Silica-induced alterations of murine lymphocyte immunocompetence and suppression of B lymphocyte immunocompetence: a possible mechanism.
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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.
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.
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.
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.
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.
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.
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.
To better understand the role of immunocompetent cells in the defense mechanism of the inner ear, the distribution patterns of those cells were investigated in the endolymphatic sac (ES) of mice maintained in three different conditions: germ-free (GF), specific pathogen-free (SPF), and conventional (CV). In another experiment, the recruitment of lymphocyte subsets was examined in the ES of SPF rats undergoing a perilymphatic antigen challenge after systemic presensitization. In the ES of GF mice, no immunocompetent cells were found. In the ES of SPF and CV mice, cells positive for IgG, IgA, IgM, and Lyt-1 were present in much smaller numbers than in the nasal mucosa. Cells positive for Lyt-2 were not seen in the ES of any mice. In the ES of rats that underwent a perilymphatic antigenic stimulation after a systemic presensitization, B lymphocyte subsets (positive for IgG, IgA, IgM) were mobilized in increased numbers, and T cell subsets (helper/inducer and suppressor) were also found 1 week after perilymphatic antigen challenge. These results taken together suggest that the ES is not originally equipped to possess immunocompetent cells and mount an immune response, but that once it has been activated with the inner ear antigenic stimuli, the ES can be the active site of a local immune response of the inner ear.
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.
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.
Conventional virologic and in situ nucleic acid hybridization methods were used to study immunocompetent and immunosuppressed 3-week old BALB/c mice inoculated intravitreally with 10(4) plaque-forming units (pfu) of murine cytomegalovirus (MCMV). Immunocompetent mice experienced a self-limited ocular infection with peak virus titers of 10(3.5) pfu/ml in the retina-choroid fraction on day 4 of infection. Using biotinylated MCMV DNA probes, MCMV DNA was detected in cells of the iris, ciliary body, and rarely, the retina or choroid on days 4 and 7 of infection. With few exceptions, retinal architecture was preserved. By contrast, mice immunosuppressed with cyclophosphamide (200 mg/kg on day 0 and 100 mg/kg on days 5 and 11 after MCMV inoculation) had progressive ocular infection that culminated in a necrotizing retinitis. Virus titers in the retina-choroid fraction rose progressively (nearly 10(5) pfu/ml in cyclophosphamide-treated mice on day 11 versus 10(1.5) pfu/ml in immunocompetent mice). The MCMV DNA was detected in the iris and ciliary body of the immunosuppressed mice on days 4 and 7 and in the retina, on days 7, 11, and 14. On day 14 abundant MCMV DNA was found in most retinal layers, and extensive retinal necrosis was observed. These studies indicate that immunosuppression with cyclophosphamide potentiates MCMV ocular disease in mice, a finding analogous to CMV retinitis in immunosuppressed humans.
Immunocompetent cells of the Indian fruit bat (P. giganteus) were characterized by differential surface adhesiveness and surface topography. We observed three cell types: (1) plastic adherent with pseudopodia; (2) nylon wool adherent with small microvilli and pits; and (3) a nylon wool nonadherent with comparatively smooth surfaces. These cell types resemble, respectively, macrophages, B cells and T cells of other mammals, including mice and humans. The disposition of microvilli on the B-type cell surface changes significantly after immunization, which suggests modulation of the molecular organization of the cell membrane and its fluidity. The proportions of these three cell types are not much different from those found in mice. Follicular dendritic cells, capable of retaining antigen for long periods in mice, have also been detected in bats. Further characterization of immunocompetent cells wil help in understanding the mechanism of immune responses in bats.
The phenotype of inflammatory cells in lymph nodes from 16 patients with culture-proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Eight patients were suffering from a symptomatic HIV1 infection and 8 patients were immunocompetent individuals without positive HIV1 serology. In addition, the lymph nodes of 2 AIDS patients with Mycobacterium avium-intracellulare infection were examined using the same techniques. Characteristic granulomas with or without caseation were observed in the 8 immunocompetent and the 4 HIV1-infected patients with less marked lymphopenia of CD4+ peripheral blood lymphocytes (PBL). In lymph nodes from the other HIV1-infected patients with more severe depression of CD4+ PBL, no epithelioid cell formation was present; instead, foamy macrophages were found. The phenotype of the macrophages underwent progressive changes in parallel with the decreasing numbers of CD4+ PBL. Foamy macrophages in M. avium-intracellulare infection exhibited remarkable erythrophagocytotic activity and may represent an end-stage phenotype. They were positive for S100 protein and did not produce lysozyme or alpha-1-antichymotrypsin. They lost the antigen which was detected by monoclonal antibody Mac387 whereas positivity for HLA-DR, CD68 and KI-M8 was preserved. While many lymphocytes expressed CD25 (IL2 receptor) in cases with typical granulomas, there was no such CD25 expression in cases without epithelioid cell formation. Although granulomas have been produced in experimental animals independently of cell-mediated immune mechanisms, our results suggest that T-cell functions are necessary for epithelioid granuloma formation in human tuberculosis.
The survival, growth and development of Onchocerca lienalis 3rd-stage (L3) larvae implanted into mice within micropore chambers has been studied with a view to developing a vaccination model for studies of protective immunity in onchocerciasis. The influence of host genetics on worm recoveries and development (growth and moulting rate) was analysed in a panel of inbred mice (CBA, BALB/c, DBA/2, SJL, 129J, C57BL/10 (B10), C3H/He and NIH), together with mice of BALB and B10 backgrounds with different major histocompatibility complex (H-2) genes (BALB/c, BALB.K, BALB.B and B10, B10.D2/n, B10.BR, B10.S). Parasite recoveries and development were similar in all mouse genotypes tested. They were unaffected by procedures designed to block or modulate phagocytic cell function with carbon or carrageenan, or to suppress inflammation by treatment with hydrocortisone acetate. A comparison of chambers sealed with membranes designed to admit (5.0 microns pore size) or exclude (0.2 microns pore size) host cells demonstrated no effect on the percentage recovery of living larvae, although dead larvae were more frequently retrieved when cells were excluded. Recoveries and rates of development of larvae implanted into immunodeficient scid mice and athymic Hooded rats were similar to those recorded in immunocompetent controls. We conclude that host genetic factors and immunocompetence are not significant determinants of survival, growth or development of O. lienalis larvae implanted within micropore chambers into naive mice. Despite its limitations, the use of this system merits further investigation as an approach to the study of protective immunity against developing larvae in onchocerciasis.
This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non-supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function.
Esophagitis due to herpes simplex virus is a well-recognized entity in immunocompromised patients but has only rarely been described in apparently immunocompetent hosts. We report four cases and review 27 additional cases identified in the English-language literature. Odynophagia, retrosternal chest pain, and fever are the most common symptoms. Single-contrast esophagography is insensitive and nonspecific, but double-contrast esophagography may be of more diagnostic value. Esophagoscopy with biopsy or collection of aspirate for cytologic examination and culture are required to make a definitive diagnosis. Patients are predominantly male, and most cases are associated with primary infection. Viral isolates were typed in 13 cases and were always type 1. Herpes simplex esophagitis in the immunocompetent patient is a self-limited infection; however, therapy with acyclovir may attenuate infection and hasten resolution of symptoms.
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.