bluuebunny/crossref_metadata_2025_split huggingface dataset:
Future Perspectives for Vaccine Development
Authors: STEVENS V. C. 
Published: July 2006

The successful development of an anti‐fertility vaccine necessitates overcoming obstacles in eliciting an immune response to self species body constituents. The feasibility of accomplishing this task has been demonstrated for certain antigens described in this workshop: however, additional vaccine candidate antigens may yet be revealed from the application of recent advances in molecular biology. Improvements in vaccine design are likely to occur from discovery of more appropriate epitopes on targeting antigens, new carrier molecules for lerminating immunological tolerance, expression of vaccine antigens in suitable live vectors, the co‐immunization with more than one antigen, the use of safer and/or more effective adjuvants and vehicles, more efficient immunization by targeting antigens to specific lymphoid cells, and the development of superior vaccine delivery systems. Research directed to restricting the immune response to the gential tract and to intentionally reverse the effects of immunization will likely be pursued in the future.All of these areas need to be addressed if vaccines are to be developed that are not only safe and effective but also highly acceptable as birth control methods.
Immunoblot Analysis of Sera from Ethiopian Cutaneous Leishmaniasis by Antibody Class
Authors: MENGISTU G. , AKUFFO H. , FEHNIGER T. E. 
Published: July 2006

We have determined the specificity of the classes of anti‐leishmanial antibodies which are delectable in serum from patients with active cutaneous leishmaniasis. On immunoblots, differences exist in the patterns of antigen recognition by IgG, IgM, IgA and IgE antibodies present in localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL) patient serum. Each class of antibody showed differing patterns of banding to the various molecular species of parasite antigens. There was significant variation in the specificities of the IgG antibody reactivities between individual patients. The patterns of IgM binding were generally homogeneous and restricted to antigens with Mr 40 kDa. The only class of anti‐Leishmainia antibodies which showed shared patterns of common antigen recognition by all of the patients studied were IgA antibodies. The reactivities of IgE antibodies encompassed two antigens of Mr 36 and 46‐48 kDa which were not recognized by any of the other isotypes. Such antibody class associated reactivity may be useful in the design of serodiagnostic assays for the detection of Leishmania infection or other infectious agents.Gennene Mengistu, Department of Infectious Diseases, K. Karolinska Institute, Huddinge Hospital, 14186 Huddinge, Sweden
Cytokine Responses to Parasite Antigens: In Vitro Cytokine Production to Promastigotes of L. aethiopica by Cells from Non‐Leishmania Exposed Donors may Influence Disease Establishment
Authors: AKUFFO H. O. 
Published: July 2006

The various cytokine responses associated with stimulation by parasites is discussed with emphasis on Leishmania parasites.Cells from normal individuals can respond to Leishmania antigen in vitro but the State of the antigen used for stimulation influences the outcome. We have used cells from non‐Leishmania exposed donors and stimulated them in vitro with variously treated promastigotes of L. aethiopica. The levels of some cytokines released into the supernatant were measured. All the Leishmania preparations tested induced high levels of IL‐6. whereas IFN‐γ production to the different stimuli was variable in the individual donors. The ability of these supernatants to inhibit intracellular forms of L. aethiopica was sometimes stronger in L. aethiopica‐induced than in PHA‐induced cultures. Such strong non‐Leishmania specific responses, if they exist in vivo, may influence whether disease is established when the host encounters Leishmania parasites.
Anergy and Suppression in B‐Cell Responses
Authors: ELLIOTT J. I. 
Published: July 2006

SummaryTwo main ideas have been put forward to explain the unexpectedly low anti‐hapten antibody titres which can result from pre‐priming a mouse with carrier before hapten‐carrier immunization. The first involves the interaction of a network of idiotype‐specific suppressor T cells, the second instead arguing for the role of intrinsic B‐cell anergy. This paper proposes that the data available can equally be interpreted as reflecting the suboptimal interaction between T and B cells at differing stages of maturity, provided that memory B cells can be divided into two subsets. Further, it is suggested that these considerations must be taken into account in the analysis of B‐cell anergy in receptor transgenic mice.
Aberrant Tolerance Induction with Cationic Antigens
Authors: JACOBS M. J. M. , VAN DEN HOEK A. E. M. , VAN DE PUTTE L. B. A. , VAN DEN BERG W. B. 
Published: July 2006

We studied the induction of tolerance in female C57B1/6 mice by oral and intravenous (i.v.) administration of protein antigens before immunization. Native proteins [chicken egg albumin (OVA), bovine serum albumin (BSA)] and their cationic derivatives [amidated (a)OVA, aBSA, methylated (m)BSA] were compared in their capacity to suppress cell‐mediated immunity (CMI), as measured by a delayed type hypersensitivity test (DTH). Oral feeding of 0.5 mg negative proteins gave a clear suppression. By contrast, cationic derivatives (50 μg to 50 mg) did not suppress CMI. Data from cross experiments, where aOVA was fed in OVA‐immune mice, showed no suppression at all. When OVA was fed in aOVA‐immune mice, only a partial suppression was achieved.The potency to induce tolerance differed also when the antigens were administered i.v.: 25 μg OVA was sufficient to induce a clear suppression, whereas a much higher amount ofaOVA (500 μg) caused marginal suppression in OVA‐ and aOVA‐immune mice, respectively. Nevertheless, when concentrations of aOVA up to 2.5 mg were tested in a chronic model of arthritis, a significant suppression was achieved.The differences in inducing a CMI suppression may have implications for the feasibility of immunointervention. Successful modulation of human arthritis may be highly dependent on the nature of the antigen involved.
Idiotypic Vaccination: Immunoprotection Mediated by Anti‐idiotypic Antibodies with Antibiotic Activity
Authors: POLONELLI L. , LORENZINI R. , DE BERNARDIS F. , GERLONI M. , CONTI S. , MORACE G. , MAGLIANI W. , CHEZZI C. 
Published: July 2006

Anti‐Id antibodies were raised in mice against a monoclonal antibody (MoAb KT4) that neutralized the in vitro activity of a Pichia anomala yeast killer toxin. Monoclonal antibody was administered to BALB/C syngeneic mice with different schedules of immunization before intravenous challenge with increasing amounts of yeast killer toxin‐sensitive Candida alhicans cells. The course of candidosis was studied in comparison with mice non‐immunized and immunized with an isotypc‐matched unrelated MoAb subdivided into control groups. Protection was reflected by statistically significant increases in survival rate of mice immunized with MoAb KT4 which showed variable serum levels of yeast killer toxin‐like anti‐Id antibodies. MoAb KT4 affinity chromatography purified mouse anti‐Id antibodies were capable of killing in vitro the yeast ceils of the Candida albicans strain used for the experimental infection.This is the first report of antimicrobial protection that exploits the role of anti‐idiotypic antibodies presumably acting in vivo as antibiotics (idiotypic vaccination).
In Vitro and In Vivo Measurement of Cell‐Mediated Immunity in Patients with HIV‐1 Infection
Authors: BORLEFFS J. C. C. , SCHUURMAN H.‐J. , VREHEN H. M. , SCHAIK M. VAN , BAST E. J. E. G. 
Published: July 2006

We studied the usefulness of the in vitro lymphoproliferation assay and the in vivo skin lest in HIV‐1‐infected patients by using Chotridium tetani and tuberculin as testing antigens. Moreover, the relationship between data obtained from both assays was studied.In 56 HIV‐infected patients not receiving antiretroviral therapy CD4+ cell counting was performed. In addition, in vitro (lymphocyte proliferation assay) and in vivo (delayed type hypersensitivity skin test) measuring of the immune status was done using C. tetani atid tuberculin as testing antigens.When using C. tetani a significant correlation between the results of both tests and the CD4+ cell count was found. In contrast to earlier reports from African countries, in vivo skin testing using tuberculin did not yield clinically significant information on the degree of Immunodeficiency. We explain our findings by the fact that healthcare policy in The Netherlands encompasses vaccination with C. tetani. which enables the application of C. tetani as testing antigen for measuring immune function both in vitro and in vivo.
The Structure of the Variable Regions of Mouse Monoclonal Antibodies to Hepatitis B Virus Core Antigen
Authors: SKRIVELIS V. , STEINBERG Yu. , BICHKO V. , GREN E. , TSIMANIS A. 
Published: July 2006

From a panel of monoclonal antibodies (MoAbs) directed against E. coli‐derived native and denatured hepatitis B virus (HBV) core antigen we have selected a set of specific MoAbs which recognize different linear antigenic determinants: MoAb C1‐5—cl epitope; MoAb 14K8—less immunogenic N‐terminal region; and MoAbs 13C9, 10F10 and 14E11, 14G3—the immunodominant region between amino acids 134 and 140.We have applied the polymerase chain reaction technique to clone Ig VH and YL, region genes, and appropriate full‐length cDNA clones were obtained and characterized by nucleotide sequence analysis. Among the six heavy chain variable region sequences examined, three Yh families were represented. Two of them belong to the 7183 (MoAb Cl‐5) and 3609 (14B8) families respectively and four, having only two amino acid changes in the CDR2 region, to the J558 family. These four probably are derived from a single expanded B‐cell clone. The light chain sequences indicate that their YL are encoded by YK21, VK19 and YK3 germline genes. Unlike YH genes, light chain genes are closely related to known representatives of mouse kappa light chain families and are employed also by MoAbs raised against other antigens.
Antibody Response to Meningococcal Polysaccharides A and C in Patients with Complement Defects
Authors: BISELLI R. , CASAPOLLO I. , D'AMELIO R. , SALVATO S. , MATRICARDI P. M. , BRAI M. 
Published: July 2006

Patients with defects of terminal complement components are particularly exposed to the risk of developing neisserial infections and seem to respond poorly to meningococcal capsular polysaccharide (PS) C via natural immunization. The sole meningococcal PSC is. on the other hand, an excellent immunogen in normal people. Considering the great importance of vaccine prophylaxis for the prevention of meningococcal infections in patients with complement defects, it is crucial to study the antibody response to the sole meningococcal PS in these patients. We therefore analysed the levels of anti‐PSA and PSC antibodies in the members of four families including patients with homozygous and heterozygous defects of C7, C8 or factor H, before and after vaccination with the sole PSA+C.Surprisingly, we found the highest levels of antibodies before vaccination In homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapability to respond to sole meningococcal PS.In conclusion, this study demonstrates (1) the capacity to respond to meningococcal PS via natural immunization by patients with total complement defects, and (2) the low responsiveness to meningococcal PS via vaccine immunization by the same patients. We propose that vaccination should be given to patients lacking specific antibodies and their serological response should be assessed. In addition this study confirms previous observations on a likely lower immunogenic power of meningococcal serogroup C via natural immunization compared with the better immunogenicity of the sole PSC.
Cell‐Mediated Immune Responses in Renal Transplant Recipients treated with Cyclosporin and Prednisolone with or without Azathioprine
Authors: WRAMNER L. , MJÖRNSTEDT L. , RYDBERG L. , OLAUSSON M. 
Published: July 2006

The cell‐mediated immune response was studied, using mixed lymphocyte reactivity (MLR) and cell‐mediated lympholysis (CML) tests, in patients with well‐functioning kidney grafts from living donors at 6 and 12 months and at 2–5 years after transplantation. The patients were allocated to treatment with cyclosporin A (CyA) and prednisolone (group A) or with CyA, prednisolone and azathioprine (group B). The MLR towards a third party were in the range of that of untreated controls while the anti‐donor activities were reduced after 6 months in both groups. The CML activities in group A towards a third party were in the range of that of untreated controls at all times, while the anti‐donor activities were decreased. By contrast, the CML activities in group B towards a third party were decreased during the first year and were in the range of that of normal controls at 2–5 years. The anti‐donor CML activities were low at all times in group B.In summary, the two CyA protocols allowed the induction of donor‐specific unresponsiveness within the first post‐transplant year. The anti‐third party activities were low during the first post‐transplant year in recipients with triple therapy but not in those without azathioprine.
Antibody Response of Restricted Isotype to Heat Shock Proteins in Juvenile Chronic Arthritis
Authors: NUALLÁIN E. M. Ó , MONAGHAN H. , REEN D. J. 
Published: July 2006

Synovial fluid and peripheral blood mononuclear cells from juvenile chronic arthritis (JCA) patients have previously been shown to exhibit substantial proliferative responses to both human and mycobacterial heat shock protein (hsp) 65. We investigated the nature of the antibody response to mycobacterial and E. coli hsp 65 and human and E. coli hsp 70 in 56 JCA patients using an ELISA.Elevated levels of antibodies to both human and E. coli hsp 70 were demonstrated. With hsp 65, raised levels of antibodies to the mycobacterial but not the E. coli protein were detected. Overall, 48% of patient serum samples contained antibodies of at least one isotype to mycobacterial hsp 65. These antibodies were predominantly of IgG and IgM isotype, a finding in contrast to adult rheumatoid arthritis, where IgA and IgG isotypes are most often detected.
Up‐Regulation by Cyclosporine (CsA) of the In Vitro Release of Soluble CD23 (sCD23) and of the In Vitro Production of IL‐6 and IgM
Authors: HORNUNG N. , DEGIANNIS D. 
Published: July 2006

In the present study, we examined the effect of CsA on the in vitro production of Ig and on the in vitro production of molecules known to have B‐cell growth and differentiation activities, such as IL‐6 and sCD23. For the purpose of this study, we developed an experimental In vitro system closely resembling an In vivo model of ongoing B‐cell activation.Pre‐activated B cells proliferated and produced IgM optimally when they were re‐cultured in the presence of IL‐2/IL‐6. CsA down‐regulated the IL‐2/IL‐6‐induced proliferative responses of pre activated B cells by at least 50%., but it up‐regulated IgM production in the same experiments. This up regulating effect was not cytokine‐related since it was also seen when cells were re‐cultured in the absence of any cytokines. Optimal release of sCD23 was observed when SAC‐pre‐activated B cells were re cultured in the presence of IL‐4 or IL‐4 plus IL‐2 and CsA up‐regulated significantly the release of this molecule in these cultures. Finally, CsA was shown to inhibit PHA‐induced cell proliferation of PBMC and to up‐rcgulate IL‐6 production in the same cultures.We conclude that CsA can amplify in vitro both the production of Ig and the release of sCD23 by pre activated B cells. This finding, in combination with the CsA‐induced up‐regulation of lectin‐induced IL‐6 production, may have clinical implications in disease states with an ongoing immune activation, where prolonged administration of CsA might be anticipated.
B‐Cell Abnormalities in AIDS: Stable and Clonally‐Restricted Antibody Response in HIV‐1 Infection
Authors: MÜLLER S. , WANG H. , SILVERMAN G. J. , BRAMLET G. , HAIGWOOD N. , KÜHLER H. 
Published: July 2006

Antibodies in sera of HIV‐1 infected individuals against the HIV‐1 core protein (p24), HIV‐1 envelope gtycoprotein (gp120) and reverse transcriptase (RT) are characterized by a skewed light chain isotype expression. The kappa/lambda ratios of antibodies to p24 and gp120 in infected individuals were found to be unique in each individual, but constant over several years independently from disease progression. The oligoclonal nature of the anti‐HIV‐1 antibodies suggested by skewed kappa/lambda expression was confirmed with isoelectric focusing of affinity purified antibodies to p24 and gp120. Analysis of the utilization of V gene families in purified anti‐p24 and anti‐gp120 antibodies revealed a restricted and biased VH gene family usage. In contrast, the utilization of VK gene families appeared to be random.The finding of stable and restricted antibody responses in infected individuals could be one of the causes for the failure to produce antibodies to HIV‐1 that are effective against escape virus variants.
Expression of a Mast Cell Tryptase in the Human Monocytic Cell Lines U‐937 and Mono Mac 6
Authors: HUANG R. , ÅBRINK M. , GOBL A. E. , NILSSON G. , AVESKOGH M. , LARSSON L. G. , NILSSON K. , HELLMAN L. 
Published: July 2006

Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U‐937 and the Mono Mac 6, and in normal human peripheral blood(PB) monocytes. In the U‐937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3–50 fold following phorbol ester (PMA)‐induced differentiation, but no such induction was seen after retinoic acid, interferon‐γ or vitamin D3 exposure.The tryptases expressed in PMA‐induced and non‐induced U‐937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U‐937 cell line was found to express a tryptase identical to one of the previously cloned mast‐cell β tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned α tryptase. By northern blot analysis with oligonucleotide probes specific for the α and β tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRN A levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non‐induced U‐937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC‐ 1. This shows that the expression of a single tryptase, in this case the a tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer.The family of human mast‐cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected.The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP‐6, is presented. No expression of the MMCP‐6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the ‘mast cell tryptases’.
Purification of Amyloid‐Associated Heparan Sulphate Proteoglycans and Galactosaminoglycan Free Chains from Human Tissues
Authors: STENSTAD T. , MAGNUS J. H. , HUSBY G. , KOLSET S. O. 
Published: July 2006

Basement membrane‐associated heparan sulphate proteoglycans have been demonstrated immunohistochemically in organs from patients afflicted with various types of amyloidosis. In a recent report, we were able to isolate and partly characterize a basement membrane‐associated heparan sulphate proteoglycan from human hepatic amyloid. In the present study proteoglycans were extracted with guanidine from human amyloid‐laden kidney, spleen and lymph nodes. All tissues extracted with guanidine contained both heparan sulphate proteoglycan (HSPG) and galactosaminoglycan (CS/DS) free chains.Tissue staining using a monoclonal antibody against basement membrane HSPG revealed the presence of HSPG in amyloid deposits in kidney and spleen. Furthermore, following SDS‐PAGE of HSPG from kidney after deaminative cleavage of the HS chains, a 15‐kDa and 80‐kDa protein appeared, probably representing the core protein(s). In lymph node HSPG, three core proteins of 65, 30 and 25 kDa could be demonstrated on SDS‐PAGE, the first reacting with the anti‐basement membrane HSPG antibody when subjected to Western blotting subsequent to SDS‐PAGE. By immunohistochemistry, we failed to demonstrate any staining of the renal and splenic tissue sections employing an antibody against the decorin core protein.
The Alternative Binding Site for Protein A in the Fab Fragment of Immunoglobulins
Authors: IBRAHIM S. , KAARTINEN M. , SEPPÄLÄ I. , MATOSO‐FERREIRA A. , MÄKELÄ O. 
Published: July 2006

Twenty‐six new human or murine monoclonal immunoglobulins (IgM, IgA, murine IgGl or human IgG3) with a known V‐region sequence were tested for alternative (non‐Fc) binding to Staphylococcal protein A. Seven of them did not bind at all. Four immunoglobulins (all mouse IgGl) were bound but easily eluted (at pH 6). They were probably bound via the Fc part. All eleven were classified as negative for alternative binding. Fifteen immunoglobulins were found to bind more firmly; they came off the protein A column at pH 4–3 (alternative binders).Amino acid sequences of immunoglobulins that have been typed in the present work or earlier (25 binders and 26 non‐binders) were compared. The light chain, the C region of the heavy chain and the D and JH segments look irrelevant for alternative binding. The N‐terminal portion (amino acids 1–94) of the H chain probably forms the ligand of protein A. A peptide making the ligand cannot be reliably localized within this stretch but binder proteins had a high homology in residues 6–29.All mouse immunoglobulins expressing Vh genes of families J606 or S107 were alternative binders; those expressing other families were non‐binders.