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PubMed2003

Comparison of functional immune responses in humans after intranasal and intramuscular immunisations with outer membrane vesicle vaccines against group B meningococcal disease.

A serogroup B meningococcal outer membrane vesicle (OMV) vaccine was delivered either intranasally or intramuscularly to 12 and 10 volunteers, respectively. The mucosal vaccine was given as four weekly doses followed by a fifth dose after 5 months; each dose consisted of OMVs equivalent to 250 microg of protein. The intramuscular (i.m.) vaccine, consisting of the same OMVs but adsorbed to Al(OH)(3), was administered as three doses each of 25 microg of protein, with 6 weeks interval between first and second doses and the third dose after 10 months. Both groups of vaccinees demonstrated significant immune responses when measured as specific IgG antibodies against live meningococci, as serum bactericidal activity (SBA) and as opsonophagocytic activity. Two weeks after the last dose, the anti-meningococcal IgG concentrations were significantly higher in the i.m. group (median IgG concentration: 43.1 microg/ml) than in the intranasal group (10.6 microg/ml) (P=0.001). The corresponding opsonophagocytic activity was 7.0 and 3.0 (median log(2) titre) (P=0.001), and the SBA was 5.0 and 2.0 (median log(2) titre) (P=0.005), for the i.m. and intranasal groups, respectively. The last immunisation induced an enhanced immune response in the i.m. group, whereas the intranasal group showed no significant booster response. Accordingly, affinity maturation of anti-OMV-specific IgG antibodies was seen only after i.m. vaccination. The IgG1 subclass dominated the responses in both groups, whereas the significant IgG3 responses observed in the i.m. group were absent in the intranasal group. Although the intranasal OMV vaccination schedule used here induced functional immune responses relevant to protection, an improved vaccine formulation and/or a modified mucosal immunisation regimen may be needed to achieve a systemic effect comparable to that seen after three doses of intramuscular vaccination.

Administration, Intranasal↗

PubMed1994

Relationship between nutritional status and immune function of elderly people.

Thirty-four malnourished subjects between the ages of 61 and 97 years were given appropriate food supplement(s) for a period of 6 consecutive months. They were followed for a subsequent 6 months during which time there was no nutritional intervention. Nutritional assessment and immunological evaluation were performed at 0, 6, and 12 months. Nutritional assessment included anthropometry, biochemistry, and clinical examination. Immunological evaluation included serum complement C3 concentration, delayed cutaneous hypersensitivity skin test, and the enumeration of total lymphocytes, rosetting T-cells, CD4+ cells, and CD8+ cells. Immune function improved by the end of the supplementation period. Six months of nutritional supplementation significantly increased the percentage of lymphocytes represented by mature T-cells.

Aged↗

PubMed1999

[Effect of -6 degrees head-down-bed-rest on human cellular immune function].

OBJECTIVE: To observe the effect of -6 degrees head-down bed-rest on proliferation of lymphocyte and production of certain cytokines. METHODS: 6 healthy young men served as the subjects. Peripheral blood lymphocyte was assayed 1d prior to and on the 3rd day and 6th day of bed rest. RESULTS: The production of IFN-alpha on the 3rd day was markedly decreased (P < 0.05), but killing activity of NK was significantly enhanced (P < 0.05), production of IFN-gamma and expression of IL-2 receptor were all slightly reduced. Both production of IFN-alpha and killing activity of NK resumed to the control level on the 6th day, production of IFN-r and CD25 were significantly lowered (P < 0.05) on the 6th day, a lymphocyte proliferation and production of IL-2 were gradually decreased with time, but production of IL-6 was gradually increased. CONCLUSION: -6 degrees head-down bed-rested has certain effect on cellular immune function in man.

Adult↗

PubMed1982

Alterations in immune function in rats caused by dietary lipotrope deficiency: effect of age.

Weanling male Sprague-Dawley rats were maintained on a control (C), folacin-deficient (F) or marginal methionine-choline diet (M/C) for 3 weeks, 3 months or 12 months. The immunocompetence of the animals was determined by in vivo (response to infection with salmonella typhimurium) and in vitro (lymphocyte transformation assay) methods. It was found that young animals were most sensitive to dietary lipotrope deficiency, and the in vivo response to bacterial infection did not always correlate with in vitro assessment of immune function. Histopathologic examination of spleens from S. typhimurium-infected rats maintained for 3 weeks on the experimental diets showed an overall decreased cellularity especially in the follicular areas, compared to controls. No differences were seen in the spleens of infected animals at later time points. A short-term (3-week) lipotrope deficiency resulted in a depressed lymphocyte transformation response to concanavalin A (Con A) in the spleen, thymus and lymph nodes; to phytohemagglutinin A (PHA) in the spleen and lymph nodes only. After 3 months on the F or M/C diets, a depressed Con A-induced transformation response was still seen in the spleen, but the normal aging-induced immunosuppression resulted in a low response in all animals, with few significant differences existing among groups.

Aging↗

PubMed1987

Endorphinergic modulation of immune function: potent action of the dipeptide glycyl-L-glutamine.

Glycyl-L-glutamine (GLG), the carboxy terminal dipeptide of B-endorphin, inhibits brainstem neuronal activity. It also occurs along with B-endorphin in pituitary secretory vesicles suggesting a neurosecretory role for this dipeptide. We have evaluated potential immunoregulatory actions of this compound using the Phytohemaglutinin (PHA) blastogenesis and the concanavalin A (ConA) suppressor cell induction assays. GLG in low doses (10(-12) M) enhanced the response of human lymphocytes to PHA induced blastogenesis, however; with higher doses of the dipeptide (10(-7) M) immunosuppression was consistently observed. In the suppressor cell induction assay, when GLG was used together with ConA, we observed a dose-dependent inhibition of suppressor activity. These results clearly indicate that GLG produces a dose dependent bidirectional modulation of at least two indicies of immune function, and confirm the presence of a second pituitary peptide with the potential for potent immunomodulatory action.

Concanavalin A↗

PubMed2002

[Influence of combined therapy of guben yiliu III, moxibustion and chemotherapy on immune function and blood coagulation mechanism in patients with mid-late stage malignant tumor].

OBJECTIVE: To observe the supplementary effect of moxibustion and Guben Yiliu III (GBYL), a Chinese herbal compound preparation, in combination with chemotherapy. METHODS: Eighty-one patients of mid-late stage malignant tumor were randomly divided into 3 groups: 16 in Group A treated with chemotherapy and placebo; 35 in Group B treated with chemotherapy and GBYL and 30 in Group C treated with chemotherapy and GBYL plus moxibustion. The short-term effect of treatment, changes of blood picture, cell mediated immune function and blood coagulation in patients were observed. RESULTS: After chemotherapy, the lymphocyte count was significantly lowered in Group A and B (P < 0.01), but not in Group C (P > 0.05); lymphocyte subset T3 raised significantly in Group B; the average level of T-lymphocyte subsets was reduced in Group A while it increased in the other two groups; and a bi-directional regulation on plasma fibrinogen concentration was shown in Group C (P < 0.05). CONCLUSION: Moxibustion prevented dropping of lymphocyte count caused by chemotherapy. Combination of GBYL and moxibustion could prevent the lowering of T-lymphocyte subsets caused by chemotherapy, and moxibustion could regulate bi-directionally the patients' abnormality in part of blood coagulation mechanism.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Modification of immune function during pregnancy by products of the sheep uterus and conceptus.

The preimplantation sheep conceptus produces several molecules that inhibit lymphocyte responses in vitro to mitogens or allogeneic cells, including prostaglandin E-2 and a lactosaminoglycan-containing glycoprotein of Mr 800,000-900,000. Additionally, the definitive placenta releases immunosuppressive factors when placed in culture. One of these is a heat- and protease-stable, carbohydrate-containing molecule released by explants of cultured fetal cotyledons. The pregnant uterus also produces molecules that alter lymphocyte responsiveness in vitro, including a dialysable, heat- and trypsin-stable factor and a high-molecular weight factor (Mr greater than 4 x 10(6]. An important regulator of uterine immune function is progesterone. This hormone can induce the production of uterine immunosuppressants such as seen during pregnancy and prolong the life of skin allografts placed in utero. Taken together, results suggest that the conceptus resides in an immunosuppressive environment throughout most of gestation, a situation that may be critical to maintenance of pregnancy.

Animals↗

PubMed2001

Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine.

This study investigates the in vitro effects of oxidized low-density lipoproteins (ox-LDL), 'physiological' pro-oxidants, N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, and their combination on human peripheral blood mononuclear cell functions. We found that treatment with ox-LDL induced a significant down-regulation of proliferative response to mitogens, antigens and interleukin-2. Lipid extracts from ox-LDL were able to reproduce the same effect as the lipoprotein. On the other hand, NAC exposure induced a significant up-regulation of proliferative responses to all the stimuli used. Moreover, we showed that natural killer (NK) cell-mediated cytotoxic activity was significantly down-regulated by ox-LDL while treatment with NAC induced a significant up-regulation of NK-cell activity. Finally, we found that ox-LDL and NAC exerted opposite effects on the cytokine network, interfering both at the protein secretion level and the messenger RNA synthesis level. More importantly, when NAC was used in combination with ox-LDL the proliferative responses, NK-cell-mediated cytotoxic activity and cytokine production were restored to values comparable to controls. These data indicate that ox-LDL and NAC modulate immune functions, exerting opposite effects reflecting their pro-oxidant and antioxidant behaviours. Our results add new insights to the key role played by redox imbalance as a modulator of immune system homeostasis and suggest that an antioxidant drug such as NAC could be useful against pathologies associated with an increase in lipid peroxidation.

Acetylcysteine↗

PubMed2003

Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission.

The past 30 years of immunological research have revealed much about the proximate mechanisms of maternal antibody transmission and utilization, but have not adequately addressed how these issues are related to evolutionary and ecological theory. Much remains to be learned about individual differences within a species in maternal antibody transmission as well as differences among species in transmission or utilization of antibodies. Similarly, maternal-effects theory has generally neglected the mechanisms by which mothers influence offspring phenotype. Although the environmental cues that generate maternal effects and the consequent effects for offspring phenotype are often well characterized, the intermediary physiological and developmental steps through which the maternal effect is transmitted are generally unknown. Integration of the proximate mechanisms of maternal antibody transmission with evolutionary theory on maternal effects affords an important opportunity to unite mechanism and process by focusing on the links between genetics, environment and physiology, with the ultimate goal of explaining differences among individuals and species in the transfer of immune function from one generation to the next.

Adaptation, Biological↗

PubMed1998

Modulation of orphanin FQ or electroacupuncture (EA) on immune function of traumatic rats.

Orphanin FQ(OFQ) is a recently discovered 17-amino acid neuropeptide[1-2]. In present paper, influence of intracerebroventricular(ICV) administration of OFQ or electroacupuncture(EA) on the surgical trauma-induced inhibition of the splenic natural killer(NK) cell activity in rat was observed. The results showed that administration of 0.1 microgram(0.0055 nmol) and 1 microgram (0.055 nmol) OFQ had no effect on the NK cell activity, while 5 micrograms(2.75 nmol) OFQ reduced the NK cell activity in normal rats. However, 0.1 microgram, 1 microgram or 5 micrograms OFQ were found to antagonise the immune function depression caused by surgical trauma. The NK cell activity was reduced in normal rats after repeated ICV treatment with antisense oligonucleotide (ASO) complementary to bases of translated region of rat OFQ receptor mRNA to block the translation of OFQ receptor mRNA into protein. EA stimulation of Zusanli(St. 36) and Lanwei(Extra. 37) points also obviously improved the immunosuppression produced by trauma. OFQ combined with EA showed antagonism on the suppression, but there was no significant differences compared with OFQ(ICV) or EA alone. When blocking the translation of OFQ receptor mRNA with the ASO, the OFQ induced anti-immunosuppression effect was completely reversed, but EA still improved the inhibition on NK cell activity. The results suggested that the OFQ played a role in the regulation of immunosuppression. EA could modulate the suppression of NK cell activity induced by surgical trauma. The mechanisms of the modulation of OFQ or EA on the immunosuppression induced by surgical trauma need further study.

Acupuncture Therapy↗

PubMedDate not supplied

Hypothalamic-pituitary-adrenocortical axis activity and immune function after oral exposure to benzene and toluene.

Benzene and toluene, commonly used solvents, possess neurotoxic and immunotoxic effects. Male CD-1 mice were continuously fed drinking water containing 0, 31, 166 and 790 mg/l benzene and 0, 17, 80 and 405 mg/l toluene, respectively. The concentrations of hypothalamic norepinephrine (NE) and its metabolite vanillylmandelic acid (VMA), circulating corticosterone and adrenocorticotropic hormone (ACTH), and lymphocyte-derived interleukin-2 (IL-2) activity were evaluated after 28 days of exposure to each solvent. Serum corticosterone was also measured at pretreatment, 2, 7, and 14 days of exposure. The concentrations of NE, VMA, ACTH and corticosterone were increased following exposure to these solvents. Benzene increased corticosterone levels in mice after 7 days (166 and 790 mg/l) and at 28 days (790 mg/l). Toluene elevated corticosterone levels at 14 and 28 days at the 405 mg/l exposure. IL-2 production by mouse T-lymphocytes was suppressed in the two higher benzene-treated groups, while toluene decreased IL-2 synthesis at the highest level only. Both benzene and toluene exposures stimulated hypothalamic-pituitary-adrenocortical (HPA) activity. Elevated corticosterone has been reported to inhibit IL-2 production and impair immunocompetence. Organic solvents may have, at least partially, an additive adverse effect on immune function via activated HPA status.

Adrenocorticotropic Hormone↗

PubMed1996

[Experimental studies on effects of zinc and germanium on immune function and anti-oxidation in mice].

Zinc and germanium concentrations in serum, liver and muscle of mice, T-lymphocyte subgroup proportion, serum superoxide dismutase (SOD) activity and malonodialdehyde (MDA) were determined to study whether there exist synergism or antagonism between zinc and germanium. Results showed there existed, to certain extent, competitive effects of serum zinc and germanium in mice. When concentration of serum zinc increased, that of germanium decreased, or vise versa. There existed certain relationship between zinc and germanium concentrations in serum and those in muscle and liver of mice, and between those and CD3 count and SOD activity. Immune function in mice was influenced and their T-lymphocyte subgroup proportion changed with changes in serum zinc and germanium concentrations. With increased germanium and decreased zinc serum concentrations, CD3 and CD1 counts decreased, CD8 count unchanged, and the ratio of CD1 to CD3 decreased, which showed certain antagonist effects of them as they operated together. But, no antagonism was observed in their anti-oxidant effects, SOD activity increased to varied extent, and the level of MDA decreased.

Adjuvants, Immunologic↗

PubMedDate not supplied

A pilot study of the safety and efficacy of supplemental arginine to enhance immune function in persons with HIV/AIDS.

OBJECTIVE: We collected preliminary data on the safety and efficacy of supplemental arginine to improve natural killer cell cytotoxicity in a sample of persons with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). METHODS: In a randomized, double-blind, placebo-controlled pilot study in an academic medical center-based infectious disease clinic, 11 clinically stable, HIV-infected adults had been treated with highly active, antiretroviral therapy and had HIV plasma RNA levels of less than 10 000 copies/mL. Participants were randomly assigned to receive 19.6 g of arginine/d (n = 6) or placebo (n = 5) for 14 d. Plasma HIV RNA levels, neuropsychologic functioning, and self-reported adverse events were analyzed for safety of treatment. Efficacy was measured by natural killer cell cytotoxicity. RESULTS: None of the participants experienced any adverse clinical, virologic, or neuropsychologic events that necessitated withdrawal from the study. The arginine-supplemented group showed a mean natural killer cell cytotoxicity increase of 18.9 lytic units, whereas the placebo group showed an increase of 0.3 lytic units. This difference was not statistically significant (P = 0.79). CONCLUSIONS: Short-term arginine supplementation is safe for persons with HIV/AIDS. Additional studies with larger samples and longer periods are warranted to determine the effects of arginine supplementation on other indices of immune function and on clinical outcomes such as intercurrent illnesses.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Early nutrition support modifies immune function in patients sustaining severe head injury.

BACKGROUND: Immunosuppression after severe head injury has been characterized by a depressed CD4 (T-helper/inducer)-CD8 (T-suppressor/cytotoxic) ratio and decreased T-lymphocyte responsiveness. Some investigators propose that this immunocompromized state is the result of an injury-associated hypermetabolic response and inadequate nutrient delivery during the immediate postinjury recovery phase. Previous observations from our institution demonstrated a preserved CD4-CD8 ratio in severe closed-head injury (CHI) patients receiving early parenteral nutrition (PN). It was unclear whether early PN or other aspects of patient care eliminated the characteristic depression in cellular immunity. The purpose of this study was to further investigate the effect of early PN on the immune function of CHI patients. METHODS: Nine patients sustaining severe CHI were prospectively randomized to either early PN (n = 4) at day 1 or delayed PN (n = 5) at day 5. Total nutrient administration was delivered at 2 g of protein/kg per day and 40 nonprotein kcal/kg per day for at least the first 14 days of hospitalization. Analysis for T-lymphocyte expression of CD4 and CD8 cell surface antigens and interleukin-6 was performed on days 1, 3, 7, and 14 of hospitalization. T-lymphocyte activation in response to stimulation by concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogens (PWM) was also assessed on these days. RESULTS: Significant increases in total CD4 cell counts (2048 +/- 194 to 2809 +/- 129 vs 1728 +/- 347 to 1825 +/- 563, p < .05) and CD4% (42.6 +/- 4.4% to 56.2 +/- 2.6% vs 36.6 +/- 6.6% to 36.6 +/- 11.3%, p < .05) were observed at day 14 in patients receiving early vs delayed PN. An improved lymphocyte response from baseline to day 14 after Con A stimulation was demonstrated in the early PN group (3850 +/- 1596 to 16144 +/- 5024 cpm, p < .05). A significant rise in the CD4-CD8 ratio over baseline to day 14 was also noted in the early PN group (1.43 +/- 0.17 to 2.38 +/- 0.54, p < .05). CONCLUSIONS: The early aggressive nutrition support of CHI patients appears to modify immunologic function by increasing CD4 cells, CD4-CD8 ratios, and T-lymphocyte responsiveness to Con A.

Adolescent↗

PubMed1989

[Permanent decrease in immune function in patients with splenectomy for trauma].

The authors describe the peripheral blood analyses in patients splenectomized for trauma in consideration on the concentration of the immunoglobulins total complement CH50 levels, T and B lymphocyte populations and compare this with the control group. The levels of the IgM were significantly decreased (p0.001) in splenectomised while the levels of the IgA and IgG were significantly increased (for IgA - p0.001, for IgG p0.01). Total lymphocyte count averaged 54501999 in splenectomized, with number of T cells 2463930 and B lymphocyte 460236. The control group showed total lymphocyte count 460236. The control group showed total lymphocyte count 520235 (p0.001) with number of T cells 314147 (p0.001) and number of B cells 7434 (p0.001), what is significantly less than in splenectomized population. The level of total complement CH50 in splenectomized population was 11216 (p0.01), what is significantly less than in the control group 12515. These data demonstrate persistent abnormalities in immune function and suggest a possible explantation for the increased rizu of sepsis in this group of patients.

Adolescent↗

PubMed1997

Effect of food restriction on life span and immune functions in long-lived Fischer-344 x Brown Norway F1 rats.

Life-long food restriction is known to slow aging and reduce the rate of occurrence of age-associated disease processes, but the mechanism by which this is accomplished is unknown. In this study we have examined the effect of food restriction on the proliferative response of spleen cells to mitogens and lymphokine production in 6-, 18-, and 30-month-old AL and FR Fischer-344 x Brown Norway (F-344 x BNF1) female rats whose average life span is 137 weeks on an ad libitum (AL) diet and 177 weeks on a food-restricted (FR) diet. In addition, the ability of food restriction to recall antigens was tested in 10-month-old rats by immunizing them with keyhole limpet and hen's egg albumin and measuring proliferative response of draining lymph node cells to these antigens. Our results indicated that the spleen-cell proliferative response to phytohemagglutinin and concanavalin A (Con A) was equal in 6- and 18-month-old rats but declined significantly in 30-month-old AL rats compared to FR rats. Although flow cytometric analyses did not reveal differences for CD4, CD8, and Ig+ cells with age, a significant rise in memory T cells (Ox-22low) in both CD4+ and CD8+ T-cell subset lineage was noted in AL-fed rats at 30 months of age. In FR rats, however, only a minimal shift of naive T cells (Ox-22high) to memory cells was observed. In FR rats, the observed changes in the naive and memory T-cell subsets correlate well with the observed higher levels of the antiinflammatory interleukin-2 (IL-2) and lower levels of the proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha. The ability of food-restricted animals to recall antigens was lower compared to their age-matched controls, though the proliferative response to T-cell mitogen Con A and superantigen staphylococcal enterotoxin B was higher. These findings indicate that food restriction may selectively act to maintain a lower number of antigen-induced memory T cells with age, thereby maintaining the organism's ability to produce higher levels of IL-2 with age. In summary, the increased cell-mediated immune function noted in aged FR rats appears to be due to the presence of a higher number of naive T cells, which are known to produce elevated levels of the antiinflammatory cytokines, which may in part be responsible for reducing the observed age-related rise in disease.

Aging↗

PubMed1993

Association of in vitro immune functions with the severity of the disease in rheumatoid arthritis.

The production of immunoglobulins in vitro by lymphocytes from rheumatoid patients has been earlier shown to be defective. This report describes a 2-year follow up study which shows that this defect is associated with the severity of RA. Pokeweed mitogen and Staphylococcus aureus Cowan I were used to stimulate in vitro immunoglobulin production by lymphocytes from patients with recent onset RA, and the relationship of responses to clinical characteristics were studied. Impaired polyclonal IgM synthesis, already detectable at the onset of disease, associated with joint destructions observed after a 2-year follow up period. Further, phytohaemagglutinin-induced interleukin-2 (IL-2) release by the cells of patients with erosive disease was found to be reduced compared to cells from patients without eroded joints. The results indicate that altered immune functions--manifested as decreased production of IgM and IL-2--in RA are involved in the progression of the disease and affect the outcome of patients and, thus, represent an unfavourable prognostic feature.

Adolescent↗

PubMed2006

Altered CD45 expression in C77G carriers influences immune function and outcome of hepatitis C infection.

BACKGROUND: A polymorphism in exon 4 (C77G) of CD45 that alters CD45 splicing has been associated with autoimmune and infectious diseases in humans. OBJECTIVE: To investigate the effect of C77G in hepatitis C virus (HCV) infected individuals and study the phenotype and function of peripheral blood mononuclear cells (PBMC) from healthy and hepatitis C infected C77G carriers. RESULTS: C77G individuals showed an increased proportion of primed CD45RA and effector memory CD8 T cells and more rapid activation of the lymphocyte specific protein tyrosine kinase (Lck) following CD3 stimulation. Transgenic mice with CD45 expression mimicking that in human C77G variants had more activated/memory T cells, more rapid proliferative responses, and activation of Lck. CONCLUSIONS: Changes in CD45 isoform expression can alter immune function in human C77G variants and CD45 transgenic mice. The C77G allele may influence the outcome of HCV infection.

Animals↗