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Biomedical subjects

D W Scott

Publications and source records attributed to D W Scott.

At least 181 records · Page 10Linked to original sources
PubMed1984

Conversion of a tolerogenic to an immunogenic signal by P388AD.2 cells, a lymphoid dendritic cell-like tumor line.

The lymphoid dendritic cell-like tumor P388AD.2 is capable of converting a tolerogenic signal into an immunogenic one. In the present study, adherent P388AD.2 cells were pulsed with the tolerogen, fluoresceinated (FL) sheep gamma-globulin (SGG), washed, and incubated with normal spleen cells. After 24 hr, the spleen cells were harvested and challenged in secondary cultures with immunogenic doses of FL-thymic independent (TI) antigens. The plaque-forming cell response on day 3 of secondary culture was increased as much as 400% compared with control spleen cultures exposed to untreated P388AD.2 cells. The increased response was specific for the FL-hapten and occurred only when P388AD.2 cells were pulsed with FL-Ig or FL-F(ab')2 fragments, but not with FL-synthetic tolerogens or other FL-antigens. Furthermore, the augmentation required histocompatible T cells in the primary cultures. Additional experiments showed that if cultures were devoid of Lyt-1+ cells but not Lyt-2+ cells, no augmentation occurred. A variety of other macrophage-like tumor cells, some with known antigen presenting properties, were tested for the ability to present tolerogen in an immunogenic fashion. Only an I-A+ J774 clone was able to present tolerogen in an immunogenic fashion. However, we failed to find a correlation between the presence of surface Ia antigen and tolerogen-presenting ability. The results suggest that certain types of cells may play a role in immune regulation by abrogating the tolerogenicity of Ig tolerogens via their presentation in an immunogenic mode.

Animals↗
PubMed1984

Pitfalls in immunofluorescence testing in dermatology. III. Pemphigus-like antibodies in the horse and direct immunofluorescence testing in equine dermatophilosis.

Indirect immunofluorescence testing for pemphigus-like antibodies was performed on 79 horses: 28 horses with various nonpemphigus dermatologic diseases, 21 horses with various nondermatologic diseases, and 30 normal horses. Pemphigus-like antibodies were detected in 6 horses: 3 normal horses with titers of 1:40, 2 horses with dermatophilosis at titers of 1:10 and 1:80, and 1 horse with lymphosarcoma at a titer of 1:320. It was concluded that equine pemphigus-like antibodies are a potential source of misinterpretation and misdiagnosis in indirect immunofluorescence testing. Direct immunofluorescence testing for whole immunoglobulin, IgG, IgM, and IgA was performed on skin lesions from 2 horses with dermatophilosis. Diffuse intercellular deposition of whole immunoglobulin and IgG was found in both horses. It was concluded that equine dermatophilosis is a potential source of misinterpretation and misdiagnosis in direct immunofluorescence testing.

Actinomycetales Infections↗
PubMed1984

Mechanisms in immune tolerance.

Self:nonself-discrimination is critical for the function of the immune system and survival of vertebrate species. The failure to respond to one's own antigens has been called self-tolerance. The mechanisms whereby such tolerance may be induced are reviewed herein. Emphasis is placed on the role of self-recognition involving suppressor T-cell pathways as well as on studies involving putative clonal deletion mechanisms. The important parameters for the induction of tolerance and the roles played by surface isotypes in discriminating immunogenic vs. tolerogenic signals will be emphasized. The possible involvement of multiple pathways for self or experimental tolerance is emphasized with the ultimate goal being the modulation of aberrant immune responses.

Animals↗
PubMed1983

Cellular events in tolerance IX: maintenance of immunological tolerance in the presence of normal b-cell precursors and in the absence of demonstrable suppression.

The cellular events involved in immunological tolerance to fluoresceinated sheep gammaglobulin (FL-SGG) were analyzed at the level of hapten-specific B cells. One single iv injection of FL-SGG induced tolerance as measured by challenge with thymus-dependent (FL-KLH) or thymus-independent (FL-Ficoll) antigens in vivo or thymus-independent (FL-LPS) antigen in vitro. As noted earlier, unresponsiveness was maintained until 6-8 weeks after tolerance induction. Limiting-dilution precursor analysis demonstrated a reduction in B-cell precursors on Day 7 after tolerogen treatment; precursor frequencies returned to control levels by 3-4 weeks. This recovery of precursors in the presence of stable tolerance was not due to suppressor activity. Rather, results show that tolerant hapten-specific B cells are clonally anergic and display a reduced burst size in response to antigen. Hence, unresponsiveness is maintained in the presence of apparently normal precursor levels by an intrinsic defect in antigen-specific B cells.

Animals↗
PubMed1983

Generation of antigen-responsive B-cell line by somatic cell hybridization.

An antibody-secreting hybridoma specific for the fluorescein hapten has been fused with a nonsecreting pre-B-cell tumor line to yield an inducible antigen-binding hybrid with very little antibody secretion. Upon stimulation with fluoresceinated LPS (FL-LPS), the amount of specific antibody secreted by this hybrid increased up to five-fold. Although unhaptenated LPS alone induced a small response (two-fold increase), several lines of evidence suggested that the stimulation induced by the haptenated LPS involved an interaction with the fluorescein specific surface immunoglobulin receptor. However, since a variety of other antigens bearing the same hapten failed to induce a secretory response, a role for mitogenic focusing and/or B-cell subset triggering can also be envisaged. This is the first report of a monoclonal, antigen-specific and responsive hybrid, which can serve as a model for studying the differentiation of specific B lymphocytes into antibody-secreting cells.

Animals↗
PubMed1983

Role of self carriers in the immune response and tolerance. VIII. Suppression of the MOPC-104E idiotypic response by idiotype-modified self, but not by dextran-modified self.

We have investigated the suppression of the anti-dextran B1355S immune response using our model of modified self. The anti-dextran response is idiotypically well defined in BALB/c mice. This system enables us to examine the contribution of various predominant idiotypes to the antibody response under conditions of suppression by antigen or by idiotype-specific suppressor cells. Our results demonstrate that the total anti-dextran response can be inhibited by pretreatment of animals with dextran-coupled syngeneic spleen cells; however, the representation of major idiotypes constituting this response are not reduced in percentage. In contrast, pretreatment of mice with MOPC-104E-coupled spleen cells leads to a specific suppression of the private IdI-104E idiotype. The total anti-dextran response remains unchanged, as well as proportions of other major idiotypes known (IdI-588 and IdX). This suppression is mediated by Thy-1.2+, Lyt-2.2+ T cells, as demonstrated by adoptive transfer assays. This system will allow the molecular dissection of the regulation of an idiotypically well-defined system for the suppression by either antigen- or idiotype-specific suppressor T cells.

Animals↗
PubMed1983

Augmentation of syngeneic tumor-specific immunity by semiallogeneic cell hybrids.

Hybrid cell lines were established from fusions between lipopolysaccharide- (LPS) stimulated C57BL/6J spleen cells and MPC-11 tumor cells (45.6TG1.7, abbreviated M45), and were tested for their ability to immunize semiallogeneic mice against a parental tumor challenge. These hybrids were tumorigenic in syngeneic (BALB/c X C57BL/6J) F1 (CB6F1) mice but did not grow in semiallogeneic (BALB/c X A/J) F1 (CAF1) mice. All hybrids express both parental major histocompatibility antigens (H-2b and H-2d) as detected by indirect immunofluorescence and by their ability to function as either stimulators or targets for allogeneic cytotoxic lymphocytes (CTL). M45 tumor-associated antigens (TAA) were expressed on the hybrid surface as shown by their ability to act as either stimulators or targets for syngeneic CTL specific for M45 TAA. Immunization of semiallogeneic CAF1 mice with the hybrids i.p. followed by a challenge with M45 tumor cells resulted in extended survival when compared to untreated mice or animals immunized i.p. with M45 tumor cells. This immunity was specific and was not due to an allogeneic effect; immunization with an unrelated H-2bd tumor, 70Z/3, or H-2bd B6D2F1 spleen cells or with semiallogeneic spleen cells plus M45 did not protect mice from M45 challenge. Interestingly, prophylactic priming with semiallogeneic hybrid tumor cells or parental myeloma cells led to M45-specific CTL and "help" for an in vitro CTL response; however, the degree of CTL priming by hybrid tumors was not augmented when compared to the level of CTL achieved with parental tumor alone. Hence, stimulation of CTL activity per se by hybrid tumor cells cannot explain the protective effect of hybrid tumor immunization. These studies nevertheless confirm that semiallogeneic hybrids, which we show express TAA and alloantigens, can be used to immunize mice against a lethal syngeneic myeloma tumor challenge.

Animals↗
PubMed1983

A novel role for macrophages: the ability of macrophages to tolerize B cells.

We investigated the ability of macrophages (M phi) to present the tolerogen fluoresceinated sheep gamma-globulin (FL-SGG) to B cells. M phi pulsed with FL-SGG or murine FL-IgG2 were able to tolerize normal spleen B cells specifically as assessed by the plaque-forming cell (PFC) response to the antigens FL-Brucella abortus (FL-BrA) and FL-polymerized flagellin (FL-POL). Tolerance was not induced when M phi were pulsed with a variety of other FL antigens or the synthetic tolerogen FL-D-glutamic acid-D-lysine (FL-D[G,L]). The ability of M phi to tolerize B cells was not T cell-dependent, because populations of both T-depleted B cells and hapten-specific B cells were tolerizable. M phi-induced B cell tolerance did not exhibit genetic restriction with regard to the H-2 haplotype of the presenting M phi or the responding B cells. A variety of different types of peritoneal M phi, including normal resident M phi and those elicited by thioglycollate or concanavalin A (the latter are predominantly la+), could tolerize B cells after being pulsed with FL-SGG. We compared tolerogen-pulsed M phi to soluble tolerogen for the ability to tolerize B cells and found that tolerogen bound to M phi was more than 10 times as potent as an equivalent amount of soluble tolerogen. In contrast to the ability of M phi to present FL-SGG in a tolerogenic fashion to B cells, the P388AD lymphoid dendritic cell-like tumor line presented FL-SGG in an immunogenic mode to B cells. Tolerogen bound to P388AD cells could specifically augment a PFC response to both FL-BrA and FL-POL. We suggest that certain types of M phi may play a role in unresponsiveness by enhancing the tolerogenicity of soluble antigen, whereas other accessory cells may present the same moieties in an immunogenic fashion.

Animals↗
PubMed1983

Pitfalls in immunofluorescence testing in canine dermatology.

Indirect immunofluorescence testing for pemphigus-like antibodies was performed on 100 dogs: 50 dogs with various nonpemphigus dermatologic diseases, 25 dogs with various nondermatologic diseases, and 25 normal dogs. One dog (generalized demodicosis) was positive for pemphigus-like antibodies at a titer of 1:10. It was concluded that canine pemphigus-like antibodies are a potential source of misinterpretation and misdiagnosis in indirect immunofluorescence testing. Direct immunofluorescence testing for IgG, IgA, IgM, and C3 was performed on the footpads of 11 normal dogs. Granular deposition of IgM at the basement membrane zone was demonstrated in 5 of the 11 dogs. It was concluded that direct immunofluorescence testing of canine footpads using only polyvalent immunoglobulin antisera or anti-IgM antisera may lead to misinterpretation and misdiagnosis in up to 45% of all dogs tested.

Animals↗
PubMed1983

Pitfalls in immunofluorescence testing in dermatology. II. Pemphigus-like antibodies in the cat, and direct immunofluorescence testing of normal dog nose and lip.

Indirect immunofluorescence testing for pemphigus-like antibodies was performed on 75 cats: 25 cats with various nonpemphigus dermatologic diseases, 25 cats with various nondermatologic diseases, and 25 normal cats. Pemphigus-like antibodies were not detected. It was concluded that neither true pemphigus antibodies, nor pemphigus-like antibodies are commonly detected by indirect immunofluorescence testing in the cat. Direct immunofluorescence testing for IgG, IgA, IgM, and C3 was performed on the nose and lip of 15 normal dogs. Granular deposition of IgM at the basement membrane zone of the nose was demonstrated in 11 of the 15 dogs. Lip was consistently negative. It was concluded that direct immunofluorescence testing of canine nose by only polyvalent immunoglobulin antisera or anti-IgM antisera may lead to misinterpretation and misdiagnosis in up to 73% of all dogs tested.

Animals↗
PubMed1983

Hapten-specific murine colony-forming B cells. III. Delineation of functional B cell subpopulations grown under different conditions.

The influence of anti-immunoglobulin M (IgM) and anti-IgD on the ability of fluorescein (FL)-specific B cells to proliferate in a colony-forming assay, and of their progeny to further differentiate in response to different FL-antigens was studied. Splenic FL-specific B cells were purified on FL-gelatin plates and were then cultured in semisolid agar in the presence or absence of anti-mu, and anti-delta, or both. Experiments were performed under conditions of either sheep red blood cell (SRBC)-potentiated or SRBC + lipopolysaccharide (LPS)-potentiated colony growth. The resulting colonies were then tested in secondary filler cell-dependent microcultures for the ability to be triggered by different classes of FL-antigens to yield plaque-forming cells (PFC). Anti-delta inhibited 47% of colony growth under both agar culture conditions. Anti-mu inhibited 55% of colony growth in SRBC + LPS-potentiated agar cultures, and inhibited 72% if only SRBC was present. If anti-delta and anti-mu were added together, inhibition was nearly additive. When anti-Ig-treated colonies were tested for PFC responses against FL-polymerized flagellin (POL), both normal and anti-delta resistant colonies, grown under both agar culture conditions, responded well. Anti-mu resistant colonies were refractory to FL-POL challenge. Only normal or anti-delta resistant colonies grown in SRBC + LPS agar cultures were able to respond well to FL-Ficoll, whereas even normal SRBC-potentiated colonies responded poorly. All except SRBC-potentiated, anti-mu treated colonies were able to respond to nonspecific signals present in cultures containing FL-KLH and activated T cell help. These data suggest that addition of specific anti-Ig antibodies, and variation of agar culture conditions, can select for B cell subpopulations responsive only to certain types of antigens.

Animals↗
PubMed1982

Observations of the immunopathology and therapy of canine pemphigus and pemphigoid.

Immunopathologic evaluation of 27 dogs with pemphigus and pemphigoid demonstrated that direct immunofluorescence testing was vastly superior to indirect immunofluorescence testing for diagnosis. Therapeutic studies in 31 dogs with pemphigus and pemphigoid demonstrated that glucocorticoids given for systemic effect were unsatisfactory as the sole form of treatment because of lack of efficacy of unacceptable side effects, or both, in over 50% of the cases.

Animals↗
PubMed1982

Dermatologic use of glucocorticoids. Systemic and topical.

In human medicine, about one-half of the prescriptions written by dermatologists is for glucocorticoids. Although such figures apparently are not available in veterinary medicine, certainly it would be safe to assume that the usage of glucocorticoids in dogs and cats at least paralles that in humans. In general, this is nothing to apologize for. Let's face it, where would we dermatologists (and our patients) be without "the silver bullet"! Strict attention to diagnosis and therapeutic adjuncts and alternatives, followed by careful adherence to all phases of appropriate glucocorticoid therapy, will usually result in the satisfactory management of many dermatoses.

Administration, Oral↗