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1.
The antibody response to RGG of 8-wk old mice of various strains was assessed in terms of half-lives (T12) of lightly iodinated rabbit gamma globulin (131I-RGG) elimination. T12 was increased if the small aggregate content in 131I-RGG was reduced. The effect of aggregates was least in AKR, largest in Balb/c and SJL and intermediate in the majority of strains, typified by A mice. Differences between various strains, in the degree of tolerance to aggregate freed RGG (centrifuged at 123,000 g), were observed. The level of residual responsiveness was greatest in SJL mice. More profound tolerance could be induced with biofiltered RGG. Resistance of SJL mice to tolerance induction was also observed when human gamma globulin (HGG) and bovine serum albumin served as tolerogen. Tolerance to RGG and sheep red cells was induced in cyclophosphamide-treated SJL animals.  相似文献   

2.
The tolerance of low oxygen stress in insecticide-resistant and susceptible populations of mosquitofish (Gambusiaaffinis) was investigated. Dissolved oxygen was reduced chemically with formaldehyde and sodium sulfite treatment. Available oxygen was reduced physically through barriers, both by preventing oxygen exchange at the air-water interface and by preventing the fish from contacting the surface of the water. In all cases, the tolerance to low oxygen stress was reduced in the insecticide-resistant population compared to the susceptible population. The results indicate that although tolerance of pesticides in the resistant population has been dramatically increased by environmental selective pressures, tolerance to other stresses has not been concomitantly increased.  相似文献   

3.
The half-lives of elimination (T12) of 131I-RGG from the body of normal A or Balb/c animals was much longer than the T12 of SJL mice. At all ages, the T12 of normal hybrids (A × SJL, SJL × A, Balb/c × SJL) was similar to or longer than that of the A or Balb/c parents. Thus, in terms of the T12 of normal animals, the SJL responsiveness to 131I-RGG appeared to be a recessive trait. Tolerance could be induced in newborn animals and, in terms of T12, the degree of unresponsiveness at the age of 6 weeks, was the same in A, Balb/c, A × SJL, and Balb/c × SJL animals but was much shorter in SJL mice. Thus, in neonatally induced tolerance, the duration of tolerance was recessive for the SJL type. The average Tbuilt12 after tolerance induction in 3-week-old hybrids (A × SJL, SJL × A, Balb/c × SJL) was similar to that of the A or Balb/c parent, but by the 8th and 12th week it approached the average T12 of the SJL parent. Comparing 8-week-old hybrids, the average T12 was longest in A × SJL hybrids and identical in SJL × A and Balb/c × SJL mice. An examination of T12 distribution in various 8- and 12-week-old crosses and backcrosses revealed a fairly large proportion of individuals with a T12 which was intermediate between SJL and the other parent. There was a tendency for this number to decrease in 12 weeks as compared to 8-week-old mice. In 8-week-old mice, the number of animals with intermediate Tbuilt12 was smallest when SJL was the maternal animal [(SJL × A); SJL × (A × SJL); SJL × (SJL × A)]. There was no link between T12 of tolerant animals and either the immunoglobulin allotype (MuAl/MuA2) or the C5 eniotype (MuB1 positive/MuB1 negative).  相似文献   

4.
The effect of splenectomy on the induction of neonatal tolerance to histocompatibility antigens was studied. Newborn BN (Ag-B3Ag-B3) rats were splenectomized or sham splenectomized prior to transfer of a tolerance-inducing inoculum of Lewis/BN (Ag-B1Ag-B3) bone marrow cells. Twenty-two percent of the splenectomized animals were found to be highly tolerant of subsequent Lewis skin allografts, compared to 53.8% of the shamsplenectomized group. In addition seven of eight incompletely splenectomized animals were found to be highly tolerant. The relevance of these data to currently postulated mechanisms of classical neonatal tolerance induction is discussed.  相似文献   

5.
Antibody responses and host resistance to the tapeworm, Hymenolepis microstoma, were investigated using AKRJ and C3HeBFeJ strains of mice. AKR mice were significantly more resistant than controls to a secondary infection following exposure to a 3-, 21-, or 40-day primary infection. During a primary infection, intestinal anti-worm antibody responses measured by an enzyme-linked immunosorbent assay were elevated in the more resistant AKR strain, whereas serum antibody titers did not differ between the two strains. However, during a secondary infection, serum IgA titers were higher in AKR mice than C3H mice. Suppression of the serum IgA anti-worm response by oral administration of lipopolysaccharide also suppressed resistance to a secondary infection. Intraperitoneal immunization with worm antigen resulted in a minor degree of protection in AKR mice. This protection was associated with increased intestinal antibody titers compared to mice not demonstrating protection. These results suggest that the protective responses observed in AKR mice relative to C3H mice reflect differences in mucosal antibody responses to H. microstoma.  相似文献   

6.
The role of T cells in the development and expression of antigen-nonspecific immunosuppression in experimental African trypanosomiasis was addressed. Nude (nunu) C57BL/ 6 NIH mice and their thymus-bearing (nu+) littermates were infected with Trypanosoma rhodesiense and examined for suppression of splenic B-cell responses in vitro to the mitogen LPS. All animals developed splenic unresponsiveness to LPS. Further, both nu/nu and nu/ + infected mice displayed suppressor cell activity in their spleen cell populations upon transfer to normal uninfected mouse spleen cell cultures. On the basis of these findings we suggest that both the generalized immunosuppression and the development of suppressor cell activity in the spleens of mice infected with T. rhodesiense are T-independent processes.  相似文献   

7.
C57BL/6J-bgJbgbg mice are reported to be less susceptible to tumor induction by threshold doses of Moloney murine sarcoma virus than their +/bg littermates, and there are no significant differences between bgbg and +/bg mice in which tumors were induced with respect to tumor latency, size, and regression rate. The difference in tumor frequency cannot be accounted for by M-MSV boosting of activity in bgbg mice or by depression of activity in +/bg animals.  相似文献   

8.
The courses of infection in inbred mouse strains were compared following infection with three Stabilates of high, intermediate, and low virulence of Trypanosoma vivax stock Zaria Y486. Mouse strains could only be shown to differ in their resistance to T. vivax infections as judged by the height of the initial parasitemia and survival times when a trypanosome population of low or intermediate virulence was used. A T. vivax population of high virulence was uniformly lethal. Comparison of lytic antibody titers between groups of resistant (C57B16) and susceptible (Balbc) mice did not show any significant differences in titers of the surviving mice but the mice in either group which did not control the initial parasitemia had lower lytic antibody titers than those which did. A significantly larger number of Balbc mice failed to control the initial infection as compared to the C57B16. Treatment with cyclophosphamide did not ablate differences in susceptibility between the two strains. The use of congenic mice showed that these differences in susceptibility were not related to differences in the major histocompatibility complex between these strains.  相似文献   

9.
The specific activities of glutathione peroxidase and glutathione reductase, and the level of thiobarbituric acid-reactive products in muscles from chickens and mice with genetic muscular dystrophy were increased over those of control animals. These findings indicate the occurrence of lipid peroxidation and the activation of an invivo lipid peroxidation protective system in these dystrophic animals. A partial explanation for some of the metabolic changes that occur in dystrophic species is provided by this work.  相似文献   

10.
S R Snider  D Sahar  A L Prasad  S Fahn 《Life sciences》1977,20(6):1077-1085
In vitro studies have demonstrated that rat adrenal dopamine beta-hydroxylase activity is controlled by neural input and by glucocorticoid production. However, beta-hydroxylation of dopamine in vivo is a first-order reaction and may be considerably slower than the maximal rate determined by in vitro methods. To estimate the in vivo reaction rate the concentrations of dopamine (substrate) and of beta-hydroxylated catecholamine (product) were measured as a function of endogenous glucocorticoid production. Beta-hydroxylated catecholamine changed little but dopamine was increased 2-fold or more 17.5 h after the inhibition of steroidogenesis with metyrapone. Dopamine was also increased by metyrapone in animals with pre-existing adrenal denervation. ACTH 17.5 h before sacrifice caused only slight changes in normal rats but reduced the increase in dopamine caused by stress. The results indicate that adrenal dopamine concentration is inversely related to glucocorticoid production at a given level of neural input and provide in vivo evidence that glucocorticoids maintain dopamine beta-hydroxylase activity in the adrenal gland.  相似文献   

11.
Anne E. Goodbody  Paul Trayhurn 《BBA》1982,680(2):119-126
The properties and activity of brown adipose tissue have been investigated in suckling, pre-obese, obob mice in order to determine whether decreased thermogenesis in the tissue precedes the development of obesity in this mutant. At 14 days of age there was no difference between the obob and normal animals in the total amount of interscapular brown adipose tissue, and the DNA content, protein content, and cytochrome oxidase activity of the tissue were similar in the two groups of mice. Respiration rates of brown adipose tissue mitochondria in the presence of albumin were, however, greater in the normal than the obob animals, although after the addition of GDP to recouple the mitochondria there was no difference between the two groups. The mitochondrial membrane potential, measured with [3H]methyltriphenylphosphonium, was less affected by exogenous GDP in obob mice than in normal animals. GDP binding to brown adipose tissue mitochondria, an index of the proton conductance pathway, was much greater in normal than in obob mice at both 10 and 14 days of age; the decreased GDP binding in the mutant animals was found to result from a reduction in the number of binding sites. It is concluded that brown adipose tissue mitochondria of pre-obese obob mice are more tightly coupled than those of normal siblings, and that the activity of the ‘thermogenic’ proton conductance pathway is lower in the mutant animals. A decrease in thermogenesis in brown adipose tissue is therefore an early event in the development of the obob mouse and precedes the appearance of obesity.  相似文献   

12.
Appropriately immunized mice display a response that is biologically equivalent to rat rapid expulsion. Only two inbred strains (NFRN and NFSN derived from NIH Swiss mice) have been shown to respond in this manner. Mice of the Balbc, CBA, AHe, C3H, SJL, or C57Bl strains are “nonresponders” which require approximately twice as much intestinal exposure (in days) to Trichinella spiralis to elicit a response half as effective. Genetically, the responder is dominant, autosomal, and does not appear to be linked to the MHC. The characteristics of mouse and rat rapid expulsion of T. spiralis are not identical but share these features: initial rejection within 24 hr of challenge; a rejection efficiency >90%, from 1 to 5 weeks after the primary; induction of response does not require exposure to the complete infection; rapid expulsion is immunologically specific for preadults; adult worms are resistant. While a genetic basis for responsiveness exists in mice there is, as yet, no evidence for genetic control in rats. In both mice and rats, rapid expulsion is distinguished from the intestinal hyperreactivity associated with rejection of the primary infection by the kinetics and amplitude of the rejection of transplanted adult worms.  相似文献   

13.
Cardiac structures and functions change with advanced age, but the underlying mechanisms are not well understood. Autophagy and apoptosis play important roles in the process of cardiac remodeling. This study was designed to explore changes in cell autophagy and apoptosis during age-related left ventricular remodeling and to determine whether the mitogen-activated protein kinase (MAPK) pathway is an underlying mechanism. Eight 5-month-old (adult group) and eight 24-month-old male C57bl/6 mice (aged group) were studied. The heart mass index, left ventricular mass index and hydroxyproline content of both groups were compared. Western Blotting was used to quantitate the protein expression of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, caspase-3, B-cell leukemia-2 (Bcl-2) and MAPKs in the left ventricles of adult and aged mice. Our results showed that the heart mass index, left ventricular mass index and hydroxyproline content in the left ventricles of the aged mice were increased significantly compared with the adult mice, indicating that left ventricular remodeling occurs with aging. The expression of LC3 and Beclin-1 in the left ventricles of aged mice were decreased significantly compared to adult mice. Meanwhile, the level of myocardial caspase-3 in adult mice remained the same in aged mice, and the level of myocardial Bcl-2 increased significantly in aged mice. There were no differences in the expression level of myocardial extracellular signal-regulated kinase 1/2 (ERK1/2), activated/phospho-ERK1/2, c-Jun N-terminal kinase 1/2 (JNK1/2) and p38 between aged and adult mice. However, the expression of myocardial activated/phospho-JNK1/2 increased significantly in aged mice, while activated/phospho-p38 decreased significantly. These findings indicate that autophagy decreases without a concurrent change in apoptosis during age-related left ventricular remodeling in mice. The MAPK pathway may be involved in the regulation of age-related left ventricular remodeling by modulating autophagy.  相似文献   

14.
Both invitro and invivo, increased exposure to visible light decreases the regenerability of the visual pigment. Isolated opsin irradiated with increasing periods of white light decreased in pigment formation yields on combination with 9- or 11-cis retinal. The yield of regeneration of the visual pigment extracted from albino rats depended on the amount of light to which the animal had been exposed. Animals exposed to normal room light demonstrated lower regeneration yields than dark-reared animals, but these yields increased on dark adaption. Opsin from animals exposed to sunlamps did not regenerate any pigment. On dark adaption, the pigment yields increased but the opsin level remained below that for the control group.  相似文献   

15.
Abrogation of peripheral tolerance in transgenic mice that express a uniform B-cell receptor may create a powerful tool to examine the molecular mechanisms that underlie the autoimmune response in B cells. Here we report that processes that induce a systemic lupus erythematosus-like syndrome in normal mice, namely chronic graft vs host reaction, trigger systemic autoimmunity in a well-established transgenic mice model of B cell receptor peripheral tolerance. The induction of graft vs host reaction in mice that carry both a rearranged B cell Ag receptors specific for hen egg lysozyme and expressing chronically circulating hen egg lysozyme Ag resulted in induction of high and sustained levels of circulating anti-hen egg lysozyme autoantibodies and glomerulonephritis with proteinuria. This was associated with marked changes in expression of cell-surface proteins, such as CD23 and complement receptor 2. B cells from the graft vs host-induced mice could proliferate in vitro in response to self-Ag, and upon stimulation with anti-IgD demonstrated rapid phosphotyrosine phosphorylation of specific proteins, which could not be induced in the anergic double transgenic B cells. Conversely, loss of tolerance was not associated with a higher induction in the level of Syk kinase phosphorylation following stimulation with anti-IgD. Taken collectively, these data establish that 1) processes that induce a systemic lupus erythematosus-like syndrome in normal mice can abrogate peripheral tolerance in transgenic mice expressing self-tolerized B cells, and that 2) loss of tolerance in this model is associated with marked changes in surface expression of B cell coreceptors as well as with selective changes in IgD-induced signaling by discrete tyrosine-phosphoproteins, but not Syk kinase.  相似文献   

16.
Dose-response relations for pokeweed mitogen (PWM)-induced B- and T-cell proliferation and differentiation of human peripheral blood B lymphocytes were derived. For each tested concentration of PWM used in stimulating mononuclear cells, proliferation, assayed by cell population size and distribution of cells with respect to cell cycle phases; and differentiation, assayed by incidence of cytoplasmic immunoglobulin, were determined as a function of time following PWM stimulation. Balanced T- and non-T-cell proliferation occurred without necessarily being associated with B-cell differentiation. Differentiation, in contrast, was not observed without proliferation. The onset of balanced T- and non-T-cell proliferation preceded the differentiation of B lymphocytes into plasmacytoid cells bearing detectable cytoplasmic immunoglobulin. The dose-response relations for PWM-induced proliferation and differentiation were dissimilar. Optimum proliferation occurred at a PWM concentration 1100 of that required to induce differentiation. The results indicate that while B- and T-cell proliferation may be necessary for B-cell differentiation, it is not sufficient. Proliferation can be uncoupled from differentiation. The dissimilarity of the dose-response relations for the two responses makes it improbable that PWM triggers a unique cellular process seminal to proliferation coupled inevitably to subsequent differentiation.  相似文献   

17.
Animal models make it possible to perform studies that normally can not be done in human beings. In the present work, the cellular response pattern of the lungs both to the environment and to a challenger strain of bacteria were analyzed in two mouse mutations-cribriform degeneration (cri) and motheaten (me)-. The mice were submitted to an infective aerosol containing Staphylococcus aureus and were killed either immediately or 4 h after exposure; pulmonary washings were performed in these animals as well as in non-infected controls. The results showed neither quantitative differences in the total cell count nor in cell viability between the different groups. However, there were qualitative changes in the differential cell content characterized by a neutrophilic response in cri/cri mice and a giant cell response in me/me mice. Since most of the cystic fibrosis patients suffer from chronic lung infection, with a persistently high proportion of neutrophils, these findings point to the cri/cri mouse as a promising animal model for cystic fibrosis studies.  相似文献   

18.
Fructose 2,6-bisphosphate levels in freeze-clamped livers of C57BL6Jobob mice were 6-fold higher than the level in their lean (+/?) littermates. Overnight starvation reduced the hepatic level of this unique sugar diphosphate to 0.2 nmol/g in both the obese and lean mice. The elevated level in the obese mouse is consistent with the hyperinsulinemia of these animals.  相似文献   

19.
To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between VH gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-month-old, and 6-month-old mice. The experimental strategy provided that the hybridomas were monoclonal at initial evaluation, so the Ag binding and V gene frequencies of the entire population could be determined. Initially, 1032 Ig-producing hybridomas were evaluated for binding to six Ag; VH gene family use was determined in 119 anti-DNA and anti-rabbit thymus extract (RTE) antibodies (autoantibodies) and in 233 age-matched Ig that did not bind to any of the six Ag (nonbinders). Neonatal B cells, including cross-reactive IgM autoantibodies and nonbinder IgM, used relatively 3' VH genes. The majority of B cells in adult mice used VH genes of the J558 family. Although J558 use was significantly higher among the autoantibodies (anti-DNA and anti-RTE) than among the nonbinder Ig, this difference was due to a higher frequency of J558 use by 1-month-old mice. At 3 months, J558 use by the nonbinder Ig increased to the same frequency of J558 use as in the autoantibody population. J558 use in both groups of antibodies exceeded a previously reported estimation of J558 expression in the functional B cell repertoire of young adult MRL-lpr/lpr mice. Several subgroups of antibodies that share properties with pathogenic Ig, including IgG, cross-reactive Ig, and anti-dsDNA autoantibodies, demonstrated a marked preferential expression of the J558 family. These results suggest that there is an age-related bias in the activation of B cells using J558 VH genes in MRL-lpr/lpr mice that is under the influence of a selective force distinct from, or in addition to, an ssDNA or RTE auto-Ag-driven response.  相似文献   

20.
Membranes from mammary glands of mildly hypothyroid mice show a 70–85% reduction in prolactin binding while those from hyperthyroid mice bound 66% more prolactin compared to similar preparations from euthyroid animals. The prolactin binding data for mammary glands correlate well with the ability of the tissue from animals in various thyroid states to respond to prolactin invitro with increased lactose synthetase activity. Binding of prolactin to mammary membranes is enhanced when explants from mid-pregnant mice are cultured overnight in the presence of insulin, hydrocortisone and 10?9 M L-T3. This enhancement is not blocked by puromycin. These data suggest that thyroid hormones control the level of prolactin binding in mouse mammary tissue. This may be accomplished, at least in part, by activation of preexisting receptor molecules.  相似文献   

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