Occurrence of multiple lymphoepithelioma-like carcinomas and MALT-type lymphoma in the stomach: detection of EBV in carcinomas but not in lymphoma

A multifocal lymphoepithelioma-like carcinoma and a low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-type) were found simultaneously in the stomach of a 65-year-old patient. Carcinoma and lymphoma were intimately associated forming complexes resembling lymphoepithelial lesions at the primary gastric site and in lymph node metastases. The two tumours had developed on a background of severe chronic-atrophic gastritis of the mucosa of antrum and fundus. Autoantibodies to normal gastric glandular tissue could be demonstrated in the patient's sera. Using non-radioactive in situ hybridization (ISH), Epstein-Barr virus (EBV) sequences were detected in virtually all carcinoma cells but neither in the non-neoplastic mucosa nor in the lymphoma. These findings suggest that a focal EBV infection occurred early in the development of the carcinoma followed by a subsequent clonal expansion of the EBV-containing tumour cells. A neoplastic transformation in MALT-type lymphoma is not EBV-related but might be triggered by altered immune mechanisms.     

IgG subclass response to Helicobacter pylori and CagA antigens in children

Specific serum IgG subclass antibodies against Helicobacter pylori antigens and recombinant CagA were analysed in 75 symptomatic children with histologically confirmed H. pylori infection. H. pylori stimulated an IgG1 predominant response, and IgG3 titres showed a positive association with peptic ulcer disease, chronicity of antral inflammation and density of H. pylori colonization. Two methods used for assessing serum IgG CagA antibody status, i.e. Western blotting and enzyme-linked immunosorbent assay (ELISA), were concordant. CagA stimulated an IgG1 and IgG3 predominant humoral response. Total CagA IgG titres were higher in children with active and more severe chronic antral inflammation. These findings suggest that in children the systemic humoral immune response to H. pylori infection may reflect gastroduodenal pathology.     

CagA和机体免疫反应在幽门螺杆菌致病中的作用及相互关系

目的　探讨幽门螺杆菌 (Helicobacterpylori,Hp)菌型差异和机体免疫反应在Hp致病中的作用及其相互关系。方法　采用间接ELISA法检测了 175例患者血清抗HpCagA IgG和抗HpIgE。结果　①Hp感染者抗HpCagA IgG的阳性率 (80 % )明显高于抗HpIgE(5 8 2 9% ,P <0 0 1)。②血清抗HpCagA IgG在慢性活动性胃炎 (ACG)和十二指肠球部溃疡 (DU)患者显著高于胃溃疡 (GU)、胃癌(GCa)、慢性非活动性胃炎 (NACG)和对照组 (P <0 0 1) ,而后 4组之间差异无显著性。③血清抗HpIgE在ACG显著高于DU、GU、GCa、NACG和对照组 (P <0 0 1) ,并且在中重度胃炎显著高于轻度胃炎(P <0 0 0 1)。④血清抗HpCagA IgG和抗HpIgE无明显相关性 (r=0 2 45 9,P >0 0 5 )。结论　CagA和血清抗HpIgE参与了Hp的致病过程 ,但是两者之间无明显相关性 ,并且它们在疾病中的含量也有一定差异 ,这说明二者在Hp的致病过程中是相互独立的因素 ,Hp感染引起疾病是多因素的综合作用。     

Immune response to a recombinant fragment of the CagA protein of Helicobacter pylori in blood donors and patients with gastric cancer: relation to ABO(H) blood group phenotype, stage of the disease and tumor morphology

IgG immune response to CagA was evaluated by enzyme-linked imunosorbent assay (ELISA) using a recombinant fragment of CagA as antigen in 171 patients with gastric cancer and 298 blood donors to determine whether it could be related to the ABO(H) blood group phenotype, stage of cancer or tumor morphology. The CagA-ELISA showed a good specificity (93.5%) and sensitivity (88.5%) as compared with immunoblotting for blot CagA-negative and -positive donors. The Helicobacter pylori seropositive blood group A donors revealed the lowest proportion (37.6%) of strong responders to CagA: A<O (51.2%)<B (56.9%)<AB (62.5%). The proportion of strong responders to CagA was significantly lower among the H. pylori-seropositive patients with non-cardial cancer (35.4%) than in donors (48.8%). A significant suppression of immune response to CagA was found in the patients with advanced cancer. The proportion of CagA strong responders was higher at the first stage of gastric cancer in only blood group O and A individuals as compared with related controls. The overall CagA seroprevalence was not influenced by tumor histology. Thus, the IgG immune response to CagA is dependent on the ABO(H) blood group phenotype of the host and the stage of cancer. The host-dependent differences in the immune response to CagA may be more pronounced than those related to the putative disease-specific features of the H. pylori infection. Received: 18 November 1998     

The inflammatory response in CD1 mice shortly after infection with a CagA+/VacA+ Helicobacter pylori strain

To investigate the early events of Helicobacter pylori infection in a mouse model, CD1 mice were infected with a type I (CagA+/VacA+) H. pylori strain. Up to 4 weeks after infection the majority of gastric tissue biopsies were positive in culture. Immunohistochemical analysis showed that inflammatory changes started to occur after 3 weeks. Four weeks after infection a significant increase in T cells was observed in the cardia/corpus region of the stomachs of infected mice. These T cells were CD4+ and CD8+, and they were located in an area with increased expression of MHC class II antigens. In 50% of the infected mice also an increased number of mast cells was seen. Furthermore, aggregates of B and T cells were present in the submucosa. Characterization of cytokines by immunohistochemistry showed an increase in IL-5-secreting cells in the inflamed area of the infected stomach. No difference was observed between interferon-gamma (IFN-gamma)-, IL-4- and IL-10-secreting cells in control and infected mice. These results suggest that no polarized T-helper cell response was present at this early phase of infection. Infection with H. pylori also induced a serum response and especially IgG was increased after 4 weeks of infection. However, no particular increase in IgG1, IgG2a or IgG3 isotype was observed. Part of the serum antibodies was directed against lipopolysaccharide (LPS), but no evidence for anti-Lewis antibodies or antibodies against epitopes on the gastric mucosa was found.     

幽门螺杆菌相关抗原及宿主免疫应答的研究进展

幽门螺杆菌与多种胃肠道疾病诸如慢性胃炎,胃肠溃疡,胃腺瘤及胃癌等密切相关的结论已得到证实,预防和治疗幽门螺杆菌感染是控制其广泛传播的有效途径,此项工作虽早已开始,但至今未找到可行的方案.近来对幽门螺杆菌相关毒素的研究越来越多,这可作为研究幽门螺杆菌菌苗的重要依据;幽门螺杆菌诱发的宿主免疫应答以TH1反应为主,幽门螺杆菌感染者可出现系统和局部的抗体反应,这些抗体反应对机体不具保护作用且自身抗体对宿主上皮细胞还可能带来不良影响,阐明宿主免疫应答的机制对预防和治疗幽门螺杆菌感染具特殊意义.因此,本文主要介绍了脲素酶、空泡细胞毒素、cag相关基因蛋白,中性粒细胞蛋白等几种毒素及宿主免疫应答的研究现状,并对幽门螺杆菌的研究前景进行综述.     

CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model

Helicobacter pylori causes various gastro-duodenal diseases, including gastric cancer. The CagA protein, an H. pylori virulence factor, induces morphological changes in host cells and may be associated with the development of peptic ulcer and gastric carcinoma. The present study has analysed the role of CagA protein in the pathogenesis of H. pylori infection in the Mongolian gerbil model. Mongolian gerbils were challenged with wild-type H. pylori strain TN2, which has a functional cag pathogenicity island or isogenic mutants with disrupted cagA (DeltacagA) or cagE (DeltacagE) genes. They were sacrificed at 7, 13, and 25 weeks after inoculation. Pathological changes of the gastric mucosa were determined and apoptosis was assessed by the TUNEL assay. Immunohistochemistry for PCNA, phospho-IkappaBalpha, and phospho-Erk was also performed. All of the bacterial strains colonized the gerbil stomach at similar densities; however, the DeltacagA mutant induced milder gastritis than did the wild type. The extent of apoptosis and lymphoid follicle formation in the epithelium appeared to depend on intact cagA. The DeltacagA mutant induced less phosphorylation of IkappaBalpha and Erk, and less expression of interferon-gamma and interleukin-1beta mRNA in the epithelium than did the wild type. It is concluded that CagA protein may be essential for the induction of severe gastritis in the Mongolian gerbil model.     

Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori

The gastric carcinoma risk index is a histological criteria to Helicobacter pylori-infected patients with a high risk of gastric cancer. The aim of this study was to examine the applicability of this index for the intestinal-type gastric cancer in Japanese patients with H. pylori infection. In 55 patients with early intestinal-type gastric cancer and 69 control subjects, we calculated the gastric cancer risk index score by evaluating the grade of mononuclear cell (MNC) and polymorphonuclear cell (PMN) infiltration and the presence of intestinal metaplasia. The gastric cancer index score was significantly higher in patients with gastric cancer (P<0.01). The presence of intestinal metaplasia was significantly more frequent in cancer patients than in controls, while infiltration of MNCs or PMNs in the corpus was not different in the two groups. Within the gastric cancer risk index, the presence of intestinal metaplasia was the only criteria associated with the development of intestinal-type gastric cancer in Japan. The gastric cancer risk index may not be applicable to identify H. pylori-positive patients at high risk of developing intestinal-type gastric cancer in Japan. Received: 6 October 1999 / Accepted: 22 December 1999     

CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions

The C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3’ region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p <0.001). In 54 strains, the CM motifs were identical to those common in Western strains. Thirteen strains from the low-risk area contained two different CM motifs: one of Western type located within the EPIYA-C segment and another following the EPIYA-C segment and resembling the CM motif found in East Asian strains. These strains induced significantly shorter projections in AGS cells and an attenuated reduction in levels of CagA upon immunodepletion of SHP-2 than strains possessing Western/Western motifs. This novel finding may partially explain the difference in GC incidence in these populations.     

Helicobacter pylori antigen in the glomeruli of patients with membranous nephropathy

 Renal biopsy specimens from patients with membranous nephropathy (MN) were studied using immunohistochemical labelling to clarify the aetiological significance of Helicobacter pylori antigen in this disease. Sixteen specimens were examined, from 7 male and 9 female MN patients. Renal specimens from patients with diabetic nephropathy and IgA nephropathy, and from autopsied patients without renal diseases were obtained as controls. Immunohistochemical labelling was performed using one polyclonal antibody and three monoclonal antibodies against H. pylori. Specimens from 11 of the MN patients revealed granular deposits along the glomerular capillary walls, which reacted positively with polyclonal antibody after trypsin pretreatment. None of the control specimens revealed positive labelling. The MN specimens showed no positive reaction with the primary antibody, which had been treated for immunoabsorption testing using sonicated H. pylori.We also determined H. pylori status in these MN patients histologically and/or serologically. Of the 11 patients whose glomeruli were positive for anti-H. pylori antibody, 7 were suitable for analysis, and all were regarded as positive for H. pylori infection. These results suggest that the presence of a specific antigen in the glomeruli of patients with MN and H. pylori infection may be involved in the pathogenesis of MN. Received: 18 October 1996 / Accepted: 3 March 1997     

Helicobacter pylori infection produces reversible glycosylation changes to gastric mucins

 The protective ability of gastric mucins may depend largely on their oligosaccharide chains. We evaluated the effects of H. pylori infection on the glycosylation of gastric mucins. Gastric biopsy specimens from 20 H. pylori-infected patients before and after cure of the H. pylori infection and 8 normal uninfected volunteers were examined by immunostaining for simple mucin-type glycoproteins and blood-group-related antigens bearing type 1 chain backbone. The immunoreactivity in different gastric compartments was evaluated. Simple mucin-type glycoproteins and blood-group-related antigens were expressed in surface mucous cells. Simple mucin-type glycoproteins showed antrum-predominant expression in normal volunteers and were found in significantly fewer surface mucous cells in infected patients than in normal volunteers; their expression was restored after eradication of H. pylori. Sialyl Lewis^a and Lewis^b were expressed in fewer surface mucous cells after than before eradication. The patterns of glycosylation of gastric mucins vary in different gastric compartments and are reversibly altered by H. pylori infection. These alterations may affect the protective functions of gastric mucins. Received: 23 April 1998 / Accepted: 2 July 1998     

Sex hormones and the immune response in humans

In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more resistant to certain infections, and suffer a higher incidence of autoimmune diseases. Disease expression is also affected by the reproductive status of the female. As sex steroids--estrogens, progesterone and testosterone--differ between gender and within different reproductive stages, a lot of research has focussed on the effects of sex hormones on immune responses. Although there is also a vast literature on the effects of sex hormones on immune responses in animals, in this review we will focus on the most intriguing effects and mechanisms by which sex hormones affect different components of the immune system in humans.     

幽门螺杆菌免疫奶羊的应答性实验研究

目的　以Hp全菌抗原免疫奶羊 ,观察羊奶中特异性抗体产生规律。方法　采用 6× 10 9CFU mLHp全菌抗原 ,通过滴鼻、多点皮下注射、妊娠期肌肉注射 3种途径免疫 3只产奶山羊。前两组于 0、14、2 1、2 8d接受 4次免疫接种 ,妊娠组于分娩前后 1个月每隔两周注射 1次。收集血清、乳清 ,以酶联免疫吸附试验进行样本中的IgA、IgG抗体测定。结果　 3种途径免疫奶羊后都激发了奶羊的系统免疫 ,使血清中IgG较免疫前都有很大升高 ;羊奶中IgA抗体水平滴鼻组 >妊娠组 >皮下组 ,IgG抗体水平妊娠组 >皮下组 >滴鼻组。结论　 3种途径都能激发奶羊机体的免疫应答 ,尤其是滴鼻免疫能够诱导机体同时产生不同部位的粘膜免疫和系统免疫 ,是一种敏感、安全、可行有效的免疫途径     

以壳聚糖为佐剂的Hp疫苗诱导的体液免疫应答及其免疫保护效应

目的：探讨以壳聚糖为佐剂的Hp疫苗的免疫保护作用及其机制。方法:BALB/c小鼠随机分为9组：①空白对照组：PBS溶液；②壳聚糖酸溶液组；③壳聚糖颗粒组；④Hp抗原组；⑤Hp抗原+壳聚糖酸溶液组；⑥Hp抗原+壳聚糖颗粒组；⑦Hp抗原+CT组；⑧Hp抗原+壳聚糖酸溶液+CT组；⑨Hp抗原+壳聚糖颗粒+CT组，各组于第0、7、14、21 d 灌胃各免疫1次，免疫后4周给予1×1012CFU/L的SS1 Hp菌液每只 0.5 mL进行攻击，隔日1次，共2次。4周后，采用定量Hp培养和病理改良Giemsa染色法检测胃黏膜内Hp感染。用ELISA法检测血清抗Hp IgG、IgG1、IgG2a及唾液和胃黏膜内抗Hp IgA，用SP免疫组织化学法检测胃黏膜内分泌型IgA（sIgA）。结果:①以壳聚糖为佐剂的Hp疫苗的免疫保护率达60%，与以CT为佐剂的Hp疫苗的免疫保护率（58.33%）相似，显著高于单纯Hp抗原组及其它不含Hp抗原组（P<0.01或P<0.05），同时以CT＋壳聚糖为佐剂的Hp疫苗的保护率为84.62%、85.71%，其Hp的定植评分显著低于无佐剂组及以CT为佐剂组（P<0.01，P<0.05）。②含佐剂的Hp疫苗所诱导产生的Hp IgG水平显著高于对照组及无佐剂组（P<0.01，P<0.05），而以CT＋壳聚糖为佐剂组所产生的抗Hp IgG水平显著高于仅以 CT或壳聚糖为佐剂组（P<0.05）。③胃黏膜内sIgA及特异性抗Hp IgA水平在壳聚糖为佐剂组与以CT为佐剂组无差别（P>0.05），显著高于无佐剂组，而壳聚糖与CT联合应用组显著高于单以CT为佐剂组（P<0.01，P<0.05）。结论:以壳聚糖为佐剂的Hp疫苗对Hp感染具有免疫保护作用，并可成功诱导黏膜局部的特异性体液免疫应答，从而发挥免疫防御作用。     

幽门螺杆菌感染小鼠及其抗原免疫小鼠后体液免疫应答的比较

目的：比较BALB／c小鼠感染H.pylori后以及经H.pylori UreB抗原口服免疫后的体液免疫应答的差异。方法：80只BALB／c小鼠分为感染组和免疫组，感染组灌喂H.pylori小鼠适应株；免疫组灌喂重组H.pylori UreB抗原和佐剂LTB。在试验的0，2，6和10周时每组分别取10只小鼠收集唾液及血液标本，用ELISA法检测抗UreBIgG和IgA抗体，同时采集胃组织作H.pylori感染检测。结果：感染组小鼠在灌喂H.pylori后2，6，10周，感染率均为100％，其血清中抗UreB IgG增高明显，但血清及唾液中均未见IgA的明显升高，；免疫组小鼠在初次免疫后第6，10周后，血清及唾液中抗UreB,IgG和IgA抗体的均显著升高。结论：H.yplori感染BALB／ c小鼠不能诱导其产生明显的特异性黏膜免疫应答，而重组UreB可作为良好的免疫原诱导其产生分泌型IgA抗体。     

Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies

 In the course of time, chronic gastritis may result in gastric atrophy, as in type A gastritis, where autoimmune reactions against parietal cells result in a loss of corpus glands. Two antigastric autoantibodies have been detected in Helicobacter pylori gastritis and are described as anti-luminal and anti-canalicular autoantibodies. The aim of this study was to determine whether increased apoptosis may be responsible for the loss of gastric epithelium and whether this apoptosis is correlated with antigastric autoimmunity. Gastric biopsies from normal mucosa and Helicobacter pylori gastritis were analysed for the presence of apoptosis using the TUNEL method. Helicobacter pylori gastritis was divided into cases (1) without autoantibodies, (2) with anti-luminal, and (3) with anti-canalicular autoantibodies. Apoptotic cells of the foveolar and of the glandular epithelium in the antrum and corpus were counted. The number of apoptotic cells in the gastric mucosa was significantly increased in all cases of gastritis. The highest number of apoptotic cells was observed in the gastric glands of the corpus mucosa in Helicobacter pylori gastritis with anti-canalicular autoantibodies. Apoptosis contributes to the development of gastric atrophy and there are various types of Helicobacter pylori gastritis. The positive correlation between apoptotic cell loss in the glandular zone of the corpus mucosa and the presence of anti-canalicular autoantibodies indicates a possible link between antigastric autoimmunity and atrophy in this type of Helicobacter pylori gastritis – similar to that in classic type A gastritis. Received: 19 November 1997 / Accepted: 24 March 1998     

Immune response to Helicobacter pylori and its association with the dynamics of chronic gastritis in the antrum and corpus

The aim of the study was to establish possible factors which play a role in progression of gastritis to atrophic gastritis in long-term follow-up among the Estonian population, to assess the association between the host immune response and different Helicobacter pylori antigens and autoantigens in relation to the histological parameters of gastritis in the antrum and corpus. ELISA and immunoblot were used for detection of IgG to H. pylori acid glycine-extracted cell surface proteins, CagA protein, and H. pylori HSP60. Anticanalicular autoantibodies (ACAB) in the serum were evaluated according to Faller et al. (1996). Apoptosis was evaluated using the TUNEL method. Study subjects were 1958 persons from an unselected Estonian population, and 70 persons from a sample from Saaremaa Island, who had been investigated over a period of 18 years. Seropositivity for CagA was a sign of gastritis activity [OR=14.8 (4.5-50.3)] and atrophy [OR=7.0 (2.1-23.1)] and might predict development of atrophy, particularly in the corpus [OR=7.1 (1.8-27.7)]. The prevalence of ACAB increased significantly with duration of H. pylori gastritis from 22% in 1985 to 46% in 1997 (p=0.004). Immune response to H. pylori HSP60 indicates chronic inflammation in the antrum (p=0.003). Apoptosis of gastric epithelial cells is largely dependent on grade of activity of gastritis, and, particularly in the antrum, on grade of H. pylori colonization (p=0.01; p=0.02), but is not associated with development of atrophy. Seropositivity for different H. pylori antigens (CagA, HSP 60) serves as a marker of different histological manifestations in the antrum and corpus mucosa.     

Circulating antibodies to the 60-kD heat shock protein (hsp) family in patients with Helicobacter pylori infection

Whilst the mechanism by which Helicobacter pylori causes different gastroduodenal diseases is uncertain, strains producing the cytotoxin-associated protein (CagA) have greater pathogenicity. Hsps are immunogenic molecules induced by inflammatory mediators. The aim of this study was to assess pathogenicity of hsp antibodies in H. pylori-infected patients. ELISA techniques were used to assay sera of H. pylori-positive patients with gastritis, gastric atrophy, duodenal or gastric ulcer, and H. pylori-negative controls, for antibodies to CagA and to human, mycobacterial, and in 20 sera, H. pylori (hspB) 60-kD hsp. IgA antibodies to mycobacterial hsp60 in atrophy patients were elevated compared with patients with gastritis (P < 0.05) and with H. pylori-negative controls (P < 0.0005). IgA antibodies to human hsp60 in gastric atrophy patients were elevated compared with H. pylori-negative controls (P < 0.05). Patients with atrophy (P < 0.0005) and gastritis (P < 0.05) who were CagA-positive had raised titres of anti-mycobacterial hsp60 IgA antibodies compared with controls. IgA antibody levels to hspB were positively correlated with those to mycobacterial hsp60 (mhsp60) (P < 0.05) and human hsp60 (hhsp60) (P < 0.005). IgA antibodies to hsp60 are associated with gastroduodenal disease, particularly gastric atrophy, in H. pylori-infected patients. Increased humoral responses to hsp60 could either contribute to gastric atrophy or result from greater gastric mucosal damage induced by CagA-positive strains of H. pylori.     

Induction of a non-oscillating, long-lasting humoral immune response to an internal network antigen

B lymphocyte antigen receptors form an internal idiotypic networkwhich is also connected by idiotypic interactions with the Tlymphocyte compartment. Idiotypic-anti-idiotypic activationof lymphocytes has mainly been measured at the cellular levelwhile the kinetics of primary anti-idiotypic humoral responseshas so far not been determined. Here, we describe the inductionof an anti-idiotypic immune response to the major idiotype (ld_Ox1)of the primary immune response in BALB/c mice to the hapten2-phenyl-5-oxazolone coupled to chicken serum albumin. A primaryanti-idiotypic humoral response could be induced with the phOx-bindingand ld_Ox1-expressing, germline-encoded antibody H11.5 (µ,k) coupled to keyhole limpet hemocyanin. Compared to that ofconventional antigens, the anti-idiotypic response showed alag phase of 3 weeks. When the anti-ld_Ox1 serum titers had declinedto background levels, a secondary anti-ld_Ox1 response couldbe induced even with soluble H11.5. This response showed asfast an increase as conventional antigens, but the antibodyplateau did not exceed that of the primary response. Duringthis secondary anti-ld_Ox1 response and probably to a small extentalso during the primary response, the mice developed an idiotypicallynon-related IgM-anti-phOx response. In contrast, soluble H11.5—eitherpassively injected or transiently expressed during the earlyprimary anti-hapten response—suppressed the anti-idiotypicresponse to H11.5 for up to 7 months in the majority of mice,while individual mice exhibited an early release from this suppressionat various times. The differences and similarities between externaland internal antigen-induced immune responses as well as theimplications for idiotypic network regulation are discussed.