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Biomedical subjects

R Bomford

Publications and source records attributed to R Bomford.

At least 37 records · Page 2Linked to original sources
PubMed1987

Antibodies to interleukin-1 raised with synthetic peptides: identification of external sites and analysis of interleukin-1 synthesis in stimulated human peripheral blood monocytes.

Rabbit antibodies against peptides corresponding to amino acids 1-18, 45-65 and 71-90 of mature human interleukin-1 beta (IL-1 beta) precipitated 125I-labelled IL-1 beta, showing that these sites are accessible to antibody and located externally. Immunoprecipitation of 35S-methionine-labelled LPS-stimulated human peripheral blood monocytes followed by SDS-PAGE revealed the expected major bands of molecular weights 35,000 and 17,500. The 35,000 protein was found in the cell lysate and extracellularly in the medium, but the 17,500 protein was exclusively in the medium. A previously undescribed 31,000 band was also detected in the medium. These results are most simply explained by the hypothesis that the 35,000 IL-1 beta precursor is released from the cell and processed extracellularly to the 17,500 mature form. The 31,000 molecule may represent a processing intermediate.

Animals↗
PubMed1985

Adjuvant activity of saponin: antigen localization studies.

The adjuvant saponin potentiates the antibody response of mice to the antigen keyhole limpet hemocyanin (KLH). Studies using 125I-labelled KLH show that saponin significantly prolongs the retention of antigen at the subcutaneous injection site and also increases the amount reaching the spleen. Both these phenomena were associated with the inflammatory response to saponin and were markedly reduced following abolition of the inflammatory action of saponin by addition of cholesterol-containing liposomes. The adjuvant action of saponin was not modified by this treatment. Further evidence that neither antigen retention nor splenic localization is implicated in the adjuvant action of saponin for KLH is the demonstration that digitonin, which shares hemolytic and cholesterol binding activity with saponin, caused similar antigen retention and splenic localization but was not adjuvant active.

Adjuvants, Immunologic↗
PubMed1982

A comparison of saponin with other adjuvants for the potentiation of protective immunity by a killed Plasmodium yoelii vaccine in the mouse.

The protective immunity conferred by subcutaneous injection of outbred CD-1 mice with a killed Plasmodium yoelii (YM strain) vaccine was strongly potentiated by saponin. By adjusting the dose of antigen, the number of immunizations and the number of living parasites in the challenge infection, conditions were defined where antigen alone was non-protective but 100% protection was obtained by the addition of saponin. Inbred BALB/c, CBA/CA and C57 B1 mice were much less responsive than the CD-1 mice. The following adjuvants were compared with saponin: mineral oil emulsions (Freund's incomplete and complete adjuvants); A1(OH)3(Alhydrogel); bacteria and synthetic bacterial derivatives (Bordetella pertussis, Corynebacterium parvum and muramyl dipeptide); surface active materials (digitonin, vitamin A, Arquad 18, dimethyldioctadecyl ammonium bromide, and the polyene antibiotics, Nystatin and Amphotericin B). None of these adjuvants were as effective as saponin, although FCA, A1(OH)3 and C. parvum augmented immunity considerably. The possible reasons for the efficacy of saponin as an adjuvant for protozoal vaccines are discussed. The P. yoelli/mouse system provides a sensitive and rapid screening assay for comparison of potential adjuvants suitable for use with a malaria vaccine.

Adjuvants, Immunologic↗
PubMed1982

Studies on the cellular site of action of the adjuvant activity of saponin for sheep erythrocytes.

Saponin, which complexes with cholesterol in cell membranes, is a powerful adjuvant for antigens such as whole cell protozoal vaccines and SRBC. Saponin attached to SRBC ghosts potentiated the humoral response; but injection of saponin 1 or 2 days before or after SRBC at the same subcutaneous site was also effective. After the subcutaneous injection of saponin and SRBC the cellularity of the draining lymph node increases sixfold, and indirect PFC appear in it and the spleen. Splenectomy increases immunopotentiation by saponin, but T cell depletion abolishes it. The data show that attachment of the saponin to the antigen is not essential, and suggest that the adjuvant effect, which is T cell dependent, is exerted on host cells in the draining lymph node.

Adjuvants, Immunologic↗
PubMed1982

Cellular mechanisms of specific immunostimulation.

The mechanisms of action of immunological adjuvants at the cellular and pharmacological level are reviewed. Many adjuvants cause the accumulation of lymphocytes in the draining lymph node, lymphocyte trapping. The possible role of complement activation by adjuvants, leading to prostaglandin E2 release, in this process is discussed. Adjuvants show selective activity with different antigens, and may stimulate different components of the immune response. These effects have not yet been explained at the cellular level. Current studies of the cellular basis of adjuvant action indicate that many different adjuvants act through the macrophage of helper T lymphocyte, and there is limited evidence for effects on suppressor cells or B lymphocytes.

Adjuvants, Immunologic↗
PubMed1981

The adjuvant activity of fatty acid esters. The role of acyl chain length and degree of saturation.

Water-in-oil emulsions of metabolizable fatty acid esters, with the non-toxic surfactant Pluronic L122 as emulsifying agent, potentiated the humoral response to bovine serum albumin and staphylococcal toxoid in the mouse. Adjuvant activity was increased by changing the chemical nature of the esters as follows: (i) using a series of ethyl esters, adjuvant activity appeared when the acyl chain length of the fatty acid component was 16 or greater; (ii) isobutyl and isopropyl esters of palmitic acid (C16:0) were superior to ethyl; (iii) the ethyl esters of oleic (C18:1) and linoleic (C18:2) acids were better than stearic (C18:0). Since emulsions prepared with longer chain saturated esters are very viscous or solid at room temperature, and unsaturated esters are chemically reactive, emulsions were prepared with differing proportions of ethyl caprate (C10:0) and butyl stearate. At a ratio of 9:1 the emulsions possessed the low viscosity of ethyl caprate, but gained the adjuvant activity of butyl stearate. 125I-labelled BSA was retained in the footpad to a significantly greater extent than with a caprate emulsion, but reasons are given for believing that slow release of antigen is not the only mechanism of adjuvant activity. The ester emulsions caused more acute but less chronic local inflammation (footpad swelling) than Freund's incomplete adjuvant.

Adjuvants, Immunologic↗
PubMed1980

Saponin and other haemolysins (vitamin A, aliphatic amines, polyene antibiotics) as adjuvants for SRBC in the mouse. Evidence for a role for cholesterol-binding in saponin adjuvanticity.

The hypothesis that the adjuvant, as well as the haemolytic, activity of saponin depends on binding to cholesterol in cell membranes is supported by showing that cholesterol absorbs out adjuvant activity, and inhibits immunopotentiation in vivo when added to the injection mixture. Also, out of a range of haemolytic substances, chosen for their known properties as adjuvants or for cholesterol binding, the only materials which displayed a comparable activity to saponin were the polyene antibiotics Nystatin and Amphotericin B, whose binding to membrane cholesterol causes similar morphological changes to that of saponin.

Absorption↗
PubMed1980

The comparative selectivity of adjuvants for humoral and cell-mediated immunity. I. Effect on the antibody response to bovine serum albumin and sheep red blood cells of Freund's incomplete and complete adjuvants, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin.

A comparison was made of seven recognized adjuvants, Freund's incomplete and complete, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin, administered with BSA or SRBC by the S.C. route of immunization. Strong selectivity as well as differences in potency were revealed in relation to these two antigens. Only FIA, FCA, alhydrogel and MDP promoted the primary response to 50 microgram of BSA, and FIA was significantly superior to FCA. Immunological memory to a low dose (0.5 microgram) of BSA, which did not evoke a primary response with any adjuvant, was potentiated by alhydrogel and by MDP and, relatively poorly, by FIA. Radioimmunoelectrophoresis showed that potentiation of the response with MDP was confined to IgG1, whereas alhydrogel, FIA and FCA stimulated both IgG1 and IgG2. Saponin was outstandingly the best adjuvant for both primary and secondary haemagglutinin responses to SRBC. Of the others, alhydrogel for the primary, and alhydrogel and B. pertussis for the secondary were active to a lesser degree. The results show that the relative potency of adjuvants differs markedly according to the antigen used, and suggest that saponin may be a particularly effective adjuvant for antigens in cell membranes.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

The comparative selectivity of adjuvants for humoral and cell-mediated immunity. II. Effect on delayed-type hypersensitivity in the mouse and guinea pig, and cell-mediated immunity to tumour antigens in the mouse of Freund's incomplete and complete adjuvants, alhydrogel, Corynebacterium parvum, Bordetella pertussis, muramyl dipeptide and saponin.

Corynebacterium parvum was the only adjuvant of those tested which consistently potentiated delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in the mouse, although this required the antigen-adjuvant mixture to be injected subcutaneously in the footpad rather than the flank. For induction of DTH to ovalbumin (OVA) in the guinea pig, C. parvum and MDP could be substituted for the mycobacteria in FCA. C. parvum was effective in aqueous solution provided that the OVA was absorbed onto alhydrogel. Saponin also potentiated DTH when injected with OVA in aqueous solution. C. parvum was the sole adjuvant of those tested to promote protective cell-mediated immunity (CMI) to M4 fibrosarcoma cells. It is concluded that C. parvum is a promising candidate adjuvant for promoting CMI induction without recourse to a water-in-oil emulsion.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Corynebacterium parvum as an adjuvant for Trypanosoma cruzi epimastigote vaccines: a comparison with saponin and Bordetella pertussis.

The effect was compared in CBA mice of adding Corynebacterium parvum, saponin, and Bordetella pertussis to living or killed Trypanosoma cruzi (Y strain) epimastigote vaccines on the induction of protective immunity against subcutaneous (s.c.) challenge with blood trypomastigotes. The addition of C. parvum to a low dose of T. cruzi vaccine, which alone was non-protective, generated a greater degree of protection than did saponin or B. pertussis. C. parvum alone increased resistance to infection to a variable and usually weak extent. The addition of C. parvum to larger doses of T. cruzi vaccine, which were themselves sufficient to elicit some degree of protection, improved resistance when the challenge was given 1 or 12 weeks after immunization, but lowered it at 3 weeks. It is concluded that the comparative efficacy of adjuvants for T. cruzi vaccines needs to be assessed on 3 parameters: (1) the dose of antigen, (2) the dose of adjuvant and (3) the time interval between immunization and challenge.

Adjuvants, Immunologic↗
PubMed1978

Antitumor activity of purified cell walls from Corynebacterium parvum.

Cell walls (CW), containing peptidoglycan and carbohydrate, were prepared from Corynebacterium parvum and tested for lymphoreticular stimulation and antitumor effects in CBA-T6T6 mice. CW did not induce splenomegaly. Peritoneal macrophages became cytostatic to Rl leukemia cells in vitro after ip injection of CW or of peptidoglycan but not of carbohydrate; however, on a dry-weight basis the activity was low (less than 10%) compared with that of C. parvum. Tumor outgrowth was significantly suppressed after sc injection of mixture of M4 fibrosarcoma cells and CW, but again the activity of CW was less than 10% of the of C. parvum. In contrast to injection of C. parvum, intratumor injection of CW failed to retard tumor growth in normal mice, although a suppressive effect was found in mice presensitized to C. parvum. Again, unlike C. parvum, CW did not act as an adjuvant for tumor-specific transplantation antigen, as judged by a lack of enhanced resistance to tumor challenge after injection of mixtures of CW and irradiated M4 cells. The distribution and persistence of 125l-labeled C. parvum and CW after sc or ip injection were similar. CW activity was not restored by attachment to oil droplets or emulsification in Freund's incomplete adjuvant.

Animals↗
PubMed1977

An analysis of the factors allowing promotion (rather than inhibition) of tumour growth by Corynebacterium parvum.

The following factors were found to determine whether C. parvum (CP) treatment promoted rather than inhibited the growth of methylcholanthrene-induced fibrosarcoma cells injected into CBA mice. (1) The dose of tumour cells. Promotion occurred only with low doses, around the TD50. (2) The route of injection of CP. Greater promotion was caused by intravenous (IV) than by subcutaneous (SC) administration. Addition of irradiated tumour cells to SC CP resulted in tumour inhibition. (3) The dose of CP. Promotion increased with increasing dose of either SC or IV CP. (4) The time of CP injection relative to tumour challenge. Promotion only occurred when CP was given before tumour cells, except when using IV CP and very few tumour cells. With increasing doses of tumour cells, first post-treatment with IV CP and then pre-treatment became inhibitory. The effect of CP on established immunity to tumour cells was also studied. Mice were immunized by tumour amputation. The resistance to tumour challenge thus generated could be abrogated by CP given before challenge, most effectively by a high dose IV. The data are interpreted according to the following hypothesis. (1) CP suppresses the expression of cell-mediated immunity to tumour antigens. (2) This is caused by trapping of anti-tumour effector cells at the site of CP deposition. (3) Promotion can only occur when CP is given before effector cells have reached the tumor site.

Animals↗
PubMed1977

Mechanism of the anti-tumour effect of glucans and fructosans: a comparison with C. parvum.

The anti-tumour activity induced by glucans (lentinan, yeast cell walls, pseudonigeran, dextran, DEAE-dextran and dextran sulphate) and fructosans (levan and carboxymethyl-levan) was compared with the activity of C. parvum. The following effects on tumour systems in CBA mice were assayed: (a) adjuvant activity on the immune response against tumour-specific transplantation antigens (TSTA) with a methylcholanthrene-induced fibrosarcoma; (b) cytostatic activity of peritoneal macrophages against radiation-induced leukaemia cells; and (c) inhibition of tumour nodule formation in the lungs following i.v. injection of fibrosarcoma cells. All the polysaccharides induced cytostatic macrophages, but the dextrans and levans did so only after i.p. and not i.v. injection. Only lentinan, yeast cell walls and pseudonigeran were active in the lung-nodule inhibition test; and only lentinan and dextran sulphate showed slight adjuvant activity for TSTA. It is concluded that the anti-tumour activity induced by these polysaccharides is predominantly non-specific macrophage-mediated and much weaker than that found with C. parvum.

Animals↗
PubMed1976

Comparison of the potentiation of specific tumor immunity in mice by Corynebacterium parvum or BCG.

Two independent studies have compared killed C. parvum (CP) vaccine with viable BCG (Pasteur) and BCG (Glaxo) vaccines, respectively, for potentiation of antitumor immunity when injected with irradiated tumor cells into B6D2F1 AND CBA-T6T6 mice. Both studies concurred that, for a given number of irradiated tumor cells, larger amounts (dry weight equivalent) of BCG than CP were required to produce similar degrees of tumor immunity. Evidence also showed that stronger and more protracted immunity was mediated by CP than by BCG.

Animals↗