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T R Jerrells

Publications and source records attributed to T R Jerrells.

At least 73 records · Page 4Linked to original sources
PubMed1983

Role of T-lymphocytes in production of antibody to antigens of Rickettsia tsutsugamushi and other Rickettsia species.

The requirement of thymus-dependent lymphocytes for antibody production to Rickettsia tsutsugamushi, Rickettsia akari, Rickettsia conorii, and Rickettsia typhi was investigated by comparing antibody production in athymic (nu/nu) or thymus-bearing BALB/c mice. Athymic BALB/c mice produced antibody after infection with R. akari, R. conorii, and R. typhi as measured by indirect fluorescent antibody titration or radioimmunoassay. Antibody production in these mice was a great or greater than in the thymus-bearing mice and demonstrated similar kinetics. In contrast, athymic BALB/c mice infected either intraperitoneally or subcutaneously with the Gilliam strain of R. tsutsugamushi failed to produce demonstrable antibody. The requirement of thymus-dependent lymphocytes for antibody production to R. tsutsugamushi was further suggested by the demonstration of antibody production after transfer of immune thymus-dependent lymphocytes to athymic mice and the demonstration of R. tsutsugamushi-specific T helper cells in immune thymus-bearing mice. The antibody produced in athymic mice after infection with R. akari, R. conorii, and R. typhi was predominantly immunoglobulin M, based on isotype-specific radioimmunoassays and sucrose gradient fractionation. Furthermore, the antibody produced by athymic mice in response to R. akari infection reacted with a carbohydrate-containing outer membrane component.

Animals↗
PubMed1983

Association of an inflammatory I region-associated antigen-positive macrophage influx and genetic resistance of inbred mice to Rickettsia tsutsugamushi.

Strains of C3H mice differing in susceptibility to intraperitoneal infection with the Gilliam strain of Rickettsia tsutsugamushi were used to investigate the role of the I region-associated (Ia) antigen-bearing macrophage in the genetic resistance of mice to this organism. Resistant mice (C3H/RV) were found to produce a quantitatively greater Ia antigen-positive macrophage response after infection compared to mice (C3H/HeDub) which underwent a lethal infection. The macrophage influx produced in response to infection of the C3H/HeDub mice was deficient in Ia antigen-bearing cells, as evaluated by antigen presentation function and by the use of macrophages as stimulator cells in a mixed lymphocyte response. The resistance to infection, as well as the Ia-positive macrophage response in C3H/RV mice, was sensitive to 450 to 600 rads of irradiation. C3H/HeDub mice produced exudates rich in Ia-positive macrophages if stimulated with concanavalin A or after challenge with R. tsutsugamushi (if previously immunized), ruling out an innate inability of this strain of mice to produce Ia-positive macrophages exudates. Challenge of either strain of mice immunized by a prior subcutaneous infection resulted in a rapid (3 to 5 days) peak of Ia-positive macrophages responding to the peritoneal cavity. It also was noted that subcutaneous infection alone resulted in an increase in the proportion and number of "resident" macrophages which were Ia positive. These data suggest that the macrophage influx in terms of Ia-bearing cells is at least associated with the genetic resistance of C3H/RV mice to infection with this rickettsiae and may play a role in resistance. Furthermore, it would appear that the Ia-positive macrophage is a factor in acquired immunological resistance to reinfection.

Animals↗
PubMed1982

Host defenses in experimental scrub typhus: delayed-type hypersensitivity responses of inbred mice.

Delayed-type hypersensitivity responses of inbred mice during the course of lethal and chronic infections with strains of Rickettsia tsutsugamushi were evaluated by using the influx of radiolabeled cells into antigen-injected ears. Congenic strains of C3H mice, which previously have been shown to be resistant (C3H/RV) or sensitive (C3H/HeDub) to lethal intraperitoneal infection with the Gilliam strain of rickettsiae, both expressed delayed-type hypersensitivity early in the course of infection (5 to 7 days). The sensitive C3H/HeDub mice, however, exhibited a marked decline in reactivity just before death. In contrast, reactivity of C3H/RV mice remained high through day 9 and declined slowly through day 15 after infection. Similar results were obtained when BALB/c mice were infected with either the Karp or the Gilliam strain of rickettsiae, which produce a lethal or nonlethal infection, respectively, in this strain of mice. Rechallenge of C3H/RV mice elicited a rapid increase in reactivity, suggesting a secondary memory response. To analyze delayed-type hypersensitivity during chronic infection, C3H/HeDub mice were immunized by subcutaneous infection with the Gilliam strain of R. tsutsugamushi, and both delayed-type hypersensitivity reactivity and resistance to intraperitoneal challenge were examined. Delayed-type hypersensitivity reactivity developed slowly and peaked at 21 days postimmunization, which correlated with resistance to intraperitoneal challenge. Delayed-type hypersensitivity reactivity declined thereafter, but resistance to intraperitoneal challenge remained through 28 days postimmunization. Delayed-type hypersensitivity reactivity increased after secondary challenge at 28 days, again suggesting antigen memory generated by primary immunization. Transfer of delayed-type hypersensitivity reactivity was accomplished by using immune thymus-derived splenic lymphocytes isolated with nylon-wool columns. Abrogation of the ability of immune spleen cells to transfer delayed-type hypersensitivity reactivity after treatment with anti-Thy 1.2 alloantiserum and complement further supported the view that delayed-type hypersensitivity responses to scrub typhus rickettsiae were mediated by thymus-derived lymphocytes.

Animals↗
PubMed1982

Role of macrophages in innate and acquired host resistance to experimental scrub typhus infection of inbred mice.

Mechanisms of innate resistance to infection with the Gilliam strain of Rickettsia tsutsugamushi were examined using congenic strains of mice resistant (C3H/RV) or susceptible (C3H/He) to intraperitoneal infection. Both strains of mice were resistant to infection with 1,000 50% mouse lethal doses of rickettsiae if given intravenously. In both systems rickettsial replication occurred after intravenous infection, as evidenced by an increase in rickettsial numbers in the spleens of infected animals, followed by a decrease in rickettsiae to low levels by day 14 postinfection. Administration of the antimacrophage agents silica and carrageenan to C3H/He mice intravenously rendered these animals susceptible to lethal infection. Neither irradiation nor silica given individually rendered C3H/RV mice susceptible to intravenous infection. However, if silica and irradiation were given together, a lethal infection occurred after intravenous infection. C3H/RV mice became susceptible to lethal infection after sublethal doses of irradiation only if they were infected intraperitoneally. Administration of silica or carrageenan had no effect on the outcome of intraperitoneal infection of these mice with Gilliam rickettsiae. These data suggest that both strains of mice share innate resistance mechanisms to intravenous infection that consist of fixed macrophages. Resistance of C3H/RV mice to intraperitoneal infection, in contrast, apparently was dependent only on an irradiation-sensitive process.

Animals↗
PubMed1981

Host defenses in experimental scrub typhus: inflammatory response of congenic C3H mice differing at the Ric gene.

Two strains of C3H mice differed in their susceptibility to lethal infection with Rickettsia tsutsugamushi strain Gilliam. Adult C3H/RV mice were markedly more resistant to lethal infection than C3H/HeDub mice, and both were histocompatible as assessed by mixed-lymphocyte cultures and graft-versus-host responses. The inflammatory response of susceptible C3H/HeDub mice to intraperitoneal infection was evident approximately 5 days postinfection, and the magnitude of the cellular influx increased until death of the animal. The inflammation consisted of an early polymorphonuclear leukocyte response, followed by a mononuclear cell influx which persisted until death of the animal. The C3H/RV mice evidenced similar kinetics of cell influx, but the inflammatory response was significantly reduced in magnitude, and the response of C3H/RV animals to Gilliam was predominantly mononuclear in nature, with little influx of polymorphonuclear leukocytes into the peritoneal cavity. C3H/RV mice were rendered susceptible to Gilliam infection by induction of a nonspecific inflammation with thioglycolate if given 3 days after infection. Conversely, treatment of C3H/HeDub mice with indomethacin, an anti-inflammatory agent, prolonged survival after infection with Gilliam. The results of this study indicate that genetic resistance to Gilliam is not due simply to a greater host response to infection or, conversely, that susceptibility is due to a host response quantitatively lacking in a cellular component necessary for antirickettsial immunity.

Animals↗
PubMed1980

Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokines.

Monocytes were separated from peripheral blood mononuclear cells of normal human donors by adherence on plastic conditioned by cell lines (microexudate-coated plastic) and harvested by exposure to ethylene diamine tetra-acetic acid. Cytolytic activity was tested by incubating effector cells for 48 h with the murine SV40-transformed TU5 kidney line or the human lung cancer-derived CaLu line prelabelled with tritiated thymidine. Lymphokine-containing supernatants were obtained from in vitrocultures of lymphoid cells with phytohemagglutinin (PHA), purified protein derivative (PPD), or with Corynebacterium parvum strains CN6134 or CNS888. The monocytes had significant levels of spontaneous cytotoxicity and exposure to lymphokine supernatants markedly enhanced their tumoricidal activity. Augmentation of monocyte-mediated cytotoxicity required a minimal exposure to lymphokine supernatants for 4 h and was maximal after 24 h of preincubation. Treatment of the effector cells with anti-human T-cell serum and complement did not affect either their spontaneous or their lymphokine-stimulated cytotoxicity, whereas silica impaired both reactivities. Supernatants of cultures with PHA, PPD and C. parvum CN6134 had significant levels of interferon (IF). Since partially purified human fibroblast or leukocyte IF was able to stimulate monocyte-mediated cytotoxicity, the IF in these supernatants could play some role in the stimulation of the monocytes. However, C. parvum CN5888 supernatants, which had little IF, enhanced monocyte cytotoxicity as effectively as the C. parvum CN6134 supernatants, strongly suggesting that lymphocyte mediators other than IF can augment the tumoricidal activity of these effector cells. Mature macrophages obtained by in vitro cultivation of monocytes for 4-7 days retained natural cytolytic activity and showed enhanced cytotoxicity in the presence of lymphokines. However, more prolonged in vitro cultivation (> 10 days) resulted in cultures of epithelioid and multinucleated cells which had little natural cytotoxicity and were not responsive to lymphokines.

Adult↗
PubMed1979

Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.

Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F-265). The effector cells were adherent and were probably monocytes. Sephadex G-10 column passage or adherence to plastic removed most growth-inhibitory activity. Adherent cells recovered from plastic flasks (88-94% monocytes) were strongly growth-inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth-inhibitory activity was not species-restricted, since human effector cells and also effector cells from tumor-bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL-5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non-adherent and have little reactivity against F-265 or RBL-5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F-265 resulted in similar degrees of reduction in the number of target cells and in [3H] thymidine uptake.

Animals↗
PubMed1979

Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts.

Monocytes from the peripheral blood of 10 normal adult human donors were tested for their cytolytic activity on untransformed or SV40-transformed, early passage, human fibroblasts. Two pairs of human fibroblast lines (2303 and SV40-2303, 2931 and SV40-2931) were used and lysis was assessed in terms of release of [3H]thymidine from prelabelled target cells over a 72-h incubation period. High levels of cytolytic activity were consistently observed on transformed fibroblasts at attacker to target cell (A:T) ratios ranging from 5:1 to 40:1. Low, but significant, lysis of untransformed cells was observed only with two donors at the highest (40:1) A:T ratio tested. With all donors, the cytolytic activity on transformed lines was significantly greater than on untransformed fibroblasts. Thus natural human monocyte-mediated cytotoxicity is preferentially expressed on transformed, as compared to untransformed, cells although sparing of the latter is not absolute.

Adult↗
PubMed1979

Assessment of immunobiological effects induced by chemicals, drugs or food additives. I. Tier testing and screening approach.

The indications of immunologic dysfunction following low level exposure of rodents or even man to certain chemicals and drugs have raised concern regarding methodology and approaches for routine assessment of immunobiological effects. The immunogiological effect observed may either indicate impaired immunopotentiation or hypersensitization. The assays selected for testing should be relevant to the human experience and adaptable to certain practical considerations such as cost, reproducibility of data, ease of performance and application to routine toxicology studies. Using these considerations, a tier approach was proposed consisting of assays for screening for immunologic effects (Tier I) and assays to help define the mechanisms responsible for the immunobiological effects observed (Tier II). A tier of assays was also proposed for measuring the sensitization potential of certain compounds. Certain assays from the screening tier were assembled into a hypothetical and practical test battery to screen for immunological effects of a chemical with potential immunosuppressive properties. Information provided by this test battery should provide a reasonable and sensitive data base from which a standard of evaluation could be made regarding the safety of the test (1) compound.

Animals↗
PubMed1978

Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts.

Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity.

Adenocarcinoma↗