Silica-induced alterations of murine lymphocyte immunocompetence and suppression of B lymphocyte immunocompetence: a possible mechanism.
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Aerosols↗
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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↗
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↗
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↗
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↗
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↗
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↗
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↗
The postnatal development of the white pulp in the rat spleen and the onset of immunocompetence against a thymus-independent and a thymus-dependent antigen.
The spleen of the rat contains 5 well delineated compartments: a central and peripheral part of the periarteriolar lymphatic sheath (PALS), the marginal zone and the follicle with centre and corona. A study was made on the development of these compartments in correlation with the onset of immunocompetence of the spleen. The spleens of animals in the age range from 1-40 days were studied with the light and electron microscopes. Immunocompetence was assessed by measuring serum antibody levels 5 days after intravenous antigen administration. Comparable doses of paratyphoid vaccin (PTV) and sheep red blood cells (SRBC) were used: PTV as a thymus-independent, SRBC as a thymus-dependent antigen. At the first day of life few lymphocytes are present around small arterioles. The marginal zone is first present at 9 days of age. At 14 days of age the typical thymus-dependent area develops. Interdigitating cells, which seem to develop from monocytes, and lymphocytes are present in close apposition. Primary follicles were first seen on 20 days of age, follicle centres at 25 or 30 days of age. The appearance of "typical" dendritic cells coincided with the appearance of follicle centres. The first titre against PTV was seen after antigen administration at 9 days after birth, against SRBC after injection in 14 days old animals. As PTV is a thymus-independent antigen it needs only B-cells for a primary IgM response. The appearance of functional B-cells in sufficient numbers to give a measurable response therefore coincides with the appearance of the marginal zone. Although T-cells are present from birth, the response against SRBC is delayed until the thymus-dependent area has developed. Thus, in the first 2 weeks of life, T-cells are either immature, or they are not able to react, because their microenvironment is not yet adequate.
Animals↗
Effects of intravenous nutrition on tumor growth and host immunocompetence in malnourished animals.
To evaluate the effects of oral and intravenous nutritional repletion on tumor growth and host immunocompetence in malnourished animals, 60 adult purified protein derivative (PPD) positive Buffalo rats were inoculated with Morris hepatoma 5123 and were fed a regular diet for 14 days. All animals then were switched to a high carbohydrate, protein-free diet for the next 14 days, at which time only 30% of the animals remained PPD positive. Rats then were divided into three groups: group I underwent superior vena cava catheterization and received a constant infusion of 25% dextrose--4.25% amino acid solution; group II was switched to the regular protein diet orally ad libitum; and group III remained on the oral protein-free diet. PPD reactivities were measured prior to death 7 days later. Group I animals gained an average of 14 gm of body weight, and 91% of the animals were PPD positive. Group II animals lost an average of 17 gm of body weight, but 78% of the animals were PPD positive. Group III animals lost an average of 23 gm of body weight, and only 12% of the animals remained PPD positive. Absolute tumor weight and tumor weight: body weight ratios were not significantly different among the three groups of animals. Provision of adequate nutrition intravenously to malnourished tumor-bearing animals restores body weight and host immunocompetence without adversely stimulating tumor growth out of proportion to growth of the host.
Animals↗
Comparative effects of cyclophosphamide, isophosphamide, 4-methylcyclophosphamide, and phosphoramide mustard on murine hematopoietic and immunocompetent cells.
The effects of equimolal doses of cyclophosphamide (CY), isophosphamide (IP), 4-methylcyclophosphamide (4-MCY), and phosphoramide mustard (PM) on murine hematopoietic spleen colonies and adoptively transferred antibody-forming cells in vivo were compared. Equimolal doses of the drugs produced significantly different effects. All the drugs exerted an increasing effect against the ability of adoptively transferred immunocompetent cells to produce a significant anti-sheep red blood cell titer as the length of time between cell transfer and drug administration was increased. The maximum effect was seen when a drug was given 48--72 hours after antigen and spleen cell transfer. CY and IP produced significantly greater immunosuppressive effects than did the other drugs at all times after cell transfer and at all doses administered. PM had the least immunosuppressive effect at each dose evaluated. Against hematopoietic spleen colonies, the cytotoxic effects of 4-MCY and PM were similar and, at most doses studied, significantly greater than the effect of either CY or IP. Inasmuch as PM is an active metabolite of CY, it appeared either that one of the prior metabolites of CY was responsible for this marked immunosuppressive effect or that due to differences in polarity, PM was differentially distributed within the two cell systems as compared to CY. The differences in hematopoietic effects among all drugs were much less than those seen against immunocompetent cells and were not dependent on time of drug administration.
Animals↗
Models for assessing the effect of toxicants on immunocompetence in mice. II. Effect of cyclophosphamide on the antibody responses to type III pneumococcal polysaccharide and tetanus toxoid in BALB/c female mice.
A mixture of antigens was used to detect alterations in immunocompetence. Type III pneumococcal polysaccharide (S3) and tetanus toxoid (TT) stimulate different cellular components, and can therefore be used to assess different compartments of the immune mechanism. Cyclophosphamide (CP), a known immunosuppressant, had a potent effect upon the antibody responses to both S3 and tetanus toxoid. All doses of CP administered within 2 days of priming with S3 resulted in a dose-related immunosuppressive action which persisted even after reinjection of S3. 300 mg/kg of CP given up to 14 days prior to or following primary immunization resulted in a marked suppression of antibodies to S3. Doses of S3 which were partially tolerogenic were made even more so by injections of CP. The effect persisted over a 96 day experimental period. CP also suppressed the formation a memory cells necessary for induction of a secondary-type IgG response to TT. The time of injection for maximum suppression was days 10 to 14 after priming. Therefore, the suppression must involve cellular mechanisms different from those responsible for S3 antibody suppression. In addition, there was a difference in the degree and persistence of the suppressive effect, since the suppressed animals were able to mount an immune response to subsequent injections of TT. Double injections of a high dose (300 mg/kg) of CP 4 weeks after priming completely suppressed the acquired immunity to both S3 and TT. Low and moderate doses of CP appeared to induce a mild augmentation of S3 antibody response when given 4 weeks after priming. However, an immunosuppressive effect occurred if the primed animals were reinjected with S3 or challenged with TT within a period of 2 days prior to or after receiving the CP treatment. Doses of CP, injected prior to challenge and resulting in suppressed tetanus antitoxin production, elevated the titers of specific IgE antibody. This class of antibody is associated with adverse hypersensitivity reactions. These data provided background for the development of models to assess immunocompetence in mice, based on a study of immune profiles following exposure to selected T-dependent and T-independent antigens. Such models may be used to detect potentially hazardous chemicals found in the environment of incorporated into foods, drugs, or cosmetics.
Animals↗
[Treatment with immunocompetent cells and cellextracts (author's transl)].
The therapy of inborn or acquired defects of the cellular immune function is still in an experimental stage. Basicly, it is possible to replace the non-functioning T-cells by immunocompetent lymphocytes. Bone marrow, fetal liver and/or thymus, or cultivated thymus can serve as the source of such cells. Under certain conditions humoral factors derived from immunocompetent lymphocytes can induce a lacking immune response. Possibilities as well as limitations of these two therapeutic concepts are discussed.
Bone Marrow Cells↗
[The influence of highly purified hCG on the immunocompetence of human lymphocytes and DNA repair system].
PHA-stimulation of human T-lymphocytes, a parameter of cellular immunocompetence, can be suppressed by highly purified human chorionic gonadotropin (hCG) in a dose-dependent manner. This was shown spectrophotometrically and by the mitosis index. Our results are in agreement with H3-thymidine incorporation studies. We further investigated the DNA repair system in UV-light- and hCG-explsed lymphocytes. It could be shown that DNA repair-replication is disturbed by hCG. Such repair disturbances may cause reduced H3-thymidine incorporation in PHA-stimulated and hCG-treated lymphocytes. It is probably on this molecular level that hCG influences the immunocompetence of human lymphocytes.
Antibodies↗
The effects of bleomycin on immunocompetence in man.
Bleomycin was administered to six patients with advanced cancer. Multiple parameters of both antibody- and cell-mediated immunity were followed serially to characterize the effects of bleomycin on immunocompetence in humans. Antibody-mediated immunity, including primary vaccination with keyhole limpet hemocyanin, was not depressed. While there was no significant suppression of cell-mediated immunity, phytohemagglutinin-stimulated lymphocyte blastogenesis was reduced after treatment with bleomycin. The in vitro effects of bleomycin on lymphocyte stimulation were studied, and while thymidine incorporation was significantly inhibited by bleomycin, leucine incorporation was not reduced even at high concentrations of bleomycin. We have concluded that bleomycin does not suppress immunocompetence in man.
Antibody Formation↗
Intrahepatic Exhausted Antiviral Immunity in an Immunocompetent Mouse Model of Chronic Hepatitis B.
BACKGROUND & AIMS: Targeting exhausted immune systems would be a promising therapeutic strategy to achieve a functional cure for HBV infection in patients with chronic hepatitis B (CHB). However, animal models recapitulating the immunokinetics of CHB are very limited. We aimed to develop an immunocompetent mouse model of CHB for intrahepatic immune profiling. METHODS: CHB mice were created by intrahepatic delivery of the Sleeping Beauty transposon vector tandemly expressing the hepatitis B virus (HBV) genome and fumarylacetoacetate hydrolase (FAH) cDNA into C57BL/6J congenic FAH knockout mice via hydrodynamic tail vein injection. We profiled the viral and intrahepatic immune kinetics in CHB mice with or without treatment with recombinant IFNα or the hepatotropic Toll-like receptor 7 agonist SA-5 using single-cell RNA-seq. RESULTS: CHB mice exhibited sustained HBV viremia and persistent hepatitis. They showed intrahepatic expansion of exhausted CD8+ T (Tex) cells, the frequency of which was positively associated with viral load. Recruited macrophages increased in number but impaired inflammatory responses in the liver. The cytotoxicity of mature natural killer (NK) cells also increased in CHB mice. IFNα and SA-5 treatment both resulted in viral suppression with mild hepatic flares in CHB mice. Although both treatments activated NK cells, SA-5 had the capacity to revitalize the impaired function of Tex cells and liver-recruited macrophages. CONCLUSIONS: Our novel CHB mouse model recapitulated the intrahepatic exhausted antiviral immunity in patients with CHB, which might be able to be reinvigorated by a hepatotropic TLR7 agonist.
Animals↗
[Double urologic tumors: reduced immunocompetence?].
55 patients with primary multiple neoplasias underwent immunostaging with determination of the immunoglobulins, B- and T-lymphocyte counting, H3-lymphocyte stimulation (ConA, PWM, PHA) and DNCB-epidermal test. There were no significant differences between the PMN-group and a group of patients with solitary tumors, whereas both cancer patient groups revealed a diminished immunocompetence compared with a non-malignant control group of patients.
Adult↗
Immunocompetence of the guinea pig's middle ear.
Immunocompetence of the middle ear was studied in guinea pigs in two series of experiments. The first, afferent phase, consisted of grafting iso and allografts in the guinea pig's middle ear to sensitize the animals which were later to receive a skin graft on the back. The second, efferent phase, first sensitized the animals with a skin graft on their back and later in the middle ear. The results show a rather low capacity of the middle ear to elicit a second-set rejection of the skin grafts. This lack of sensitization is explained by the authors by the concept of tolerance.
Animals↗