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PubMedDate not supplied

Immunogenicity and protectivity of Plasmodium falciparum EBA-175 peptide and its analog is associated with alpha-helical region shortening and displacement.

EBA-175 protein is used as a ligand in the binding of P. falciparum to red blood cells (RBCs). Evidence shows that the conserved peptide 1779 from this protein (with high red blood cell binding ability and known critical erythrocyte binding residues) plays an important role in the invasion process. This peptide is neither immunogenic nor protective; analogs having critical residues replaced by amino acids with similar volume or mass but different polarity were synthesized and inoculated into Aotus monkeys, and elicited different immunogenic and protective responses. Nuclear Magnetic Resonance (1H-NMR) studies revealed that peptide analog 21696 (non-immunogenic and non-protective) presents a large helical fragment, that the peptide 14012 (immunogenic and non-protective) helical fragment is smaller, while the peptide 22812 (immunogenic and protective) alpha-helix is shorter in a different region and possesses greater flexibility at its N-terminus. The presence of methionine residues could affect the structural stability of peptide 22812 and ultimately its immunological response. Our results suggest a new strategy for designing a new malaria multi-component subunit-based vaccine.

Amino Acid Sequence↗
PubMed2003

Recombinant hepatitis B vaccine (Engerix-B): a review of its immunogenicity and protective efficacy against hepatitis B.

Engerix-B (Hep-B[Eng]) is a noninfectious recombinant DNA vaccine containing hepatitis B surface antigen (HBsAg). It is produced from genetically engineered yeast (Saccharomyces cerevisiae). Intramuscular Hep-B(Eng) [0-, 1-, 6-month schedule] has excellent immunogenicity in healthy neonates and infants, children, adolescents and adults, with seroprotection rates of 85-100% seen approximate, equals 1 month after the final dose of vaccine; seroprotection was defined as an antibody against HBsAg (anti-HBs) titre of > or =10 IU/L. The use of alternative Hep-B(Eng) immunisation schedules (e.g. a 0-, 1-, 2-, 12-month schedule in neonates and infants, 0-, 12-, 24-month or two-dose schedules in children and adolescents, and accelerated schedules in adults) have also been associated with high rates of seroprotection. Seroprotection rates were generally similar with Hep-B(Eng) and the recombinant vaccine Recombivax HB (Hep-B[Rax]) or plasma-derived vaccines (PDVs) approximate, equals 1 month after the final dose (although anti-HBs geometric mean titres were significantly higher with Hep-B[Eng] than with Hep-B[Rax]). One month after the final dose, adults had significantly higher seroprotection rates with the recombinant triple-antigen vaccine Bio-Hep-B (Hep-B[Bio]) than with Hep-B(Eng), although seroprotection rates in healthy infants were similar with Hep-B(Eng) and Hep-B(Bio). Hep-B(Eng) had excellent immunogenicity in several groups considered at high risk of acquiring hepatitis B (e.g. neonates born to hepatitis B carrier mothers and healthcare workers). The immunogenicity of Hep-B(Eng) was reduced in patients with conditions associated with impaired immune function (e.g. patients undergoing haemodialysis or being treated for malignancy), although it had good immunogenicity in patients with diabetes mellitus.Hep-B(Eng) had excellent protective efficacy against HBsAg carriage in healthy infants and children, and in neonates born to hepatitis B carrier mothers (protective efficacy of 95-99%). Hep-B(Eng) also demonstrated good protective efficacy in a number of other high-risk groups. Hep-B(Eng) is generally well tolerated with a tolerability profile similar to that of Hep-B(Rax), Hep-B(Bio) and PDVs. In conclusion, Hep-B(Eng) is a well established, highly immunogenic hepatitis B vaccine with good tolerability and excellent protective efficacy; it offers flexibility through a variety of immunisation schedules. In addition, it appears that Hep-B(Eng) confers immunity for at least 10 years. Hep-B(Eng) has an important role in mass vaccination campaigns against hepatitis B, as well as in groups considered at high risk of acquiring hepatitis B.

Hepatitis B↗
PubMed2003

Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability.

UNLABELLED: Three combined hepatitis A and B vaccine preparations are commercially available in various countries: a two-dose paediatric formulation (Ambirix) [administered at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult vaccine provides consistent, marked immunogenicity which is at least similar to that of its constituent vaccines used together and with a tolerability profile that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also shown immunogenicity similar to that of the monovalent vaccines given concurrently, and now has an emerging role in adults likely to travel to hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1 month. The adult vaccine appears effective and generally well tolerated when given concurrently with monovalent typhoid vaccine (Typherix). Immunogenicity of the two-dose paediatric vaccine is high and appears to be similar whether administered as a month-0, -6 or month-0, -12 schedule and when compared to that of the three-dose paediatric vaccine (months 0, 1, 6), both of which provide a similar degree of protection to the adult vaccine. Although both preparations also provide high end-of-schedule seroprotection against hepatitis B surface antigen, protection between the first and second doses of the two-dose regimen appears lower than with the three-dose schedule. Therefore, the three-dose paediatric vaccine is a practical option in individuals at risk of immediate exposure to HBV, while the two-dose regimen may have an important function in immunisation programmes in regions where such risk is low. Combined hepatitis A and B vaccines are generally well tolerated. The most frequently reported adverse events in clinical trials were injection-site pain and redness, and general fatigue and headache; most events were mild and transient. Pharmacoeconomic models suggest the combined vaccine is cost effective compared with no vaccine (in children/adolescents) or monovalent hepatitis B vaccine (in children/adolescents and prison inmates). CONCLUSION: The three commercially available combined hepatitis A and B adult and paediatric vaccines are highly immunogenic and generally well tolerated; the adult vaccine demonstrates immunogenicity at least as marked as that of monovalent hepatitis A and B vaccines. While further research is required to confirm potential advantages such as improved cost effectiveness, the combined vaccines have established a key role in the prevention of hepatitis A and B in defined risk groups, and have an expanding role in population-based vaccination programmes with younger age groups.

Age Factors↗
PubMed1996

[TNF-alpha gene therapy for nonimmunogenic tumor using immunogenic variant induced with mutagen (N-methyl-N'-nitro-N-nitrosoguanidine)].

We have already reported that a combination of TNF-alpha and immunogenic variant was effective for immunotherapy of nonimmunogenic tumor. Immunogenic variants (A2 and A7) were obtained from nonimmunogenic fibrosarcoma (parent cell: 1767-3) by mutagen treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In this study, we studied about the possibility of TNF-alpha gene immunotherapy for nonimmunogenic tumor. We established two types of TNF-alpha producing cell lines. One is TNF-alpha producing nonimmunogenic variant (1767 TR 2), and another is TNF-alpha producing immunogenic variant (A7 TR3). We compared them about the ability of producing specific immunity against parent tumor. TNF-alpha producing immunogenic variant (A7TR3) could induce strong specific immunity to parental cell compared to TNF-alpha producing nonimmunogenic variant (1767TR2). Immunogenicity of tumor is very important when we want to perform TNF-alpha gene immunotherapy against cancer.

Animals↗
PubMed1992

The effect of hydrophilicity-hydrophobicity and solubility on the immunogenicity of some natural and synthetic polymers.

The general effects of solubility and hydrophobicity-hydrophilicity on the immunogenicity of synthetic and natural polymers are presented. The degree of hydrophobicity or hydrophilicity was determined from contact angle measurements. The surface tension components, obtained from the contact angles, were then correlated with the degree of immunogenicity for each substance. The results indicate that highly hydrophobic and highly hydrophilic polymers are not immunogenic. Moderate hydrophobicity as well as moderate hydrophilicity, and solubility in water favor immunogenicity (provided the molecular mass be at least 10,000 Da). For example, the solubilization of zein (a hydrophobic insoluble maize protein) prior to immunization causes zein to become immunogenic.

Animals↗
PubMed2006

Immunogenicity of kappa-casein and glycomacropeptide.

Glycomacropeptide (GMP), arising from the cleavage of kappa-casein by chymosin or pepsin, has been correlated with a wide variety of biological activities including immunosuppression capacity, inhibition of pathogen invasion, and induction of satiety. Due to the interest in exploiting such potential of GMP, we aimed at characterizing the immunogenic properties of GMP as an indication of its potential allergenicity. Immunogenicity of kappa-casein and GMP were investigated using 2 animal models based on different routes of immunization: 1) mice immunized intraperitoneally or subcutaneously with either kappa-casein, polymerized GMP, GMP coupled to the immunogenic carrier ovalbumin, or GMP alone; 2) mice coadministered kappa-casein or GMP and cholera toxin. The specific antibody response to GMP was evaluated as well as the antigen-specific T-cell response. The results demonstrated that immunization or feeding with kappa-casein induced GMP-specific antibodies, whereas GMP per se lacked immunogenicity independently of the mode of presentation. The size of the presented form of GMP did not influence its immunogenicity. Because the results showed that GMP did not induce a specific T-cell response, we postulate that GMP lacks the ability to stimulate antigen-specific T cells.

Animals↗
PubMed1999

Successful adoptive immunotherapy of murine poorly immunogenic tumor with specific effector cells generated from gene-modified tumor-primed lymph node cells.

We previously reported that cytokine gene transfer into weakly immunogenic tumor cells could enhance the generation of precursor cells of tumor-reactive T cells and subsequently augment antitumor efficacy of adoptive immunotherapy. We investigated whether such potent antitumor effector T cells could be generated from mice bearing poorly immunogenic tumors. In contrast to similarly modified weakly immunogenic tumors, MCA102 cells, which are chemically induced poorly immunogenic fibrosarcoma cells transfected with cDNA for IL-2, IL-4, IL-6, IFN-gamma, failed to augment the host immune reaction. Because priming of antitumor effector T cells in vivo requires two important signals provided by tumor-associated Ags and costimulatory molecules, these tumor cells were cotransfected with a B7-1 cDNA. Transfection of both IFN-gamma and B7-1 (MCA102/B7-1/IFN-gamma) resulted in regression of s.c. tumors, while tumor transfected with other combinations of cytokine and B7-1 showed progressive growth. Cotransfection of IFN-gamma and B7-1 into other poorly immunogenic tumor B16 and LLC cells also resulted in the regression of s.c. tumors. Cells derived from lymph nodes draining MCA102/B7-1/IFN-gamma tumors showed potent antitumor efficacy, eradicating established pulmonary metastases, but this effect was not seen with parental tumors. This mechanism of enhanced antitumor efficacy was further investigated, and T cells with down-regulated L-selectin expression, which constituted all the in vivo antitumor reactivity, were significantly increased in lymph nodes draining MCA102/B7-1/IFN-gamma tumors. These T cells developed into potent antitumor effector cells after in vitro activation with anti-CD3/IL-2. The strategy presented here may provide a basis for developing potent immunotherapy for human cancers.

Animals↗
PubMedDate not supplied

Antitumor protection using murine dendritic cells pulsed with acid-eluted peptides from in vivo grown tumors of different immunogenicities.

Peptides extracted from tumor cells after mild acid treatment can function as antigenic epitopes when presented by cultured dendritic cells. Peptides were extracted from four tumors syngeneic to C3H mice, three weakly immunogenic tumors (FSA, MCAK, HCA) and one non-immunogenic tumor (NFSA). Dendritic cells pulsed with peptides extracted from the three weakly immunogenic tumors partially protect mice from a tumor challenge with the parental cell line. This protection was evident by a slower rate of tumor appearance and a slower tumor growth curve when compared to control, non-immunized mice. However, vaccination of mice with dendritic cells pulsed with peptides derived from the non-immunogenic cell line NFSA did not elicit a protective response. Neither the route of immunization, the number of immunizations, nor the amount of peptides significantly affected the antitumor protection. Dendritic cells genetically engineered to produce IL-2 did not increase the protective effect of peptide-pulsed dendritic cells. These results suggest that only a partial protection against immunogenic tumors can be achieved when dendritic cells pulsed with acid-eluted tumor peptides are used as antitumor vaccination.

Acids↗
PubMed2000

Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth.

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells. Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death. It was previously reported that in vivo ligation of OX-40R by administration of OX-40L:immunoglobulin fusion protein or OX-40R monoclonal antibody (mAb) resulted in a significant prolongation of survival of tumor-bearing mice in four histologically distinct solid tumors. In this study, we demonstrate that the therapeutic efficacy of OX-40R mAb was influenced by the tumor burden, the intrinsic immunogenicity of the tumor as well as by the histological site of tumor growth. Whereas subdermal and intracranial growth of weakly immunogenic MCA 203 and MCA 205 sarcomas and GL261 glioma were susceptible to the mAb treatment, established pulmonary MCA 205 metastases were refractory to the same regimen of treatment. Furthermore, the mAb administration had no impact on the growth of the poorly immunogenic B16/D5 mela noma. Tumor regression mediated by OX-40R mAb was dependent on the participation of both CD4 and CD8 T cells and as a result of tumor rejection, a long-term tumor-specific immunity was established. Analysis of tumor-infiltrating T cells revealed the presence of a far greater number of OX-40R+ T cells of both CD4 and CD8 phenotypes in the intracranial immunogenic GL261 glioma than that in the poorly immunogenic B16/D5 melanoma. These results suggest that ligation of OX-40R on activated T cells in situ in the tumor may provide a necessary costimulatory signal to augment immune responses leading to tumor regression and immunological memory.

Animals↗
PubMed2001

Technology evaluation: C242-DM1, ImmunoGen Inc.

C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a potential treatment for colon tumor. It consists of a colon cancer-specific humanized antibody, C242, conjugated to the maytansine derivative DM1. In preclinical studies, C242-DM1 caused complete tumor regression in animal models of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J-591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective, antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells in vitro and in vivo with low systemic toxicity. Results from studies in monkeys showed that C242-DM1 had no significant toxicity or side effects, when administered at doses higher than those that were previously shown to completely eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to evaluate, and an option to license, technology related to maytansines from Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45 million development and commercialization agreement for C242-DM1 [313493]. In August 1997, Immunogen received an SBIR grant to advance development of huC242-DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of ansamitocin (maytansine) derivatives. Takeda holds several patents for the production of ansamitocin and its analogs, the first one being JP-53124692.

Animals↗
PubMed2001

Safety and immunogenicity of a new mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in adults.

BACKGROUND: Previous data showed that new recombinant hepatitis B virus vaccine, which contains the S-protein component of the HBV surface together with the Pre-S1 and Pre-S2, is considerably more immunogenic than a second-generation recombinant HBV vaccine. OBJECTIVES: To compare the immunogenicity and safety of a novel recombinant HBV vaccine S1, Pre-S1 and Pre-S2 protein components of the hepatitis B surface antigen--BioHep, 10 micrograms dose, to a licensed vaccine containing only the S-protein component--Engerix-B, 20 micrograms dose. METHODS: A prospective randomized study included 524 adults--260 in the Bio-Hep group and 264 in the Engerix-B group. Both vaccines were administered in a three-dose regimen given at 0, 1 and 6 months, and adverse events were recorded on a diary card 5 days after each vaccination. Immunogenicity was tested by measuring anti-hepatitis B surface antibody. RESULTS: One month after the third injection, 98% of the BioHep subjects were found to be seroprotected vs. 85.1% of the Engerix-B group. In addition, the geometric mean titers were 2,203 mIU/ml and 326 mIU/ml in the Bio-Hep-B and Engerix-B groups respectively. An immunogenic advantage of Bio-Hep-B was suggested by the rapid onset of antibody response--66.5% were seroconverted one month after the first injection as compared to 19.3% in the Engerix-B group. No unexpected adverse events were observed, and the recorded events were mild in both groups. CONCLUSIONS: BioHep, a novel recombinant HBV vaccine containing S, Pre-S1 and Pre-S2 protein components, at a lower dose, is safe and more immunogenic than the conventional HBV vaccine that contains only S protein.

Adolescent↗
PubMed2002

[Relative quantitative analysis of corneal immunogenicity].

OBJECTIVE: To quantitate the relative immunogenicity of three major corneal cell layers (epithelium, stroma, and endothelium) among the whole corneal immunogenicity respectively. METHODS: Cellular immunity: Three porcine major corneal cell layers were heterotopically allografted to subcutaneous layer of 40 BALB-c mice respectively. Twelve days later, the peripheral white blood cells of recipients were double directly stained with anti-mouse IgG-fluorescein conjugate mAb and analyzed by flow cytometry. Humoral immunity: The suspension of porcine cornea or corneal epithelium was used as antigen to produce anti-porcine immune sera in C57BL-6 mice. With the anti-porcine immune sera, enzyme linked immunosorbent assay was performed. RESULTS: On cellular immunity detection, the immunogenicities of intact endothelium, epithelium and stroma, equal in thickness, were 70.75%, 27.63%, and 1.62% respectively. On humoral immunity detection, the immunogenicities were 62.11%, 31.77% and 6.12% in the three respective layers of equal thickness. CONCLUSION: These findings indicate that the immunogenicity of corneal stroma is the lowest among the three corneal cell layers of equal thickness. The preliminary results provide the experimental basis for clinical application of xenogenic graft of corneal stroma.

Animals↗
PubMed1997

Are There Any Interrelations Between Immunogenic Activity of Chemical Carcinogens and Tumour Antigens in Cancer Patients?

Some interrelations between generation of antibodies to polycyclic aromatic hydrocarbons and immunogenic capacity of carcinoembryonic antigen were studied in patients with mammary and gastrointestinal types of cancer. IgM, IgG and IgA antibodies to polycyclic aromatic hydrocarbons were determined by a method of enzyme-linked immunosorbent assay. Immunogenic activity of carcinoembryonic antigen was evaluated by its ability to form circulating immune complexes. It was found that in patients with mammary cancer, generations of IgA to polycyclic aromatic hydrocarbons was interrelated with high immunogenic form of carcinoembryonic antigen, whereas IgG synthesis was associated with its low immunogenic form. Alternatively, patients with gastro-intestinal cancer did not exhibit any appreciable interrelation between generation of immunoglobulins and immunogenic activity of carcinoembryonic antigen.

Journal Article↗
PubMed1991

Biological activity of bacterial surface components. Immunogenicity and immunomodulatory properties of a bacterial extract from Escherichia coli.

The immunogenic and immunomodulatory properties of a lysed fraction from selected E. coli strains (OM-89, Uro-Vaxom) were determined in vivo and in vitro. It could be demonstrated that OM-89 constitutes an active immunogen in mice. Maximum OM-89-specific antibody titers were obtained after 4-5 i.p. immunizations; the titers could be further enhanced by the simultaneous injection of lipopeptide adjuvants. It was shown by ELISA that the antibodies obtained bound to the bacterial strains used for the preparation of the OM-89 extract. Immunogenicity was observed both after intraperitoneal and oral application of the extract. Besides being active as an immunogen. OM-89 was able to act in vitro as a polyclonal lymphocyte activator, as determined in splenocyte cultures of different inbred murine strains, and in cultures of human peripheral blood lymphocytes. Our results show that the B lymphocyte stimulating activity of the bacterial extract OM-89 was comparable to that of lipopeptide adjuvants. In conclusion, the bacterial extract both an active immunogen in vivo, and a polyclonal B cell activator in vitro. These findings may be of importance for the understanding of the therapeutic effect of OM-89.

Adjuvants, Immunologic↗
PubMed1978

Mammary tumor virus oncogenesis and tumor immunogenicity in three sublines of the C3H mouse.

Mammary tumorigenesis and mammary tumor transplantation immunogenicity have been studied and compared in three sublines of the C3H strain: in standard mammary tumor virus (MTV-S)-infected C3H/He mice; in MTV-S-infected C3H/Ki mice; and in MTV-S-free C3Hf/He mice. The age at the appearance of the first tumor, the growth rate of the tumors in their first transplant generation, and the immunogenicity of each tumor in syngeneic female recipients have been determined for the first tumor to appear in each of 25 breeding females from each of the three sublines. Two statistically significant trends were evident among the tumor characteristics compared in the three sublines: (a) an early appearance of tumors was related to the presence of the MTV-S. The genetically dissimilar sublines, C3H/He and C3H/Ki, both infected with the MTV-S, developed mammary tumors at an average age of about 10 months, 11 months before MTV-S-free C3Hf/He mice; (b) the tumor characteristics of immunogenicity and growth stimulation were related to host genetic factors. The genetically similar sublines, C3H/He and C3Hf/He, developed similar proportions of immunogenic and growth-stimulating mammary tumors; the genetically divergent C3H/Ki subline developed tumors that were not immunogenic and tended to be strongly growth stimulating.

Age Factors↗
PubMed1990

Synthetic peptide immunogens eliciting antibodies to Plasmodium falciparum sporozoite and merozoite surface antigens in H-2b and H-2k mice.

Peptides representing conserved (MSA2/1A and MSA2/1B) and variant (MSA2/2, MSA2/6 and MSA2/7) regions of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum (FCQ-27/PNG isolate) were coupled to either peptide NP(NANP)5NA or peptide C(NANP)6 both of which contained the core sequence (NANP)n. The coupling was done via the N-terminus of one peptide and a cysteine residue on either terminus of the other. BL/10 (H-2b) and B10.BR (H-2k) mice were immunized with these MSA2-(NANP)n conjugates. The mice were also immunized with the unconjugated MSA2 peptides and with NP(NANP)5NA and C(NANP)6. Antibody responses were evaluated by 1) ELISA, in which the MSA2 peptides and C(NANP)6 were used as Ag; 2) immunofluorescence assays (IFAT) against intact sporozoites and merozoites; and 3) immunoblotting experiments against solubilized P. falciparum blood stage proteins. High titer antibodies to (NANP)n were elicited in both BL/10 and B10.BR mice after immunization with all the conjugates except MSA2/7-(NANP)n which gave only a very limited response in B10.BR mice. These antibodies recognized unfixed sporozoites. The conjugates also elicited antibodies to MSA2 as shown by ELISA, IFAT, and immunoblotting except for mice immunized with MSA2/1B-(NANP)n where an anti-MSA2 response was only detectable by immunoblotting. Immunization with unconjugated MSA2 peptides showed that MSA2/2 was immunogenic in both BL/10 and BR.10 mice, with MSA2/6 and MSA2/7 being immunogenic only in BL/10 mice. The antibodies elicited recognized both merozoites and the MSA2 protein. However, the antibody titers were lower overall than those seen when these peptides were used in the conjugated form. No anti-MSA2 antibodies were detected after immunization with MSA2/1A and MSA2/1B. Immunization of mice with the peptide NP(NANP)5NA produced antibodies in BL/10 (H-2b) mice only, and the immunogenicity of this preparation was poor. In contrast, C(NANP)6 produced a strong antibody response in both mouse strains. The antibodies elicited by NP(NANP)5NA and C(NANP)6 recognised sporozoites in IFAT. The MSA2 peptides studied (or their derivatives) were previously shown to be recognized by human T cells. Their immunogenic potential shows promise in that complex anti-P. falciparum responses can be elicited with simple synthetic immunogens based on these peptides.

Amino Acid Sequence↗
PubMed1987

[Antibodies to Yersinia enterocolitica in immunogenic thyroid diseases].

In 1976 Shenkman et al. revealed that in patients with thyroid disorders antibodies against Yersinia enterocolitica could be demonstrated in increased frequency. In 1983 Ingbar et al. first established that the gram-negative bacterium Yersinia enterocolitica shows on its surface saturable binding sites for thyrotropin (TSH). If such binding sites resemble immunologically human TSH receptors this would indicate that TSH receptor antibodies could be produced in selected individuals having been infected with bacteria showing TSH receptors. The aim of our study was to compare the incidence of antibodies against Yersinia enterocolitica in two groups of thyroid disorders which are either immunogenic (Graves' disease and Hashimoto thyroiditis) or non-immunogenic (toxic adenomas, endemic goitre). In our series of 111 patients antibodies against Yersinia enterocolitica were demonstrated in a significantly higher percentage (36.3%) in patients suffering from immunogenic than in patients with non-immunogenic thyroid disorders (19.6%). The antibody titres were mainly directed towards Yersinia subtypes 8 and 3. It may, therefore, be assumed that the gram-negative bacterium Yersinia enterocolitica may have an active part in triggering immunogenic thyroid diseases such as Graves' disease or Hashimoto thyroiditis.

Adolescent↗
PubMed1979

Influence of immune status on the metastasis of three murine fibrosarcomas of different immunogenicities.

Three fibrosarcomas of different immunogenicities were tested for their ability to form spontaneous and experimentally induced metastases in normal, sham-suppressed, immunosuppressed, and immunologically restored syngeneic mice. Immunosuppression, achieved by adult thymectomy and sublethal X-irradiation (450 R), affected experimental metastasis of the three tumors in different ways. Upon i.v. injection, the highly immunogenic fibrosarcoma formed more pulmonary tumor colonies in immunosuppressed mice than in normal, sham-suppressed (sham thymectomy and 450 R), or immunologically reconstituted animals (thymectomy, X-irradiation, plus 10(7) normal syngeneic lymphocytes given i.v.). A fibrosarcoma of intermediate immunogenicity also formed more pulmonary metastases in immunosuppressed recipients, but this increase could not be reversed by reconstitution with 10(7) lymphocytes. In contrast, the least immunogenic tumor formed fewer pulmonary tumor colonies in immunosuppressed mice than in normal, sham-suppressed, or immunologically reconstituted mice. We conclude that the role of the immune system in experimental cancer metastasis varies for different tumors and that tumor immunogenicity is an important factor in the relationship between host immunity and tumor dissemination.

Animals↗