IDIOTYPICNETWORKAB模型动力学行为的进一步研究

计算Ｌｙａｐｕｎｏｖ指数来探讨免疫理论中ｉｄｉｏｔｙｐｉｃｎｅｔｗｏｒｋＡＢ模型γ＝２．０，δ∈（０，０．１）和μ∈（０，０．０２）参数域内动力学行为。周期振荡与混沌运动相互嵌套、交替出现。对于极限环，一个主周期内Ａｉ，Ｂｉ（ｉ＝１，２）的极大值出现次数有成简单比例现象。理论结果表明在实验中有可能发现周期现象。

A clinical trial of active immunotherapy with anti-idiotypic vaccine in nasopharyngeal carcinoma patients

To investigate the effect of active immunotherapy with anti idiotypic vaccine i n patients with nasopharyngeal carcinoma (NPC) Methods Anti idiotypic antibodies (2H4/5D3) bearing the internal image of the NPC antig en were used in active immunotherapy in NPC patients receiving radiotherapy Antibodies and cytokine levels in patient sera were determined using ELISA befo re and after active immunotherapy IL 2 mRNA expression in the peripheral bloo d mononuclear cells (PBMC) was measured by in situ hybridization Results Nineteen patients with NPC at stage Ⅳ were treated with alum precipitated 2H4 or 5D3 Neither hypersensitivity nor adverse side effects were observed The l evels of anti anti idiotypic antibodies (Ab3) and anti NPC antibodies (Ab1’) were increased Human anti mouse antibodies (HAMA) were seen in 19 patients of the experimental group; the levels of Ab1’ did not increse in the control group Serum IL 2, IFN γ and TNF α levels were increased in most patients in th e experimental group, while no differences were observed in Ab1’ and cytokine le vels between pre and post therapy in the control group In addition, IL 2 m RNA expression in PBMCs from NPC patients was closely related to serum IL 2 ( r =+0 8829) levels by in situ hybridization Conclusions Anti idiotype vaccine is safe for clinical active immunotherapy Anti idiotyp ic vaccine might be able to enhance humoral and/or cellular immunity in NPC pati ents receiving radiotherapy

Preparation of Anti-Idiotypic Antibody against Avian Influenza Virus Subtype H9

To generate monoclonal anti-idiotypic antibodies(mAb2)against avian influenza virus subtype H9(H9 AⅣ), BALB/c mice were immunized with purified chicken anti-H9-AⅣ IgG and the splenocytes of immunized mice were fused with myeloma cells NS-1.Hybridoma cells were screened by indirect enzyme-linked immunosorbent assays with both chicken and rabbit anti-H9-AⅣ IgG as coating antigens.One hybridoma cell clone secreting monoclonal antibody against idiotypes shared by both chicken and rabbit anti-H9-AⅣ IgG was established.Experiments demonstrated the mAb2 was able to inhibit the binding of hemagglutinin to anti-H9-AⅣ IgG and to induce chickens to generate hemagglutination inhibition antibodies,indicating this anti-species-sharing-idiotypic antibody bore the internal image of hemagglutinin on avian influenza virus.Cellular & Molecular Immunology.2005;2(2): 155-157.

Anti-fecundity immunity in mice immunized with anti idiotypic monoclonal antibody NP30 of Schistosoma japonicum

Objective To observe the effects of anti fecundity and anti embryonation immuntiy of anti idiotypic monoclonal antibody NP30 of Schistosoma japonicum on female adult worm Methods The active immunization of C57BL/6 mice was conducted by means of three intraperitoneal injections of NP30 The control group was injected with SP2/0 ascites intraperitoneally Results On the twenty seventh day after challenge infection, the number of eggs in the liver tissue and in uterus of the group immunized with NP30 decreased by 30 91% and by 38 55%, respectively On the thirty ninth day after the challenge infection, the number of mature eggs in the liver tissue of the group immunized with NP30 decreased by 66 63% and the number of dead eggs increased by 60 66% Conclusions NP30, with which mice were actively immunized, possesses double effects of anti fecundity and anti embryonation immunity on female adult worm of Schistosoma japonicum , therefore it can be used as a promising candidate of anti pathologic vaccine molecule against Schistosomiasis japonica

Treatment strategies for nodal and gastrointestinal follicular lymphoma:Current status and future development

In recent years,therapies for follicular lymphoma (FL) have steadily improved.A series of phase Ⅲ trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival.Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy.For patients with relapsed or refractory FL,phase Ⅱ studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS),oblimersen sodium (a Bcl-2 antisense oligonucleotide),bendamustine,and rituximab,as well as veltuzumab,a new humanized anti-CD20 antibody,and epratuzumab.In addition,the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported.Furthermore,three phase Ⅲ studies on an idiotype vaccine are near completion.Unfortunately,these vaccines,which appeared highly effective in phase Ⅰ and Ⅱ trials,do not appear to result in prolonged PFS.This report will summarize the current knowledge on therapies for treatment of FL,and will conclude with a brief discussion of feasiblefuture options for effective treatments.Lastly,we added descriptions of the management of gastrointestinal FL,which is considered to be controversial because it is rare.

Preparation and Identification of Rat Monoclonal Anti-idiotope Antibody to the Antibody against Erythrocytic Stages of Plasmodium Falciparum

A hybridoma cell line secreting monoclonal antibody to idiotope of the monoclonalantibody 94D1 specific for asexual erythrocytic stages of Plasmodium falciparum was established byfusion of SP2/0 mouse myeloma cells with spleen cells of Wistar rats immunized with monoclonalIgG of 94D1 purified from ascitic fluid of BALB/C mouse by affinity chromatography on ProteinA- Sepharose CL- 4B. Specificity of the anti - idiotope antibody (anti - Id), 41RF5, was deter-mined with indirect enzyme-linked immunosorbent assay (ELISA). The results showedthat 41RF5 reacted only with 94D1 IgG2b, not with normal mouse IgG and other seven mousemonoclonal antibodies - five specific for erythrocytic stages of P. falciparum, one for erythrocyticstages of P. inui, and one for Dengue fever virus type III, which indicates that 41RF5 does recognizespecifically the idiotope of 94D1 monoclonal antibody. In 41RF5 heterohybrid culture supernatant,anti-Id titre measured by ELISA was above 1:1 280. Up to the present, the heterohybrid cell linehas been cultured stably for 16 months.

Idiotype vaccines for lymphoma:Potential factors predicting the induction of immune responses

Over the last two decades,lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand,as well as clinical benefit on the other.More recently,however,three large-scale,independent,randomized clinical trials on idiotypic vaccination have failed to achieve their main clinical endpoints for reasons likely to depend more on flaws in each clinical trial’s study design than on each vaccination strategy per se.Independently of these considerations,a major hurdle for the development of this substantially innocuous and yet potentially very effective type of treatment has been the fact that,even to date,no factors ascertainable before vaccination have been prospectively singled out as predictors of subsequently vaccine-induced,idiotypespecific immune as well as clinical responses.The aim of this review article is precisely to analyze what has been and what could be done in this respect in order to give a greater chance of success to future trials aimed at regulatory approval of idiotype vaccines.

Construction,Expression and in vitro Biological Effects of Idiotype Ig Fab Fragment of B-Chronic Lymphocytic Leukemia

The purpose of this study was to construct expression vectors of idiotype （Id） SmIg in patients with B-chronic lymphocytic leukemia and to express them in E.coli to obtain recombinant Id, and to investigate the effect of the protein on the proliferation and secretion of IL-2 and IFN-γ of stimulated peripheral blood mononuclear cells （PBMC） in vitro. Light chain gene and Fd fragment of heavy chain gene were inserted into fd-tet-DOG2 vector to construct fd-tet-DOG2-Fab. Fab gene was further cloned into expression vector pHEN2 to construct the soluble expression vector pHEN2-Fab. After induction by IPTG, Fab protein was purified by Ni-NTA-chromatography. MTT was used to determine the effects of purified protein on the proliferation of stimulated PBMC in vitro and the concentrations of IL-2 and IFN-γ in the culture supernatants were detected by ELISA. The results showed that recombinant pHEN2-Fab expression vector was constructed successfully. Fab protein was expressed in positive clone after induced by IPTG and two specific bands at 24-25 kD position were observed by SDS-PAGE electrophoresis. Proliferation of PBMC could be induced by purified Fab and the concentrations of IL-2 and IFN-γ in culture supernatants were increased significantly af- ter induction. It was suggested that the expression vector of SmIg Fab fragment was constructed suc- cessfully, and expressed and secreted from E. coli. The Fab protein could induce proliferation of PBMC and promote secretion of IL-2 and IFN-γ.

Monoclonal anti-idiotype antibody bearing the internal image of nasopharyngeal carcinoma associated antigen

Objective To generate and characterize anti-idiotypic monoclonal antibody (Ab2) that bears the internal image of nasopharyngeal carcinoma (NPC) associated antigen. Methods Using NPC monoclonal antibody (Ab1) as immunogen, hybridoma cells were obtained by fusion of SP2/0 myeloma cells with immunized murine spleen cells. Positive clones were screened by Sandwich ELISA and a binding inhibition test. To determine whether Ab2 possess the internal image of the original antigen or not, mice were immunized with Ab2. ELISA and the competitive inhibition assay tested anti-anti-idiotypic antibodies (Ab3) in anti-sera. Cell-mediated immunity to tumors induced by Ab2 was investigated by a delayed-type hypersensitivity response and the mouse T-cell proliferation assay. Results Anti-idiotypic monoclonal antibodies against the monoclonal anti-NPC antibodies FC2 and HNL5 were generated that recognize NPC associated antigens. These Ab2, which were designated 2H4 and 5D3, could inhibit the binding of FC2 or HNL5 to NPC cell lines. Anti-sera from the immunized mice, which contained Ab3, could compete with FC2 or HNL5 for binding with NPC cell by a competitive inhibition assay. Mice immunized with 2H4 or 5D3 coupled with keyhole limpet hemocyanin (KLH), showed a positive and specific delayed-type hypersensitivity (DTH) reaction after stimulation by NPC cells. The mouse T cell proliferative assay indicated that there was a significantly higher proliferative response of the splenocytes in the experimental groups than that in control groups. Conclusions Anti-idiotypic antibodies 2H4 and 5D3 are Ab2 beta bearing the internal image of the epitope of NPC associated antigen. Either 2H4 or 5D3 expressing three-dimensional shapes that resemble the structure of natural antigens could induce humoral and cellular immune response.

Monoclonal Anti-CD4 Antibody MT310 Binds HIV-1 gp120 Binding Site on CD4

Tests show the monoclonal anti CD4 antibody (mAb) MT310 recognizes the gp120 binding site on CD4 as part of its mechanism for strongly inhibiting human immunodeficiency virus type 1 (HIV 1) infection of CD4 + T cells. In competition tests, mAb MT310 and mAb Leu3a (an anti CD4 mAb recognizing the gp120 binding site) all inhibited gp120 binding to CD4 + T lymphocytes, while mAb MT405 did not. This result suggests that MT310, like Leu3a, recognizes the gp120 binding site on CD4. To further confirm whether MT310 recognizes the gp120 binding site on CD4, we prepared rabbit anti idiotypic antisera (Ab2) against MT310 (Ab1). The anti idiotypic antisera against MT310 inhibited binding of MT310 and Leu3a to human CD4 + T lymphocytes, but did not block binding of MT151 with the second domain of CD4, while rabbit anti idiotypic antisera to MT151 could block binding of itself to these cells, but could not inhibit the binding of MT310 and Leu3a, further indicating that MT310 recognized the gp120 binding site on CD4.

Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed

Phosphocholine （PC） is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae （SPn）, and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M 167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag-/- mice. We have now shown that B cells expressing M603HK8L PC-specific receptors also delete in Rag-/- mice, whereas those expressing T15HK22L transgenes do not delete. However, T15HK22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603H^8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.