Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens.

We evaluated the cellular immune competence of 101 subjects living in an area of South Kalimantan (Borneo) where Malayan filariasis is endemic. All patients with elephantiasis but none with other clinical stages of filariasis reacted with adult worm antigens. The majority of subjects without clinical or parasitological evidence of filariasis and approximately one-half of those with amicrofilaremic filariasis reacted with microfilarial antigens. In contrast, most patients with patent microfilaremia did not respond to microfilarial antigens. The in vitro reactivity of all patient categories to nonparasite antigens was similar to that of the distant control group. These results indicate that patent microfilaremia is associated with a state of specific cellular immune unresponsiveness and are consistent with the current hypothesis that the various clinical manifestations of filariasis result from different types of immune responses to distinct antigens associated with different developmental stages of filarial worms.     

Antigen specific stimulation of immune responses during long-term repeated skin testing with multiple antigens

Delayed-type hypersensitivity (DTH) skin testing as an assay of immune competence is a widely used technique. Accordingly, clinical situations frequently occur which require that skin tests be performed many times on the same patient. In the present investigation, in vivo and in vitro immune responses were studied over a 7-month period in 22 normal human volunteers, each of whom were skin tested 6 times at monthly intervals with multiple antigens. Patterns of responses to the 7 specific skin test antigens observed during repeated skin testing in vivo indicated non-significant, but detectable, declines in skin test reactivity to tetanus, diphtheria and streptococcus antigens and increases in reactivity to trichophyton, tuberculin, candida and proteus antigens. In vitro lymphocyte transformation assays (LTAs) of cell-mediated immune (CMI) activities revealed that repeated skin testing, e.g., 3-5 serial skin tests, induced significantly increased levels of CMI reactions with 3 of the 4 skin test antigens used as challenge antigens. Since no significant changes in in vitro CMI responses were detected using 3 control "non-skin test" antigens, the effects observed were confirmed to be antigen specific. Increased IgG antibody responses were detected for only the toxoid antigens during the skin testing period. For the group of 22 normal volunteers, positive statistical correlations were not observed between any individual skin test antigen and the immune reactions assayed specifically for that antigen, including DTH responses and levels of circulating antigen-specific antibodies. Short term differences were detected between tetanus, diphtheria and streptococcus antigens in their LTA response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)     

结核酶联免疫斑点试验与抗结核抗体平行检测比较

5.25%,抗体检测分别为73.91%和59.46%;2种方法阳性预测值和阴性预测值比较差异均有统计学意义(χ2=3.941,P=0.047;χ2=5.268,P=0.022).采用T-SPOT.TB与ELISPOT检测结果进行配对比较,差异无统计学意义(χ2=0.500,P=0.480).结论 结核分枝杆菌ESAT-6抗原特异性IFN-γ的细胞免疫检测技术在结核病临床辅助诊断的应用价值显著高于结核菌特异性抗体检测,值得进一步优化和推广.     

Clinical application of ultrasonography to the autoimmune thyroid disease]

US images can detects exactly the size of thyroid gland. B-mode images with high resolution USG shows fine structure of thyroid gland. Furthermore, recent progress of ultrasonography can clarify the vascularity of thyroid gland using 3D-images. The thyroid gland of Graves' disease shows diffuse and remarkably increased vascularity. On the other hand, that of destructive thyroiditis reveals hypovascularity in hypoechoic lesion. There is the possibility that ultrasonographic images is useful tool to clarify the pathogenesis of autoimmune thyroid disease.     

Applying peptide antigens onto bare skin: induction of humoral and cellular immune responses and potential for vaccination.

The development of non-invasive immunisation procedures is a top priority for public health agencies when it is realised that the current immunisation practices are unsafe, particularly in developing countries due to the widespread reuse of non-sterile syringes. There is a risk of abscess formation resulting in impairment of meat quality or the value of the hide, and the risk of transmission of infectious diseases when vaccines are administered to food animals by injection. Recently, the skin has emerged as an alternative route for non-invasive delivery of vaccines. Topical application of various types of antigens (mainly proteins and toxoids) with an adjuvant resulted in the induction of systemic and mucosal immune responses. However, due to skin barrier constraints and the physicochemical properties of large molecular weight proteins, the immune responses are variable and require further optimisation. Small molecular size synthetic peptides when applied onto bare skin with an adjuvant are effective immunogens, inducing both humoral and cellular immune responses. Their use as vaccines offers considerable advantages over conventional preparations in terms of safety, purity, stability, availability and cost. Therefore, they could be the most suitable candidate immunogens for skin immunisation. This review describes our recent observations on the immunogenicity of synthetic peptides applied onto bare skin in relation to vaccination.     

Immunoadsorption as a tool for the immunomodulation of the humoral and cellular immune system in autoimmune disease.

Immunoadsorption onto staphylococcal protein A is a newly developed semiselective extracorporeal adsorption technique for immunoglobulins applied in patients suffering from severe autoimmune disease. Its effect on the humoral and cellular immune system was investigated using standard immunological assays. The elimination capacity for total IgG and IgG subclasses 1, 2, and 4 was more than 90% but for subclass IgG3 varied between 30 and 90%. Autoantibodies, e.g., anti-dsDNA, anti-glomerular basement membrane (anti-GBM), anti-cardiolipin, and anti-human leukocyte antigen (anti-HLA) antibodies, were eliminated in comparable amounts. The affinity of protein A for circulating immune complexes (CIC) was 300 times greater than for soluble IgG. HLA-II expression on monocytes and T lymphocytes was reduced over time during repeated IAs (IA). The number of activated T lymphocytes declined while the percentage of naive T cells increased. A diminished CD4/CD8 ratio normalized during IA treatment. These results indicate that IA actively modulates the humoral as well as the cellular immune system in addition to its immunoglobulin reducing effect.     

Humoral and cellular immune responses to Salmonella typhi in patients with typhoid fever

Humoral and cellular immune responses to Salmonella typhi have been studied in nine children with typhoid fever. By using dot immunobinding assay, anti-O-polysaccharide chain and antilipid A antibody titers have been evaluated during the course of the disease. Anti-O-polysaccharide chain antibody titers are lower at the first week and increase up to the third week of the infection. On the other hand, antilipid A antibody levels, which are already higher at the beginning of the disease, progressively augment during the following weeks. Concerning cellular immunity to S. typhi, antibacterial activity mediated by typhoid peripheral mononuclear cells has been determined. Results show this function to be depressed in the initial phase of typhoid, increasing with the time. Together, these data bring new insight on immunity in typhoid patients.     

甲状腺自身抗体在自身免疫性甲状腺疾病诊断中的应用价值

目的 探究甲状腺自身抗体在自身免疫性甲状腺疾病(AITD)诊断中的应用价值.方法 选择2019年5月至2020年5月我院收治的80例AITD患者作为AITD组,其中34例为桥本甲状腺炎(HT),46例为毒性弥漫性甲状腺肿(Graves病);另选取同期我院50例健康体检者作为对照组.比较各组的促甲状腺激素受体抗体(TRA...     

Ultrasonography of the thyroid gland in pregnancies complicated by autoimmune thyroid disease

Thyroid function and ultrasonographically determined thyroid volume were studied in nine pregnant women with diagnosed autoimmune thyroid disease at regular intervals during pregnancy and two months after delivery. The results were compared to the findings in ten healthy pregnant women. In ultrasound examinations seven of the patients showed definite morphological changes such as hypoechogeneity and inhomogeneity of the thyroid gland, which did not change during the course of pregnancy nor during the post-partum period of eight weeks. There were no morphological changes in the thyroid glands of the control group. The mean thyroid volume did not significantly change during pregnancy and after delivery in both the patient group and controls. The mean thyroid volume was smaller in the study group, with 7.55 ml (SD 6.01) compared to the controls with 11.29 ml (SD 5.61), a difference which was not statistically significant. Neither course of pregnancy nor fetal outcome was influenced by inactive autoimmune disease of the thyroid. © 1993 John Wiley & Sons, Inc.     

Celiac disease occurring in a patient with hypoparathyroidism and autoimmune thyroid disease

Patients with an underlying autoimmune endocrine disorder are at an increased risk of developing other autoimmune diseases. We describe a patient with idiopathic autoimmune hypoparathyroidism who developed hyperthyroidism due to Graves disease and subsequently was diagnosed with celiac disease. Malabsorption of L-thyroxine was the only clue regarding the presence of celiac disease. This particular association of these three autoimmune disorders occurring in the same patient has not, to our knowledge, been previously reported. The presentation, investigations performed, and treatment provided are discussed and the literature pertaining to similar cases is reviewed.     

Apoptosis in the pathogenesis of autoimmune thyroid disease]

Apoptosis is a physiological process of cell death that occurs as part of normal development and in response to a variety of physiological and pathophysiological stimuli. The effector mechanisms, which carry out the death program, are well preserved across species and evolution. This article summarizes the recent studies on apoptosis in view of its molecular mechanism and the relation to autoimmune thyroid diseases. In Hashimoto's thyroiditis, which is a typical organ-specific autoimmune disease, Fas-FasL-mediated apoptosis has been demonstrated as the mechanism of follicular epithelial cell death. In Graves' disease, Anti TSH receptor antibody inhibits Fas antigen-mediated apoptosis of thyrocytes through the inhibitory effect of Fas antigen expression, resulting in the promotion of growth of the thyroid gland.     

维生素D与自身免疫性甲状腺疾病的研究进展

自身免疫性甲状腺疾病(AITD)是一种T淋巴细胞介导的器官特异性自身免疫性疾病,主要包括桥本甲状腺炎(HT)和Grave病(GD),其发病机制尚不明确,可能与遗传、环境及免疫等有关。维生素D除具有调节骨和钙磷代谢,防治骨质疏松外,近年研究发现维生素D可能通过影响T淋巴细胞的增殖与分化,参与免疫调节,维持免疫内稳态。本文综述维生素D与AITD相关性的研究进展,旨在为AITD的预防与治疗提供新的思路。     

The specificity of cellular immune responses in guinea pigs. I. T cells specific for 2,4-dinitrophenyl-o-tyrosyl residues

Guinea pigs immunized with the hapten 2,4-dinitrophenyl (DNP) coupled directly to Mycobacterium tuberculosis of strain H37Ra (DNP-H37) show a variety of cell-mediated immune responses to DNP coupled to protein carriers. The cells responsible for this specific response are thought to be T lymphocytes for the following reasons: Guinea pigs immunized with DNP-H37 displayed delayed hypersensitivity reactions to several DNP-proteins and contact sensitivity to dinitrofluorobenzene. Peritoneal exudate lymphocytes (PELs) obtained from DNP-H37 immune animals respond to DNP-proteins with DNA systhesis and cause inhibition of macrophage migration. PELs are highly enriched in T lymphocytes and contain few immunoglobulin-bearing cells. Further depletion of immunoglobulin-bearing cells from this population does not diminish the in vitro proliferative response to antigen. Nitrophenyl conjugates of proteins lacking a paranitro group stimulated DNA synthesis poorly or not at all, indicating the importance of the paranitro group of DNP in antigen recognition by T cells in this system. In this respect, the specificity of T cells resembles that of DNP-specific antibody from the same animals. On the other hand, DNP conjugates of copolymers of glutamic acid and lysine and DNP conjugated to proteins via an interposed beta-alanyl-glycyl-glycyl spacer failed to stimulate DNA synthesis, although such compounds bind very efficiently to anti-DNP antibody. By contrast, DNP conjugates of synthetic polypeptide carriers containing as little as 7% tyrosine strongly stimulated DNA synthesis in DNP-H37 immune PELs. That the determinant responsible for this stimulation was DNP coupled to the hydroxyl group of tyrosine was shown by selective removal of DNP from tyrosine by thiolysis with 2-mercaptoethanol, which abolished their ability to stimulate T cells.     

Humoral and cellular immune responses of atopic individuals in a tropical environment

In this study we compared immediate, intermediate and delayed skin test reactivity, total and specific serum IgE, IgG, A, M antibody and lymphocyte proliferative responses, between atopic and normal individuals in the tropical environment of Caracas, Venezuela (Lat. 10 degrees N). The allergenic extracts tested were prepared from house dust, mixed moulds and Aspergillus fumigatus. In lymphocyte stimulation the mitogen Concanavalin A was also employed, the cultures being supplemented with either autologous plasma, or a gamma globulin-depleted pool. The results revealed the association of immediate skin reactions with IgE antibody against house dust, and intermediate reactions with IgG, A, M antibody against moulds. No relation was, however, detected between delayed skin reactivity and in vitro lymphocyte transformation; skin reactions occurred at the highest frequency with moulds, while house dust provoked the strongest in vitro stimulation. Also, although the areas of positive delayed reactions were greatest in the atopic individuals, the lymphocyte proliferative responses were clearly highest in the normal subjects. The significance of the positivity of lymphocyte transformation tests in all of the study group, but lower reactivity in the atopics, is considered.     

Assessment of serum dipeptidyl peptidase-IV levels in autoimmune thyroid disease

ObjectiveDecreased serum dipeptidyl peptidase-IV (sDPPIV) levels have been reported in patients with autoimmune diseases. However, few studies have analyzed the association between sDPPIV levels and autoimmune thyroid disease (AITD). This study aimed to evaluate the association between sDPPIV levels and three types of AITD: Graves’ disease (GD), Graves’ ophthalmopathy (GO), and Hashimoto’s thyroiditis (HT).MethodsPatients newly diagnosed with GD (n = 65), GO (n = 22), and HT (n = 27) and healthy individuals (n = 30) were recruited. Clinical characteristics and thyroid function data were collected. sDPPIV was measured using enzyme-linked immunosorbent assays.ResultsCompared with controls (786.3 ± 46.95), patients with GD and GO had significantly lower sDPPIV levels (662.2 ± 38.81 and 438.4 ± 31.78). Additionally, sDPPIV levels were negatively associated with antithyroid peroxidase antibody (r = −0.20) and antithyroglobulin antibody (r = −0.19), but there was no significant relationship between thyroid hormone and sDPPIV levels. GO cases were divided by proptosis with and without muscle thickening; sDPPIV levels were lower in the muscle thickening group than those in the without muscle thickening group. Logistic regression analysis showed that sDPPIV was negatively correlated with GO and GD.ConclusionssDPPIV concentrations were abnormal in patients with GD and GO, and reduced sDPPIV expression may be involved in the progression of GO and GD.     

血清甲状腺球蛋白抗体、甲状腺微粒体抗体、甲状腺过氧化物酶抗体对自身免疫性甲状腺疾病的诊断价值

目的探讨血清甲状腺球蛋白抗体（TGAb）、甲状腺微粒体抗体（TMAb）、甲状腺过氧化物酶抗体（TPOAb）对自身免疫性甲状腺疾病（AITD）的诊断价值。方法100例甲状腺功能异常患者根据血清中三碘甲状腺原氨酸（B）、甲状腺素（Td）、促甲状腺激素（TSH）水平分为甲亢组和甲减组,每组50例;另选择50例甲状腺功能正常人群作为对照组。各组患者均采集静脉血5mL,分离血清,放射免疫法测定患者血清中TGAb、TMAb、TPOAb、L、T4、TSH水平。观察各组患者血清中TGAb、TMAb、TPOAb阳性率;比较各组TGAb、TMAb、TPOAb阳性患者血清水平。结果甲亢组和甲减组血清TPOAb阳性率均明显高于血清TGAb、TMAb阳性率;甲亢组、甲减组患者血清TGAb、TMAb、TPOAb阳性率均明显高于对照组;甲减组患者血清TGAb、TMAb、TPOAb阳性率均明显高于甲亢组。甲亢组和甲减组患者血清TGAb、TMAb、TPOAb水平均明显高于对照组。甲减组患者血清中TGAb、TMAb、TPOAb水平均明显高于甲亢组。结论TPOAb在AITD的诊断中具有重要意义,为AITD的诊断、治疗及预后评估提供了重要依据。     

Antigen recognition and the immune response. Humoral and cellular immune responses to small mono- and bifunctional antigen molecules

L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT. Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both. Immunization with symmetrical bifunctional RAT-(SAC)_n-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.     

Mercuric chloride induced autoimmune disease in Brown-Norway rats: sequential search for anti-basement membrane antibodies and circulating immune complexes

Mercuric chloride induces in the Brown-Norway rat a biphasic autoimmune disease characterized initially by linear IgG deposits along the glomerular basement membrane followed later by granular IgG deposition. In the present study, anti-glomerular basement membrane antibodies and immune complex-like material were sequentially assessed in serial serum samples. Both were transiently found at the same period. Glomerular linear IgG deposits were present on day 11 but circulating anti-glomerular basement membrane antibodies were only found later on day 16. Circulating immune complexes were first detectable on day 8 before the earliest granular IgG deposits were first observed in the spleen vessels on day 16. The disappearance of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes, although HgCl2 injections were pursued, is in agreement with the self-limited character of mercuric chloride induced autoimmune disease and suggests the induction of immunosuppressive mechanisms.