体液细胞免疫在进行性肌营养不良症发病过程中的作用

探讨体液免疫和细胞免疫在进行性肌营养不良症（ＰＭＤ）发病过程中的作用。方法应用免疫组化ＳＰ法及免疫荧光一步法。结果ＰＭＤ肌组织中免疫球蛋白ＩｇＭ、ＩｇＧ和补体Ｃ３的阳性表达率分别为５０．０％、３１．１％和１１．１％，ＩｇＭ与对照组相比，差异有显著性意义（Ｐ＜０．０５），主要定位于肌膜和间质小血管壁上，与肌纤维萎缩性病变有关；ＰＭＤ肌组织中有巨噬细胞和Ｔ淋巴细胞浸润，阳性反应率分别为１００．０％和５５．５％，巨噬细胞聚集在坏死灶中，Ｔ细胞分布于退变肌纤维和血管周围，以ＣＤ８＋Ｔ细胞为主，多数表达ＨＬＡ－ＤＲ。结论提示免疫因素可能参与ＰＭＤ的病变过程。     

Lack of suppression by gangliosides of humoral or cellular immunity in vivo

Gangliosides inhibit the proliferative responses of murine and human lymphocytes in vitro, and it has been suggested that they are immunosuppressive in vivo, although no in vivo studies have been performed. In view of the use of gangliosides to treat patients with a variety of neurological disorders, experiments were undertaken to evaluate the possible immunomodulatory effects of gangliosides in vivo. BALB/c mice were injected 5 days a week with buffer, mixed brain gangliosides, or GM1 ganglioside at dosage levels of 30 mg/kg, 60 mg/kg or 90 mg/kg. After 30 days of treatment, the mice were immunized with keyhole limpet hemocyanin or pneumococcal type III polysaccharide and the ganglioside treatment was continued. No differences between treated and control groups were noted in either the magnitude or duration of the antibody response. No differences between groups were noted in the proliferative responses of splenic mononuclear cells to concanavalin A or allogeneic antigens after 9-10 weeks of treatment, nor in the generation of cytotoxic effector cells after 90 days of treatment. Thus, despite the well-documented immunosuppressive effects of gangliosides in vitro, no evidence for a suppressive effect on humoral or cellular immunity in vivo was obtained in these studies.     

自身免疫性脑炎患儿的细胞免疫及体液免疫功能特征研究

目的探讨自身免疫性脑炎(AE)患儿的细胞免疫及体液免疫功能,以证实该病免疫特征。方法选取徐州市儿童医院神经内科收治的84例AE患儿作为研究组,另选取80例健康幼儿作为对照组。采集两组的空腹静脉血,使用全自动生化分析仪进行血清免疫球蛋白(IgA、IgG、IgM)水平检测,使用流式细胞仪测定血清CD3、CD4、CD8、CD54水平。所有入组对象还要采集血液标本的上清液测定抗谷氨酸脱羧酶(GAD)抗体与抗N-甲基-M-天冬氨酸受体(NMDAR)抗体水平,研究组患儿还需采集脑脊液测定抗GAD抗体及抗NMDAR抗体水平。对比、分析两组的各项指标检测结果。结果研究组患儿的血清及脑脊液抗GAD抗体、抗NMDAR抗体检测结果均为阴性,对照组儿童的血清抗GAD抗体、抗NMDAR抗体检测结果也为阴性。研究组的IgM、IgA、IgG水平均显著高于对照组(P<0.05)。研究组的CD3、CD4水平均显著低于对照组(P<0.05);两组的CD8、CD54水平接近(P>0.05)。结论 AE患儿普遍存在细胞免疫及体液免疫功能紊乱,抗GAD抗体与抗NMDAR抗体并非AE致病的主要因素,临床观察患儿细胞及体液免疫指标的变化,可为AE的诊断与治疗提供一定的参考依据。     

Characterization of humoral and cellular immunity in the central nervous system of HAM/TSP

In HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) immunopathological processes in the central nervous system (CNS) have not been clarified. We compared the humoral and cellular immunity within the CNS and in the systemic circulation of 24 patients with HAM/TSP (8 men and 16 women) to 6 asymptomatic HTLV-I carriers, 7 patients with active multiple sclerosis, 6 patients with acute viral encephalitis, and 39 patients with other non-inflammatory neurological diseases. Significant differences were observed between the HAM/TSP patients and one or more of the control groups: HAM/TSP cerebrospinal fluids (CSF) exhibited higher levels of IgG, IgG index, de novo IgG synthesis rate, and β₂-microglobulin, and also a predominance of CD8⁺ cells that expressed CD11a and CD45RO but lacked CD28 antigens. Results in the 6 patients with acute viral encephalitis suggested that the CD8⁺ population in the CSF which is positive for CD28 and CD45RO is important for the elimination of virus from infected CNS tissues. Therefore, potentially cytotoxic T cells of a unique CD8⁺ CD11a⁺CD45RO⁺CD28⁻ phenotype may play a key role in the CNS pathogenesis of HAM/TSP.     

The effects of exposure to dietary nickel and zinc upon humoral and cellular immunity in SJL mice

We are interested in potential interactions between environmental trace metal exposures and immune function. In particular, we have wondered whether dietary exposure to nickel and zinc cations can influence T and B cell proliferation and function. To study this question, we fed SJL female mice supplemental nickel and zinc sulfate from 4-8 weeks of age, and immunized the animals intraperitoneally (i.p.) with keyhole limpet hemocyanin (KLH) at 8 weeks. Eight days later, we measured antibody responses to KLH. Both IgG and IgM antibody responses to KLH were significantly depressed in vivo in the nickel fed animals (p less than 0.005). In vitro antigenic responsiveness to KLH of splenocytes from nickel fed animals was also depressed compared with control and zinc supplemented animals (p less than 0.002). This altered antigenic responsiveness persisted even after cells had been cultured for 5 days in standard media. The zinc supplemented diets did not seem to affect antibody responsiveness and proliferation. The proliferative responses of B cells to the mitogen lipopolysaccharide (LPS) were significantly depressed in Ni fed mice, but were not affected in the zinc fed animals. T cell mitogenic responses to concanavalin A were not affected in the nickel fed animals, and were enhanced in zinc fed animals. We conclude that dietary exposure to certain trace metals may induce persisting alterations in immunity in this animal model.     

Central corticotropin-releasing hormone reduces cellular immunity.

Corticotropin-releasing hormone (CRH) acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to those observed after stress. A reduction of splenic natural killer (NK) activity has also been described following the central administration of CRH. In this study, we examined whether other in vitro measures of cellular immunity, including peripheral and splenic NK activity, lymphocyte responses to mitogen stimulation, and numbers of splenic T and NK cell subpopulations, are altered following CRH. Synthetic rat CRH (1.0 microgram) microinjected into the lateral ventricle reduced splenic and peripheral blood NK activity, lymphocyte responses to mitogenic stimulation, and percentage of splenic NK cell numbers. Numbers of splenic lymphocytes and T cell subpopulations were not altered by central CRH. These findings suggest that central CRH acts to reduce a number of in vitro cellular immune measures similar to the effects of inescapable stress.     

Social stress, dominance and blood cellular immunity.

The impact of chronic social coexistence on distribution and function of blood immune cells was examined in Long Evans rats. At the beginning of a 7 day period of chronic coexistence (confrontation), a wall was removed between two neighboring cages each consisting of a male-female pair. Winner and loser males were classified based on differences in their defensive behavior. On day 2 and 7 of confrontation, losers showed reductions in numbers of blood CD4 and CD8 T cells as well as profound suppression of in vitro NK activity and lymphocyte (LYM) proliferation. Numbers of granulocytes (GRAs) were more than doubled. Winner males showed similar immunological alterations only on day 2 of confrontation. On day 7 most changes were reversed. The persistent changes in loser males may reflect a less favorable state for effective immune response.     

Multiple sclerosis: cellular and humoral immune responses to several viruses.

One hundred and eight multiple sclerosis (MS) patients and 108 matched controls were studied for antibody levels and cellular immune responses to several viruses. There were significant increases in the mean titers of complement fixation (CF) or hemagglutination inhibition (HI), and complement-mediated cytotoxicity (CMC) tests for measles antibodies in MS patients; there was no increase in antibody titers to herpesviruses 1 and 2, or cytomegalovirus (CMV). The direct migration inhibition (DMI) tests showed no difference between MS patients and controls for measles, CMV, herpesviruses 1 and 2, or vaccinia virus antigens. Lymphocyte-mediated cytotoxicity (LMC) tests showed no difference between patients and controls, using cultures infected with measles and CMV viruses. In a study of stimulation or blocking of the LMC response by serum or cerebrospinal fluid (CSF), no effect was found. Therefore, increased levels of measles antibody in serum were again demonstrated in MS patients, but there was no difference in these patients' cellular immunity to measles virus versus that of the controls, and there was no abnormality of cellular immunity against the other viruses tested.     

Ocrelizumab effect on humoral and cellular immunity in multiple sclerosis and its clinical correlates: a 3-year observational study

Journal of Neurology - We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and...     

Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice.

Physical restraint administered to C57BL/6 mice significantly altered the inflammatory response to influenza virus infection and depressed anti-viral cellular immunity. Restraint-stressed animals showed a pattern of reduced mononuclear cell infiltration and lung consolidation which coincided with elevated plasma corticosterone levels. Furthermore, cellular immunity to virus was significantly depressed; interleukin-2 secretion was reduced by 96% and 59% in the mediastinal lymph nodes and spleens, respectively, as compared to a non-restrained group. However, the magnitude of the humoral immune response to influenza virus was unaffected by restraint stress. Anti-viral IgG antibody levels in restrained/infected mice did not differ when compared to a non-restrained/infected control group 14 days post-infection.     

新生儿缺氧缺血性脑病（HIE）患儿的体液免疫功能改变

目的探讨HIE（新生儿缺氧缺血性脑病）患儿相对于正常新生儿的体液免疫功能改变。方法分析2012年6月至2013年7月在我院新生儿中心接受治疗的58例HIE患儿的临床资料。并选取一般资料相似的正常新生儿40例作为对照组。比较两组新生儿的一般资料、免疫功能指标以及观察组中不同病情程度的患儿免疫功能指标差异。结果本研究共纳入新生儿研究对象98例,其中观察组患儿58例,对照组正常新生儿40例。观察组患儿的IgA（t=2.943,P〈0.01）、C3（t=2.433,P=0.017）、C4（t=5.366,P〈0.01）、CD19＋（t=2.791,P〈0.01）、CD19＋CD25＋（t=3.121,P〈0.01）水平均低于对照组,差异均有统计学意义。轻度、中度、重度HIE患儿的IgA（F=14.02,P〈0.01）、IgM（F=8.732,P〈0.01）、C3（F=4.277,P=0.018）、C4（F=15.72,P〈0.01）、CD19＋（F=5.779,P〈0.01）、CD19＋CD25＋（F=4.394,P=0.018）、组间均有统计学差异,且病情越重,相应的免疫功能指标越低。结论 HIE患儿相对于正常新生儿,体液免疫功能受到抑制,且病情越重,受抑状态越显著。     

Cellular and humoral immunity to acetylcholine receptor in myasthenia gravis

At the same time in 21 myasthenic patients we measured a. the cellular immune response against acetylcholine receptor (AChR) of peripheral lymphocytes, T lymphocytes and non rosette forming lymphocytes (50% B lymphocytes); b. the antibodies to AChR and c. the antigenic modulation activity of their sera on rat myotube AChR. At least one of these parameters was positive in each patient and this further supports the relevance of the immune response to acetylcholine receptor in myasthenia gravis. Strict correlations between the response of lymphocytes, antigenic modulation, antibody titer and disease severity were not evident.     

Magnetic fields, brain and immunity: effect on humoral and cell-mediated immune responses.

Magnetic fields (MF) can influence biological systems in a wide range of animal species and humans. We report here on the influence of static MF, locally applied to the brain area, on immune system performances in the rat. In the first series of experiments two AKMA micromagnets (M) with the influx density of 600 Gauss were bilaterally implanted (with "N" polarity facing the cranial bones) and fixed to the skull posterior to the fronto-parietal suture (parietal brain exposure). Rats implanted with iron beads (I) and sham-operated (SO) rats served as controls. Animals were exposed to MF or I during different periods of time before and after immunization with several soluble or cellular antigens. We report here on the in vivo immunoregulating effects of centrally applied MF on plaque-forming cell (PFC) response, local hypersensitivity skin reactions and experimental allergic encephalomyelitis. The selective influence of MF applied to different brain regions on PFC response was evaluated, as well. For this purpose, two M were bilaterally implanted in the area of (a) frontal, (b) parietal and (c) occipital brain regions. Rats were under the influence of MF for 20 days before and 4 days after immunization with sheep red blood cells. Groups of nonimmunized rats were exposed for 14, 24 and 34 days to parietally implanted M or I, and the number of peripheral blood CD4+ and CD8+ cells determined by mouse anti-rat W3/25 and MRC OX 8 monoclonal antibodies. The results show an overall in vivo immunopotentiation of humoral and cell-mediated immune responses in rats exposed to MF. Furthermore, these immunomodulating effects of centrally applied MF depend on at least two basic parameters, time of exposure and brain region exposed. The highest immune performance was obtained after exposure of the occipital brain region for a total period of 24 days. The results provide further evidence of the complex interrelationship between the environment, the central nervous system and the immune system.     

Stress-related impairments in cellular immunity

The percentages of total T-lymphocytes (OKT-3+), helper T-cells (OKT-4+), and suppressor T-cells (OKT-8+) were significantly lower in blood samples obtained from 40 medical students during examinations, compared to baseline values obtained 6 weeks earlier. In addition, the response of T-lymphocytes to stimulation by phytohemagglutinin and concanavilin A was also significantly lower during examinations, compared to baseline. Self-report data documented significantly greater distress associated with examinations. The data have implications for immunosuppressive disorders and stress-related illnesses.     

Effects of anticonvulsants on cellular immunity

The effects of anticonvulsants on cellular immunity were examined in murine models. Fresh splenocytes were obtained from mice which had been intraperitoneally given 1 mg of phenytoin, 2 mg of phenobarbital, or 20mg of valproate for 28 days. The serum concentration of phenytoin, phenobarbital and valproate in these animals were 10-20 micrograms/ml, 30-40 micrograms/ml and 50-70 micrograms/ml, respectively. The proliferative response of splenocytes to mitogens was assessed by 3H-thymidine incorporation. The cytotoxic activities of cells such as natural killer (NK) cells, cytotoxic T lymphocytes (CTL), and lymphokine-activated killer (LAK) cells were estimated by a 4 hr-51Cr release assay. Phenytoin suppressed lymphocyte proliferation, NK activity, and CTL activity, but never LAK activity. Phenobarbital suppressed proliferative response to rIL-2 and CTL activity, but did not suppress NK activity nor LAK activity. In turn sodium pyruvate never suppressed any activity on cellular immunity.     

Aspects of cellular immunity in multiple sclerosis. Antigen-reactivity of lymphocytes and lymphokine activity.

Some new results of cell-mediated immunity in multiple slcerosis (MS) are presented, based on the determination of charge-changing lymphokines as products of antigen sensitive lymphocytes (C PAL), obtained by several forms of the electrophoretic mobility (EM) method. Lymphocytes from MS react to myelin basic protein (BP), the reactivity in other neurological diseases depending on the degree of destruction of nervous parenchyma. Applying a membrane-associated antigen from normal brain (NTA), positive reactivity of MS lymphocytes was obtained. Besides the usual determination of lymphokines in vitro the sensitive EM test allows the demonstration of lymphokine activities in vivo; i.e. in body fluids such as cerebrospinal fluid (CSF) and serum. In CSF of MS a high lymphokine activity was found. The differentiation of lymphokines and comparison between in vitro and in vivo activity were carried out. Moreover, a characteristic lymphokine pattern for MS with high activities in all regions of molecular weight, especially in the CSF, could be detected. On the basis of these findings, important also from the pathogenetic point of view, a diagnostic scheme for MS is suggested, consisting of a program of determination of the immuno-reactive CSF syndrome and some special procedures, including examination of lymphocyte reactivity.     

Immunoregulation disturbance in experimental allergic neuritis. The cellular and humoral mediated immunological damage]

The cellular and humoral mediated immune responses were investigated in the rabbits with experimental allergic neuritis (EAN) induced by the myelin basic protein (MBP) purified from the human sciatic nerve. The cellular mediated immunity to MBP were assayed by skin testing and lymphocytes transformation. The antibodies to myelin and muscle, the immunoglobulin deposits in the nerve and tissues respectively were detected by indirect and direct immunoenzyme assays. In rabbits with EAN, the skin tests became positive at the onset of EAN. There was a significantly higher index of the lymphocytes transformation in the EAN than in normal animals. At the height of the disease, the anti-muscle antibody titres were high. The granular deposits containing IgG were found in sciatic nerve and heart. The results favour cellular and humoral mediated immunological damage as the most important pathogenetic mechanism in EAN.