Biomedical subjects

R G Bell

Publications and source records attributed to R G Bell.

At least 55 records · Page 3Linked to original sources

PubMed1992

Variation in responsiveness to Trichinella spiralis infection in inbred rat strains.

An analysis of interstrain variation between 12 inbred and 4 congenic rat strains in the expression of immunity against Trichinella spiralis is reported. All rat strains expressed strong rapid expulsion which resulted in the elimination of 88-98% of a challenge infection of muscle larvae. In contrast, substantial interstrain variation in the rate of adult worm expulsion in the primary infection was evident. By day 10 after infection, BUF and YO strains had less than 50 worms left in the intestine whereas BI and WKA strain rats had barely begun rejection, with approximately 1000 worms present in the gut for both strains. All other rat strains fell within these extremes in a continuous gradation. There was no clustering of rat strains into phenotypic groups with comparable worm burdens as seen with mice. The number of muscle larvae that established after the primary infection showed less variation than had adult worm burden in the primary infection and there was only a weak correlation of muscle larvae burden with numbers of intestinal adults present at 10 days. Comparison of MHC-matched or MHC-disparate rat strains on a PVG background suggested that non-MHC genes determined the principal adult worm rejection characteristics of a given strain. The absence of phenotypic variation in the expression of rapid expulsion in rats reinforces the biological distinction between rat rapid expulsion and the 'rapid expulsion' defined for mice.

Animals↗

PubMed1992

Rapid expulsion of Trichinella spiralis in adult rats mediated by monoclonal antibodies of distinct IgG isotypes.

The role of IgG in rapid expulsion of Trichinella spiralis in adult rats was analysed. In this experimental model, rats were first infected with an unrelated nematode Heligmosomoides polygyrus, then 5-14 days later, immune serum, its fractions, or IgG monoclonal antibody (mAb) was transferred. Rats were challenged with T. spiralis muscle larvae 24 hr after antibody transfer and intestinal worms counted at various times, up to 24 hr, after challenge. Provided rats were exposed to H. polygyrus first, immune serum, affinity chromatography-isolated immune IgE, IgE-depleted immune serum, or monoclonal antibodies of IgG1, IgG2a and IgG2c isotypes were all able to transfer rapid expulsion. Protection varied from 40 to greater than 90% larval T. spiralis rejection and was dose dependent, requiring, for IgG1, a minimum of 5 mg of transferred protein. Antibody specificity was predominantly against the dominant larval secreted/cuticular antigen TSL-1 for IgE and was exclusively so for the mAb. A comparison of quantitative differences in effective amounts of transferred antibody as well as the distinct priming requirements suggest that IgE functions through an intestinal mechanism that is different from that for IgG1 and IgG2c. Whether or not IgG2a functions homocytotropically, or as the other IgG has not been resolved. Since neither the T-helper (Th) cell transfer or the H. polygyrus form of intestinal priming confers protection by itself, these data suggest that rapid expulsion is predominantly an antibody-mediated process albeit with a required intestinal element. The results support earlier data in showing that two steps are required for rapid expulsion to be expressed and this is so for both IgE- and IgG-mediated mechanisms. Finally, the results show that IgG of various isotypes and IgE have a functional role in the expression of intestinal immunity.

Animals↗

PubMed1992

Characterization of cellular and molecular immune effectors against Trichinella spiralis newborn larvae in vivo.

The cellular and molecular immune effectors that participated in host immunity against Trichinella spiralis newborn larvae were characterized in vivo using AO rats. Donor rats were immunized with 2,000 muscle larvae orally or 11,400 newborn larvae i.v. Immune serum and cells from spleen, peripheral lymph nodes, mesenteric lymph node, thoracic duct lymph and the peritoneal cavity were obtained from donor rats 10-21 days after infection and transferred into normal recipient rats. The control recipients received either no cells and serum or normal cells and normal serum obtained from normal donors. Newborn larvae (20,000-50,000) were injected either i.v. or ip into these recipients and immunity against newborn larvae was measured either by muscle larvae burden of the recipients three weeks later or by direct recovery of newborn larvae from the peritoneal cavity of the recipients. The experiments demonstrated that immune lymphocytes conferred no protection in the recipients but that immune serum and immune peritoneal cells were protective and these effects were synergistic. Cell adherence to the cuticle and killing of newborn larvae were observed in the peritoneal cavity of immune rats. Positive fluorescence was observed on newborn larvae incubated with fractionated IgM and IgG(E) antibody isotypes. Massive deposition of antibody molecules on newborn larvae was demonstrated by scanning electron microscopy. Studies using transmission electron microscopy revealed that the larval adherent cells were stimulated macrophages, neutrophils and eosinophils.

Animals↗

PubMed1991

A role for IgE in intestinal immunity. Expression of rapid expulsion of Trichinella spiralis in rats transfused with IgE and thoracic duct lymphocytes.

In these experiments we characterize the protective antibodies in immune serum that interact synergistically with immune thoracic duct lymphocytes (TDL) to induce rapid expulsion (RE) of Trichinella spiralis in adult rats. Antibodies with both reaginic and nonreaginic activity mediated RE upon passive transfer to adult rats that had been adoptively transfused with immune TDL 7 days earlier. In serum collected 28 days after a primary infection, the most important antibody was homocytotropic IgE. Native IgE produced by active infection was isolated from 28-day immune serum by salt precipitation and/or by sequential affinity chromatography. The murine mAb A2 and B5 (anti-rat IgE) were conjugated separately to Sepharose 4B affinity columns for affinity separations. IgE was shown to be pure by gel electrophoresis and Western blots and its m.w. was estimated at approximately 190,000. As little as 183 micrograms of purified IgE could induce RE after passive transfer to adult rats. The IgE was shown to be functional by PCA activity, Ag-binding on Western blots, and skin sensitization; the latter could be blocked by pretreatment with 1R162, a rat myeloma IgE. Monoclonal IgG of any isotype transferred in amounts up to 35 mg/rat could not transfer RE to rats previously transfused with TDL cells. Immune serum collected 3 mo after the primary infection contained insufficient IgE to transfer RE, but complex non-IgE fractions were protective. The data thus demonstrate that IgE is a functional Ig in the rat capable of mediating the rejection of challenge nematode infections of the gut in the absence of other specific Ig. Secondly, other Ig may also play a role, in particular, several weeks after the primary infection when specific IgE levels in serum have declined.

Animals↗

PubMed1991

Separation and isolation of the isomers of bacitracin by high-performance liquid chromatography and their relationship to microbial activity.

Bacitracin, a polypeptide antibiotic produced from strains of Bacillus licheniformis, is one of the most commonly used antibiotics in the world. Actually, the various products generally referred to as 'bacitracin' are mixtures of similar polypeptides which may differ by only one amino acid. The approved method of analysis for bacitracin is microbial. To correlate the microbiological method with an HPLC method, bacitracin was chromatographed using a YMC basic column with UV detection. Adequate separation of the isomers were obtained to scale up this procedure to preparative HPLC using a 250 x 21 mm YMC basic column. The various fractions were separated, isolated and examined for microbial activity. The chromatograms can accurately predict in minutes the microbiologically-determined potency which usually takes 16-24 h to develop. The chromatographic procedure also provides information on the amounts of isomers and degradation products present in the sample, whereas the microbiological assay only provides activities or potencies of the antibiotic. The reported HPLC method also possesses some advantages over some other published HPLC methods in terms of accuracy and time of analysis.

Bacitracin↗

PubMed1991

Characterization of the thoracic duct T-helper cells that co-mediate, with antibody, the rapid expulsion of Trichinella spiralis in adult rats.

Thoracic duct cells that act synergistically with immune serum or antibody to transfer rapid expulsion of a challenge infection with Trichinella spiralis muscle larvae were characterized as OX38+, OX8-, OX22- T helper cells. Protective capacity was confined to the dividing T helpers that appeared on days 3-5 in the thoracic duct of rats during a T. spiralis infection. To realize their intestinal priming potential in recipient rats. MHC-compatibility between donor and recipient rat was required. Fractionation of immune serum with 40% saturated ammonium sulphate left transferable protective activity in both the precipitate and supernatant fractions. Absorption of immune serum with muscle larvae antigen removed the capacity to transfer protection.

Animals↗

PubMed1990

Intraintestinal migration to the epithelium of protective, dividing, anti-Trichinella spiralis CD4+ OX22- cells requires MHC class II compatibility.

We have measured the intraintestinal migration of activated Th cells belonging to the OX8- OX22- and OX8- OX22+ subsets derived from thoracic duct lymph of rats infected with Trichinella spiralis. Cells in S-phase were labeled with 125I-UdR or 3H-TdR in vitro and transfused i.v. Identical proportions of both helper cell subsets localized in the small intestine but three to four times as many OX22- cells as OX22+ cells migrated to the intestinal epithelium. Experiments using MHC class I and II recombinant rats indicated that localization of OX8- OX22- cells in the lower lamina propria (LP) and muscularis was reduced by 50% in MHC class II incompatible rats as assessed by total gamma-counts but by a factor of three when labeled cells were counted. Movement of labeled OX8- OX22- cells to the epithelium was reduced by a factor of five to seven when assessed by the same methods. Quantitative cellular localization in the gut and further movement to the epithelium were normal in class I-mismatched rats. The movement from the lower-mid LP to the epithelium was undertaken principally by dividing cells as indicated by a progressive loss of grain counts in labeled cells and the appearance of doublet-cells in mitosis. In allogeneic combinations, extravasating cells remained localized close to their primary site of exit in the muscularis and lower-mid LP. The results suggest that the requirement for MHC class II compatibility for adoptive transfer of immunity in rats to T. spiralis is functionally related to localization of the protective OX22- cell subset in the epithelium.

Animals↗

PubMed1990

Synergistic interaction between immune serum and thoracic duct cells in the adoptive transfer of rapid expulsion of Trichinella spiralis in adult rats.

Rapid expulsion of Trichinella spiralis could be transferred to naive adult rats with thoracic duct lymphocytes and immune serum. Thoracic duct cells collected from Days 3-5 and immune serum collected on Day 28, respectively, after infection were effective. Both cells and serum were unable to transfer rapid expulsion when given alone, even in large volumes. Recipients of immune serum and cells eliminated a significantly higher number of larvae than control rats by 1 hr after challenge with muscle larvae. Rapid expulsion produced 30-80% larval worm rejection but could not be increased by the transfer of more cells or immune serum. Mucus trappings did not appear to play a role in the rejection process. After transfer of 2 x 10(8) cells and 4.0 ml immune serum, rapid expulsion persisted for less than 1 week. However, after adoptive transfer of cells alone, the gut remained functionally receptive to the passive transfer of immune serum for 7 weeks. Therefore, the changes effected by transfer of cells were long lived in contrast to the 1 week, or less, of functional persistence by transferred immune serum. The data indicate that two separate processes, one cell mediated and the other immune serum mediated, interact synergistically in the intestine and lead to the expression of rapid expulsion.

Animals↗

PubMed1990

Trichinella spiralis: murine strain variation in response to monoclonally defined, protective, nonstage-specific antigens.

Nine hybridoma cell lines secreting monoclonal antibodies (mAbs) against Trichinella spiralis muscle larvae (ML) excretory/secretory antigens (ESA) were developed. Two mAbs, 6-D8-E3 (6D8) and 6-B1-G10 (6B1), were studied in detail. Western blot analysis using ML ESA showed that 6D8 recognized 35- and 40-kDa constituents whereas 6B1 identified a doublet of 33 kDa. However, Western blots of SDS-PAGE of crude ML homogenate showed that 6D8 identified proteins of approximately 35 and 43-60 kDa, whereas 6B1 recognized bands of 42-50 kDa. These results indicated substantial apparent MW differences between secreted and nonsecreted proteins recognized by both mAbs. Neither 6D8 nor 6B1 reacted with adult worm ESA, but both recognized antigens in aqueous extracts of homogenates of whole adult worms. Competitive inhibition experiments using ML ESA as a target demonstrated that the antigen epitopes recognized by monoclonals 6D8, 6B1, a rat mAb, 9D4, and a 37-kDa antigen previously defined were noncross-reactive. MAbs 6D8, 6B1, and 9D4 were used to isolate proteins possessing target determinants by affinity chromatography from crude ML homogenates. Each mAb isolated distinct protein species as determined by SDS-PAGE (6B1, approximately 42 kDa; 6D8, approximately 28, 37, and 61 kDa; 9D4, approximately 29, 33, 38-57, 80, and 86 kDa). NFS mice responded in a dose-dependent manner to affinity-purified antigens and were 25-fold more effective (by weight of antigen) than either C3Heb/Fe(C3H) or B10.BR mice. Immunization of mice with 6D8, 6B1, or 9D4 antigens induced strong protection against a subsequent challenge infection in NFS mice as indicated by accelerated intestinal adult worm expulsion, reduced fecundity of the female worms, and reduction of ML burden. Affinity-isolated antigens stimulated in vitro proliferation of spleen and MLN cells from immune mice; however, the mitogenic response to these antigens barely varied among NFS, C3H, and B10.BR strains.

Animals↗

PubMed1990

3-Methylcholanthrene-induced immunosuppression in mice to Trichinella spiralis antigens.

The immunosuppressive effects of in vivo (subcutaneous) exposure to 40 or 80 mg/kg 3-methylcholanthrene (MC) were examined in aryl hydrocarbon hydroxylase (AHH) responsive C57BL/6 (B6) and AHH non-responsive DBA/2 (D2) inbred strains of mice. Twenty-four hours after treatment with carcinogen or vehicle alone, animals were primed with crude L1 muscle larvae antigen from T. spiralis. Immune status was assessed in vitro after six days as antigen-specific lymphoproliferation. The proliferation of splenocytes from MC-treated D2 and B6 mice was significantly impaired compared to controls. To examine the cellular basis of the immunosuppression, primed splenocytes from control and MC-treated mice were separated into adherent and non-adherent fractions on Sephadex G-10 columns. When antigen-pulsed adherent cells from MC-treated B6 and D2 mice were recombined with control non-adherent cells from syngeneic and B6D2F1 mice, T-cell proliferation was significantly reduced. This suppression was not observed with the addition of increased numbers of adherent cells. Non-adherent cells from MC-treated mice showed a decreased capacity to respond to the presence of control antigen-pulsed adherent cells from appropriate mice. These results suggest that MC treatment has a similar suppressive effect on the immune responses of both B6 and D2 mice that involves the quality of accessory cell-T-cell interactions.

Animals↗

PubMed1990

Antigen-specific lymphocyte proliferative responses in inbred mice after Trichinella spiralis infection.

The in vitro antigen-specific lymphoproliferative response of spleen, mesenteric lymph node (MLN), and coeliac lymph node (CLN) cells taken from various strains of inbred mice infected with Trichinella spiralis was assessed. In most experiments cell populations were stimulated with excretory/secretory antigens (ESA) derived from adult and larval worms. Lymphoid cells collected 5-7 days postinfection were usually the most responsive to ESA as measured by [3H]thymidine uptake. Spleen cells were more responsive than either MLN or CLN cells. There was a correlation between in vitro ESA stimulation and worm rejection in strong- and weak-responder strains of mice. Spleen and MLN cells of NFS mice showed higher antigen-specific responsiveness, whereas the same cells from B10.BR (H-2k) and B10.Q (H-2q) strains of mice were less responsive. Among intermediate responder strains 2 patterns were observed. Spleen and MLN cells of BuB and DBA/1 mice responded more strongly than those of C3H mice. Dose-response experiments demonstrated that increasing the infective dose of larvae to the host usually increased subsequent in vitro antigen-specific lymphoproliferation. Furthermore, non-MHC-linked genes appear to be the primary determinant of antigen-specific T-cell-proliferative responses in inbred mice infected with T. spiralis.

Abdomen↗

PubMed1990

T-helper subset function in the gut of rats: differential stimulation of eosinophils, mucosal mast cells and antibody-forming cells by OX8- OX22- and OX8- OX22+ cells.

Thoracic duct lymphocytes (TDL) collected 3 days after infection of rats with Trichinella spiralis (TS) and adoptively transferred into normal, uninfected recipients, increased the numbers of both mucosal mast cells (MMC) and eosinophils (EOS) in the intestine. The CD4+ T-helper cell population was separated into two subsets (OX22+ and OX22-) using OX22 monoclonal antibody (mAb) and panning techniques. After adoptive transfer of these T-helper subsets i.v., rats were challenged with TS 24 hr later. The intestine of recipient rats was examined histologically at intervals from Day 3 to Day 21. On Day 9 after transfer, OX22+ T helpers induced a substantial mastocytosis [94 +/- 3, mean +/- SE/villus crypt unit (VCU)], whereas the OX22- T-helper subset increased resident EOS numbers (60 +/- 2/VCU) compared to the challenge control (18 +/- 1 MMC, 27 +/- 1 EOS/VCU). The time of peak eosinophilia was advanced by 3-6 days for recipients of OX22- cells and that of mast cells by 9-12 days for recipients of OX22+ cells. The recipients of OX22-, but not OX22+, cells also showed a large increase in the numbers of B cells in the spleen and mesenteric lymph node (MLN) secreting antibody against adult TS. Recipients of OX22- cells displayed an even increase in EOS throughout the villi, lamina propria (LP) and muscularis, whereas in OX22+ cell recipients mast cells were only present in the lower villus and the epithelium just above the crypt as well as the muscularis layer. Only the CD4+ OX22- cell subset conferred protection against TS in the intestine. We conclude that the OX22+ and OX22- T-helper cells exert distinctive effects in the intestine on MMC and EOS. Because protection was established in the presence of an OX22- T-helper-induced eosinophilia but without a concurrent mastocytosis, the results suggest that MMC are probably not involved in expulsion of TS to terminate the primary infection.

Animals↗

PubMed1990

Genetic analysis of the relationship between interleukin production and worm rejection in Trichinella spiralis-infected inbred mice.

The production of interleukin 1 (IL-1), IL-2, and IL-3 by peritoneal macrophages, mesenteric lymph node (MLN), or spleen cells from inbred strains of mice infected with Trichinella spiralis was examined. The mice belonged to the worm rejection phenotypes previously characterized as strong (NFS), intermediate (C3H, BUB, DBA/1, SWR, CBA, etc.), or weak (B10.Q, B10.BR, etc.). Strong responder NFS mice produced approximately twice as much IL-1 as intermediate responder C3Heb/Fe or weak responder B10.BR mice. IL-3 production varied slightly among strains but did not show any relationship to the phenotype of rejection (highest: C3Heb/Fe, B10.BR; lowest: B10.Q). Of 16 strains of inbred mice and 6 F1 hybrid crosses assessed, marked variations occurred in IL-2 production from MLN cells in response to T. spiralis antigen challenge in vitro. When 16 mouse strains were compared IL-2 production ranged from 5.1 units/ml (A/J) to 29.8 (NFS). Variations in IL-2 production among mouse strains did not relate directly to MHC haplotype, and the capacity of an individual strain to release IL-2 or IL-3 did not correlate with adult worm rejection phenotype. Genetic linkage studies proved that the gene(s) regulating IL-2 production in T. spiralis infection were not linked to the gene(s) regulating adult worm rejection. Regression analysis showed a weak correlation of high IL-2 production with weak worm rejection suggesting that IL-2 production or an associated process is a negative factor in primary worm rejection.

Animals↗

PubMed1989

IL-2 production, IL-2 receptor expression, and IL-2 responsiveness of spleen and mesenteric lymph node cells from inbred mice infected with Trichinella spiralis.

The in vitro production of IL-2 and IL-2R expression by lymphoid cells of inbred mice of strong (NFS), intermediate (C3H), or weak (B10.BR) in phenotype of Trichinella spiralis (TS) rejection was measured during a primary infection. Maximum production of IL-2 by spleen and mesenteric lymph node (MLN) cells occurred at 5 days postinfection. Cell depletion experiments demonstrated that Lyt-1.2+ T cells were predominantly responsible for in vitro IL-2 production. Cells from strong-responder NFS mice produced more IL-2 than cells from intermediate-responder C3H or weak-responder B10.BR mice. Similarly, after TS infection, NFS mice had significantly more IL-2R expressing MLN cells than B10.BR or C3H MLN cells. All mouse strains displayed a dose-dependent increase in in vitro IL-2 production after infection with 100 to 800 TS. This effect was most pronounced in NFS mice. Limiting dilution analysis of day 5 infected MLN cells demonstrated that the frequency of TS-reactive CD4+ cells was threefold higher in NFS mice than B10.BR and fourfold higher than in C3H mice. Finally, MLN cells taken from infected NFS mice responded to an exogenous source of IL-2, whereas MLN cells from infected C3H or B10.BR mice were unable to do so. We conclude that strong responsiveness in parasite rejection may be related to the amount of IL-2 produced as well as to the capacity of the lymphocytes of each mouse strain to respond to IL-2. Although these differences help explain the strong rejection phenotype of NFS mice, they fail to separate C3H and B10.BR mice where TS-responsive CD4+ precursors, IL-2 production, and dose responsiveness are all lower for the intermediate phenotype (worm rejection) C3H than the weak phenotype B10.BR mice.

Animals↗

PubMed1989

Intestinal immunity to Trichinella spiralis is a property of OX8- OX22- T-helper cells that are generated in the intestine.

The phenotype of T-helper cells conferring protection against Trichinella spiralis (Ts) was studied using adoptive transfer procedures and T-helper cell subsets isolated by monoclonal antibodies. With these techniques OX8- OX22+ and OX8- OX22- T-helper cell populations were isolated from thoracic duct lymph (TDL) of infected rats three-five-fold more concentrated than in unfractionated lymph. The OX8- OX22- cell subset alone transferred enhanced rejection of adult worms from the intestine. The origin of protective OX8- OX22- cells was examined in mesenteric lymphadenectomized (MX) rats. After MX, protective cells were found in the cell population draining directly from the intestine on Days 2-3 after infection. Protective cells first appeared in the mesenteric lymph node (MLN) and efferent lymph at Day 3. MX rats rejected T. spiralis at the same time as intact controls and showed enhanced rejection when immune TDL were transfused. No evidence was found for a direct role of the MLN in the generation or expression of parasite rejection. Depletion of migrating OX8- OX22- blast cells by 48-hr drainage of TDL did not influence the expression of an anamnestic response to challenge infection. This suggests that an intestinally resident cell population has a substantial role in mediating primary worm rejection and anamnestic immunity. Day 2 OX8- OX22- cells from MX rats proliferated in response to the presentation of adult and muscle larvae antigens in vitro. We conclude that protection resides in the OX8- OX22- T-helper cell subset that is produced and functions in the intestine.

Animals↗

PubMed1988

Trichinella spiralis: quantitative relationships between intestinal worm burden, worm rejection, and the measurement of intestinal immunity in inbred mice.

The effect of widely different doses of Trichinella spiralis muscle larvae on time to rejection of intestinal adults and on host survival was assessed in mice of the three rejection phenotypes; strong, intermediate, and weak. Rejection is weak with doses of less than 50 larvae per mouse. At these doses all mice rejected worms at a similar rate and no phenotypic variation was evident among strains. In contrast, rejection time was shortest for all strains and phenotypic variation among strains was evident in the range 50-100 muscle larvae/mouse. Above this dose the time taken to rejection increases monotonically with dose for all mouse strains examined. Despite this, the relative strength of rejection (i.e., phenotype) of a given strain of mouse was not changed at higher doses. Based on an end point of 98% rejection of the infective dose, time to rejection was predictable to +/- 1 day for all mouse strains and doses tested over the range 100-1000 worms administered. The principal reason for the increased time to complete rejection with larger worm doses was a delay in the initiation of intestinal rejection. This delay was evident above a dose of 50-100 larvae per mouse and occurred in all strains. Once begun, rejection was faster and eliminated more worms in unit time at higher doses (400-800 more) than at lower doses of worms. This appeared to be due to a stronger immune response of the host at higher doses. However, the increase in the rate of rejection was still not as great as the increase in the dose. We postulate that the delay in rejection with increased dose is due to a requirement for a "critical mass" of effectors/worm required to cause rejection. As dose increases, more time is required to reach the level at which worm rejection commences. Deaths due to higher doses of worms also occurred in a strain-specific manner and were temporally biphasic. The intestinal phase of infection produced mortality from 1 to 5 days after infection and the strongest rejection phenotype (NFS) was also the most resistant to intestinal deaths. Deaths occurring after Day 5 were due to the parenterally migrating newborn larvae. The weakest rejection phenotype, that of the B10 congenics, was also the least resistant to intestinal deaths. An experimental formula describing 98% worm rejection time with different doses was derived from the data.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Genetic analysis of expulsion of adult Trichinella spiralis in NFS, C3H/He, and B10.BR mice.

The genetics of T. spiralis rejection from the intestine was examined in inbred mice belonging to three phenotypic categories of expulsion: strong (NFS), intermediate (C3H), and weak (B10.BR). Experiments used various worm doses to analyze the day of worm rejection, defined as the day at which 98% expulsion of the infectious dose occurred. The F1 of NFS (strong) x B10.BR (weak) was a strong responder and the F1 of the cross C3H (intermediate) x B10.BR (weak) was intermediate. Analysis of time of rejection among offspring of the (NFS/B10.BR) x B10.BR backcross showed three segregating phenotypic categories which occurred in a ratio of 1:2:1 strong:intermediate:weak. Segregation analysis of C3H/B10.BR intercross (F2) mice produced a ratio of 3:1, intermediate:weak. The backcross C3H/B10.BR to the C3H parent produced 100% intermediate offspring and the backcross to the B10.BR parent segregated in a 1:1 ratio of intermediate:weak. Taken together the results of both sets of crosses demonstrated that strong responsiveness was a consequence of the additive effects of two dominant genes; either gene by itself conferred intermediate responsiveness. The additive nature of these dominant genes suggested that two distinct processes each lead to the expression of worm expulsion that is phenotypically intermediate and kinetically identical.

Animals↗

PubMed1988

Antibody-mediated in-vivo cytotoxicity to Trichinella spiralis newborn larvae in immune rats.

The antibody-dependent cell-mediated larvicidal response of AO rats against Trichinella spiralis newborn larvae was studied in vivo. Rats were immunized with 2000-3000 muscle larvae orally and then challenged 6-20 days later with 10,000-20,000 newborn larvae intraperitoneally. Newborn larvae recovery from the peritoneal cavity decreased significantly and was accompanied by cuticular cell adherence and killing of newborn larvae by day 9 of infection. Similar effects were observed when newborn larvae were incubated with blood obtained from immunized rats. The cell adherence and larvicidal responses reached their peak by day 16 of the primary infection. Passive transfer experiments demonstrated that newborn larvae infectivity was substantially impaired once cell adherence occurred. Cuticular adherence took place in vitro only when immune serum was added to the incubation medium. Complete destruction of newborn larvae in vivo after passive transfer, as measured by muscle larvae burden was only evident after exposure to both immune serum and immune cells, not to either alone. Non-specific stimulation of the peritoneal cavity with a sterile intestinal infection failed to induce cuticular adherence or larval killing in these rats. We conclude that a stage-specific antibody-dependent cell-mediated larvicidal response is rapidly generated in vivo after the host is exposed to newborn larvae. It is a systemic response which impairs the infectivity of newborn larvae and can destroy them before they reach muscle tissue.

Animals↗