用生物素——抗生物素EIA法研究桥本氏病自身抗体产生机制

<正>为阐明桥本氏病自身抗体产生机制,本文建立了敏感度高的抗体测定法,研究末稍血淋巴细胞(PBL)对各种抗原刺激的反应和Ia阳性T细胞的作用。 方法:用生物素—抗生物素(B—A)EIA法测定甲状腺球蛋白(Tg)抗体价和微粒体(Mic)抗体价。在无刺激、特异抗原刺激及核系分裂原刺激下,研究PBL产生     

伤寒沙门氏菌及其抗原检测方法的近年进展

伤寒病的诊断,来自病原学的证据最为可靠。检测伤寒特异性抗体,对诊断有重要的参考价值,但特异抗原刺激机体产生有关抗体,有一定的时间过程,而且受各种因素影响。在一些免疫功能紊乱或缺陷的患者中,检测抗体往往易产生假阳性或假阴性反应,而检测抗原则可     

伤寒沙门氏菌及其抗原检测方法的近年进展

伤寒病的诊断,来自病原学的证据最为可靠。检测伤寒特异性抗体,对诊断有重要的参考价值,但特异抗原刺激机体产生有关抗体,有一定的时间过程,而且受各种因素影响。在一些免疫功能紊乱或缺陷的患者中,检测抗体往往易产生假阳性或假阴性反应,而检测抗原则可更早、更准确地作出诊断。为此,如何提高病     

白术多糖对小鼠免疫功能调节的研究

目的将白术多糖作为抗原刺激小鼠免疫系统,探讨其对免疫功能调节作用,为多糖在免疫调节功能方面的应用开发及在药物鉴定方面的应用提供科学依据。方法分别给予小鼠自术多糖、可溶性淀粉多糖、伤寒多糖抗原刺激,检测小鼠血清中的相应抗体及交叉抗体,探讨补益类水溶性多糖对小鼠免疫功能的调节作用。结果多糖抗原均能刺激机体产生特异性IgG类抗体（P〈0.05）;也能在一定程度上激发非特异性IgG类抗体即交叉抗体的产生;但不激发病理性抗体产生（RF阴性）。结论补益类水溶性多糖能激发免疫反应与其他多糖可能有共同的途径和机制。     

杂交瘤技术(综述)

<正>一、前言 天然抗原总是以复合物的形式存在,它包含有多种不同性质的分子。每个抗原分子上又带有若干不同的抗原决定簇。因此人体或动物体受抗原刺激后产生的抗体是由多种抗体组成的混合物,即所谓多克隆抗体(polyclonal Antibody)。抗体是从浆细胞产生的。浆细胞又是从B淋巴细胞转化出来。它只能识别一种抗原或一个抗原决定簇,即每个B细胞系只能产生一种它专有的、针对一种它能识别的特异性抗原决定簇     

白细胞介素:可溶性免疫介质

<正>引言 炎症,微生物侵袭,抗原刺激和创伤能引起具有免疫应答能力的宿主产生复杂的生物学反应。该反应,在很大程度上是由淋巴网状内皮系统的效应和调节细胞介导的。特别是,胸腺依赖性淋巴细胞(T细胞),抗体形成淋巴细胞(B细胞)和巨噬细胞(MΦS)在宿主对抗原刺激和炎症的起始和持久反应上起着关键的作用。除了它们各     

肿瘤坏死因子受体相关因子3调节调节性T细胞的效应器功能和体液免疫应答

调节性T细胞（Treg细胞）控制免疫应答的不同方面,但其如何调控效应器功能尚不完全明确。该研究鉴定了肿瘤坏死因子受体相关因子3（TRAF3）是 Treg细胞的功能效应器。在 Treg细胞中特异性敲除TRAF3后,CD4＋ T细胞稳态受损,表现为Th1型效应／记忆T细胞增加。此外,Treg细胞中TRAF3敲除还增加抗原刺激引起的滤泡辅助性T细胞（TFH细胞）激活,伴随着生发中心形成增加及高亲和性IgG抗体产生。虽然TRAF3敲除并没有减少Treg细胞的总比例,但减少滤泡调节性T细胞（TFR细胞）的抗原刺激产生。Treg细胞中TRAF3信号通路是保持较高水平可诱导共刺激分子（ICOS）所必需的,也是TFR细胞生成和抑制抗体反应所必需的。该研究表明,TRAF3作为Treg细胞的功能效应器,具有调节抗体反应的功能,提示其在Treg细胞介导ICOS表达中起重要作用。     

布鲁氏菌rOmp3148-74-BLS蛋白的多克隆抗体制备与检测

目的:研究布鲁氏菌Omp31分子的免疫原性.方法:利用IPTG诱导rOmp3148-74-BLS融合重组蛋白表达,经过His-tag镍柱进行亲和纯化之后,作为抗原免疫家兔制备多克隆抗体.结果:rOmp3148-74-BLS重组蛋白能够被大肠杆菌正确表达,而且,能够作为有效的抗原刺激家兔产生可以相互识别的多克隆抗体.结论:Omp31分子具有较好的免疫原性,可以引起较强的免疫反应.     

全球抗体药物研发态势分析

<正>1引言抗体(antibody,Ab)是指浆细胞(效应B细胞)在抗原刺激下产生并释放的可与其发生特异性结合的免疫球蛋白(immunoglobulin,Ig),是机体免疫系统的一个重要组成部分。根据抗体结合抗原决定簇的数量,抗体一般可以分为单克隆抗体(monoclonal antibody)和多克隆抗体(polyclonal antibody)。其中,单克隆抗体及其与药物的偶联物因其高特异性、高有效性和高安全性等特点,形象地被称为"生物导弹",现有的抗体药物大多属于此类抗体。     

草鱼免疫应答的初步研究

研究了草鱼在不同水温条件下受抗原刺激后其中和抗体的变化。15℃培养条件下中和抗体上升缓慢,9周内滴度低于1:8;20℃时,3周后抗体可上升到1:256,最高达1:5270,而在25℃时,1周中和抗体即达到1:570,最高可达1:20000以上。并探索了从草鱼血清中提纯抗体的条件,研究其抗体的特性。草鱼血清中的抗体为大分子蛋白,容易解离为抗原性相同,分子量近似于人IgG的较小分子,含有较多的二硫键,具有类似IgM的某些特性。     

Mathematical modeling of humoral immune response suppression by passively administered antibodies in mice

Although passively administered antibodies are known to suppress the humoral immune response, the mechanism is not fully understood. Here, we developed a mathematical model to better understand the suppression phenomena in mice. Using this model, we tested the generally accepted but difficult to prove "epitope masking hypothesis." To simulate the hypothesis and clearly observe masking of epitopes, we modeled epitope-antibody and epitope-B-cell receptor interactions at the epitope level. To validate this model, we simulated the effect of the antibody affinity and quantity as well as the timing of administration on the suppression, and we compared the results with experimental observations reported in the literature. We then developed a simulation to determine whether the epitope-masking hypothesis alone can explain known immune suppression phenomena, especially the conflicting results on F(ab')2 fragment-induced suppression, which has been shown to be no suppression, or similar to or up to 1000-fold weaker than the suppression by intact antibody. We found that suppression was caused by a synergistic effect of both epitope masking and rapid antigen clearance. Although the latter hypothesis has lost support because FcgammaRI/III mutant mice show antibody-mediated suppression, our simulations predict that, even in FcgammaRI/III mutant mice, the immune response can be suppressed according to the antibody affinity. Our model also effectively reproduced the conflicting results obtained using F(ab')2 fragments. Thus, in contrast to the idea that the F(ab')2 results prove the FcgammaRIIb involvement in suppression, our mathematical model suggests that the epitope-masking hypothesis together with rapid antigen clearance explains the conflicting results.     

Optimal strategies in immunology III. The IgM-IgG switch

Summary During a primary immune response generally two classes of antibody are produced, immunoglobulin M (IgM) and immunoglobulin G (IgG). It is currently thought that some lymphocytes which initially produce IgM switch to the production of IgG with the same specificity for antigen. During a secondary immune response IgG is the predominant antibody made throughout the response. In this paper we address the question of why such apparently complicated modes of response should have been adapted by evolution.We construct mathematical models of the immune response to growing antigens which incorporate complement dependent cell lysis. By comparing the times required to eliminate antigen we show that under certain conditions it is advantageous for an animal to switch some of its lymphocytes from IgM to IgG production during a primary response, but yet to secrete only IgG during a secondary response. The sensitivity of such a conclusion to parameter variations is studied and the biological basis and implications of our models are fully discussed.Portions of this work were performed under the auspices of the U.S. Department of Energy. A.S.P. was also supported by the National Science Foundation under Grant No. ENG-7904852 and BRSG grant S07 RR05664-11 awarded by the Biomedical Research Support Grant Program, Division of Research Resources, National Institute of Health. A.S.P. is the recepient of an NIH Research Career Development Award 1K04 AI 00357-01. S.R. was a recipient of NIH Fellowship 5 F32 AI05107-02     

Verification of immune response optimality through cybernetic modeling

An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included.     

Mathematical model of immune processes

In the model the time lags of the antibody production and immune memory formation are taken into account explicitly. The antibody-antigen reaction is supposed to be very fast. The cases of a reproducing antigen as well as that of a non-reproducting antigen are considered. The conditions of the infinite increase of the antigen quantity and of the antigen elimination are obtained. For the rapidly reproducing antigen the latter condition includes the requirement for the time lag of the immune response to be not too short or not too long. In the case of the poorly catabolized non-reproducing antigen the cyclic appearance of the antibody producing cells due to the immune memory is described in the frame-work of the model.The mathematical structure of the model is similar to that of the Volterra-Lotka jequations. The only difference is the presence of the time lags in the non-linear terms. The time lags lead to the instability of the stationary state. In the prolonged reaction the antigen quantity may perform several oscillations before the elimination of the antigen.     

Optimal strategies in immunology

Summary The optimal strategy available to the immune system for responding to a non-replicating thymus-independent antigen is examined. By applying Pontryagin's maximum principle to a set of mathematical models of lymphocyte populations and their antibody production, it is found that the optimal strategy of bang-bang control appears robust. In a variety of structurely related biological models, similar behaviour is observed.The models that we consider assume that antigen triggers a population of B-lymphocytes. These triggered lymphocytes can either proliferate and secrete modest amounts of antibody or differentiate into nondividing plasma cells which secrete large amounts of antibody. For biologically reasonable parameter values it is found that for low doses of antigen, immediate differentiation into plasma cells is optimal, while for high antigen doses a proliferative state followed by differentiation is the best strategy.Work performed under the auspices of the U. S. Energy Research Development Administration.Work supported by NSF Grant No. BMS 75-18897.     

Adjuvants and antibody production: dispelling the myths associated with Freund's complete and other adjuvants

Adjuvants have been used for more than 70 yr to enhance the immune response of the host animal to an antigen. Among the mechanisms that adjuvants use to enhance the immune response are the "depot" effect, antigen presentation, antigen targeting, immune activation/modulation, and cytotoxic lymphocyte induction. The immunostimulatory properties of adjuvants result in inflammation, tissue destruction, and the potential for resulting pain and distress in the host animal. The inflammatory lesions produced by adjuvants such as Freund's complete adjuvant (FCA) have led some to conclude that pain and distress are present, even in cases where the scientific evidence fails to support this conclusion. Recommendations and regulations in the literature, based on available scientific evidence, provide guidance on total adjuvant volumes, volumes per site, routes of injection, booster injections, and adjuvants used for antibody production. Among the numerous adjuvants that are used for experimental antibody production reviewed in this article, many claim to be less inflammatory, tissue destructive, and painful than FCA while producing equal or superior antibody responses. Although no adjuvant surpasses FCA for experimental antibody production against a wide range of antigenic molecules, many produce excellent antibody responses with less inflammation and tissue destruction. Balancing the requisite degree of immuno-stimulation and the extent of inflammation, necrosis, and potential pain and distress requires consideration of the nature of the antigen, the host immune responsiveness, the adjuvant's mechanisms of action, and the desired end-product. In cases where the antigen is a weak immunogen or has a very limited availability, the type and role of adjuvant becomes a critical component in producing an acceptable immune response and humoral antibody response.     

The influence of TRPM8 ion channel activation on immune response at different temperature conditions

In experiments on rats it was shown that it is possible to modulate the immune response in a whole organism by activating cold-sensitive TRPM8 ion channel by its agonist menthol. The most pronounced changes in the conditions without external temperature stimulation were related to immune parameters for the spleen cells and immunoglobulin level in blood: the activation of TRPM8 ion channel by menthol enhances antigen binding and inhibits antibody formation in spleen, significantly reduces the level of IgG in blood. Activation of TRPM8 ion channel changes the effect of subsequent temperature exposure—cooling or heating. Preliminary application of menthol eliminates the inhibitory effect of deep cooling on immune response. Stimulation of the antigen binding in spleen at deep heating is inversed to suppression in case of heating on the background of TRPM8 activation by menthol. On the contrary, suppression of antibody formation caused by deep heating is eliminated if heating is carried out on the background of TRPM8 stimulation.     

Decision-making by the immune response

Decisions by uncommitted cells to differentiate down one lineage pathway or another is fundamental to developmental biology. In the immune system, lymphocyte precursors commit to T- or B-cell lineages and T-cell precursors to CD4 or CD8 independently of foreign antigen. T and B cells must also decide whether or not to respond to antigen and when a response is initiated, what sort of response to make such as the type of antibody, CD4 or CD8, and CD4 Th1 or Th2. The two basic mechanisms for these decision-making processes are selection and instruction. Selection depends on prior stochastic production of precommitted cells, which are then selected to respond by an appropriate signal; for example, CD8 and CD4 responses selected by peptide presented in association with major histocompatibility complex class I or II. In contrast, instruction occurs when an uncommitted precursor embarks upon a differentiation pathway in response to a particular set of signals; for example, Th1 and Th2 lineage commitment. In this paper, the signals that determine Th1 and Th2 differentiation are examined with a mathematical model and shown to act as a bistable switch permitting either Tbet or Gata3 to be expressed in an individual cell but not both. The model is used to show how the Tbet Gata3 network within an individual cell interacts with cytokine signals between cells and suggests how Th1 and Th2 lineage commitment can become irreversible. These considerations provide an example of how mathematical models can be used to gain a better understanding of lymphocyte differentiation in an immune response.     

β-Adrenoreceptor participation in the formation of the thermoregulatory and immune responses under the effect of rapid deep cooling

The effect of β-adrenoantagonist (obzidan) iontophoresis to skin on the thermoregulatory response and immune response to antigen was analyzed to elucidate the significance of β-adrenoceptors in formation of these responses at deep rapid cooling in rats.

On the background of β-adrenoceptors blockade in thermoneutral conditions the skin and core temperatures decreases; at rapid cooling non-shivering thermogenesis is attenuated and shivering thermogenesis is considerably enhanced.

Administration of β-adrenoantagonist affect the modulating influence of cold exposure on the immune response—the immunosuppressive effect of deep cooling on the immune response is abolished. This concerns both antigen binding function of spleen and peritoneal cells and antibody formation.

The results support the idea that β-adrenoceptors participates in the processes of the stimulation of thermogenesis and suppression of the immune response to antigen at rapid deep cooling.