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Biomedical subjects

V Wicher

Publications and source records attributed to V Wicher.

At least 37 records · Page 2Linked to original sources
PubMed1992

Strain- and age-associated differences in lymphocyte phenotypes and immune responsiveness in C4-deficient and Albany strains of guinea-pigs.

Spleen lymphocytes from C4-deficient (C4D) and Albany strains of guinea-pigs, 1-7 days, 3-6 and 12-16 months old, genetically related to inbred strains 13 and 2 respectively, were analysed in terms of their expression of cell surface markers, allogenic and T- and B-cell mitogenic responses, and interleukin-1 (IL-1) and IL-2 production. There were strain- and age-associated differences in phenotypic expression and immune responsiveness levels. In both strains a significant shift in immunocompetence apparently occurs postnatally before 3-6 months of age, with no further significant changes noticed in animals 12-16 months old. Phenotypic changes in cell surface markers did not always correlate with functional capability of lymphoid cells. H159+ (pan T) and H155+ (CD4) lymphocyte number and levels of T-cell responsiveness (mitogenic and allogenic responses, and IL-2 production) were higher in C4D neonates compared with age-matched Albany guinea-pigs or with young animals of the same strain. On the other hand, 31D2+ (B) lymphocytes in a significantly higher proportion in Albany neonates compared with similarly aged C4D, did not correlate at this age or at any other time with their proliferative response to lipopolysaccharide (LPS) or dextran sulphate (DS), two B-cell-specific mitogens.

Aging↗
PubMed1991

Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols.

Treponema pallidum-susceptible guinea pigs of strain C4D were immunized with recombinant T. pallidum antigens TmpA, TmpB, TmpC, and TmpA plus TmpB plus TmpC; with Escherichia coli membranes; or with adjuvant alone. Animals in groups of five received six immunizing injections, each of 100 micrograms of antigen incorporated in RIBI adjuvant. After the sixth immunization, all experimental and nonimmunized controls were intradermally challenged with 3 x 10(6) T. pallidum Nichols freshly extracted from infected rabbit testes. Although high titers of antitreponemal antibodies in the fluorescent-treponemal-antibody test or an enzyme-linked immunosorbent assay were evoked in all animals immunized with recombinant antigens, only guinea pigs receiving TmpB antigen demonstrated protection expressed by the development of significantly (P less than 0.01) smaller, atypical lesions of significantly (P less than 0.01) shorter duration and devoid of or containing fewer T. pallidum organisms than lesions in the remaining immunized and control animals.

Animals↗
PubMed1991

Enteric infection with an obligate intracellular parasite, Encephalitozoon cuniculi, in an experimental model.

Rabbits were intrarectally infected with 3 doses (5 x 10(3), 5 x 10(5), and 5 x 10(7] of an obligate intracellular parasite, Encephalitozoon cuniculi, with or without prior colonic lavages. Although chronic administration of enemas seems to interfere to some degree with the intestinal translocation of the parasite, systemic infection was observed in both manipulated and nonmanipulated animals. The animals responded with antibodies of immunoglobulin A (IgA) and IgG isotypes, reflecting the route of infection. They also produced significant amounts of circulating immune complexes composed of IgA and IgG antibodies and E. cuniculi antigens. Lesions compatible with encephalitozoonosis were seen in the liver, kidney, lung, and brain. In all instances, nonmanipulated animals had more severe lesions than manipulated rabbits given the same dose of parasites. Levels of serum antibodies, circulating immune complexes, and histopathologic changes were associated with the infection dose. The presented data suggest that human microsporidiosis may also be transmitted via the rectal route. It is, therefore, of clinical relevance in view of several reports of microsporidian infections in patients with acquired immunodeficiency.

Administration, Rectal↗
PubMed1991

Pathogen-specific humoral response in Treponema pallidum-infected humans, rabbits, and guinea pigs.

Molecular analysis of the humoral response to pathogen-specific polypeptides was done using sera from patients at different stages of syphilis and sera from Treponema pallidum-infected rabbits and guinea pigs collected at various times after infection. The sera were examined by ELISA, fluorescent treponemal antibody absorption test (FTA-ABS), and immunoblot before and after sequential adsorption with cyanogen bromide-activated Sepharose 4B coupled individually to five sonicated nonpathogenic treponemes. Guinea pig antisera were also adsorbed with rabbit proteins. After adsorption, sera from all three species reacted neither by ELISA nor by immunoblot with nonpathogenic treponemes, nor did guinea pig sera react with rabbit proteins. Regardless of the species of treponema used for initial adsorption, none by itself could effectively remove all cross-reactivities. Nine pathogen-specific polypeptides (15, 17, 33, 37, 39, 43, 45, 47, 97 kDa), eight (15-47 kDa) known as integral membrane or endoflagellar components, were commonly recognized by the tree species when chancre immunity developed. The substantial reduction in immune reactivity after adsorption suggests that most of these peptides consist of specific and common treponemal epitopes. Throughout the various stages of the human disease, pathogen-specific antibodies were exclusively of the IgG isotype.

Animals↗
PubMed1990

Experimental neonatal syphilis in a susceptible (C4D) and a resistant (Albany) strain of guinea pig.

Despite similar levels of natural antibodies and treponemicidal activity, 83% of fourth complement component-deficient (C4D) mother guinea pigs developed ulcerative lesions to a challenge of 5 x 10(7) Treponema pallidum, whereas 75% of offspring 1 to 5 days old were temporarily (2-3 months) resistant to development of dermal lesions. In contrast, only 17% of Albany-strain mothers developed small papular lesions, while 68% of 1- to 5-day-old newborns developed large papular or ulcerative lesions within 9-15 days postinfection. These findings, together with the late development of both dermal lesions and antibodies in C4D neonates, preclude the concept of an antibody-associated natural resistance. T. pallidum infection in either C4D or Albany neonates was not associated with depletion of any particular cell population in lymphoid tissue. However, marked age- and strain-dependent histologic differences were noted. Histologic examination of lymph nodes and spleens from 17-day-old and 3- to 4-month-old animals showed that maturation of lymphoid tissues in C4D animals lagged behind the Albany strain at either age. Moreover, 75% of C4D newborns contained significantly higher levels of immunomodulatory alpha 1 fetoprotein than Albany neonates. The possibility that differences in susceptibility to T. pallidum infection between C4D and Albany guinea pigs as neonates and again as adults is the result of genetically associated changes in immunologic recognition is discussed.

Animals↗
PubMed1990

Immunocompetence of inflammatory cells in rabbit testes infected with Treponema pallidum.

Systematic studies were conducted in rabbits to delineate factors favoring the predilection for multiplication of T. pallidum in testes. The results strongly suggest that, in addition to the mucoid material produced during lesion development regardless of the site of infection, a whole array of testicular substances with immunomodulatory activity may largely contribute to the propagation and delayed clearance of the pathogen from the testicular environment and most likely from the host.

Animals↗
PubMed1990

Autoimmunity in syphilis.

The autoimmune response in natural and experimental syphilis, apparently triggered as a secondary reaction to T. pallidum infection, is represented by the production of various antibodies to self-antigens. In addition to the classic Wassermann (cardiolipin) antibodies, the following autoantibodies are associated with the disease: (1) biphasic hemolysin (known also as Donath-Landsteiner antibody), (2) antilymphocytic antibodies, (3) rheumatoid factor, (4) cryoglobulins, (5) antifibronectin, (6) anticollagen, (7) antilaminin, and (8) anticreatine kinase. Although less explored, the autoimmune reaction seems also to involve the cellular arm of the immune response. Transient sensitization of lymphocytes to homologous organ antigens have been reported in T. pallidum-infected rabbits. Questions of whether the humoral and cellular autoimmune responses--which are apparently harmless and of transient nature--play a role in immunoregulation and consequently affect the course of infection remain to be answered.

Animals↗
PubMed1989

Treponema pallidum-immobilizing antibodies in guinea pig experimental syphilis.

Treponema pallidum-immobilizing (TPI) antibodies were examined in intradermally infected inbred strain 13 and adoptively immune inbred strain 2 guinea pigs. Both strains of animals produced TPI antibodies at or after 90 days of infection. TPI antibodies were not associated with the protective mechanism(s) operative after challenge in adoptively immune animals.

Animals↗
PubMed1989

Immunogenicity of three recombinant Treponema pallidum antigens examined in guinea pigs.

The immunogenicity of recombinant treponemal antigens TmpA, TmpB and TmpC incorporated in RIBI adjuvant and injected into inbred strain 2 guinea pigs has been examined. The immune status of these animals has been challenged by infection with Treponema pallidum, Nichols. The immune response evaluated by the fluorescent-antibody test, microhemagglutination test and ELISA demonstrated high titers of antibodies to the T. pallidum antigens. The immunoblot analysis proved that the antibodies were directed to the 43-(Tmp A) 34- (Tmp B) and 35-kdalton (Tmp C) polypeptides. Antibodies cross-reacting with Treponema phagedenis biotype Reiter were, however, also detected. In spite of high titers of antibodies the animals were not protected against challenging infection with 10(8) organisms of T. pallidum.

Adjuvants, Immunologic↗
PubMed1989

Experimental syphilis in guinea pig.

The infrequent use of guinea pig in experimental syphilis, the not well genetically and immunologically characterized strains of animals originating from places with unspecified conditions of husbandry, and the various strains of Treponema pallidum used for infection provided inconsistent and discouraging results. For eight decades the rabbit has been the major animal model in studies of syphilis. However, the lack of readily available inbred strains of rabbits--necessary for adoptive transfer experiments--has been a stumbling block in revealing the mechanisms responsible for immunity, susceptibility, and resistance to T. pallidum infection. These difficulties have recently been overcome by demonstration of inbred strains susceptible to T. pallidum infection, paving the way to studies of adoptive immunity. The guinea pig may also be a better model than the rabbit for immunomanipulations (irradiation, injection with antibodies specific to various cell populations), allowing a closer insight into the immunopathologic mechanism operating during the course of syphilitic infection. The "rediscovery" of the guinea pig as a model for experimental syphilis and recent years of intensive studies justify a review summarizing older data and providing the most recent information. The authors, having first-hand experience with this model, will provide detailed information on (1) historical background; (2) course of infection with T. pallidum in inbred and outbred strains of guinea pigs; (3) the ID50 for various strains; (4) various routes of infection; (5) age and sex-dependent susceptibility to infection; (6) kinetic of the humoral response to specific and non-specific treponemal antigens; (7) appearance of autoantibodies and immune complexes; (8) cellular response, including lymphoproliferative response, macrophage inhibitory factor(s) production, chemotaxis and adoptive transfer of immunity by purified T cells; and (9) a complete list of references.

Animals↗
PubMed1989

Kinetics of pathogen-specific humoral response in Treponema pallidum-infected young and old inbred strain 2 guinea pigs.

The kinetics of the humoral response to pathogen-specific polypeptides was examined in Treponema pallidum-infected young (3-5 months old) and old (10-20 months old) inbred strain-2 guinea pigs. Sera collected before and at various times after infection were pooled and examined by immunoblotting and two serologic tests (ELISA and FTA) before and after sequential adsorption with CNBr-activated sepharose coupled to normal rabbit proteins and antigens from five nonpathogenic treponemal species. Prior to adsorption the kinetics of the humoral response to T. pallidum antigens did not seem to differ significantly between the two groups. After adsorption, however, a delay in the appearance of detectable antibodies and a milder response to various pathogen-specific polypeptides was observed in the older group. After adsorption, a sharp drop in ELISA-TP, ELISA-TR and FTA titres occurred in both groups. Six months post-infection, between 9 and 10 pathogen-specific polypeptides (97, 57, 47, 45, 43, 39, 37, 33, 17 and 15 kD) were recognized by both groups. The effect of age and levels of natural treponemal antibodies on the clinical symptoms of primary lesions and humoral response to pathogen-specific polypeptides is discussed.

Aging↗
PubMed1988

Effect of irradiation and depletion of C3-complement component on the course of Treponema pallidum infection in a resistant guinea pig strain.

The role of complement and ionizing radiation in the natural resistance to Treponema pallidum infection of Albany guinea pigs was explored. Depletion of C3 by cobra venom factor for a period of 14 days affected neither the host's susceptibility to infection nor the humoral response. Total body irradiation with 420 or 800 R was fatal within 20-30 days and there was no multiplication of treponemes in the infected host. Animals showing lethal signs were euthanized and tissues removed for examination. Exposure to a nonlethal dose of 300 R increased the susceptibility to infection (46% symptomatic lesions) and facilitated multiplication of treponemes at the site of inoculation and in the lymphoid organs, but the humoral response was not different from that of non-irradiated controls. The results seem to suggest a defect in antigen recognition by the immunocompetent cells in the resistant Albany guinea pigs.

Animals↗
PubMed1987

Humoral response in Treponema pallidum-infected guinea pigs. II. Circulating immune complexes and autoimmune responses.

Guinea pigs of inbred strain 2 and of a strain deficient in complement component 4 (C4D) responded to intradermal infection with Treponema pallidum by production of antibodies to treponemal antigens, normal rabbit serum proteins, fibronectin, and creatine kinase and with formation of circulating immune complexes (IC). IC started to appear at low concentrations 1 mo after infection and increased between 3 and 5 mo post-infection. Antibodies to fibronectin appeared after the second month but were not detectable 30 days later. Antibody activity to creatine kinase was detectable at the fourth month and became significantly higher at 5 mo post-infection. Reinoculation with a dose similar to that used for primary infection caused a significant increase in all antibodies and IC. Dissociation products of IC formed after primary infection consisted predominantly of treponemal antibodies and antigens, whereas IC detected after reinfection consisted predominantly of antibodies and normal rabbit serum proteins. Antibodies to fibronectin and creatine kinase are considered autoantibodies, and the underlying mechanism responsible for their production in syphilis is discussed.

Animals↗
PubMed1987

Adoptive transfer of immunity to Treponema pallidum Nichols infection in inbred strain 2 and C4D guinea pigs.

T lymphocytes purified from lymph nodes and spleens of chancre-immune, inbred strain 2 guinea pigs, when infused into syngeneic guinea pigs, conferred protection against challenge with Treponema pallidum subsp. pallidum Nichols. No protection was conferred by similar injections of cell suspensions from normal guinea pigs or guinea pigs immunized with T. phagedenis biotype Reiter or T. pallidum-free testis supernatants from infected rabbits. Similar results were obtained with homozygous C4D guinea pigs. After several months of infection, 2 of 11 strain 2 and 1 of 8 strain C4D recipients of T. pallidum-immune cells developed an erythematous reaction of short duration at the injection site; 2 of these recipients were positive for T. pallidum. Throughout the experimental period the humoral response to treponemal antigens was substantially lower in the adoptively immune guinea pigs than in various unprotected control groups. Passive immunity to infection with T. pallidum, however, seems to be dose related, since asymptomatic infection persisted for as long as 3 months after challenge in strain 2 guinea pigs transfused with 10(8) T. pallidum-immune lymphocytes, but not in C4D recipients of twice as many immune cells.

Animals↗
PubMed1987

Increased production of antibodies to spermatozoa and seminal fluid in rabbits used as semen donors.

Sera of 20 male rabbits that were used as frequent donors of semen and age-matched normal male and female rabbit controls were examined by an enzyme-linked immunosorbent assay (ELISA), with sperm and seminal fluid as antigens. Five of the 20 semen donors developed an especially high humoral response to seminal fluid and spermatozoa, similar to that observed in some female breeders. The antibodies increased gradually during the 9 months of semen collection. The specificity of the antibodies was demonstrated by total or partial absorption with seminal fluid or spermatozoa. The antibodies were virtually all IgM and were directed against the acrosomal cap region of the spermatozoa, but variable fluorescence was also observed in the postnuclear region and tail.

Acrosome↗
PubMed1987

Humoral response in Treponema pallidum-infected guinea pigs: I. Antibody specificity.

Young male inbred strain 2 guinea pigs were infected intradermally with 8 X 10(7) Treponema pallidum extracted from a rabbit orchitis, and 5 months later reinfected with 10(7) T. pallidum. Ninety percent of the animals developed symptomatic lesions after initial infection but none on challenge. Immunoblotting of sera obtained at intervals after infection or reinfection showed antibodies against T. pallidum antigen (TP), nonpathogenic treponemes--T. phagedenis biotype Reiter (TR), T. refringens strain Noguchi (TN), and T. vincentii (TV)--as well as normal rabbit serum (NRS) and normal rabbit testes extract (NRT). Antibodies reacting with TP were detected as early as 17 days (five polypeptides) and steadily rose (at 3 months 17 polypeptides were seen). Cross-reacting antibodies to TR, TN, TV, or rabbit proteins decreased within 3 to 5 months. After reinfection, the antibodies to NRS increased more sharply than the anti-treponemal antibodies. Adsorption with TR and NRS of sera obtained after infection or reinfection produced a reduction of antibodies to TP by 75-87%.

Animals↗