies and exhibited T-cell proliferative responses against core or envelope. In WT mice immunized with pHCVSt, cytotoxic T-lymphocyte (CTL) activities were detected against E2 but not against core or E1, whereas strong CTL activities against core could be detected in WT mice immunized with pHCVcore. In pHCVSt-immunized, transgenic mice, CTL activities against the core or envelope were completely absent, but core-specific CTL activities could be detected in pHCVcore-immunized transgenic mice. A similar pattern of immune responses was also observed in other mouse strains, including a transgenic line expressing human HLA-A2.1 molecules (AAD mice). Despite the presence of a peripheral cellular immunity against HCV, no liver pathology or lymphocytic infiltrate was observed in these transgenic mice. Our study suggests a hierarchy of CTL response against the HCV structural proteins (E2 > core > E1) in vivo when the proteins are expressed as a polyprotein. The HCV transgenic mice can be induced by DNA immunization to generate anti-HCV antibodies and anticore CTLs. However, they are tolerant at the CTL level against the E2 protein despite DNA immunization.

Adoptive Transfer↗

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↗

PubMed2002

Oral DNA vaccination in utero induces mucosal immunity and immune memory in the neonate.

Infectious diseases are responsible for a significant number of deaths during the first weeks of life. Some of the salient pathogens include HSV, HIV, hepatitis B virus, group B streptococcus, Haemophilus sp., and Chlamydia sp. The vertical transmission of many of these pathogens significantly increases the risk of neonatal infection. We recently reported that oral DNA immunization in utero induced high serum Ab titers and cell-mediated immunity in fetal lambs. In this study, we demonstrate immune memory and mucosal immunity in newborn lambs following oral DNA immunization of the fetus. A single oral exposure in utero to plasmid DNA encoding a truncated form of glycoprotein D of bovine herpesvirus-1 induced detectable immune responses in 80% (12 of 15) of newborn lambs. There was no evidence for the induction of immune tolerance in nonresponding lambs. Responding lambs displayed both systemic and mucosal immune responses and reduced virus shedding following intranasal challenge. Furthermore, strong anamnestic responses were evident for at least 3 mo after birth. The efficacy of in utero oral DNA immunization was further demonstrated with the hepatitis B surface Ag, and protective serum Ab titers occurred in 75% of immunized lambs. Thus, the present investigation confirms that oral DNA immunization in utero can induce both mucosal and systemic immune responses in the neonate and that this immunity has the potential to prevent vertical disease transmission.

Administration, Oral↗

PubMed1975

Control of the immune response. I. Depression of DNA synthesis by immune lymph node cells.

The DNA response in the regional lymph nodes draining the site of immunization with contact sensitizing agents was assessed by measuring the uptake of radioactive iododeoxyuridine. The DNA response in the regional lymph nodes reached a peak on day 3 after immunization and fell to pre-immunization levels by day 6. The hypothesis was tested that lymph node cells from mice immunized with picryl chloride might depress the DNA response to the same antigen. Immune lymph node cells were injected intravenously and the recipient mice were immunized with picryl chloride on the same day. The immune cells depressed the DNA response on day 4 by an average of about 60 per cent. Smaller but significant depression also occurred on day 3. The cells responsible for the depression appeared in the regional lymph nodes 3-4 days after immunization and disappeared by day 21. The transfer of small numbers of immune cells (less than 2-5 X 10(6)) increased the DNA response in recipients 4 days after immunization with picryl chloride. The depression of the DNA response was largely specific. Pooled data from ten experiments showed that cells immunized with 4-ethoxymethylene-phenyl oxazolone ('oxazolone') caused no depression of the DNA response to picryl chloride, although in two of these experiments significant depression of about 21 per cent was seen. Similar results were obtained when immune cells were injected into mice immunized with 'oxazolone'.

Animals↗

PubMed1984

IgG-induced experimental immune synovitis: hormonal modulation of in vitro splenic immune responses to homologous antigens.

The effect of oestrogen or anti-oestrogen administration on gross pathology and in vitro cell-mediated immune responses to homologous IgG, native and denatured interstitial collagens and PPD was studied in an IgG-induced rabbit model of immune synovitis. During induction of synovitis, rabbits were administered oestradiol valerate (0.075 mg/kg/day) or tamoxifen, an anti-oestrogen (2.0 mg/kg/day, high dose or 0.5 mg/kg/day, low dose) or placebo injections. Low dose tamoxifen administration was associated with significant improvement P less than 0.05 in immune synovitis with regard to gross pathology, when compared to placebo and the oestradiol treatment group. High dose tamoxifen treatment was not associated with significant improvement in observed synovitis. With regard to cell-mediated immune responses, spleen cells derived from immune synovitis rabbits were observed to increase 3H-thymidine uptake on incubation with native or denatured homologous collagens. Modulation of these immune responses to antigens was observed in anti-oestrogen treated rabbits with immune synovitis. In vitro cell-mediated immune responses to denatured type I, II and III collagens, PPD, as well as native type II and III collagens were not observed in the low dose tamoxifen treatment group. However, in vitro immune responses to these antigens were observed in spleen cell cultures from immune synovitis rabbits treated with either high dose tamoxifen or oestradiol valerate. The data suggest that in vivo anti-oestrogen administration can modulate the in vitro cell-mediated immune response to connective tissue constituents observed in immune synovitis. Concomitant with reduced immune responses is a significant reduction in the observed lesions of the inflammatory response.

Animals↗

PubMed1998

Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II.

Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have been reported to have serum antibodies to CA-II. Moreover, active immunization of susceptible mice with CA-II results in inflammation of submandibular glands, where CA-II is also expressed. In the present study, we attempted to produce cholangitis by immunization with CA-II using two strains of mice with different potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of human CA-II (100 microg) intraperitoneally every other week on three occasions. One week after the final immunization, mice were killed and blood and tissue samples harvested. Light and electron microscopic evaluation for inflammation was performed under coded identification. After immunization of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between cholangiocytes was also seen. Inflammation was not observed outside the liver. Morphologic evidence of cholangitis was observed in 8 (53.3%) of 15 Balb/c mice and in 3 (20%) of 15 DBA/1 J mice. In the control mice immunized with bovine serum albumin (BSA), cholangitis was observed in only 1 (6.7%) of 15 Balb/c mice and none of 15 DBA/1J mice. Balb/c mice immunized with CA-II had statistically significant cholangitis compared with those immunized with BSA (p < 0.01), whereas DBA/1J did not show a significant difference from controls. Balb/c mice immunized with CA-II showed specific antibody production after immunization, whereas DBA/1J mice immunized with CA-II had anti-CA-II antibody even in preimmune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/c mice resulted in cholangitis in two (66.7%) of three Balb/c recipients. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.

Adoptive Transfer↗

PubMed1998

Modulating the immune response to genetic immunization.

Genetic immunization, also known as DNA or polynucleotide immunization, is a novel strategy for vaccine development in which plasmid DNA encoding either individual or a collection of antigens is directly administered to a host. Such immunization leads to host expression of the delivered foreign gene, resulting in the induction of a specific immune response against the in vivo produced antigen. DNA immunization has been shown to induce protective immune responses in several infectious disease and cancer experimental model systems. Furthermore, DNA vaccines have recently entered the clinic for analysis as both prophylactic and therapeutic agents. Although the mechanisms of immunity to DNA have not yet been fully elucidated, it has become apparent that the immune response achieved by DNA vaccination is quite malleable, and can be manipulated by altering the conditions under which the vaccine is administered. Either through changing the method or location of immunization, altering the number of immunostimulatory sequences in the plasmid, altering the immunization regimen, or coadministering genes for cytokines or costimulatory molecules, one can modulate both the magnitude and orientation of the subsequent immune response. Through maximization of this feature of DNA immunization, we will likely be able to design vaccines and immunotherapeutic agents that are tailored to the correlates of protection for a particular disease, resulting in a new generation of more focused and effective immune stimulating agents.

Adjuvants, Immunologic↗

PubMed2000

The immune response and the evaluation of acquired immunity against gastrointestinal nematodes in cattle: a review.

The present review discusses the immune responses to gastrointestinal nematodes in cattle and the different immunological and parasitological parameters used to assess acquired immunity. Measuring acquired immunity to gastrointestinal nematodes in cattle (e.g. for the evaluation of candidate parasite vaccines) is hampered by the limited understanding of bovine immune responses against gastrointestinal parasites. In this paper the available data on protective immunity against gastrointestinal nematodes, and especially Ostertagia ostertagi, in cattle are compared with the current knowledge of protective immune responses against gastrointestinal nematodes in rodent models and small ruminants. In contrast to the immune response in mice, which is controlled by T helper 2 (Th2) lymphocytes and results in mast cell- or goblet cell-mediated expulsion of adult worms, bovine immune responses to O. ostertagi do not show a clear Th2 cytokine profile, nor do they result in rapid expulsion of the parasite. The first manifestation of immunity to O. ostertagi in calves is a reduction of worm fecundity, possibly regulated by the local IgA response. Worm numbers are only reduced after a prolonged period of host-parasite contact, and there are indications that O. ostertagi actively suppresses the host's immune response. Until the mechanisms of protective immunity against O. ostertagi are revealed, the use of immunological parameters to estimate acquired immunity in cattle is based on their correlation with parasitological parameters and on extrapolation from rodent and small ruminant models. Assessing the resistance of calves against a challenge infection by means of parasitological parameters is probably still the most accurate way to measure acquired immunity against gastrointestinal nematodes.

Animals↗

PubMed2001

Murine B16 melanoma vaccination-induced tumor immunity: identification of specific immune cells and functions involved.

Vaccination using inactivated B16 melanoma cells that have been treated in vitro for > 2 weeks with interferon-alpha (IFN-alpha) (B16alpha cells) has been shown to elicit a protective host antitumor immunity. In these studies, vaccination with B16alpha cells has been shown to provide protection against primary B16 tumor challenge, established B16 tumors, and metastatic B16 tumors. Specific immune cells and factors that might mediate this tumor immunity have now been evaluated. Macrophage depletion studies suggest that macrophage function is required for expression of tumor immunity either for processing of antigen or for cytokine production but that macrophage function is not involved in direct cytotoxicity against the B16 challenge tumor. CD8(+) T cell depletion studies show that cytotoxic T cell function is required for expression of tumor immunity. Syngeneic knockout mouse experiments offer further insights into the immune cells and factors that mediate the development and expression of tumor immunity. First, interleukin-12 (IL-12) knockout mouse experiments identify IL-12 as an important cytokine in mediating the development of tumor immunity. Second, specific knockout mouse experiments show that tumor immunity requires the function of CD4(+) T cells, CD8(+) T cells, and natural killer (NK) cells. Third, specific knockout mouse experiments show that tumor immunity does not require the function of B cells. The results suggest that vaccination with inactivated B16alpha cells induces an active, cell-mediated immunity to B16 melanoma cells. The tumor vaccination protocol with B16alpha cell vaccinations establishes a potent tumor immunity against B16 melanoma tumors in mice and may serve as a model for induction of tumor immunity against primary or secondary melanoma tumors in humans.

Animals↗