The effects of feeding emissions from a metal-producing plant upon the immune system of sheep

The aim of our study was to asses the effects of feeding emissions of a plant producing metals from heavy metal-containing ore upon the humoral immunity in sheep. Three-year-old sheep of the Wallachian breed were included in an experiment and they were divided into two groups. The experimental group (5 animals) was administered emission-containing (prevailingly Cu and Zn) capsules for 3 weeks at a dose amounting to the twofold and during week four the threefold of the daily intake of sheep bred in the exposed area. The animals were subcutaneously immunized with ovalbumin (OVA, SIGMA A 5503) in 10% alhydrogel at a dose of 2 mg/100 kg l.w. In weekly intervals, blood samples were analyzed for specific antibody and total immunoglobulin levels. In both groups, OVA antibody formation was most pronounced in the 3rd and 5th weeks of observation. It was significantly (P < 0.01) higher in the experimental animals than in the controls (1.021, 0.641 and 1.138 vs. 0.435, 0.265 and 0.673 in the 3rd, 4th and 5th weeks, respectively). In the experimental group, total immunoglobulin concentrations slightly increased from 33.5 U ZST (starting value) to 38.72 U ZST (final value). As to the total immunoglobulin levels, no significant differences were determined between the two groups. It can be seen from the results that short-term administration of emissions promotes increased specific OVA antibody formation and a slight increase in total immunoglobulin levels. At the same time the ELISA method was proved to be suitable for specific antibody detection as a part of humoral immunity assessment.     

Effects of growth hormone, insulin-like growth factor-I, and cortisol on periparturient antibody response profiles of dairy cattle

The objectives of this study were to determine hormone and antibody response profiles from the prepartum period to peak lactation, and evaluate potential immunomodulatory effects of the classic endocrine hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and cortisol. Specifically, 33 Holstein cows were immunized with ovalbumin (OVA) and Escherichia coli J5 at weeks -8 and -3 prior to parturition. At parturition (week 0), cows received an additional immunization of OVA. Blood was collected at weeks -8, -3, 0, 3 and 6 relative to parturition and various samples were used to determine plasma hormone concentration, serum immunoglobulin (Ig), and specific antibody response to OVA and E. coli. Colostrum and milk samples were also collected post-parturition to monitor local immunoglobulin and antibody responses. Results indicated that not all periparturient cows exhibited depressed immune response, and that antibody response to OVA could be used to partition cows into 3 groups recognizing animals with sustained measurable antibody response before and after parturition (Group 1), animals which responded poorly to immunization at parturition (Group 2), and animals which did not respond to immunizations at week -3 or parturition (Group 3). Cows with the highest antibody response to OVA (Group 1) also tended (P < or = 0.10) to have the highest response to E. coli J5 at parturition and had the lowest incidence of disease, particularly mastitis. Antibody response to OVA measured in milk tended to be higher in Group 1 cows, particularly at week 0 (P < or = 0.06) compared to cows of Group 3. IGF-I was higher (P < or = 0.05) in cows of Group 1 than Group 3 at peak lactation (week 6).     

Coupling of palmitate to ovalbumin inhibits the induction of oral tolerance

Oral tolerance is a phenomenon that may occur in animals exposed to protein antigens for the first time by the oral route. They become unable to produce immune responses at the levels normally observed when they are immunized parenterally with antigen in the presence of adjuvants. Lipids have been used as adjuvants for both parenteral and oral immunization. In the present study we coupled ovalbumin with palmitate residues by incubating the protein with the N-hydroxysuccinimide palmitate ester and tested the preparation for its ability to induce oral tolerance. This was performed by giving 20 mg of antigen to mice by the oral route 7 days prior to parenteral immunization in the presence of A1(OH)3. Mice were bled one week after receiving a booster that was given 2 weeks after primary immunization. Specific antibodies were detected by ELISA. Despite the fact that the conjugates are as immunogenic as the unmodified protein when parenterally injected in mice, they failed to induce oral tolerance. This discrepancy could be explained by differences in the intestinal absorption of the two forms of the antigen. In fact, when compared to the non-conjugated ovalbumin, a fast and high absorption of the lipid-conjugated form of ovalbumin was observed by "sandwich" ELISA.     

Oxidative stress and mitochondrial DNA mutations in human aging

The effects of chemical sympathectomy on the mucosal compartments of the immune system were examined in adult rats. Ablation of the sympathetic nervous system using 6-hydroxydopamine in recipient animals reduced the migration into Peyer's patches and mesenteric lymph nodes (MLN) of adoptively transferred cells from MLN of normal donors. The mucosal immune response to ovalbumin (OVA), assessed by enumeration of anti-OVA antibody containing cells (AOCC) in the lamina propria after intestinal immunisation, was reduced in animals sympathectomized prior to immunization. In order to identify whether this reduction in AOCC response in intestinally immunized sympathectomized animals was due to a defect in migration of AOCC precursors to the intestinal lamina propria, the effect of chemical sympathectomy on the appearance of AOCC in the gut of immunized animals after adoptive transfer of AOCC precursors was investigated. The IgA-specific AOCC response was significantly reduced in sympathectomized recipients compared to the control group. Taken together these results demonstrate that the peripheral sympathetic nervous system influences the migration and accumulation in vivo of both naive and memory/effector lymphocytes in mucosal lymphoid tissues.     

Roger Brown

Salmonella abortusovis strain Rv6 (Sao Rv6) is a live attenuated vaccine used for a few years to protect ewes against abortive salmonellosis. As Salmonellae, particularly Salmonella aro mutants, have considerable potential as vehicles for the presentation of heterologous vaccine antigens, Sao Rv6 was tested in order to develop a vaccinal vehicle for small ruminants. Five vector plasmids were tested in Sao Rv6; these plasmids, which carry Maltose Binding Protein (MBP) expressed as protein, but differ in their promotors, had been previously tested in S. typhimurium strain SL3261, and were transferred into Sao Rv6. The five plasmids were stable in vitro, and the recombinant Sao Rv6 expressed MBP at various levels. Intraperitoneal infection of OF1 mice with the recombinant bacteria did not modify the characteristics of Sao Rv6; dissemination and infection levels were similar in all groups and all mice developed antibodies to Salmonella antigens as measured by ELISA. In contrast, only animals immunized with Sao Rv6 carrying the pNTE plasmid developed a serum antibody response to MBP. This plasmid was then tested in sheep; following subcutaneous immunization with Sao Rv6-pNTE, dissemination and infection levels were not modified in comparison with sheep immunized with Sao Rv6 lacking plasmid. Antibodies specific to MBP were detected in sera of sheep immunized with Sao Rv6-pNTE, purified MBP, and with S. typhimurium SL3261-pNTE as positive controls. These results demonstrate that Sao Rv6 can be used as a vehicle for heterologous antigens in sheep with pNTE as plasmid vector.     

Ischaemic preconditioning: present position and future directions

Antibodies generated against a synthetic growth hormone (GH) peptide in a number of animal species were shown to enhance the efficacy of GH. However, the ability to produce the effective antibodies diminished over the time and repeated boosters failed to overcome the hurdle. Therefore, this study was designed to address the issue on the fallen antibody responses by employing different GH peptide antigen preparations in cattle. Holstein steers were repeatedly immunized with a synthetic peptide corresponding to an amino acid sequence 54-95 of porcine GH (pGH). The peptide was conjugated to ovalbumin (OVA) as a carrier. Animals initially responded to the antigen well and elicited antibodies specific to the peptide. However, the 4th challenge with the same OVA-peptide antigen rendered animals unresponsive, resulting in a decline in antibody production. This unresponsiveness was overcome by switching the antigen at the 5th immunization from OVA-peptide to a recombinant peptide preparation which was composed of maltose binding protein (MBP) as a carrier. Antibodies generated in cattle after the 5th immunization recognized not only the pGH(54-95) peptide, but also bovine GH (bGH) and pGH. These antibodies were not immunoreactive with an unrelated control peptide. Hypophysectomized (hypox) rats were used for functional analysis and bGH was active in promoting the growth of these GH-deficient rats. The growth-promoting effect of bGH was significantly enhanced by mixing with bovine anti-peptide antibodies prior to administration. Therefore, the present findings suggest that peptide 54-95 induces cattle to elicit antibodies capable of not only recognizing bGH but also augmenting the somatogenic effectiveness of bGH in hypox rats.     

Injection of detergent-denatured ovalbumin primes murine class I-restricted cytotoxic T cells in vivo

Complex adjuvant formulations have been used to introduce soluble protein antigens into the "endogenous" processing pathway and hence to elicit specific, major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) responses. We tested if simple modifications of a model protein antigen, i.e. ovalbumin (OVA), can render it immunogenic for murine class I-restricted CTL when injected into mice in soluble form. Injection of 1-100 micrograms native OVA into C57BL/6 (H-2b) mice did not stimulate a class I-restricted CTL response. In contrast, immunization of mice with 0.5 to 10 micrograms sodium dodecyl sulfate (SDS)- or deoxycholate (DOC)-denatured OVA efficiently primed CD8+ CTL specific for the well-characterized Kb-restricted OVA257-264 epitope. Gel-purified SDS-denatured OVA devoid of protein fragments and excess detergent efficiently stimulated a specific CTL response in vivo. OVA preparations denatured by heat or urea treatment were not immunogenic for murine CTL. Injection of non-treated or detergent-treated, antigenic OVA257-264 peptide into mice did not elicit a CTL response. Thus, denaturation of OVA by simple detergents such as SDS or DOC dramatically enhances its immunogenicity for class I-restricted CTL but not all modes of denaturation are equally effective.     

Abattoir survey of congenital reproductive abnormalities in ewes

A survey of abnormalities of the reproductive tract of female sheep was undertaken at two abattoirs in the south west of England over a period of 12 months. During the survey, 9970 reproductive tracts from cull ewes and 23,536 tracts from nulliparous sheep (prime lambs and hoggets) were examined. A total of 655 (6.57 per cent) ewes and 459 (1.95 per cent) nulliparous sheep had abnormalities of the reproductive tract. Of these, congenital abnormalities of the paramesonephric ducts accounted for 2.4 per cent of the ewes and 7.4 per cent of the nulliparous sheep, congenital abnormalities of the ovaries accounted for 2.6 per cent of the ewes and 7.4 per cent of the nulliparous sheep and cystic structures that were considered to have been of congenital origin accounted for 27.2 per cent of the ewes and 52.7 per cent of the nulliparous sheep. The most common lesion was paraovarian cysts (26.6 per cent of ewes and 39.0 per cent of nulliparous sheep), but few of these appeared to have affected the sheep's reproductive function. Several specific conditions were recorded, including some described for the first time in sheep. Uterus unicornis occurred in 20 sheep and other forms of segmental aplasia of parts of the paramesonephric ducts occurred in a further 13 animals. Uterus didelphys occurred in six sheep, and 11 animals were intersex. Intersex sheep had vestigial structures that were derived from the paramesonephric ducts, hypoplastic or masculinised gonads and some had masculinised external genitalia. Ovarian hypoplasia occurred in 34 sheep, and in a further 12 mainly nulliparous animals, the ovaries were fused. Sixty nulliparous animals and two ewes had hydatids of Morgagni.     

Conformation and DNA binding properties of a single-stranded DNA binding region of sigma 70 subunit from Escherichia coli RNA polymerase are modulated by an interaction with the core enzyme

We have explored how IL-15 influences Th1 or Th2 type immune response in vivo. Intraperitoneal application of an IL-15-IgG2b fusion protein (FP) to mice did neither significantly affect the footpad swelling nor the production of hemagglutinizing antibodies in a delayed type hypersensitivity reaction to sheep red blood cells. In contrast, in an established murine Th2 model of sensitization to ovalbumin (OVA), IL-15-IgG2b FP plus OVA sensitization resulted in massively accelerated and enhanced allergen-specific IgE and IgG1 antibody production. In vitro, stimulation of spleen cells from OVA-sensitized mice with OVA+IL-15 or OVA+IL-15-IgG2b resulted in a significantly enhanced IgE production. IL-4 secretion was significantly induced by IL-15 but not by IL-15-IgG2b. An IL-2-IgG2b FP with the same Fc tail as the IL-15-IgG2b FP was used as control in both models. In striking contrast to the IL-15-IgG2b FP, IL-2-IgG2b significantly inhibited the Th2 type antibody production in vivo. The current study suggests that IL-15-IgG2b may be employed as a potent accelerator and enhancer of Th2 type immune responses in vivo, while IL-2-IgG2b can suppress the latter.     

Survival of long-lived plasma cells is independent of antigen

Recent studies have shown that persistent specific antibody titer is provided by long-lived plasma cells (PC) which constitute a new kind of 'memory-providing cells'. In the present study, we examine the role of antigen for the long-term survival of PC and the maintenance of specific serum antibody titers. Using a novel cytometric technology, to identify and isolate antigen-specific PC, we analyzed long-lived PC of BALB/c mice, during their development (between day 1 and 10) after secondary immunization with ovalbumin (OVA) and in the phase of the established immune reaction. Most if not all OVA-specific PC were generated within a few days after immunization. Within approximately 3 weeks, they matured, as indicated by down-regulation of expression of MHC class II. These PC are long lived and located in spleen and bone marrow. Upon adoptive transfer, OVA-specific PC from bone marrow, but not memory B cells, conferred specific and long-lasting antibody titers to antigen-free IgH syngeneic recipients. In response to antigenic challenge, new OVA-specific antibody-secreting cells were generated from transferred memory B cells. Antibody secretion by long-lived PC was not affected. Our results confirm that persistent antibody titers are provided by long-lived PC, independent of memory B cells and demonstrate that this humoral memory is inert to antigen.     

The muramyl dipeptide analog GMTP-N-DPG preferentially induces cellular immunity to soluble antigens

GMTP-N-DPG (N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamyl- L-alanyl-dipalmitoylpropylamide) is a lipophilic derivative of the immunologically active compound MDP and has adjuvant properties. GMTP-N-DPG was compared with other adjuvants in model vaccine systems using ovalbumin (OVA) and a synthetic peptide derived from pp89 of murine cytomegalovirus as antigens. When serum from C57/Bl mice immunized with OVA was tested for the presence of anti-OVA antibody, samples from mice immunized with OVA plus GMTP-N-DPG had ELISA optical density (O.D.) readings twice as high as those from mice immunized with antigen alone. In contrast, samples from mice immunized with the liposomal monophosphoryl lipid A (MPL) formulation exhibited ELISA O.D. readings tenfold higher than samples from mice immunized with antigen alone. Relative levels of specific antibody in serum samples from mice immunized with OVA plus the saponin adjuvant QS-21 were equal to the GMTP-N-DPG samples. When spleen cells from immunized mice were tested for their proliferative response to OVA, we found that liposomal MPL was again the optimal adjuvant, whereas the proliferative responses of cells from mice immunized with GMTP-N-DPG or QS-21 were no better than cells from mice immunized with OVA alone. In contrast to the relatively low antibody and proliferation levels, spleen cells from mice immunized with GMTP-N-DPG and OVA demonstrated the highest level of anti-OVA CTL activity. Spleen cells from mice immunized with the pp89 peptide plus GMTP-N-DPG also exhibited CTL activity. Using antibody and complement mediated cytotoxicity it was determined that the CTL were CD8+. Based on these results, we believe that GMTP-N-DPG may be an excellent candidate adjuvant in vaccines for diseases in which a strong cell-mediated response is desired.     

A comparison of natural and recombinant cholera toxin B subunit as stimulatory factors in intranasal immunization

Cholera toxin B (CTB) is often envisaged and used as an immune stimulating agent in protocols for mucosal immunization. However, the nature of the CTB used (natural vs recombinant) is frequently not taken in consideration. This is important since the usage of natural CTB in mucosal immunization regimen and the mucosal response resulting from such an immunization can be effected by the presence of the CTA subunit in commercial CTB preparations. To clarify this, we have compared natural vs recombinant CTB in an intranasal (i.n.) mucosal immunization procedure using ovalbumin (OVA) as antigen. The results show that recombinant CTB induces similar immune responses like natural CTB. Furthermore, our experiments show that covalent coupling of OVA to CTB is not required for the induction of OVA specific mucosal and systemic immune responses upon i.n. immunization.     

Detection of specific and 'constitutive' antibody secreting cells in the gills, head kidney and peripheral blood leucocytes of dab (Limanda limanda)

The relative immunological importance of the gills of fish was investigated in terms of antibody production by enumerating antibody secreting cells (ASC) in the gills, head kidney and blood of dab (Limanda limanda) using the ELISPOT assay. The contribution of 'constitutive' ASC in the gill appeared more substantial than that of elicited specific ASC. The gills were found to contain a mean (+/- SD) of 4227 +/- 1029 'constitutive' ASC/10(6) cells which was fewer than the head kidney which contained a mean (+/- SD) of 15617 +/- 3723 'constitutive' ASC/10(6) cells but more than peripheral blood leucocytes which contained a mean (+/- SD) of 2650 +/- 212 'constitutive' ASC/10(6) cells. The number of specific anti-human gamma globulin (HGG) ASC following parenteral or oral administration of HGG was also determined. Anti-HGG ASC were detected in all three tissues following parenteral immunization, peaking simultaneously, 4 weeks post-immunization. The strongest response was found in the head kidney. After oral immunization, responses were much weaker: again the head kidney was the most active but the gill response was barely detectable. These data were complemented by measurement of specific antibody in the serum by ELISA. Serum antibody titres following immunization were found to correlate closely with the number of specific ASC in the head kidney following parenteral immunization whereas serum antibody titres after oral administration of antigen most closely followed the number of specific ASC in the blood. In the light of these data it is suggested that the primary immunological role of the leucocytes in the gill may be in the earliest stages of defence against infection.     

Conditioned suppression of humoral immunity in the rat.

180 Charles River rats were conditioned by pairing consumption of a novel sodium saccharin drinking solution with the effects of an ip injection of 75 mg/kg cyclophosphamide, an immunosuppressive drug. Five and 10 days after conditioning, an experimental group (Group CS) was reexposed to the saccharin drinking solution. Control Ss (Group CSo) were conditioned but were not reexposed to saccharin. On Days 10, 15, or 25 after conditioning, Ss were injected ip with sheep erythrocytes, and independent subgroups were sampled for hemagglutinating antibody titer 4, 6, or 8 days later. Antibody titers 4 days after immunization were lower than values observed 6 and 8 days after immunization, and CS Ss had an attenuated antibody response. There were no significant differences between Group CSo and a group of placebo-treated Ss, but CS Ss had lower antibody titers than placebo-treated animals 4, 6, and 8 days after antigenic stimulation. Results suggest that reexposure to a CS may have long-lasting effects, and provide further documentation of conditioned immunopharmacologic effects and the impact of behavioral factors in modifying immunologic reactivity. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of cellular location of expressed antigen on the efficacy of DNA vaccination: cytotoxic T lymphocyte and antibody responses are suboptimal when antigen is cytoplasmic after intramuscular DNA immunization

We examined the role of the cellular localization of antigen on the immune response after DNA immunization of mice with three forms of ovalbumin (OVA). DNA encoding OVA which was secreted (sOVA) generated 10- to 100-fold higher IgG responses with 50-and 100-fold higher levels of IgG1 than the cytoplasmic (cOVA) or membrane bound (mOVA) forms. An IgG2a predominance was seen only in cOVA and mOVA immunized mice. Although the antibody response was CD4+ T cell dependent, the differences in the antibody response could not be compensated for by provision of excess CD4+ T cell help in TCR transgenic mice. Together with our hapten-carrier studies, this would indicate that membrane or intracellular localization limits the availability of antigen for B cell priming which affects the magnitude and form of the antibody response. Surprisingly, stronger cytotoxic T lymphocyte (CTL) responses were generated for sOVA or mOVA than for cOVA via intramuscular (i.m.) injection. Since a cytoplasmic antigen should have best access to the canonical class I pathway for antigen presentation, our results indicate that priming of CTL responses after i.m. DNA immunization is probably by cross-presentation of antigen by non-transfected professional antigen-presenting cells. In contrast, intradermal immunization with cOVA produced optimal CTL responses but, as with mOVA, suboptimal antibody responses. This, together with our ex vivo RT-PCR analysis showing similar mRNA levels from all three constructs 7 days post-immunization, argues against the differential CTL response for i.m. injection to be due to dose.     

Intranasal immunization with CTL epitope peptides from HIV-1 or ovalbumin and the mucosal adjuvant cholera toxin induces peptide-specific CTLs and protection against tumor development in vivo

To evaluate the ability of mucosal immunization protocols using peptide immunogens to induce CTL responses, BALB/c and C57BL/6 mice were immunized intranasally (i.n.) with peptides corresponding to a known CTL epitope in HIV-1 glycoprotein 120 or OVA, respectively, and the mucosal adjuvant cholera toxin (CT). Intranasal immunization of BALB/c mice with a 10- or 15-amino acid peptide corresponding to a CTL determinant in HIV-1 glycoprotein 120 and CT induced peptide-specific CTLs in spleen cells that persisted through 35 days after the last immunization. Intranasal immunization of C57BL/6 mice with the octameric OVA peptide and CT produced similar results with detectable peptide-specific CTL in both the cervical lymph node and spleen. To test whether CTL induced by i.n. immunization with OVA peptide and CT were functional in vivo, groups of C57BL/6 mice were injected with E.G7-OVA tumor cells that express the OVA protein and monitored for tumor growth. Animals immunized i.n. with OVA and CT were protected against tumor development as efficiently as animals immunized by the potent CTL induction protocol of i.v. injection with OVA-pulsed dendritic cells. Intranasal immunization with peptides corresponding to known CTL epitopes and CT provides a noninvasive route of immunization for the induction of CTL responses in vivo.     

The roles of apoptosis in lung injury and fibrosis

The effect of recombinant porcine interferon-gamma (IFN-gamma) on the immunogenicity in vivo of inactivated suid herpesvirus-1 (SHV-1, Phylaxia strain) was studied applying two successive i.m. immunizations. The animals were injected with inactivated virus alone or inactivated virus supplemented with 10(4) or 10(6) U IFN-gamma. After the first immunization, none of the animals responded with measurable virus-neutralizing antibody (VNAb), virus-specific IgG or IgA. Following a second immunization 4 weeks later, a significantly increased VNAb response was noted in animals that had received vaccine doses containing 10(4) U IFN-gamma (p < 0.05). These animals also had significantly augmented serum levels of IgG (p < 0.01) and IgA (p < 0.05). Inclusion of 10(6) U IFN-gamma in the vaccine preparation did not affect the antibody response. In one experiment, the pigs were challenged oronasally with 10(5) TCID50 of the 75V19 strain of SHV-1, 7 weeks after administration of the second vaccine dose. Those that had received 10(4) U IFN-gamma in the vaccination developed less fever during the postchallenge period (p < 0.004). In all challenged pigs, growth performance was compromised during the first week after challenge. However, the only animals retaining an average net increase in body mass were those covaccinated with 10(4) U IFN-gamma (p < 0.05). Nasal excretion of virus was not significantly different between groups that had been vaccinated with or without IFN-gamma. Multiple linear regression analysis of variables from individual vaccinated animals revealed the VNAb response to be correlated with serum IgG levels (p < 0.025) and with postchallenge growth performance (p < 0.0001) but not with serum IgA levels (p > 0.5). On the other hand, serum IgA appeared to be inversely correlated with early nasal virus excretion after challenge (p < 0.006). Taken together, our data suggest that addition of IFN-gamma to inactivated SHV-1 vaccine may be a useful tool for enhancement of both mucosal and systemic immune responses in pigs.     

Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin

The present study investigated bystander suppression, specific suppression and anergy as mechanisms for oral tolerance. Oral tolerance was induced in mice by a single gastric intubation of 20 mg ovalbumin (OVA) and was evaluated in vitro by the absence of T lymphocyte proliferative responses to OVA after priming by OVA-complete Freund's adjuvant (CFA). T lymphocyte unresponsiveness was antigen specific, systemic and was not affected by the vehicle used for immunization. T lymphocytes derived from tolerant popliteal lymph nodes (PLN) responded to an acetone precipitate (AP) of mycobacteria present in CFA; this response was not suppressed by co-culture with OVA, thereby arguing against a mechanism of bystander suppression in our system. Responses of PLN T lymphocytes derived from OVA-CFA primed, non-tolerant mice, or those of an OVA-specific T lymphocyte line, were not suppressed by PLN or spleen cells derived from OVA tolerant mice. These results excluded the possibility that oral tolerance was induced and maintained by a mechanism of specific suppression. At the cellular level, we found that OVA-tolerant T lymphocytes did not produce interleukin-2 (IL-2) nor express IL-2 receptor in response to OVA stimulation in vitro; both observations are indicative of a state of anergy. Incubation of OVA-tolerant PLN T lymphocytes together with murine recombinant IL-2 for 5 days, released anergic T lymphocytes and a concomitant OVA-specific proliferative response of CD4+ T cells was detected. Taken together, our experimental system excludes the involvement of bystander or specific suppression in the induction of oral tolerance to OVA, and provides direct evidence to show that oral tolerance results from specific T lymphocyte anergy.     

Perinatal hypoxia suppresses immune response of adult rats

We tested the effect of perinatal (one week prenatal and one week postnatal) normobaric hypoxia on the immune response of rats in their 9th week of life. We found that perinatally hypoxic rats produced less serum antibodies after sequential immunization with ovalbumin and sheep red blood cells. Also phagocytosis of HEMA microparticles by neutrophil leukocytes from perinatally hypoxic rats was depressed as well as the oxidative burst of their peritoneal macrophages and neutrophils. These results demonstrate that perinatal hypoxia has an important effect on the immune system of the rat.     

Pituitary and plasma levels of growth hormone in Booroola sheep that are either homozygous carriers or non-carriers of the FecBB fecundity gene

The aim of this study was to examine the effect of the FecBB fecundity gene on plasma concentrations and pituitary content of growth hormone (GH) in sheep. No differences were found between homozygous carriers (BB) and non carriers (++) of the FecBB gene with regard to pituitary GH contents in both ovariectomized and intact ewes. However, ovariectomized ewes had higher levels of pituitary GH than intact ewes (P < 0.01). There were no differences between FecBB genotypes with respect to plasma concentrations of GH in 6-year-old ovariectomized ewes bled every 10 min for 12 h or in ram lambs bled weekly during their first year of life. GH levels in the rams decreased until week 27, increased to a peak at week 31 then decreased before increasing again at week 43. Mean plasma GH concentrations in the ewe lambs bled weekly for a year decreased until week 19 then remained at approximately this level for the remainder of the year. Mean GH plasma concentrations in the ram lambs were higher than in the ewe lambs (P < 0.001). Ewe lambs that were homozygous for the FecBB gene had lower body weights (P < 0.05) and had higher levels of GH (P < 0.01) than non carrier ewe lambs during their first year. Before the average age of first behavioural oestrus (36 weeks) GH levels in the ewe lambs were negatively correlated with body weights (r = -0.69, P < 0.001, n = 22). When body weight was included as a covariate in analysis of variance the genotype difference in ewe lamb plasma GH concentrations was no longer significant.(ABSTRACT TRUNCATED AT 250 WORDS)