Deficient natural killer cell activity in a patient with Fanconi's anaemia and squamous cell carcinoma. Association with defect in interferon release.
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A child with Fanconi's anaemia diagnosed at 7 years of age presented in adult life with lymphopenia, recurrent warts and Bowen's disease. The latter resulted in the development of multiple cutaneous squamous cell carcinomas which metastasized to the skeleton. Investigation of her immune function revealed selective defects in natural killer (NK) cell activity. Humoral immunity and several tests of cell-mediated responses were within normal or became normal after treatment with levamisole or transfer factor. Analysis of the defect in NK activity revealed that low levels could be induced in vitro by fibroblast interferon. Stimulation of blood lymphocytes from the patient with the interferon inducer poly (I)-poly (C) resulted in an increase in NK activity but incubation of her lymphocytes on tumour cells did not result in an increase in NK activity or the release of interferon. This contrasted with the marked increase in NK activity and interferon release observed when lymphocytes from normal controls were incubated on tumor cells. These findings suggested the absence of NK activity in this patient was secondary to a defect in interferon release from lymphocytes on exposure to tumour antigens. It is considered that these defects may have been an important predisposing factor in the development of malignancy in this patient and possibly other patients with Fanconi's anaemia. (+info)
In vitro effect of murine-derived transfer factor on Salmonella-specific rosette formation.
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The splenic lymphocytes from Salmonella-immune ICR Swiss or C3H/HeJ mice formed greater than 0.2% antigen-specific rosettes with sheep erythrocytes coated with a spent-medium protein antigen of Salmonella typhimurium. These rosette-forming lymphocytes were found to be sensitive to the effects of antithymocyte serum plus complement. Transfer factor prepared from the Salmonella-immune splenic lymphocytes of ICR Swiss mice was active in sensitizing nonimmune ICR Swiss or C3H/HeJ lymphocytes to form greater than or equal to 0.2% rosettes with salmonella antigen-coated sheep erythrocytes. These rosettes were also sensitive to antithymocyte serum and complement. Few rosettes were formed between the transfer factor-treated lymphocytes and sheep erythrocytes coated with a Listeria protein antigen. A nonimmune dialysate preparation was inactive in sensitizing nonimmune lymphocytes, as indicated by a lack of rosette formation. Neither the immune transfer factor nor the nonimmune dialysate had any enhancing or abrogating effect upon rosette formation by splenic lymphocytes from Salmonella-immune mice. The enumeration of antigen-specific rosettes may be a useful means of assaying for transfer factor activity. (+info)
Disseminated coccidioidomycosis: clinical, immunologic and therapeutic aspects.
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A patient with disseminated coccidioidomycosis initially had pulmonary and skin manifestations and survived for 14 years before dying of meningitis due to Coccidioides immitis. In addition to several courses of amphotericin B therapy the patient received injections of transfer factor derived from appropriate donors and miconazole nitrate therapy. The immunologic defence mechanisms of the patient during the course of his disease were studied and the possibility of a cell-mediated immunologic defect, potentially reversible by transfer factor, was demonstrated. (+info)
Leukocyte migration inhibition of buffy coats from patients with autoimmune thrombocytopenic purpura when exposed to normal platelets: modulation by transfer factor.
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Cellular-mediated immunity was studied in autoimmune thrombocytopenic purpura (ATP) patients by investigating leukocyte migration inhibition (LMI) following the interaction of normal platelets with patients' lymphocytes. When normal platelets were incubated with leukocyte buffy coats of ATP patients, the migration index (MI) was significantly impaired compared to buffy coats from normal subjects, employing 4 different concentrations of platelets. At the highest platelet concentration (10(9)/ml), MI was 0.87 +/- 0.04 (SEM) for ATP lymphocytes compared to 1.05 +/- 0.05 (p less than 0.01) for normal lymphocytes. Nine of 21 patients had an MI less than 0.80, whereas all control subjects had MIs greater than 0.85. Similar results were obtained at 2 different platelet membrane concentrations. At 500 micrograms/ml, the MI for ATP lymphocytes was 0.74 +/- 0.04, compared to 0.98 +/- 0.08 (p less than 0.01) for normal lymphocytes (12 experiments). An inverse relationship was noted between platelet count and lymphokine production in ATP patients (r = 0.815, p less than 0.001, 10 experiments). Transfer factor from an ATP patient in remission converted an abnormal LMI response of 0.68 +/- 0.04 from a patient with severe thrombocytopenia to 0.84 +/- 0.07 (p less than 0.005, 8 experiments). Similar results were obtained with transfer factor from 2 other patients in remission. Transfer factor from a patient with severe thrombocytopenia converted a normal response of 1.04 +/- 0.05 of normal subjects to a lower response of 0.88 +/- 0.04 (p less than 0.03, 12 experiments). Thus, lymphocytes of ATP patients are primed to recognize and be perturbed by normal platelets, whereas normal lymphocytes are not. This indicates specificity of the antigen-lymphocyte reaction in ATP patients. Transfer factor is capable of modulating this response in vitro. (+info)
Transfer of delayed hypersensitivity in mice to microbial antigens with dialyzable transfer factor.
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Dialyzable Lawrence-type transfer factor was prepared from the spleen cells of CF1 mice inoculated with Coccidioides immitis- and Candida albicans-killed vaccines and with live Mycobacterium tuberculosis vaccine (BCG). These preparations were shown to transfer antigen-specific cell-mediated immunity to naive mice, as measured by the delayed skin test and footpad-swelling methods. Reactivity could be demonstrated when the test antigens were given 24 h after the transfer factor, but not when they were given simultaneously. Coccidioides-specific transfer factor was shown to be sensitive to Pronase and resistant to trypsin and ribonuclease. A preparation of BCG transfer factor was sensitive to snake venom phosphodiesterase. (+info)
Evidence for the presence of a low molecular-weight activator of suppressor monocytes (LASM) in dialysates of T lymphocytes.
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Lysates of peripheral blood T lymphocytes from healthy individuals were found to contain a low molecular-weight peptide that inhibited phytohaemagglutinin-induced DNA synthesis in vitro by autologous or allogeneic peripheral blood mononuclear cells. The peptide was dialysable, partially heat stable, resistant to trypsin, RNase, and DNase but not to pronase, and was not part of the membrane receptor involved in rosette formation by T lymphocytes with sheep erythrocytes. It was found to act through monocytes, inducing the synthesis of second mediator responsible for the inhibition of lymphocyte DNA synthesis. This inducer of inhibition, designated as "low molecular-weight activator of suppressor monocytes' (LASM), may have a role in the depression of cellular immune response seen in various pathological conditions involving the destruction of T lymphocytes. (+info)
Immunogenicity of the ribosomal fraction of Salmonella typhimurium: analysis of humoral immunity.
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The ribosomal fraction prepared from Salmonella typhimurium LT2 was further purified by gel filtration of Sepharose 4B and afforded excellent protection against homologous challenge. The highly effective immunogens were composed of several fractions which could give different types of protection to mice. The first type of protection was heat-labile antigens which could induce humoral immunity, and the second type of protection was heat-stable antigens capable of evoking cellular resistance in mice. The former were different from O-antigens and the latter were free of endotoxin and rich in ribonucleic acid. The third type of protection was heat-resistant substances of cell wall components, which were mainly composed of O-antigens. The high immunogenicity observed in this study could be obtained only by the heat-stable antigens rich in ribonucleic acid, and the immunity conferred by this kind of antigen was due to the cellular type of protection. (+info)
A clinical and immunological study of the effects of transfer factor on multiple sclerosis patients.
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A clinical and laboratory trial was designated to test the value of a potentially active pool of transfer factor (TF) given for a period of 3 months, at weekly intervals, in 27 relapsing MS patients and controls. The pool of TF was extracted from peripheral lymphocytes of 36 normal individuals presensitized with DNCB as marker. It was biologically capable of transferring DNCB sensitivity to MS recipients and did not show any toxicity. Clinically, a slight but not significant improvement of the functional and disability indices was observed in the TF group over a period of 1 year, while both indices increased in the control group. The treatment had no influence on the number of relapses and/or on sensory and visually evoked potentials, axial tomography and electronystagmography. In laboratory tests, a significant difference was found in the total CSF protein (P less than 0 . 05) and IgG (P less than 0 . 01) levels in the two groups studied; both values decreased or were stabilized in the group receiving TF, while they increased in the control group. Whether or not these slight clinically and biologically beneficial effects were due to the high dose of TF given or to its biological activity remains to be established. This pilot study suggests that a more appropriate answer regarding TF in MS might be obtained by using biologically active material, given for longer periods of time, at a closer interval and in a larger number of patients. (+info)