Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new trypsin-like serine protease was cloned from both a murine cytotoxic T lymphocyte and a human PHA-stimulated peripheral blood lymphocyte cDNA library. In both the mouse and human system, this transcript had a T cell- and NK-specific distribution, being detected in cytotoxic T lymphocytes (CTL), some T-helper clones, and NK, but not in a variety of normal tissues. T-cell activation with Con A plus IL-2 induced mouse spleen cells to express this gene with kinetics correlating with the acquisition of cytolytic capacity. Both the mouse and human nucleotide sequences of this gene encoded an amino acid sequence with 25-40% identity to members of the serine protease family. The active-site "charge-relay" residues (His-57, Asp-102, and Ser-195 of the chymotrypsin numbering system) are conserved, as well as the trypsin-specific Asp (position 189 in trypsin). We reviewed the evidence of this serine protease's role in lymphocyte lysis and proposed a "lytic cascade." We discussed the biological and clinical implications of a cascade, proposing these enzymes as markers for cytolytic cells and as targets for rational drug therapy. Genetic and acquired deficits in the lethal hit-delivery system are considered as a basis for approaching some immunodeficiency states, including severe EBV infections, T-gamma leukemias, and T8+ lymphocytosis syndromes.
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PMID:A T cell- and natural killer cell-specific, trypsin-like serine protease. Implications of a cytolytic cascade. 305 12

The isolation of a novel arachidonic acid (Aa) metabolite from the supernatant of unstimulated human cord blood mononuclear leucocytes is reported. The metabolite, arbitrarily named 'compound 4' is neither a known lipoxygenase nor a cyclooxygenase product. 'Compound 4' was added to PHA-stimulated peripheral blood mononuclear leucocytes (PBML) from healthy blood donors, from mothers at term and from patients with immunodeficiency. 'Compound 4' induced an increase in the 3H-TdR incorporation by the maternal PBML and by the PBML from patients with various immunodeficiencies such as Wiskott-Aldrich syndrome and common variable immunodeficiency, whereas it had no effect on the proliferation of PBML from blood donors.
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PMID:A novel arachidonic acid metabolite with stimulatory effect on PHA-induced mitogenesis of lymphocytes. 310 19

The effect of 2'deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), on the proliferation of mononuclear cells from cord blood and from healthy controls as a response to the two mitogenic agents PHA and ConA was studied. The addition of dCF simultaneously with the mitogen did not modify cell proliferation either in neonates or in controls. Added 20 min before the mitogens, dCF induced in adults lymphocytes a significant inhibition in the response to PHA (68.11 +/- 10.40% of response in control cultures) and to ConA (58.78 +/- 26.23%). By contrast, in the neonatal period it induced a stimulatory effect on this response, both when PHA (117.64 +/- 26.48% of basal response) and ConA (108.18 +/- 21.72%) were employed. The possibility is discussed that this different function in lymphocyte behaviour in the newborn might contribute to the immunologic abnormality which children affected with ADA deficiency may exhibit at this age and also to the delay in the onset of clinical manifestations of immunodeficiency due to the defect in this enzyme.
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PMID:Action of 2'-deoxycoformycin on mitogen-induced lymphoproliferation in the neonatal period. 326 55

Studies were performed to determine whether pre-T cells develop normally in the bone marrow of mice displaying thymic dysplasia and T cell immunodeficiency as a consequence of a graft-versus-host (GVH) reaction. GVH reactions were induced in CBAxAF1 mice by the injection of A strain lymphoid cells. To test for the presence of pre-T cells in GVH-reactive mice, bone marrow from GVH-reactive mice (GVHBM) was injected into irradiated syngeneic F1 mice and 30-40 days later thymic morphology and function were studied. Morphology studies showed nearly normal thymic architectural restoration; moreover, such glands contained normal numbers of Thy-1-positive cells. Functional pre-T cells were evaluated by transferring thymocytes from the irradiated GVHBM-reconstituted mice into T-cell-deprived mice. These thymocytes reconstituted allograft reactivity, T helper cell function and Con A and PHA mitogen responses of T-cell-deprived mice. These results suggest that the pre-T cell population in the bone marrow is not affected by the GVH reaction. Therefore, the T cell immunodeficiency associated with the GVH reaction is not due to a deficiency of pre-T cells in the bone marrow but is more likely associated with GVH-induced thymic dysplasia.
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PMID:The graft-versus-host reaction and immune function. III. Functional pre-T cells in the bone marrow of graft-versus-host-reactive mice displaying T cell immunodeficiency. 348 49

Mitogenesis of human peripheral blood lymphocytes as measured by the uptake of [3H]thymidine was stimulated in vitro by pure orosomucoid glycoprotein when used at concentrations that are considerably lower than the physiological plasma level. The lymphocyte cultures stimulated with PHA or PWM were not affected by low concentration (67 micrograms/ml), but they were mildly suppressed by high concentration (1 mg/ml) of this glycoprotein. The stimulatory response was relatively greater with fractionated T cells than the non-T cells (B cells and monocytes). At 50 micrograms/ml concentration of orosomucoid, the lymphocyte activation was found in randomly selected blood donors which included normal healthy volunteers and patients with T cell immunodeficiency or Alzheimer's disease, demonstrating a consistent immunostimulatory action of this glycoprotein.
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PMID:Lymphocyte stimulation in vitro by orosomucoid glycoprotein. 349 44

The cell cycle progression and viability of stimulated and intact lymphocytes from 20 subjects with acquired immune deficiency syndrome (AIDS) was determined by flow cytometry. As compared to controls, 62% less AIDS lymphocytes, cultured for 72 hr in the presence of lectins (Con-A, PHA, PWM), had entered the proliferative phases of the cell cycle, while the respective value for periodic-acid (H5IO6)-stimulated cells was 34%. The helper-suppressor ratios and natural kill cell percentages of the unstimulated and PHA-activated AIDS lymphocytes increased approximately 3-fold after 72 hr in culture. The natural killer (NK) cell fraction of the PHA-stimulated and unstimulated AIDS cultures comprised approximately 20% as compared to 10% in controls. However, no changes in the percentages of T-lymphocytes were detected in the AIDS cell cultures. Throughout the culture period, viability of the unstimulated AIDS lymphocytes exceeded 90%, whereas in stimulated cultures it fluctuated within the 65-90% range. It is concluded that the liability of AIDS lymphocytes to mitogens is probably a direct consequence of the human immunodeficiency virus (HIV) infection.
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PMID:Effect of mitogens on the cell cycle progression and the quantification of T-lymphocyte surface markers in acquired immune deficiency syndrome. 349 12

A female infant with clinical and laboratory features of ataxia telangiectasia (AT) showed two clinical features exceptional for the disease, i.e. generalized skin pigmentation and an unusually early death at the age of 15 months. Her clinical features supportive of the diagnosis of AT included growth and developmental retardation and muscle weakness. Findings indicating immunodeficiency included recurrent pulmonary infections, failure of PHA stimulation of PB lymphocytes, decreased levels of serum IgM and IgA and on autopsy, an atrophic thymus without Hassall's corpuscles. Her cultured skin fibroblasts showed increased spontaneous chromosome breakages and hypersensitivity to X-ray irradiation, as would be expected for AT fibroblasts. She showed elevated blood HbF levels, macrocytic anaemia, granulocytopenia and thrombocytopenia, findings suggestive of a preleukaemic or leukaemic process. Yet aspirates of her bone marrow revealed no malignant cells. Autopsy revealed bilateral Pneumocystis carinii pneumonia, telangiectatic lesions in all the internal organs studied, sparse and degenerative Purkinje cells in the cerebellar cortex and atrophic ovaries. In view of these findings, it was concluded that the patient had a hitherto undescribed variant of ataxia telangiectasia.
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PMID:Ataxia telangiectasia with generalized skin pigmentation and early death. 373 14

Ninety-six institutionalized elderly (greater than 70 years old) (mean age: 82 +/- 7 years) subjects, negative for tetanus toxoid antibodies were primed with tetanus toxoid vaccination and dinitrochlorobenzene (DNCB). Correlations were studied between some immunological parameters, nutritional parameters prior to immunization and the immune response intensity after it. Levels of tetanus toxoid specific IgG (ELISA assay) were positively correlated with monocyte phagocytosis, DNCB response and prealbumin levels, and negatively correlated with total IgG, monocyte immune degradation and tetanus toxoid lymphocyte stimulation. No correlation was observed with IgA, IgM, PHA stimulation. Tetanus toxoid lymphocyte stimulation correlated positively with response to DNCB, and negatively with tetanus toxoid IgG as well as total IgG. DNCB response correlated with prealbumin, tetanus toxoid IgG and tetanus toxoid lymphocyte stimulation. Therefore, it appears that malnutrition, as measured by prealbumin level, is one of the main factors contributing to the inconstant senile immunodeficiency. Monocyte antigenic degradation function unaltered with age can impair immune response while conserved or increased phagocytosis enhances immune response in the elderly. High total IgG levels were linked with low specific responses to priming antigens. High specific antibody levels also correlated negatively with cellular specific response. It is assumed that regulatory IgG antibody accumulation, likely anti-idiotypic antibodies, play an important role in senile immunological depletion.
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PMID:Respective roles of immune and nutritional factors in the priming of the immune response in the elderly. 387 21

The group of patients consisted of 4 pairs of male siblings with the family history suggesting X-linked immunodeficiency. The concentration of serum immunoglobulins (Ig) and the titer of anti-E. coli and anti-Candida albicans antibodies was extremely low in comparison to the control group. Only 2 siblings showed normal number of lymphocytes with surface Ig. Four out of 8 children had the increased number of Fc-IgG bearing T cells. Blast transformation of lymphocytes revealed the decreased response to PHA and Con A in 2 children. Cellular immunoglobulin (cIg) synthesis of in vitro stimulated peripheral blood lymphocytes (PBL) was decreased in all 8 children. Prednisolone, when added to the PBL cultures, increased cIg synthesis in 2 children. Thymosin (TFX) caused an enhancement of cIg production by lymphocytes of 4 children. Cowan I--elicited stimulation of PBL was low in all but 2 children. Our data further support the view on the heterogeneity of etiopathogenesis of hypogammaglobulinemia.
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PMID:Immunoglobulin synthesis by lymphocytes of eight immuno-deficient children. 390 93

We have investigated the respective role of quantitative T lymphocyte subset abnormalities, interleukin-2 (IL-2) production and responsiveness to IL-2, in the proliferative deficiency that is observed in acquired immune deficiency syndrome (AIDS) and Lymphadenopathy syndrome (LAS) patients or even in some apparently healthy male homosexuals. 83 subjects were evaluated: 35 symptom free male homosexuals (HC), 24 LAS and 24 AIDS patients. As expected, many HC and most patients presented with T lymphocyte subset imbalance. These quantitative defects were associated with decreased reactivity to PHA and reduced production of IL-2 by PHA stimulated lymphocytes. No correlation however could be found between these two functions and variations in the T lymphocyte subset distribution. On the other hand, PHA responsiveness appeared to closely depend on IL-2 activity. Addition of exogenous IL-2 to lymphocytes from patients with low proliferative responses, stimulated with suboptimal PHA concentration, enhanced proliferation in some but not all the cases. In most instances this increase never reached the levels observed with similarly treated cells from normal individuals. In these patients, the limited number of lymphocytes which express IL-2 receptors upon PHA stimulation may explain both low PHA reactivity and reduced IL-2 responsiveness. These data indicate some possible mechanisms of immunodeficiency in AIDS and LAS.
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PMID:Is there correlation of T cell proliferative functions and surface marker phenotypes in patients with acquired immune deficiency syndrome or lymphadenopathy syndrome? 392 52


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