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Immunocompetence and prognosis in children with acute lymphoblastic leukemia: combination of two different maintenance therapies.

Intensive chemotherapy in patients with leukemia produced immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with "favorable immunocompetence" only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with "unfavorable immunocompetence," 15 relapsed and 8 remain in complete remission from 9 to 26 months.

Acute Disease

Immunologic studies of colonic cancer: evaluation of immunocompetence.

Detailed immunologic studies were done on 29 patients with colorectal cancer. The plasma level of circulating carcinoembryonic antigen, the in vitro reactivity of the peripheral blood leukocytes (PBL) to colorectal-tumor-associated antigens (CTAA), and the competence of the T cell population were determined. The in vitro reactivity of the PBL to CTAA was determined by a lymphoblastic response and leukocyte migration inhibition. The competent T cell population was determined by enumerating the T and B cells, the rosette-inhibiting titer of antithymocyte globulin, and the reactivity to skin test antigens. An arbitrary score ranging from 0 (low immunocompetence) to 100 (high) was assigned to the results of each test. The mean score on the immunocompetence quotient (ICQ) which ranged from 22 to 100 was judged to reflect the immunocompetence. The sequential ICQ of individual patients strongly suggested that this information reflected the immunocompetence of patients with cancer of the colon.

Adenocarcinoma

Immunocompetence, immunodeficiency and prognosis in cancer.

Immunocompetence and prognosis are related in solid tumors, malignant lymphomas, and acute leukemia. Among the parameters of immunocompetence vigorous delayed-type hypersensitivity responses to recall antigens or to primary immunization with Keyhole limpet hemocyanin, vigorous in vitro lymphocyte blastogenic responses to mitogens such as PHA, and relatively high B-lymphocyte levels, all correlate with a good prognosis. The spectrum of immune reactivity as measured by established delayed-type hypersensitivity to recall antigens and in vitro blastogenic responses to mitogens and antigens is similar in melanoma patients and their nontumor-bearing spouses. In melanoma, only patients with widespread inoperable metastatic disease show severe immunological deficiency and this is selective for certain antigens. There are highly significant differences in response to specific antigens when patients with melanoma and lung cancer are compared. Immunotherapy with BCG and C. parvum can boost immunocompetence as measured by recall DTH skin testing. However, the relationship between the initial immunocompetence and prognosis still holds in patients receiving BCG immunotherapy to prevent recurrence of melanoma. These data indicate that a broader survey of immunological reactivity in cancer patients is needed, that immunological testing is useful in cancer prognosis clinically, and that the results of immunological testing can be used to evaluate therapy and to indicate new pathways for improved treatment.

B-Lymphocytes

Evaluation of the immunocompetance of patients with transitional cell carcinoma of the bladder.

The cellular immunocompetence was examined by means of the quantitative DNCB hypersensitivity reaction in 152 patients with transitional cell carcinomas of the bladder of Broders grades 1-4. Against a control group of 367 normal controls of both sexes, 85 patients with transitional cell carcinomas of grades 1 and 2 showed a normal DNCB reactivity, irrespective of the frequency of tumour recurrence. In 9 patients of this group, an increase of malignancy from grade 2 to grade 3 was observed; the simultaneous deterioration of immunocompetence, however, was not statistically significant. On the other hand, with transitional cell carcinomas of grades 3 and 4, significant impairment of immunocompetence correlating with the tumour stage was noted.

Adult

A Strain of Mycoplasma hominis Causing Pleuropneumonia Infection in an Immunocompetent Patient and Recent Epidemiological Trends: Implications for Clinical Management.

Mycoplasma hominis (M. hominis) is an opportunistic pathogen linked to urogenital and neonatal infections; however, limited genetic and epidemiological data are available. Extragenital infections in healthy adults are rare, and effective antibiotics are species-specific, complicating diagnosis and treatment. Hence, this study aimed to elucidate the clinical process, update the epidemiological characteristics, and investigate the genomic features of a fluoroquinolone-resistant M. hominis isolate from an immunocompetent patient with pleuropneumonia in China. The M. hominis isolate ZY_MH01 was recovered from pleural fluid and was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Whole Genome Sequencing (WGS). The completed genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Snippy v4.4.5 was utilized to conduct a core genome single nucleotide polymorphism (cgSNP) analysis between ZY_MH01 and 144 M. hominis strains from the NCBI GenBank database. Subsequently, phylogenies were constructed using IQ-TREE v3.1.2 and visualized by iTOL. Antimicrobial resistance determinants were identified using strict criteria of Comprehensive Antibiotic Resistance Database (CARD) RGI 6.0.5 (Web portal) and broth microdilution test. Virulence genes were screened using Abricate v1.0.1 against the Virulence Factor Database (VFDB). A total of 42 strains (including ZY_MH01) from Genbank with an assembly level of Complete or Chromosome were re-annotated using Prokka v1.2.0 and pangenome analysis was performed using the Roary. The core genome constitutes only 17.1%, which may contribute to the unusually high level of polymorphism observed among M. hominis strains. No antibiotic resistance genes or virulence genes were detected in the genome of ZY_MH01. However, some resistance-associated mutations of gene parC and gyrA in the Quinolone Resistance Determining Region (QRDR) were identified. Phylogenetic analysis indicates that strains originating from the same geographic region typically exhibit reduced genetic distances; this trend is especially pronounced in regions with a higher number of publicly available strain sequences. In specific circumstances, when conventional broad-spectrum antibiotics are ineffective, even immunocompetent patients should consider the possibility of M. hominis infection. This study presents a detailed account of the diagnostic and therapeutic course of a pleuropneumonia infection caused by M. hominis in an immunocompetent patient, and performs an epidemiological analysis of all M. hominis sequences that have been recently made publicly available.

Humans

Comparative immunohistochemical identification and relative distribution of immunocompetent cells in sections of frozen or formalin-fixed tissue from human periapical inflammatory lesions.

The presence of immunocompetent cells (B, Th/i and Ts/c cells and macrophages) and the ratios of these cell populations in periapical lesions (radicular granulomas, radicular cysts and apical scars) were demonstrated immunohistochemically using paraffin and cryo-sections. Thirty-four human periapical lesions were examined for the presence of immunocompetent cells by monoclonal antibodies and the biotin-avidin-horseradish peroxidase method. The T/B cell ratio of radicular cysts was significantly higher than that of both radicular granulomas and apical scars, and the average number of Th/i cells was greater than that of Ts/c cells in the radicular granulomas. However, no significant difference was found between radicular cyst and apical scar. The number of macrophages in radicular granulomas was significantly higher than that of the other lesions. These findings suggested that periapical lesions develop as a result of both humoral and cell-mediated immunological response and indicated that the ratios of immunocompetent cells are different in the different types of periapical lesion.

B-Lymphocytes

Growth of human tumor xenografts implanted under the renal capsule of normal immunocompetent mice.

The subrenal capsule technique proved effective in demonstrating that the growth of human tumors in normal, immunocompetent animals for 6 days was quantifiable in ocular micrometer units. Positive growth was demonstrable not only with human tumors that had been established in serial transplantation in athymic nude mouse hosts, but also with primary surgical explants. Growth rates of transplantation-established xenograft systems were similar whether implanted in athymic nude or in normal immunocompetent animals indicating that the 6-day time-frame successfully evades growth inhibitory effects of immunologic origin. Immunosuppression with a single dose of cyclophosphamide did not appear to affect growth rate, but permitted the tumors to grow larger extending the time to reach peak size. Significantly, xenografts of primary surgical explants showed positive growth more frequently in 6 days (82%) in the immunocompetent animal than in 11 days (30%) in the immunodeficient athymic nude mouse.

Animals

Effect of iodoacetate on the bone marrow immunocompetence of AKR mice.

Studies were conducted to determine whether the sulfhydryl inhibitor, sodium iodoacetate, administered to preleukemic AKR mice and to mature C3H mice altered the immunocompetence of their bone marrow. Parameters investigated included the splenic plaque-forming capacity directed to sheep erythrocytes of bone marrow transferred from iodoacetate-treated aanimals to irradiated syngeneic recipients and the mitogenic responsiveness of bone marrow cells from untreated and iodoacetate-treated preleukemic AKR mice to phytohemagglutinin and concanavalin A. The administration of two 0.5-ml doses of 10 mM iodoacetate to preleukemic AKR mice and to C3H mice resulted in a significant increase in bone marrow immunocompetence. Irradiated mice given marrow transplants from iodoacetate-treated syngeneic donors exhibited greater numbers of plaque-forming cells directed against sheep erythrocytes than did recipients of marrow from control animals. This effect was abrogated when the donor marrow was previously treated in vitro with rabbit antimouse brain serum and the complement to remove thymus-derived lymphocytes. The mitogenic responsiveness of marrow cultures from iodoacetate-treated AKR mice to phytohemagglutinin was similar to that observed for control mice, while the response to concanavalin A was decreased. These findings suggest that the administration of iodoacetate potentiated the immunocompetence of bone marrow by affecting thymus-derived cells.

Animals

The circulating life span, immunocompetence and 3H-uridine uptake of small lymphocytes from thymus-grafted, neonatally thymectomized rats.

By 7 weeks post-grafting, the number of small lymphocytes in the thoracic duct lymph (TDL) and blood of the thymus-grafted neonatally thymectomized adult rats had increased to 60% of the number of cells in sham controls, or 2-1/2 times thymectomized control values. This increasing consisted almost exclusively of long-lived, recirculating small lymphocytes and corresponded to a 60% recovery of cellular immunocompetence as measured by the mixed lymphocyte reaction (MLR). Associated with the return of cellular immunocompetence was an increased incorporation of 3H-uridine by the small lymphocytes. Cells from thymectomized animals grafted with lymph node fragments demonstrated no significant increase in lymphocyte numbers nor was there a return of immunocompetence as compared to thymectomized controls.

Animals

Self-limited primary cytomegalovirus colitis in an immunocompetent individual.

Cytomegalovirus colitis in immunocompetent patients has rarely been reported without another severe illness. The prognosis is usually bad, leading to toxic megacolon or death due to multi-organ system failure. We report a case of a self-limited cytomegalovirus colitis in a young patient with no risk factor for CMV infection or associated disease. This suggests that self-limiting CMV colitis may be more frequent than is usually believed, and its prognosis may be better in young patients with normal immune functions. Therefore it should be sought systematically even in immunocompetent young patients.

Adult

Comparison of the plaque microflora in immunodeficient and immunocompetent dental patients.

The nature and extent of the immune dysfunctions in 20 immunodeficient patients, as well as the immunocompetence of 22 control subjects, were verified by cell-mediated responsiveness and immunoglobulin quantitations. Comparisons of the microbial composition of supragingival plaque between the two populations showed that a greater number of immunodeficient than control subjects harbored Candida sp. and Staphylococcus sp. Conversely, a lower number of immunodeficient than control subjects harbored Streptococcus mutans. Also, patients with immune dysfunctions had a lower dental caries experience than their immunocompetent counterparts.

Antibody Formation

Prognostic value of host immunocompetence in urologic cancer patients.

To evaluate the prognostic significance of host immunocompetence in urologic cancer patients, the subsequent clinical course of 95 patients was determined a year after skin testing with dinitrochlorobenzene. A close correlation was demonstrated between dinitrochlorobenzene reactivity and prognosis among 38 transitional carcinoma patients. Of 19 patients with impaired reactivity 13 had tumor recurrences and 11 of these died of cancer within 1 year. Only 5 of 19 patients with normal dinitrochlorobenzene reactivity had recurrences and none died during the same interval. Although not statistically significant, similar results were observed among 10 renal cell carcinoma patients of whom 3 of 5 with impaired dinitrochlorobenzene reactivity had tumor recurrences, while 4 of 5 with normal reactivity remained free of tumor. One testis tumor patient with impaired dinitrochlorobenzene reactivity died of cancer, while 3 of 4 with normal reactivity remained free of tumor. Similarly, 1 patient with carcinoma of the penis with impaired dinitrochlorobenzene reactivity died of cancer, while 2 of 3 with normal reactivity remained free of tumor. In contrast, reactivity to dinitrochlorobenzene did not correlate with the clinical course of 38 prostatic carcinoma patients. Ten of 19 patients with normal dinitrochlorobenzene reactivity and 9 of 19 with impaired reactivity were dead or had symptomatic recurrences within 1 year, while 9 of 19 with normal reactivity and 10 of 19 with impaired reactivity were either free of tumor or asymptomatic. However, a trend toward a correlation between dinitrochlorobenzene reactivity and tumor progression was observed among patients not receiving endocrine therapy. The differences with respect to the prognostic significance of host immunocompetence between transitional carcinoma patients and those with prostatic carcinoma may be explained by fundamental differences in the biologic properties of these tumors, especially the endocrine sensitivity of prostatic carcinoma.

Adenocarcinoma

Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. III. Physical fractionation of specific immunocompetent T lymphocytes by affinity chromatography using anti-idiotypic antibodies.

Anti-idiotypic antibodies made against antigen-binding receptors on T lymphocytes with specificity for certain Ag-B locus antigens selectively react with T lymphocytes with potential immune reactivity against the very same Ag-B antigens. This was shown by affinity chromatography of normal Lewis T lymphocytes on anti-Ig columns after contact with the relevant anti-idiotypic antiserum. Here, it could be shown that incubation of the cells with an anti-(Lewis-anti-BN) antiserum caused subsequent selective retention of potential graft-vs.-host (GvH)-reactive cells against BN on the anti-Ig column, whereas Lewis T cells with reactivity against DA or August (Au) (carrying distinct Ag-B antigens in comparison to BN) passed through. The retained cells could be eluted and shown to display highly increased reactivity against BN with virtually no reactivity left against DA or Au antigens. Analogous results were obtained using an anti-(Lewis-anti-DA) antiserum. The anti-idiotypic antibodies can be used in fluorescent antibody tests to directly visualize the idiotype-positive cells. Using the separation design described above we analyzed selectively enriched or deleted T lymphocytes for presence of idiotypic cells as well as specific GvH reactivity. A highly significant positive correlation was found between percentage of a given idiotype in a population of T cells and the relevant GvH potential of the same T cells that can be visualized are indeed the very same T cells that express immune reactivity against the expected antigens. The present data would thus directly demonstrate the existence of a largely nonoverlapping population of immunocompetent T cells capable of reacting against the various Ag-B locus antigens in the rat. Highly purified, functionally intact immunocompetent T lymphocytes with restricted immune reactivity can thus be produced from normal lymphocyte populations for further analysis.

Animals

Antifluorescein affinity columns. Isolation and immunocompetence of lymphocytes that bind fluoresceinated antigens in vivo or in vitro.

A new method for the isolation of specific immunocompetent lymphocytes has been described in which lymphocyte populations are exposed to fluoresceinated antigens (FLAGs) in vivo or in vitro, and the FLAG-binding cells retained on antifluorescein affinity columns. Specific cells are then eluted with an unrelated FL-labeled protein and shown to be fully immunocompetent. This methodology has been applied successfully in diverse antigenic systems including polymerized flagellin and TNP-specific B cells and alloantigen-reactive cytotoxic T lymphocytes. The method is rapid, inexpensive (requiring only antifluorescein beads), and can be applied to any antigens (or antibodies) in which a fluorescein group can be introduced.

Animals

In vivo and in vitro assays of immunocompetence in bronchogenic carcinoma.

To determine the degree of correlation among the various in vivo and in vitro assays that could be used to assess immunocompetence in bronchogenic carcinoma, the response to common recall skin antigens, primary sensitization to DNCB and lymphocyte function tests based on blastogenic response to mitogens and in mixed lymphocyte culture (MLC) were tested in 48 patients with bronchogenic carcinoma. The values were compared to responses in 94 age-matched healthy control subjects. There were impaired skin tests reactions among squamous cell carcinoma patients, with little impairment of their lymphocyte blastogenesis reactions. Anaplastic carcinoma patients had notable defects in lymphocyte function tests but less impairment of the skin test reactions. These data suggest that the mitogen concanavalin A, phytohemagglutinin, and the MLC are more useful screening assays of in vitro immunocompetence than are the other commonly used mitogens.

Aged

Correlation between tumour stage, tumour grade, and immunocompetence in patients with carcinoma of the bladder and prostate.

The cellular immunocompetence was examined in 132 patients with transitional cell carcinoma of the bladder and 85 patients with carcinoma of the prostate with reference to the tumour stage and grade. In both groups a significant correlation between tumour stage and grade was found. These two parameters were also correlated with the reduction of immunocompetence. The results are discussed and compared with those in the literature.

Adenocarcinoma

Effects of an antitumor multipeptide complex on immunocompetent and antigen-responsive cells.

The investigations, performed to study the possible mechanism of action of PTC, of its single constituents and of meta-levo-sarcolysin (m-L-SL) on the human immunocompetent system, are reported. The study entailed the evaluation of the effect of PTC, of its peptides and of m-L-SL on the various lymphocyte classes, employing all the more sophisticated immunological techniques such as: a) lymphocyte cultures stimulated with the various mitogens, (T and B lymphocytes); b) E rosettes (T lymphocytes); c) EA rosettes (lymphocytes with Fc receptors for IgG); d) EAC rosettes (lymphocytes with the C3 receptors); e) autoradiography and intracytoplasmic immunofluorescence (in vitro immunoglobulin neosynthesis); f) CdL (Complement-dependent Lymphocytotoxicity); g) LALI (Lymphocyte Antibody Lymphocytolytic Interaction); h) CML (antibody independent cytotoxicity i.e. Cell-Mediated Lympholysis). The evidence points out that the PTC effect on T and B lymphocytes is not comparable to that of m-L-SL which does not discriminate between the two lymphocyte populations while PTC, besides showing a scarce immunodepressive effect, preferentially affects B lymphocytes rather than T lymphocytes as shown also by the E rosette pattern. Significantly different appears also the influence of PTC, as compared with that of m-L-SL on the lymphocytes with Fc receptors for IgG (EA rosettes) and with receptors for the third component of complement (EAC rosettes) as well as on the cytotoxicity test and on the antibody dependent (LALI) and complement dependent (CdL) lytic effect. The data gleaned from this investigation allow evaluating both the effects of PTC on the immunocompetent system and the difference of its action from that of m-L-SL.

Animals