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Soluble extracts from larval Ostertagia ostertagi modulating immune function.

BALB/c mice were immunized with Ostertagia ostertagi antigens and keyhole limpet hemocyanin (KLH) or sheep erythrocytes (SR) for evaluation of antibody production by enzyme linked immunosorbent assay (ELISA) or modified Jerne plaque assay. One semi-purified larval antigen caused both decreased anti-KLH serum antibody levels and fewer anti-SR IgM-secreting B cells. This antigen was shown to depress lymphocyte blastogenesis to Concanavalin A when added to cultured BALB/c splenic lymphocytes.

Animals

The effects of ultraviolet irradiation of the skin on herpes simplex virus infection: alteration in immune function mediated by epidermal cells and in the course of infection.

Previously, we demonstrated that Ia+ epidermal cells (EC) have herpes simplex virus (HSV) antigen-presenting capacity in vitro and play an important role in resistance to HSV infection in vivo. In the present study, we investigated the effects of in vivo ultraviolet (UV) irradiation of the skin on the HSV-immunity function of EC both in vitro and in vivo and on the pathogenesis of HSV infection. Immune T cells cultured with EC and HSV antigen showed a proliferative response in vitro. Exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of this proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia+ EC. We also transferred these EC-stimulated T cells to intracutaneously infected nude mice. Immune T cells stimulated with EC obtained from irradiated mice did not effectively clear HSV and allowed development of zosteriform skin lesions. In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform rash. In addition, mice irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of HSV showed increased severity of infection and a higher incidence of latency compared with control mice. These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of EC both in vitro and in vivo, and affects HSV pathogenesis. The implication of our results for the better understanding of the effect of UV on acute and recurrent HSV infections is discussed.

Animals

Effects of rat cytomegalovirus infection on immune functions in rats with collagen induced arthritis.

The effect of rat cytomegalovirus (CMV) infection on immune function was studied in rats with collagen induced arthritis, an experimental model of autoimmunity targeted to cartilage and previously shown to be greatly augmented in severity by rat CMV. Rat CMV infection induced an early (7 to 14 day), 2.5-fold increase in circulating B cells (SIgG+) which was associated with moderate increases in the titers of serum IgG antirat type II collagen antibody. A significantly increased skin test reactivity (p less than 0.025) to rat type II collagen was detected at Day 14 and followed a small increase in numbers of W3/25+ T-helper cells in peripheral blood noted at Day 8. A 3-fold expansion of OX8+ peripheral lymphocytes, occurring maximally at Day 8, was tentatively identified as a natural killer cell population by functional 51Cr-release assays. Our data indicate that rat CMV augmentation of collagen induced arthritis is associated with a generalized but modest increase in immune reactivity towards rat type II collagen and with significant alterations of peripheral lymphocyte subsets.

Animals

Immune function in the malnourished host.

Deficiencies of protein, energy, and specific vitamins and minerals impair function of various components of the immunological network and therefore weaken host defense. These various deficiencies may affect specific loci within the network, but because of the interrelations between the different systems, the ultimate effect may be quite broad. Patients with PEM often suffer infections, which may also impair the immune function. It is difficult to separate effects of malnutrition from those of infection, a fact recognized in the recent coinage of the term malnutrition-infection complex. On the basis of the available information it appears that PEM and associated deficiencies of nutrients cause a major impairment in the T lymphocytes and the complement system. They have relatively less effect on the B lymphocytes and the phagocytes directly; however, normal B cell activity is dependent on regulatory influences of T cells and the phagocytic cells require mediators generated from the activation of complement. Therefore these cells also are functionally defective in PEM. The consequence of these deficiencies of function of the immune system in the malnourished host is heightened susceptibility to and a less vigorous response to infections. These defects can be generally reversed by nutritional rehabilitation.

Antibody Formation

Thymus-dependent immune functions in chickens bursectomized with colchicine applied to the anal lips.

Thymus-dependent immune functions were investigated in chickens bursectomized neonatally with colchicine solution given per anum. Antibody responses to thymus-dependent antigens sheep red blood cells (SRBC) and human gamma-globulin (HGG) were delayed, reaching the normal level after the third antigen stimulation. Also the mitogenic responses of peripheral blood lymphocytes were preserved, and no changes in the thymic morphology were found. In contrast, antibody responses to bursa-dependent antigen Brucella abortus were low and the switch of immunoglobulin isotypes from IgM to IgA and IgG was disturbed. It can be concluded that neonatal bursectomy with cloacal administration of colchicine does not significantly affect T cell functions, whereas B cell functions are partially deficient.

Animals

In vivo and in vitro effects of 1,1-dimethylhydrazine on selected immune functions.

The in vivo phase of the experiments reported here include the evaluation of immune function after short-or long-term treatment of mice with 1,1-dimethylhydrazine (UDMH). Long-term exposure (3 injections/week for 14 weeks) resulted in increased numbers of Jerne plaque-forming cells, a trend toward decreased induction of suppressor cell activity by concanavalin A (Con A), and no effects on mitogen-induced lymphocyte blast transformation (LBT), compared to saline-treated control mice. These effects were greatest at doses of 10 or 50 mg/kg, while higher doses had less of an effect. In vitro experiments were performed by adding UDMH to normal murine splenocytes in the LBT assay and con A-induced suppressor cell assay. The UDMH induced a significant enhanced response to lipopolysaccharide (LPS) at 10 and 50 micrograms/ml, and a suppressed response to both Con A and LPS at higher concentrations. The UDMH also caused a decrease in suppressor cell activity at 25 micrograms/ml. Selective abrogation of suppressor activity or alteration of the suppressor cell-helper ratio were suggested as possible mechanisms for the enhancement effect associated with UDMH.

Animals

In vitro evidence for defective afferent immune function in long-term renal allograft recipients.

Experiments were designed to evaluate afferent immune functions in 21 long-term (greater than or equal to 3 years) renal allograft recipients by using in vitro assays that included autologous and allogeneic mixed lymphocyte reactions (AMLR and allo-MLR), proliferative responses to a soluble antigen (tetanus toxoid), and the ability to generate cytotoxic T lymphocytes (CTL) following stimulation in an AMLR. The results showed that allograft recipients generated responses in the allo-MLR (means = 84,789 +/- 8242) that were comparable to those exhibited by normal controls (means = 86,082 +/- 7423). Likewise, mean responses in the AMLR were similar in recipients and controls (14,937 +/- 3243 versus 16,101 +/- 3005), although a greater percentage of recipients generated AMLRs below 5000 cpm than did normals (8/21 versus 4/20). However, 13 recipients analyzed for responsiveness to tetanus toxoid were shown to generate mean proliferative responses that were significantly depressed below normal (18,095 +/- 5545 versus 48,935 +/- 8813, P less than 0.001). Furthermore, despite significant proliferation in the AMLR means = 27,648 +/- 5168), 8 recipients generated significantly lower CTL activity in AMLR cultures than normal controls (mean percentage of cytotoxicity = 10.3 +/- 4.7 versus 24.9 +/- 4.7, P less than 0.05). These recipients generated normal CTL levels against allogeneic target cells following stimulation in an allo-MLR. Thus, these studies provide experimental support for the existence of altered T helper cell-mediated functions in long-term renal allograft recipients.

Humans

Cellular immune functions, endorphins, and alcohol consumption in males.

The effects of alcohol abuse on cellular immune functions were measured by various levels of alcohol use in adult men. Total lifelong abstainers were used as controls. Previous abusers, current abusers, and patients with alcoholic cirrhosis or pancreatitis were age-matched to controls. T-lymphocyte mitogenesis stimulated by phytohemagglutinin and concanavalin A was generally reduced in peripheral blood lymphocytes of current and previous alcohol consumers, although the decrease was not statistically significant. B-cell mitogenesis stimulated by pokeweed mitogen was not changed by previous alcohol consumption. The number of T-cells was not changed by either previous or current alcohol abuse. T-helper cells were significantly increased and T-suppressor cells increased only in the patients with alcoholic cirrhosis or pancreatitis. The percentage of T-lymphocytes with T-suppressor characteristics in controls was 27% while in alcoholic cirrhosis or pancreatitis subjects it was 16%. Plasma corticosteroid levels were significantly increased in people currently consuming alcohol (12.1 +/- 1.1 mg/dl) compared to controls (7.7 +/- 1.1). The corticosteroid levels were also higher in previous alcohol abusers although not statistically significant. Plasma endorphin levels were increased by severe alcohol abuse in the patients with cirrhosis or pancreatitis to 25.03 +/- 6.74 from 11.85 +/- 2.48 pg/ml in controls.

Adult

The effect of antidepressants on immune function in mice.

Depression or its treatment with antidepressant agents may have an impact on the normal function of the immune system. To address this issue in an animal model, we studied the effect of maprotiline and desipramine treatment of mice on several immunological activities associated with host resistance to cancer and infections. Our results indicate that chronic maprotiline treatment depressed natural killer (NK) cell function, measured in vivo as clearance of tumor cells from the lung or in vitro as cytolytic activity. Cell-mediated immunity, measured as delayed hypersensitivity in vivo and T and B lymphocyte proliferative responses in vitro, was largely unaffected. Although antidepressant toxicity at high concentrations inhibited T, B, and NK cell activity, it is unlikely that this is the basis for the in vivo effects.

Animals

Central nervous system and peripheral immune functions and the sleep-wake system.

This paper reviews the relationship of aspects of the immune system to the sleep-wake system in animals and humans. In addition to the influence of certain cytokines such as interleukin-1 (IL-1) on the sleeping-waking brain, circadian measures of plasma IL-1 and peripheral immune cellular functions, for example, natural killer cell activities and cortisol are related to the sleep-wake system in humans. Changes in the circadian patterns of immune functions over the menstrual cycle are associated with the amount of progesterone and slow wave sleep. The harmonious inter-relationship of the circadian pattern of the immune, endocrine and sleep-wake systems may be important in the cause and functions of sleep.

Animals

Effect of tamoxifen on immune functions.

Tamoxifen (20 mg twice daily) was given to ten patients with breast cancer whose immune functions were determined prior to and 3, 6, and 12 months after starting tamoxifen therapy. No consistent changes could be observed in erythrocyte rosette-forming cell counts, erythrocyte antibody rosette-forming cells, active erythrocyte rosette-forming cells, theophylline-resistant rosette-forming cells, surface immunoglobulin-positive cells, and responses to mitogens phytohemagglutinin and concanavalin A. Erythrocyte antibody rosette-forming cells decreased significantly, however, at 6 months and active erythrocyte rosette-forming cells at 12 months after starting tamoxifen. We conclude that no change in the immune capacity could be detected during tamoxifen treatment.

Breast Neoplasms

Effects of naltrexone on morphine-induced tolerance and physical dependence and changes in cellular immune function in mice.

The effects of naltrexone on tolerance/dependence, as well as alterations in cellular immune function induced by morphine administration, were determined. Mice were rendered tolerant to and physically dependent on morphine by subcutaneous implantation of pellets containing 75 mg of morphine. Implantation of naltrexone pellets (10 mg) blocked the development of tolerance to the analgesic action of morphine, as well as the development of physical dependence. Morphine suppressed lymphoid organ weights and cellularities, and this suppression was blocked by naltrexone. B-Cell proliferation was suppressed in morphine-tolerant but not in morphine-abstinent mice, and this suppression was exacerbated by naltrexone. Morphine tolerance and abstinence were associated with suppression of IL-2 production, which was completely blocked by naltrexone. NK cell activity was not significantly affected by either morphine or naltrexone exposure. The results suggest that the effects of morphine on the immune system are at least partially mediated through opioid receptors.

Animals

The prostaglandin E1 analogue, misoprostol, regulates inflammatory cytokines and immune functions in vitro like the natural prostaglandins E1, E2 and E3.

We examined whether some immune functions related to the action and production of cytokines could be regulated by the natural prostaglandins E (PGE) and the PGE1 (ester) analogue, Misoprostol. PGE1,2,3 and Misoprostol inhibited: (1) the mitogenic activity of interleukin-1 (IL-1) for mouse thymocytes; (2) spreading of mouse macrophages on glass; (3) tumour necrosis factor (TNF) (alpha and beta) production by human peripheral blood mononuclear cells and rat macrophages; (4) IL-1 production by rat and mouse peritoneal macrophages; and (5) interferon-gamma (IFN-gamma) production by human peripheral blood mononuclear cells. These PGE had little effect on IL-1 production by human monocytes. By contrast, they all enhanced IL-6 production by rat and mouse macrophages and human monocytes. These effects were noted at concentrations below 500 nM (even as low as 10 nM). The relative potency of the prostanoids tested for both inhibitory and stimulatory effects was PGE1 = PGE2 = or greater than PGE3 greater than Misoprostol greater than PGA2 much greater than PGF1-alpha = PGF2-alpha = PGD2 (no effect). There is strong evidence that PGE1,2,3 and Misoprostol bind to the same receptor(s) and trigger the second messenger, cAMP, since dibutyryl cAMP (a lipophilic analogue of cAMP) had the same effects as the PGE. These PGE also induced elevated intracellular cAMP levels in and competed with [3H]PGE2 for binding to human and rat cells with the same relative potencies as described above.

Animals

Adjuvant chemoimmunotherapy of cancer: influence of tumor burden and role of functional immune effector cells in mice.

Starting from the observation that success of combined treatment of MBL-2 tumor-bearing mice with the alkylating agent cyclophosphamide (CY; 150 mg/kg) and the immunomodulator maleic anhydride divinyl either copolymer (MVE-2; 25 mg/kg) was dependent upon a 1-3-day interval between treatment with CY and MVE-2, we have further analyzed in vitro and in vivo the relationship between tumor burden and the activity of immune effector cells in an adjuvant chemoimmunotherapy setting with CY and MVE-2. Treatment of MBL-2 tumor-bearing mice with CY (50-200 mg/kg) caused a dose- and time-dependent decrease in the i.p. tumor burden, which correlated with a significant increase in their median survival time. CY increased also the sensitivity of the residual MBL-2 tumor cells to Mø-mediated immunotherapy. The therapeutic efficacy of Mø-mediated immunotherapy with MVE-2, however, was restricted due to adverse effects of CY on the host's immune and hematopoietic functions. The time sequence with which these CY related positive effects on tumor burden and s(Tu)I, as well as the adverse effects on macrophages and hematopoietic functions occurred, gives sufficient explanation for the narrow window in time for successful immunotherapy with MVE-2 after preceding chemotherapy with CY. We therefore propose to modify the conventional chemoimmunotherapy of MBL-2 tumor-bearing mice by combining it with an intermittent in vivo transfer of in vitro cultivated Mø (therapy sequence: CY----Mø transfer----MVE-2), which would result in an increased Mø:MBL-2 tumor cell ratio at the site of the tumor while reducing the adverse effects of CY on macrophage functions.

Animals

[The effect of anaesthesia and surgery on immune function. A review (author's transl)].

This paper reviews the literature concerning the question, how the immune functions might be affected by anaesthesia and surgery. General and local anaesthetics inhibit in vitro and in vivo important functions of lymphocytes, granulocytes, and macrophages. However, the postoperative immunosuppression is not attributable to the anaesthesia but rather appears to depend on the tissue trauma itself.

Age Factors

Administration of an anti-CD5 immunoconjugate to patients with rheumatoid arthritis: effect on peripheral blood mononuclear cells and in vitro immune function.

OBJECTIVE: An immunoconjugate, CD5 Plus, composed of ricin A chain and murine IgG1 anti-CD5 monoclonal antibody is under investigation for treatment of rheumatoid arthritis. To understand better the mechanism of action of this agent, alterations in immune function and lymphocyte subpopulations were assessed in a subset of patients consecutively enrolled in 2-phase II clinical trials. METHODS: Flow cytometric and in vitro functional analyses of peripheral blood mononuclear cells from 12 patients receiving 5 daily intravenous infusions of CD5 Plus at doses of 0.20 or 0.33 mg/kg were performed before, during and after treatment. RESULTS: Peripheral CD3+ T cells were significantly depleted (p < 0.01) during treatment on Days 2 and 5 and returned towards baseline on Days 15 to 29; changes in CD5+ B cells occurred in parallel. There was no significant treatment effect on monocytes. All T cell subsets examined, including CD4, CD8, CD45RA, CD45RO, HLA-DR+, TCR-alpha beta and TCR-gamma delta, were affected equally through Day 15. On Day 29, the median CD4:CD8 ratio, elevated before treatment, was significantly decreased (p < 0.01), approaching the ratio observed in healthy controls. Proliferative responses to antigenic, allogeneic and mitogenic stimuli in vitro were depressed but detectable during the time of maximal T cell depletion and normalized to baseline values with recovery of T cell number. Spontaneous and pokeweed mitogen induced immunoglobulin secretion were unaffected in these patients. CONCLUSION: Treatment associated effects of CD5 Plus were observed for both T and B cell populations which bear the CD5 antigen, and were reversible, as measured by in vitro assays of immune cell function, phenotype and number.

Adult

Stress reduction training changed number of sexual partners but not immune function in men with HIV.

We tested the impact of stress management training on sexual behavior and immune functioning in 64 gay men infected with human immunodeficiency virus (HIV). Subjects randomized to the stress management group met for eight two-hour sessions and one all day retreat to learn systematic relaxation, health behavior change, and stress management skills. Compared to those randomized to a wait list control, treatment subjects reported significantly fewer sexual partners in the prior month at post-test (1.10 vs 2.29 for controls). There were no differences between groups in lymphocyte numbers and function.

Adult

Iron deficiency, infections, and immune function: a reassessment.

Many physicians believe that patients with iron deficiency have an increased susceptibility to infections. Data in the literature, however, are contradictory, and in many instances the reports are vulnerable to critical review. Literature available through 1976 was analyzed in an attempt to define possible relationships between infections, immune function, and states of iron imbalance, both iron deficiency and overload. Critical points that must be considered for an accurate interpretation were emphasized. It seems clear that the inflammatory response, when assessed by skin reactivity, is diminished in iron deficiency. The precise molecular defect remains undefined, but the abnormality is detected by several assays measuring cell-mediated immunity. Normal function is usually restored following iron repletion.

Anemia, Hypochromic