锌对小鼠免疫功能的影响

每天给小鼠0.2 mg 锌灌胃,连续15d,明显提高外周血 T 淋巴细胞百分率,促进 T淋巴细胞转化功能及迟发型超敏反应;对腹腔巨噬细胞吞噬功能有抑制作用、对 IgM 抗体生成及胸腺重量无明显影响。胸腺组织结构在光镜下未见明显变化,但在电镜下可见皮质淋巴细胞核形态有不规则变形。这些结果表明:一定剂量的锌对细胞免疫虽有促进作用,但对巨噬细胞吞噬功能有抑制作用,对胸腺淋巴细胞有潜在的损伤。     

妊娠期甲状腺疾病诊断及治疗的研究进展

妊娠期妇女体内激素水平会发生变化,使妊娠妇女甲状腺激素水平的测定和判断存在一定的困难,应选择适用于妊娠妇女的甲状腺激素水平特异值,进而正确评估甲状腺功能状态及对母体和胎儿的影响。孕前及妊娠期测定促甲状腺素和游离甲状腺激素有很大的必要性,因为甲状腺疾病以及单纯性甲状腺抗体阳性会导致多种妊娠不良结局,尤其是甲状腺功能减退对胎儿智力发育和认知功能具有非常大的影响。孕期甲状腺激素的监测对评估甲状腺功能状态及疾病预后具有非常大的作用,可以提示临床医师是否给予药物干预及如何调整药量。对于孕期甲状腺激素补充治疗后应达到的目标值以及甲状腺抗体阴性的亚临床甲状腺功能降低的妊娠患者是否给予干预,目前仍有异议。     

海蛇乙醇浸出物对小鼠免疫系统的影响

目的 探讨海蛇乙醇浸出物（AEBFSS）在小鼠体内、体外对免疫系统的影响。方法 体外试验：采用AEBFSS与小鼠脾细胞共孵育72h,测定T、B淋巴细胞转化功能;体内试验：采用每天灌胃给予小鼠1次AEBFSS,共6天。测定脾脏中T淋巴细胞转化功能和溶血素抗体生成水平。结果 在体外条件下低浓度AEBFSS促进T、B淋巴细胞增殖,高浓度时则作用相反;在体内条件下低浓度AEBFSS能增加B细胞生成溶血素抗体,对T细胞增殖无明显影响,高浓度则抑制T、B细胞功能。结论 AEBFSS对小鼠免疫系统有一定的双向调节作用。     

驱虫斑鸠菊注射液治疗白癜风的作用机制研究

探讨驱虫斑鸠菊(VW)注射液治疗白癜风的作用机制。进行以下实验探讨VW对小鼠免疫功能的影响:淋巴细胞转化试验测定小鼠脾T、B细胞增殖活性;脾细胞介导羊红细胞定量溶血分光光度法测定B细胞生成抗体活性,流式细胞法测定B细胞上CD19表达活性;迟发型超敏反应(DTH)试验测定T细胞活性、眼3H演-TdR掺入法测定T细胞分泌IL-2活性等。用酶学方法研究VW对小鼠体内酪氨酸酶的作用。用半定量逆转录聚合酶链反应技术检测酪氨酸酶基因表达活性。结果表明,VW可以明显抑制小鼠体内T、B细胞的增殖反应(P<0.01);对绵羊红细胞(SRBC)诱导的正常小鼠脾脏抗体形成细胞活性、CD19B细胞亚类表达、小鼠DTH反应和T细胞分泌IL-2活性也具有明显的抑制作用,这些抑制作用与药物浓度有一定的剂量效应关系。VW还可以提高小鼠血清酪氨酸酶活性,增强酪氨酸酶基因的表达。以上结果说明,VW可抑制小鼠免疫功能,可以从转录水平增强酪氨酸酶活性,进而促进黑素合成。     

玛咖醇提物对正常小鼠免疫功能的影响

本文采用小鼠碳粒廓清、植物血凝素(PHA)诱导淋巴细胞转化,以及血清溶血素和抗体生成细胞测定等实验,研究南美植物玛咖的乙醇提取物对正常小鼠免疫功能的影响。结果表明,玛咖醇提物显著提高PHA诱导的淋巴细胞转化,促进血清溶血素生成,并增加抗体生成细胞的产生,而对单核巨噬细胞的吞噬功能无显著影响。因此,玛咖醇提取物可提高正常小鼠细胞和体液免疫功能,增强机体抵抗力。     

鼠疫F1抗原和V抗原双组分候选疫苗的免疫学评价

目的通过由提取的鼠疫F1抗原和重组鼠疫V(rV)抗原组成的鼠疫候选疫苗免疫豚鼠,对其免疫效果进行评价。方法将豚鼠随机分成5个试验组,在免疫后不同时间点采血进行抗体检测、MTT法淋巴细胞增殖试验以及皮肤迟发型超敏反应(DTH)检测。结果抗体检测结果显示,双组分鼠疫候选疫苗能诱导较强的体液免疫应答;MTT细胞增殖结果显示,脾脏淋巴细胞特异性增殖不明显;中剂量组、高剂量组针对F1和rV抗原DTH阳转率均为100%。结论双组分鼠疫候选疫苗能诱导豚鼠体液免疫和细胞免疫应答,该疫苗有希望成为我国新一代鼠疫疫苗。     

锌对环磷酰胺所致小鼠免疫功能低下的拮抗作用

本文研究了在环磷酰胺导致免疫功能低下时补锌对小鼠免疫功能及胸腺结构的影响,并与正常时补锌的作用进行了比较。结果表明:给小鼠每天以0.2mg锌灌胃,连续给药25d,对正常鼠外周血白细胞数量、IgM抗体生成及胸腺重量无明显影响,却可明显对抗环磷酰胺导致的白细胞数量减少、外周血T淋巴细胞百分率升高、IgM抗体生成下降及胸腺重量降低。光镜和电镜观察表明,锌对环磷酰胺导致的胸腺退化有明显的保护作用。     

免疫诊断细胞方法(续九)

<正>七、淋巴活性因子和胸腺刺激素分离制备和检查 原理 淋巴细胞体外培养受到刺激后,上清液出现生物活性因子(淋巴因子),这种因子通常认为是迟发型超敏反应的介质可作为淋巴细胞刺激原的,有可使淋巴细胞致敏的特异性抗原或非异性致有丝分裂原。被致敏的淋巴细胞在该抗原作用下可分泌淋巴因子。     

不同近交系小鼠迟发型超敏反应的差异

<正>—、小鼠迟发型超敏反应的特征 迟发型超敏反应中包括结核菌素超敏反应,Jones-Mote型皮内过敏反应和接触性过敏症等。典型迟发型反应的特征,第一是反应出现缓慢,经24～48日小时达最高峰。向     

眼镜蛇毒注射液对免疫功能的影响

本文报告眼镜蛇毒注射液可提高动物的免疫功能,使动物免疫器官重量增加,而可的松则使免疫器官减轻;可使动物的血清溶血素水平上升（Ｐ＜０．００１）;还可明显提高小鼠网状内皮细胞的吞噬功能（Ｐ＜０．０５,Ｐ＜０．０１,Ｐ＜０．００１）;明显抑制小鼠的迟发型超敏反应。     

Immunogenicity of lysozyme derivatives lipid-conjugated to various degrees in mice treated with and without cyclophosphamide: dissociation of delayed-type hypersensitivity and helper function.

Lysozyme and a series of its lipid-conjugated derivatives without adjuvant were examined in mice for their abilities to induce delayed-type hypersensitivity (DTH), helper T-cell activity, and antibody formation. In addition, the effect of cyclophosphamide (CY) on the immune responses was assessed in mice immunized with these lysozyme derivatives. Precipitated lysozyme without lipid conjugation was a good inducer of both antibody and DTH responses. Lipid conjugation to lysozyme to intermediate degrees readily caused the failure only in inducing the antibody response. As lysozyme was lipid-conjugated more heavily, DTH response was also reduced and finally abolished. In contrast, the helper activity was little affected by any degree of lipid conjugation. These results indicate that the helper T-cell activity was dissociated from the both DTH response and the antibody production. CY pretreatment extensively enhanced DTH response induced by such lipid-conjugated derivatives that failed to induce antibody response. Furthermore, CY pretreatment in doses in a wide range enhanced not only DTH response but also antibody formation. It is, therefore, concluded that the enhancement of DTH response by CY does not necessarily entail suppression of antibody formation.     

Deterioration of cellular immunity during aging. The relationship between age-dependent impairment of delayed-type hypersensitivity reactivity, interleukin-2 production capacity, and frequency of Thy-1+,Lyt-2- cells in C57BL/Ka and CBA/Rij mice

The effect of aging on the delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in vivo and the interleukin-2 (IL-2) production capacity in vitro by spleen cells from young (17 weeks) and old (125 weeks) CBA/Rij and C57BL/Ka mice were investigated. For both CBA/Rij and C57BL/Ka mice an age-related decline in the DTH response to SRBC and the IL-2 production capacity was observed. Both parameters are mediated by Thy-1+,Lyt-2- spleen cells. For both mouse strains the proportion of Thy-1+,Lyt-2- spleen cells declined less strongly with aging than the DTH reactivity and the IL-2 production capacity. From this it was concluded that not only a quantitative but also a qualitative decrease of T-cell function occurs during senescence. It was also investigated whether the proportion of Thy-1+,Lyt-2- peripheral blood lymphocytes can be used as a predictive value with regard to the decline of DTH with aging of the corresponding mouse. This was indeed found to be the case in CBA/Rij mice, but not in C57BL mice.     

Regulation of anti-hapten antibody response by chemically modified carrier antigen preferentially provoking delayed-type hypersensitivity (DTH). II. DTH-reactivity and carrier-specific suppression of anti-DNP antibody response induced by priming with dodecanoyl-BSA are mediated by functionally distinct T cell subpopulations.

Experiments were carried out to determine whether or not the cell populations involved in DTH and in the suppression of antibody response are identical. The effects of four treatments, i.e., adult thymectomy (ATx), X-irradiation, anti-mouse thymocyte serum (ATS) and hydrocortisone (HC) on the induction of DTH and on the carrier-specific suppression of antibody response were observed in mice immunized with chemically modified antigen, dodecanoyl-BSA (d-BSA), emulsified with complete Freund's adjuvant (CFA), with the following results: 1) DTH induced by immunization with D -BSA remained constant in adult thymectomized mice, whereas the suppression of antibody response was not inducible in these animals. 2) Injection of low doses of ATS caused the depression of DTH in mice primed with D -BSA, but did not affect the suppressive activities of their spleen cells. 3) Sublethal X-irradiation 1 week prior to D -BSA priming inhibited the generation of suppressor cells but did not affect the generation of cells mediating DTH. The suppressive effect was also abrogated by sublethal X-irradiation given 2 days after immunization with DNP-BSA (14 days after priming with D -BSA). 4) The treatment of animals with HC 2 days before the footpad challenge or immunization with DNP-BSA depressed the ability of animals to induce both DTH and the suppression of antibody response. However, the latter was more sensitive to HC than the former. In addition to these results, it was also found that D -BSA-primed spleen cells were capable of suppressing anti-DNP response, but not of inducing DTH-reactivity upon transfer to recipient mice. These results suggest that DTH-reactivity and the carrier-specific suppression of anti-hapten antibody response induced by injection of D -BSA are mediated by different cell populations.     

Vaccination against cutaneous leishmaniasis in a murine model. I. Induction of protective immunity with a soluble extract of promastigotes

BALB/c mice can be protected against a fatal Leishmania major infection by immunization with whole radio-attenuated promastigotes; however, neither the antigens responsible for protection nor the protective immunologic mechanisms have been defined. In this study, the ability of promastigote fractions to elicit similar immunity to that obtained with whole organisms, and the immune responses associated with such protection were analyzed. Intraperitoneal immunization with a soluble, membrane-free parasite extract was found to induce protection against L. major challenge equal to that obtained with whole organisms. Induction of immunity (89% protection in seven experiments) was most effective with 100 micrograms of the soluble leishmanial antigen (SLA) and required concomitant injection of the bacterial adjuvant, Corynebacterium parvum (CP), followed by an i.p. boost of SLA alone 1 wk later. Vaccinated animals exhibited Leishmania-specific cell-mediated immunity, as assessed both by lymphocyte transformation and the production of macrophage-activating factors (MAF). In addition, although SLA + CP-immunized mice failed to exhibit delayed-type hypersensitivity (DTH) before challenge, splenic lymphocytes from these mice could transfer a local DTH reaction to naive recipients. Immunization also induced the production of antibodies against two major metabolically labeled proteins of m.w. 30,000 and 53,000, but failed to stimulate a detectable humoral response against promastigote surface antigens. Thus, these experiments demonstrate that vaccine-induced immunity against cutaneous leishmaniasis is strongly associated with the induction of cell-mediated immunity, but does not require the development of an antibody response to promastigote surface antigens. In addition, these studies establish the feasibility of employing soluble, nonmembrane-derived parasite material as a source of protective immunogens.     

Mycoplasma pulmonis depresses humoral and cell-mediated responses in mice

Humoral and cell-mediated immune responses to sheep red blood cells (SRBC) were studied in mice infected experimentally with Mycoplasma pulmonis. The hemagglutinating (HA) antibody against SRBC was evaluated at 0, 3, 5, 7, 14, 21 and 28 days postinfection (PI). Antibody tiers during all days PI were depressed significantly (p less than 0.05) in infected mice as compared to noninfected controls. The HA antibody, which is of the IgM class, peaks at day 5 PI. There is no shift in the kinetics of the humoral response in M. pulmonis infected mice. Cellular immune responses were evaluated by a delayed-type hypersensitivity (DTH) reaction and the lymphocyte transformation technique. Mice were sensitized at 0,3,5,7,14, 21 and 28 days PI with SRBC and challenged by footpad injection of SRBC 7 days later. The DTH reaction measured at 24 hours after challenge was depressed significantly (p less than 0.05) in all infected animals. After a transient enhancement on day 3 PI, the DTH responses remained depressed through day 28 PI. The lymphocyte transformation test showed a significantly (p less than 0.05) depressed response except on days 5 and 7 PI. These results indicate that M. pulmonis infection in mice suppresses the humoral antibody and cell-mediated immune responses.     

Effects of suramin on the immune responses to sheep red blood cells in mice. I. In vivo studies

The effect of Suramin on the cell-mediated delayed-type hypersensitivity (DTH) and the humoral immune responses elicited in mice by sheep erythrocytes was studied. The results show that administration of Suramin, at various times before or after antigenic sensitization, results in a profound inhibition of cell-mediated responses but has no adverse effect on antibody production. Suramin was particularly effective when given during the effector phase of DTH: mice which were treated with this drug, 4 days after immunization, at the time of skin testing, exhibit negative or low DTH responses compared to control mice. Evidence is presented that this short-term Suramin-induced suppressive effect on the expression of DTH is related to a defective recruitment, by sensitized T lymphocytes, of phagocytic cells at the site of the inflammatory reaction. In addition, when treatment with Suramin precedes by 8 days (Day -8) or by 1 hr sensitization with sheep erythrocytes for DTH, decreased DTH reactions over controls were observed. The inhibitory effect exerted by Suramin administered on Day -8 can be reversed by increasing the dose, from 10(6) to 10(8) sheep erythrocytes, of the sensitizing antigen. The possibility is discussed that, in this case, Suramin may interfere with the generation of DTH-mediating cells through a rapid degradation of antigen related to the Suramin-induced hyperplasia of the mononuclear phagocyte system. In contrast, DTH anergy in mice treated with Suramin 1 hr before sensitization is maintained regardless of the sensitizing antigen dose. Analysis of the sensitized lymphocyte population in these mice indicates that Suramin does not prevent the induction of DTH-mediating cells and suggests that the expression of these latter is inhibited by suppressive cells which are generated as a result of drug treatment.     

Requirement for a bacterial flora before mice generate cells capable of mediating the delayed hypersensitivity reaction to sheep red blood cells.

A delayed-type hypersensitivity (DTH) reaction can be elicited by an injection of 10(8) sheep red blood cells (SRBC) into a rear footpad of conventional (CV) mice previously immunized with small doses of SRBC. In contrast, immunization of germ-free (GF) mice with the same doses of SRBC produced no DTH when immunization was by the intravenous (i.v.) route, and only weak reactions when immunization was by the subcutaneous (footpad) route. Varying the immunizing dose of SRBC, or the time at which DTH was elicited, did not produce a state of DTH responsiveness in i.v. immunized GF mice. However, the transfer of lymphocytes from CV mice, immunized 4 to 5 days previously with SRBC, into GF mice, conferred on GF mice the capacity to express DTH. Although DTH was not readily demonstrable in GF mice immunized with SRBC, they nevertheless produced normal levels of hemagglutinating antibody to SRBC. Finally, it was shown that GF mice could generate a normal DTH response to SRBC if they were first monoassociated with a Gram-negative bacterial flora.     

IL-18 is redundant in T-cell responses and in joint inflammation in antigen-induced arthritis

IL-18 is an important cofactor in Th1 immune responses and it has additional roles in inflammation. Recent reports suggest the contribution of IL-18 to immune responses may vary between mouse strains and immune contexts. We investigated the contribution of IL-18 to T-cell activation and joint inflammation in Ag-induced arthritis (AIA) in C57Bl/6 mice. AIA and cutaneous delayed-type hypersensitivity (DTH) reactions were induced in wild-type (WT) and IL-18-/- C57Bl/6 mice, and Ag-specific T-cell proliferation and IFN-gamma and IL-4 production were measured. The humoral immune response was measured as serum antibody to the disease-initiating Ag, methylated BSA (mBSA). Splenocyte production of IL-6 was measured by ELISA. To confirm the dependence of this model on Th1-cell-mediated immunity, IL-12p40-/- mice were similarly studied. WT mice developed synovitis, joint effusion, cartilage destruction and bone damage associated with induction of DTH, and in vitro Ag-specific T-cell proliferation and IFN-gamma production. Unexpectedly, IL-18-/- mice developed AIA and indices of T-cell activation were similar to those of WT mice. In contrast, IL-12p40-/- mice did not develop AIA, DTH or T-cell activation. WT and IL-18-/- mice, but not IL-12p40-/- mice, developed significantly increased serum antibody to mBSA compared with naive controls. WT and IL-18-/- splenocytes produced high levels of IL-6, whereas IL-12p40-/- cells had significantly lower IL-6 production compared with both. In conclusion, IL-18 is redundant both as a Th1 response cofactor and inflammatory cytokine, whereas IL-12p40-/- is a key cytokine, in AIA in C57Bl/6 mice.     

Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. I. Preferential inhibition of the induction of delayed-type hypersensitivity

Culture supernatants of spleen cells from susceptible CBA mice chronically infected with Trypanosoma cruzi were able to inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens as measured by 24-hr footpad swelling, bone marrow homing, and radioactivity accumulation assays. The suppressive activity, which was also present in the serum of these chronically infected mice, appears to be specific for the induction of DTH and had no effect on the 3-hr immediate-type hypersensitivity. It also failed to modify the expression of DTH in presensitized mice. Furthermore, it did not affect the synthesis in normal recipients of specific antibody or the induction of helper T cells or cytotoxic T cells. It also failed to induce DTH tolerance as recipient mice with markedly reduced DTH were able to develop a normal DTH response after secondary immunization. The suppressive activity was produced by an Ig- macrophage-depleted splenic T cell population, whose capacity to secrete the suppressive substance was completely abrogated by treatment in vitro with anti-L3T4 antibody and complement, but not with anti-Lyt-2 antibody and complement. These results therefore demonstrate that L3T4+ T cells from mice chronically infected with T. cruzi can produce substances which interfere with the induction of DTH. This finding may help to identify the differential antigenic stimulatory requirement for the activation of the various subsets of T cells.     

Characterization and genetic control of the immune response to synthetic polypeptide antigens of defined geometry.

Both humoral and cell-mediated immune responses to the synthetic helical hapten-carrier conjugate poly-Glu-Tyr-Lys(TNP)-(Glu-Tyr-Ala)5 were found to be linked to the major histocompatibility locus in mice and guinea pigs. The responder mouse strains (H-2d haplotype) showed a primary IgM response with an IgG component appearing after the secondary immunization. The antibody response was accompanied by a positive DTH reaction in responder strains. Nonresponder mice (H-2b or H-2k haplotypes) showed neither IgM nor IgG antibodies and the DTH reaction was negative. Administration of the antigen as a complex with an immunogenic carrier was not effective in inducing a response in nonresponder mice. In guinea pig studies, it was found that strain 2 animals were able to mount an antibody response against the TNP-hapten and a DTH response against the polypeptide backbone. Strain 13 animals gave no anti-TNP antibodies at the lower dose levels and DTH activity was entirely negative for all doses of immunizing antigen. Replacement of the TNP hapten by the arsanilazo dipeptide derivative, BOC-gly-ARA-tyrosine, converted the nonresponder strain 13 guinea pigs into complete responders showing antibody and DTH reactions to both the hapten and the polypeptide backbone.