Suppression of cellular immune responses following transfer factor: Report of a case

A girl with chronic mucocutaneous candidiasis and recurrent staphylococcal infections had abnormal cellular immunity and defective granulocyte chemotaxis. Administration of dialyzable transfer factor caused conversion of the candida skin test and MIF production by candida-stimulated lymphocytes but had no effect on granulocyte chemotaxis and produced no clinical benefit.Nine months later, while her cellular immunity was still intact, she received four additional doses of dialyzable transfer factor. Following these injections, the delayed skin tests and antigen-induced lymphocyte transformation and lymphokine production temporarily became negative. There were no effects on granulocyte chemotaxis.These observations suggest that transfer factor may have both suppressive and activating immunologic activities.     

Study of the immunotropic activity of aminoglycoside antibiotics

The action of some aminoglycoside antibiotics on the immune system was studied on both intact mice and the animals with immune deficiency caused by administration of cyclophosphamide. The following tests were used: local hemolysis (the Herne test), lymphocyte transformation (LT), delayed hypersensitivity to sheep red blood cells and the local graft versus host reaction (GVHR). Amikacin was shown to have no significant action on the activity of lymphocytes in the intact mice and stimulated both cellular (LT and GVHR) and humoral (the Herne test) immunity in the animals with lowered immunological reactivity. Sisomicin had no significant action on the immune system of the animals. Gentamicin suppressed the immune response only in the intact mice. Kanamycin and streptomycin induced inhibition of humoral and cellular immunity in both the intact mice and animals with immune deficiency. On the basis of the results it was concluded that gentamicin, amikacin and sisomicin may be used in the treatment of diseases developing in the presence of immune deficiency whereas streptomycin and kanamycin should be recommended when inhibition of the immunity is needed.     

玛咖醇提物对正常小鼠免疫功能的影响

本文采用小鼠碳粒廓清、植物血凝素(PHA)诱导淋巴细胞转化,以及血清溶血素和抗体生成细胞测定等实验,研究南美植物玛咖的乙醇提取物对正常小鼠免疫功能的影响。结果表明,玛咖醇提物显著提高PHA诱导的淋巴细胞转化,促进血清溶血素生成,并增加抗体生成细胞的产生,而对单核巨噬细胞的吞噬功能无显著影响。因此,玛咖醇提取物可提高正常小鼠细胞和体液免疫功能,增强机体抵抗力。     

Detection of cellular immunity with the soluble antigen of the fungus Sporothrix schenckii in the systemic form of the disease

Sporothrix schenckii is the etiologic agent of sporotrichosis, a mycosis of world-wide distribution more commonly occurring in tropical regions. The immunological mechanisms involved in the prevention and control of sporotrichosis are not fully understood but apparently include both the humoral and cellular responses. In the present investigation, cellular immunity was evaluated by in vivo and in vitro tests in mice infected with yeast-like forms of S. schenckii. The disease developed systemically and cellular immunity was evaluated for a period of 10 weeks. The soluble antigen utilized in the tests was prepared from yeast form of the fungus through the sonication (20 min: 10 sonications at 50 W at 2-min intervals). Delayed hypersensitivity and lymphocyte transformation tests showed that the cellular immune response was depressed between the 4th and 6th week of infection when the animals were challenged with the soluble fungal antigen. This depression frequently indicates worsening of the disease, with greater involvement of the host. This is a promising field of research for a better understanding of the pathogeny of this mycosis.     

Study of the immunosuppressive effect of cyclosporine in experimental studies]

Specific immunosuppressive activity of cyclosporine prepared at the National Research Centre of Antibiotics by using its original producing culture was studied. It inhibited basic cellular immune responses such as DTH and transplant vs. host and prolonged the lifespan of tumor xenografts under the kidney capsule. Cyclosporine also suppressed the humoral immunity. Its inhibitory effect on lymphocyte blast transformation induced by lectins and in mixed lymphocyte cultures was shown in vitro. Cyclosporine inhibited activity of natural killer cells and T-suppressor cells induced by concanavalin A. It was demonstrated on the models of skin allotransplantation in mice and heterotopic transplantation of the heart in rats that cyclosporine prolonged the transplant lifespan. By the main indices of the cellular immunity and in the models of the transplantation immunity, cyclosporine prepared at the National Research Centre of Antibiotics was shown to be similar to that manufactured by Sandoz.     

Stimulation of cynomolgus peripheral blood lymphocytes with tetanus toxoid and smallpox vaccine

The cynomolgus monkey was studied as an animal model to investigate the cell-mediated immunity induced by vaccines. Optimal conditions are described to isolate peripheral blood lymphocytes. Lymphocyte transformation tests were performed with tetanus toxoid and smallpox vaccine. Antigen-specific lymphocyte transformations with smallpox vaccine could only be demonstrated when lymphocytes were obtained from vaccinated monkeys. Tetanus toxoid appeared to be a weak antigen. However, after adsorption of the toxoid to aluminum phosphate, a significant antigen-specific lymphocyte transformation was observed.     

Experimental study on impact of salmon milt DNA on T-cellular immunity]

The impact of a biologically active food supplement containing salmon milt DNA on cellular immunity was experimentally studied. It was shown that the DNA had a dose-dependent stimulating effect on lymphocyte transformation, stimulated the DTH response and protected from experimental listeriosis infection.     

Effects of social reorganization on cellular immunity in male cynomolgus monkeys

Exposure to acute stressors has been shown to impair cellular immunity in human beings and other animal species. Comparatively little is known, however, about the effects of long-term stressors on immune function and how individual behavioral characteristics may mediate differences in immune function and clinical disease susceptibility. To determine the effects of social stress on cellular immunity and reactivation of a latent herpesvirus, 20 Herpes B virus-positive male cynomolgus monkeys were exposed to four periodic reorganizations of social group memberships over 5 months. Observations were made to categorize individuals as high or low in expression of aggressive, fearful, and affiliative behaviors. Complete blood counts, lymphocyte proliferation tests, and natural killer cell cytotoxicity assays were performed immediately before and 4 days after reorganizations. Herpesvirus-specific immunoglobulin G antibody levels were measured, and oral and conjunctival swabs were cultured for virus. Reorganization was associated with increased lymphocyte counts (P = 0.0009) and decreased lymphocyte proliferation in response to phytohemagglutinin (P < 0.005), particularly among monkeys showing high levels of fear (P = 0.0137). High-aggressive monkeys showed lower baseline natural killer cell activity (P = 0.0013) and higher lymphocyte counts (P = 0.013) than low-aggressive monkeys. Herpesvirus antibody titers decreased over time (P < 0.004) and no positive virus cultures were obtained. Measures of cellular immunity and behavior were unrelated to virus-specific antibody titers. These results suggest that repeated exposure to a social stressor alters several measures of cellular immunity, and that some of these changes may be predicted by individual differences in agonistic behavior. In contrast to human studies, the results suggest that some psychological stressors may not cause reactivation of a common herpesvirus in this species. © 1996 Wiley-Liss, Inc.     

应激抑制淋巴细胞转化的时间效应

本研究吵缚方法使大鼠接受应激刺激,然后分别取大鼠应激３、６、１２、１８ｈ和解除束缚后１２、２４、４８、７２、９６ｈ的淋巴结、脾脏提取物和血清,与刀豆素Ａ同时加入正常大鼠肠系膜淋巴结细胞悬液中育７２ｈ后用噻唑蓝（ＭＴＴ）比色分析法检测肠系膜淋巴结细胞的转化,来应激抑制淋巴细胞转化作用的出现和消失过程。结果如下：（１）应激３和６ｈ大鼠的淋巴结、脾脏提取物和血清对淋巴细胞的转化都没有明显的影响;（２）应     

Experimental allergic encephalitis: study of cellular immunity to the encephalitogenic determinant.

Guinea pigs were tested for cellular immunity to the encephalitogenic tryptophan peptide, the major encephalitogenic determinant of central nervous system basic protein, representing residues 114 to 122 of the molecule. Guinea pigs sensitized with human basic protein regularly developed experimental allergic encephalitis, but did not show cellular immunity to the encephalitogenic tryptophan peptide as measured by skin test reactivity, lymphocyte stimulation, or macrophage migration inhibition, although they did show cellular immunity to the immunizing antigen, human basic protein. Animals sensitized with the synthetic tryptophan peptide also regularly develop clinical and histologic features of experimental allergic encephalitis, and show cellular immunity to the peptide but not to human basic protein. The work of others indicates that, in guinea pigs sensitized with the whole basic protein, there are determinants for cellular immunity located near the encephalitogenic tryptophan peptide. The test peptides used in these studies all included amino acid residues of the basic protein not included in the encephalitogenic tryptophan peptide used in our study. Our work indicates that the encephalitogenic peptide is not one of the determinants for cellular immunity in the basic protein molecule. Since cellular immunity to the disease-producing determinant of the molecule could not be demonstrated, this work further suggests that cellular immunity, as measured by the three tests described herein, may not necessarily be correlated with production of experimental allergic encephalitis.     

脂磷壁酸的提取工艺及免疫功能的研究

目的确定婴儿双歧杆菌脂磷壁酸（LTA）的最佳提取工艺及其免疫调节作用。方法通过对不同方法提取婴儿双歧杆菌LTA的测定及对植瘤小鼠淋巴细胞的转化来探讨LTA对小鼠细胞免疫的调节作用。结果采用脱脂后水法提取效果最好,与对照组和全菌组相比,LTA使淋巴细胞转化增加。结论婴儿双歧杆菌及其LTA均有免疫功能,但LTA的效果要优于婴儿双歧杆菌。     

Perfil inmunológico del paciente con esporotricosis linfocutánea

Sporotrichosis is characterized by a wide range of clinical manifestations from mild fixed cutaneous forms to systemic dissemination of the disease, despite an apparent regular pattern of virulence of the etiological agent, S. schenckii. These facts suggest that immunological mechanisms of the host could play an important role on the pathogenesis of the mycosis. On this basis, an immunologic survey was carried out in patients with lymphocutaneous sporotrichosis. Cell-mediated immunity was evaluated by means of lymphocyte transformation stimulated with phytohaemagglutinin and the response to several intradermal reaction antigens. Lymphocyte blastic transformation was normal as compared with a control group. All patients were positive at least against one of the antigens tested. These results indicate that this group of patients did not show any cell-mediated immunity deficiency. Serum immunoglobulins (IgG, IgM, IgA), and C3 measured to evaluate humoral immunity, were also within normality. Since many cases of sporotrichosis cure with the administration of potassium iodine, whose mechanisms of therapeutic activity are unknown, a possible impairment in the management of iodine was investigated, with the premise that iodine enhances the host defenses rather than acting against the fungus. Thyroid function tests performed in all patients to support this hypothesis, gave normal results. These data permit to conclude that susceptibility to sporotrichosis in the affected patients does not depend on gross abnormal humoral and/or cell-mediated immunity, and their response to potassium iodine is not related to deficient thyroid function.     

Vitamin B6 deficiency and the lymphoid system: I. Effects on cellular immunity and in vitro incorporation of 3H-uridine by small lymphocytes

Thoracic duct lymphocytes from vitamin B₆-deficient rats were found to have a reduced capacity to respond to foreign lymphoid cells in the mixed lymphocyte reaction (MLR), to produce normal lymphocyte transfer reactions, and to incorporate ³H-uridine in vitro. These findings indicate that specific nutritional deficiencies may impair cellular immunity and that this impairment can be monitored by the MLR. It is suggested that the reduction in MLR activity and in ³H-uridine uptake by TDL cells reflected either a shift in the proportions of T and B cells in the TDL and/or an impairment in the capacity of such cells to function in the MLR and in the in vitro test for ³H-uridine incorporation.     

Immunologic and clinical improvement of progressive coccidioidomycosis following administration of transfer factor

Three patients with progressive coccidioidomycosis were given preparations of transfer factor (TF). Adverse reactions to TF were minimal. Following TF administration two of these patients had prolonged clinical remissions in their coccidioidal disease. Cellular immune responses were sequentially evaluated by coccidioidininduced delayed-type skin tests, lymphocyte blast transformation and macrophage inhibition factor production (MIF). These three patients each exhibited different cellular immune patterns before and after TF administration. Two patients converted their coccidioidin skin tests, and one converted lymphocyte transformation response to coccidioidin. Also, TF apparently favorably affected the MIF response in all three patients.     

Persistence of naturally acquired cell-mediated immunity to rubella virus during the first trimester of pregnancy

We studied the persistence of naturally acquired cell-mediated immunity to rubella during early pregnancy. We compared lymphocyte transformation responses to phytohemagglutinin and rubella virus in 35 naturally immune women aged 17-37 years, in the first trimester of pregnancy, with 49 naturally immune age-matched nonpregnant controls. A significant lower lymphocyte transformation response to phytohemagglutinin was observed during the first trimester of pregnancy (P = 0.008), but lymphocyte transformation responses to rubella virus were not significantly different (P = 0.901). These data indicate that, in naturally immune women, cell-mediated immunity to rubella virus is not significantly altered by the physiological changes in early pregnancy.     

Studies on the methodology and evaluation of the lymphocyte transformation microtest

Optimum experimental conditions for the lymphocyte transformation microtest in healthy persons are described. The dependence of PHA stimulation on duration of culture, additions of serum and PHA concentration is investigated. A function of normal distribution pattern can be set up by determining the lymphocyte stimulability with four different PHA concentrations in the optimal stimulation range. With this function, the area under the curve, steepness, position and height of the maximum can be calculated. These parameters should serve for better interpretation of cellular immunity.     

Evaluation of immunogenicity and protective efficacy of a Microsporum canis metalloprotease subunit vaccine in guinea pigs

In order to identify protective immunogens against Microsporum canis infection, a purified recombinant keratinolytic metalloprotease (r-MEP3) was tested as a subunit vaccine in experimentally infected guinea pigs. Both humoral and cellular specific immune responses developing towards r-MEP3 were evaluated, by enzyme-linked immunosorbent assay and by in vitro lymphocyte transformation tests respectively. Vaccination induced a strong antibody response, and a significant but transient lymphoproliferative response against the protein. However, the protocol failed to prevent fungal invasion or development of dermatophytic lesions. These results show that under the present experimental conditions, r-MEP3 specific antibodies are not protective against a challenge exposure. They also suggest that in the same model, the induction of cell-mediated immunity towards r-MEP3 is not sufficient, indicating the need for further research in the field of specific immune mechanisms involved in M. canis dermatophytosis.     

Certain aspects of clinically mild, non-tropical chyluria

Chyluria despite pseudo- banality may pose several diagnostic and therapeutical problems. Its etiopathogenesis is unclear, too. Prolonged loss of the lymph observed in patients with chyluria due to inherited anomalies of lymphatic system may lead to serious deficits and homeostasis disorders. Basing on these thesis, the authors present two patients with chyluria due to inherited anomaly of extraperitoneal lymphatic system and review available literature. Particular role in the clinical follow-up of these patients plays their immunologic status. The authors did note deficiency of cell-mediated immunity measured with skin tests and lymphocyte T blastic transformation test, and increasing IgG deficit, and particularly annoying IgA deficit in the patient with long-lasting, massive chyluria.     

Cell-mediated immunity in nutritional imbalance

Marked perturbations of cell-mediated immunity are observed in nutritional imbalance, both undernutrition and overnutrition. Individuals with protein-energy malnutrition show consistent impairment of cutaneous delayed hypersensitivity and a reduced number of circulating T lymphocytes. Variable changes in lymphocyte stimulation response in vitro to mitogens and antigens are seen. There is a relative increase in the number of "null" cells and high levels of leukocyte terminal deoxynucleotidyl transferase activity. These findings suggest impaired differentiation of T cell precursors, which may be the direct result of reduced thymic hormone activity. Alterations in the production of lymphokines are not consistent. Infants with intrauterine growth retardation show a marked and long-lasting deficit in cell-mediated immunity. Specific nutrient deficiencies vary in their ability to influence cell-mediated immunity and the mechanisms underlying the immunologic abnormalities. Among others, zinc and pyridoxine deficiencies are associated with marked immunodepression. Obesity also is associated with alterations in cell-mediated immune responses. This has been observed in man, in genetically obese mice, and in states of excess intake of lipids, vitamins, minerals, and a trace elements. Nutritional modulation of cellular immunity is an important determinant of morbidity in several systemic disorders.     

The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men

A comprehensive evaluation of the cellular immune system (total T-cell, helper cell, suppressor cell, and natural killer cell numbers; in vitro interleukin-2 production, T-cell responses to mitogens and antigens, serum beta 2 microglobulin levels, and delayed hypersensitivity skin tests) was performed on 36 HTLV-III seronegative and 16 HTLV-III seropositive healthy homosexual men, 48 asymptomatic homosexual men with the chronic lymphadenopathy syndrome, 41 patients with AIDS, and 29 heterosexual controls without any known risk factors for AIDS. Our studies demonstrate that HTLV-III seronegative homosexual men have normal cellular immunity and are comparable to heterosexual controls. The abnormalities of lymphocyte subsets observed in HTLV-III seropositive healthy homosexual men are comparable to subjects with chronic lymphadenopathy. Assays of lymphocyte function, with the exception of delayed type hypersensitivity (DTH) skin tests, are similar in each group except patients with AIDS. Subjects with chronic lymphadenopathy were less responsive to DTH skin tests and HTLV-III seropositive healthy homosexuals were comparable to chronic lymphadenopathy subjects. We conclude that immunologic abnormalities in homosexual men are attributable to infection with HTLV-III.