The effect of bacterial antigens on lymphocyte immune receptors in mice

It has been shown that the treatment of a suspension of lymphocytes obtained from spleens in mice by LPS S. sonnei as well as by exotoxins Cl. tetani and Cl. botulinum has led to a notable reduction in the number of luminescent cells by comparison with control samples. The action of tested remedies was found to increase with their concentration. These was complete correlation between these results and the data obtained by the immunity rosette formation method. A reliable reduction was also noted in the number of lymphocytes forming rosettes with the sheep erythrocytes. It has been inferred that the bacterial products tested possessed a marked capacity for blocking the immune receptors of lymphocytes.     

淋巴细胞糖皮质激素受体与免疫的相互关系

糖上质激素受体介导信号是免疫细胞发育分化,克隆选择,生存与死亡平衡调节的主要机制之一,对免疫功能既有抑制作用又有促进作用,其免疫调节作用具有组织或细胞特异性和浓度依赖性。免疫功能异常影响ＧＲ表达,ＧＲ异常也引起免疫功能改变,ＧＲ结构或功能异常是某些疾病发生的直接或间接原因。     

The effect of deoxyguanosine on human lymphocyte function. II. Analysis of the interference with B lymphocyte differentiation in vitro

The differentiation of normal human peripheral blood B lymphocytes into plasma cells in vitro, studied in mononuclear cells stimulated with PWM or in purified B cells stimulated with a T cell-replacing factor (TRF), can be inhibited by both deoxyguanosine (dGuo) and guanosine. The mechanism underlying this effect, which differs from the in vivo findings in PNP deficiency, was analyzed. dGuo toxicity can be antagonized by hypoxanthine but not by deoxycytidine. PNP-deficient and HGPRT-deficient B lymphocytes are not sensitive to the intoxicating properties of (deoxy)guanosine. Inhibition of PNP activity in normal B lymphocytes by 8-aminoguanosine decreases the sensitivity for dGuo intoxication. Incubation of purified B cells (stimulated with TRF) with dGuo leads to increased intracellular levels of guanosine di- and triphosphate (GDP and GTP), whereas deoxyguanosine triphosphate (dGTP) levels remain low. These observations lead to the conclusion that inhibition of B lymphocyte differentiation by dGuo is brought about by one of the end products of the pathway starting with degradation of dGuo by PNP, followed by guanine salvage by HGPRT, and possibly further phosphorylation of GMP into GDP and GTP. According to this mechanism, B lymphocyte differentiation in PNP deficiency is not sensitive to (deoxy)guanosine; because of the absence of PNP activity, these cells cannot accumulate GMP, GDP, and GTP, and therefore escape dGuo intoxication.     

板蓝根提取物对小鼠免疫功能的影响

目的 研究板蓝根提取物对小鼠免疫功能的影响.方法 称重法检测小鼠免疫器官指数,血球分析仪分析小鼠外周血免疫细胞数量,比浊法检测小鼠血清中溶菌酶含量,溶血空斑形成实验检测B淋巴细胞抗体形成.结果 板蓝根提取物能明显增加小鼠免疫器官指数,提高小鼠外周血中免疫细胞数量.与对照组相比,外周血中淋巴细胞和白细胞数量分别增加(8.4±1.42)％和(10.52±1.63)％,血清中溶菌酶含量增加(10.82±1.08)％,溶血空斑形成数量增加(13.9±1.3)个/107脾细胞.结论 板蓝根提取物可提高小鼠的体液免疫和细胞免疫等功能.     

The effect of low-dose irradiation on unstimulated and PHA-stimulated human lymphocyte subsets

A culture system was used to evaluate the radiosensitivity of CD4+ and CD8+ T cells, Leu 19+ cells, and B cells obtained from normal adult males. Unstimulated CD8+ lymphocytes (D0 = 55 cGy) were twice as radiosensitive as CD4+ cells (D0 = 115 cGy). B cells had an intermediate radiosensitivity (D0 = 100 cGy). Leu 19+ cells were much more radioresistant and expressed a D0 of 550 cGy. When lymphoid cells were irradiated 1 or 4 days before phytohemagglutinin (PHA) stimulation, they were more radiosensitive than if they were first stimulated with PHA and then irradiated. When lymphoid cells were irradiated 1 h after PHA stimulation each lymphocyte subset was characterized by an increase in the D0 to 150 cGy for B cells to 290 cGy for CD4+ cells, and to 240 cGy for CD8+ cells. In contrast, Leu 19+ cells exhibited a decrease in their D0 to 290 cGy after they were stimulated by PHA.     

The effect of rivanol on the immune globulins of human colostrum

The behavior of immune globulins of colostrum was investigated during fractionation using rivanol and ethanol. It was found that, in contrast with serum immune globulins, a part of these proteins present in colostrum is precipitable with rivanol. It was also observed that the fraction of colostrum immune globulins which yields a heavy precipitation line in the cathode region of the immunoelectrophoreogram precipitated with normal antihuman serum, represents a heterogeneous mixture of proteins, from the point of view both of their electrophoretic mobility and of interaction with rivanol and solubility in dilute ethanol. We are dealing here with at least three types of protein molecules which all display identical antigen relationship to serum γ-and β_2A-globulins. No differences were found between serum β_2M-globulin and the colostrum protein of similar properties.     

传代人淋巴细胞免疫猪的免疫效果初探

目的用传代人淋巴细胞替代人T淋巴细胞进行猪的免疫,用于试制抗人T细胞猪免疫球蛋白(anti-human T lymphocyte porcine immunoglobulin,P-ATG)免疫猪血浆,并评价其免疫效果。方法大量培养传代人淋巴细胞至免疫所需浓度及数量,采用常规猪免疫程序进行2次基础免疫及1次加强免疫,获得免疫猪血浆,用E玫瑰花环形成抑制试验和淋巴细胞毒试验进行效价检测。结果 3批免疫猪血浆的E玫瑰花环形成抑制试验结果均达到1∶1 000(花环形成率均小于对照组平均花环形成率的75%),淋巴细胞毒试验结果均达到1∶500(淋巴细胞死亡率均大于20%),效价均达到《中华人民共和国药典》2015版(三部)中生产用免疫猪血浆的效价标准。结论传代人淋巴细胞可作为人T淋巴细胞的替代免疫原进行猪的免疫,获得了效价合格的免疫猪血浆,用于P-ATG的制备。     

The effect of levamisole on human lymphocyte mediator production in vitro

Levamisole has previously been demonstrated to increase delayed hypersensitivity reactions in anergic patients. In order to elucidate the mechanism by which levamisole stimulates the immune response in vivo, we have studied the effect of this substance on both human lymphocyte proliferation and lymphocyte-mediator production in vitro. Our results indicate that in vitro levamisole augments the production of soluble mediators by mitogen-stimulated lymphocytes, while having no effect on lymphocyte proliferation.     

Inhibition of human lymphocyte function by organic solvents

We studied the direct effect of reactive hydroxyl precursors and inhibitors on CD4+ T-cell function. We used hydrogen peroxide plus ferrous chloride as the hydroxyl radical-generating system and di-methyl sulphourea, di-methyl sulfoxide, pyrrolidine dithiocarbonate, methanol, and ethanol, at a noncytotoxic concentration, as inhibitors. The immune parameter studies were proliferation and interleukin-2 production by peripheral blood lymphocytes stimulated with anti-CD3 antibody, phytohemagglutinin and alloantigens; proliferation, interleukin-2 production and mRNA expression of interleukin-4 and interferon gamma by allogeneic CD4+ T-cell clones stimulated with alloantigens. The results show that lymphocytes produce significant amounts of reactive oxygen species as measured by malondialdehyde produced in cultures. The hydroxyl radical-generating system did not change any of the cellular responses studied although it doubled Malondialdehyde production. Hydroxyl radical scavengers signi tly inhibited all responses at doses that didn't significantly decrease malondialdehyde production. DNA analysis failed to show evidence for apoptosis. Conclusion: Hydroxyl radical scavengers inhibit lymphocyte mitogenesis by a process that is independent of scavenging hydroxyl radicals.     

Effects of resveratrol on human immune cell function.

Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol found in grapes and grape products such as red wine, has been reported to exhibit a wide range of biological and pharmacological activities both in vitro and in vivo. Because many of the biological activities of resveratrol, like the inhibition of cyclooxygenase, induction of CD95 signaling-dependent apoptosis, effects on cell division cycle and modulation of NF-kB activation, suggest a possible effect on the immune system, we evaluated the in vitro effects of resveratrol in three immune response models: i) development of cytokine-producing CD4+ and CD8+ T cells induced by stimulation of peripheral blood mononuclear cells (PBMC) with anti-CD3/anti-CD28; ii) specific antigen-induced generation of cytotoxic T lymphocytes; iii) natural killer (NK) activity of PBMC. The results showed that in vitro exposure to resveratrol produces a biphasic effect on the anti-CD3/anti-CD28-induced development of both IFN-gamma- IL2- and IL4-producing CD8+ and CD4+ T cells, with stimulation at low resveratrol concentrations and suppression at high concentrations. Similarly, the compound was found to induce a significant enhancement at low concentrations and suppression at high concentrations of both CTL and NK cell cytotoxic activity. On the whole, the results of the study indicate that resveratrol modulates several human immune cell functions and suggest that this activity may be related to its effects on cytokine production by both CD4+ and CD8+ T cells.     

The effect of ageing on human lymphocyte subsets: comparison of males and females

Background  

There is reported to be a decline in immune function and an alteration in the frequency of circulating lymphocytes with advancing age. There are also differences in ageing and lifespan between males and females. We performed this study to see if there were differences between males and females in the frequency of the different lymphocyte subsets with age.     

The Clastogenic effect of Pyrimethamine (Daraprim) on human chromosomes in lymphocyte cultures

In this study the clastogenic effect of pyrimethamine (Daraprim), a folic acid antagonist used for the treatment of toxoplasmosis and malaria on human chromosomes, was investigated. Pyrimethamine was added to in vitro lymphocyte cultures at six different concentrations: 0.05 (normal therapeutic dose), 0.1, 0.2, 0.4, 0.8, and 1.6 mg/ml. No proliferation was observed in any of the cultures containing 1.6 mg/ml pyrimethamine. The results of the cytogenetic evaluations show that the frequency of breaks and gaps increase significantly in dose-dependent manner. Thus, pyrimethamine has a clastogenic effect on human chromosomes.Abbreviations PHAM Phytohemagglutinin M - M Metaphase - G Gap - B break - R Rearrangement - NCA Number Chromosome Abnormalities - FA Folic acid - SCE Sister Chromatid Exchange     

The effect of A23187 upon calcium metabolism in the human lymphocyte

Treatment of human peripheral lymphocytes with mitogenic concentrations of the divalent cation ionophore A23187 led to an initial marked increased in the uptake of calcium by these cells, but the amount of accumulated calcium retained decreased with time so that after 8–12 h of culture, the calcium content of treated cells was only 1.5–2.0-fold higher than that of control cells. Three possible explanations for the biphasic nature of ionophore-induced calcium uptake were considered: (1) the ionophore underwent chemical or metabolic inactivation upon prolonged incubation; (2) massive accumulation of calcium caused irreversible uncouplingof mitochondria in these cells with consequent loss of accumulated calcium; or (3) with time there was a redistribution of ionophore within the cell, and sufficient ionophore was taken up by internal, most likely mitochondrial, membranes to cause an efflux of calcium from internal stores. By developing a bioassay for ionophore and examining the time-dependent effects of ionophore in the presence and absence of calcium, it was concluded that the third explanation was the most likely. The general implications of these results are discused.     

The effect of exposure to high flux density static and pulsed magnetic fields on lymphocyte function

We investigated whether a combination of static electromagnetic field (EMF) at a flux density of 4.75 T together with pulsed EMF at a flux density of 0.7 mT generated by an NMR apparatus (NMRF), could promote movements of Ca(2+), cell proliferation, and the eventual production of proinflammatory cytokines in human lymphocytes as well as in Jurkat cells, after exposure to the field for 1 h. The same study was also performed after activation of cells with 5 micro g/ml phytohaemagglutinin (PHA) immediately before the exposure period. Our results clearly demonstrate that NMRF exposure increases the [Ca(2+)](i), without any proliferative, or activating, or proinflammatory effect on both normal and PHA stimulated lymphocytes. Accordingly, the levels of interferon gamma, tumor necrosis factor alpha, interleukin-1beta, interleukin-2, and interleukin-6 remained unvaried after exposure. Exposure of Jurkat cells statistically decreased the [Ca(2+)](i) and the proliferation. This is consistent with the low levels of IL-2 measured in supernatants of these cells after exposure. On the whole our data suggest that static and pulsed NMRF exposure contribute synergistically in the increase of the [Ca(2+)](i) without any activating or proinflammatory effect either in normal or in PHA challenged lymphocytes. In Jurkat cells, by changing the properties of cell membranes, NMRF exposure can influence Ca(2+) transport processes and hence Ca(2+) homeostasis, causing a marked decrease of proliferation.     

The effect of low exposure-rate gamma irradiation on T and B lymphocyte function in the mouse

The effect of chronic irradiation on T and B cell numbers and function was studied in mice. Cobalt 60 gamma radiation at 6 R/hour reduced the numbers of anti-SRBC PFC in the spleen, with minimal levels recorded after total exposures of 1000-2000 R. Recovery was incomplete after 1000 R, reaching only 40-50 per cent of normal in four months and remaining at that level for the animal's lifetime. The long-term deficiency in PFC formation was not due to a quantitative lack of T or B cells since normal cell numbers were observed in the spleen 60-144 days after 1000 R. Adoptive transfer studies with combinations of bone marrow and thymus cells, or of splenic T and B cells, from normal and irradiated mice, revealed functional defects in both cell compartments during the first two months. Normal and near normal function of T and B cells occurred 100 days postirradiation, a time when the splenic in vivo response was still only 50 per cent of the controls. The latter observation suggests that the microenvironment of the chronically irradiated spleen alters factors regulating T and B cell interactions in response to a T-dependent antigen.     

The effect of hyposensitization on alternaria-induced lymphocyte blastogenesis

Twenty-one atopic children were treated with alternaria hyposensitization therapy. Leukocytes from these children were cultured with and without alternaria and phytohemagglutinin prior to treatment, and after 6 and 12 months of treatment. Patients demonstrating positive immediate cutaneous hypersensitivity showed significant lymphocyte transformation prior to hyposensitization whereas the skin test-negative patients did not. The skin test-negative patients developed significant lymphocyte transformation after 6 months of hyposensitization. Twelve months after the initiation of therapy both skin test-negative and skin test-positive patients showed a decreased lymphocyte reactivity, and there was no longer any significant change in the concomitant phytohemagglutinin responses indicating that hyposensitization had a specific effect on alternaria-induced in vitro lymphocyte reactivity. Plasma factors were found to have modulating effects on the lymphocyte reactivity of hyposensitized patients.