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PubMed1977

Local lymph node response in rats to allogeneic stimulus: analysis of the in vitro responding cells.

Parental strain rats were immunized in the footpads by F1 hybrid spleen cells. The draining lymph nodes were removed during the first 10 days after immunization and tested for mitogen responsiveness. Cell fractionation was performed by removal of macrophages, surface Ig positive, and F(c)-, and C3-receptor carrying lymphocytes. The depleted suspensions were tested in MLC to test the effect of lymphocyte subpopulations on the accelerated MLC response profile exhibited by the immune lymph node cells. Overall increase in mitogen stimulation was observed, but stimulation indices were slightly reduced as compared to non-immunized cells. Removal of phagocytic cells gave some increase in MLC response which was most pronounced when responder cells were tested during the first days after immunization. Depletion for non-T lymphocytes resulted in lowering of non-stimulated responder cell 14C uptake, whereas the specific accelerated MLC profile was unaltered or tended to improve acceleration. It is concluded from indirect evidence that T lymphocytes are the cell type responsible for the altered MLC kinetics, but that macrophages and non-T cells modify the response.

Animals↗
PubMed1991

Pre-travel health, immunization status, and demographics of travel to the developing world for individuals visiting a travel medicine service.

It is estimated that five million Americans will travel to the developing world over the next year. This study examines the demographic profile, past medical and immunization history, itinerary, and reason for travel of 2, 445 travelers to the developing world seen at a travel medicine service from 1984 through 1989. The travelers age ranged from three months to 85 years (mean age 43). A chronic medical condition was reported by 654 (27%). Four percent of all travelers were intolerant of sulfonamides, and 9% had contraindications to mefloquine for malaria prophylaxis. Many travelers were due to receive the primary series or updatings of routinely recommended immunizations: 43% for tetanus/diphtheria, 55% of those born after 1956 for measles, and 70% for polio if their travel itinerary included a polio risk. Most travel (71%) was for vacations, 13% was for teaching or study, 11% for business, and 5% for missionary activities. The median duration of travel was 21 days; 5% traveled for more than one year. While over 150 countries were visited, 52% of all travel was to 10 countries in East Africa, the Indian subcontinent, the Far East, and South America. Information about the epidemiology of travel to the developing world can help physicians and travel medicine services develop more effective preventive measures for travelers.

Adolescent↗
PubMed1997

The Lipoprotein Profile in HIV Infected Patients.

Infection can change plasma lipoproteins by increasing the triglycerides and decreasing the cholesterol plasma levels. This process is thought to be the result of alterations in lipoprotein metabolism produced by cytokines that mediate the immune response, including tumor necrosis factor, interleukin-1 and the interferons. The acquired immunodeficiency syndrome (AIDS) has been shown to be accompanied by increased plasma triglyceride levels and a trend toward decreased plasma cholesterol levels. Plasma low density lipoprotein (LDL) patterns are also changed by infection and patients with AIDS have increased levels of small dense LDL particles. Decreases in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I, and an increase in lipoprotein (a) [Lp(a)] are the usual lipidic disorders during HIV infection, even in those patients with CD, lymphocyte counts above 400 cells/ mm(3). Plasma lipoproteins possess well-recognized transport functions. Certain classes of these lipoproteins can also regulate selected metabolic functions of a variety of cell types. Among these bioregulatory properties is the regulation of lymphocyte function and regulation of immune response. Thus, a number of immune functions may be significantly influenced by the lipoprotein alterations present in AIDS. Furthermore, the decreased HDL-C and increased triglycerides and Lp(a) are associated with an increased risk of myocardial infarction and some cardiovascular events have been reported in HIV positive individuals. This paper describes lipoprotein alterations during HIV infection, and evaluates their relationship to immune function and atherogenic profile.

Journal Article↗
PubMed2004

Profiles of gene expression in human autoimmune disease.

Human autoimmune diseases arise from complex interactions between genetic and environmental factors, result from immune attack upon target tissues, and affect 3-5% of the population. We compared gene expression profiles (>4000 genes) in the peripheral blood mononuclear cells of normal individuals after immunization to individuals with four different autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, and multiple sclerosis). All autoimmune individuals, including unaffected first-degree relatives, share a common gene expression profile that is completely distinct from the immune profile. Therefore, this expression pattern is not simply a recapitulation of the immune response to nonself, is not a result of the disease process, and results, as least in part, from genetic factors. Surprisingly, these genes are clustered in chromosomal domains suggesting there is some genome-wide logic to this unique expression pattern. These data argue that that there is a constant pattern of gene expression in autoimmunity that is independent of the specific autoimmune disease and clinical parameters associated with any individual autoimmune disease.

Autoimmune Diseases↗
PubMed1994

IgG isotype distribution of local and systemic immune responses induced by influenza virus infection.

The IgG isotype profile of the influenza virus-specific immune response was studied by quantitation of serum antibody (Ab) levels in correlation with the enumeration of antibody-secreting cells (ASC) detected in the lung, spleen, mediastinal lymph nodes (MLN), Peyer's patches and bone marrow (BM). Distinct isotypic patterns for serum Ab and Ab produced by cells present at or close to the site of infection were found after primary or repeated infections. An elevated number of IgM ASC was found after primary challenge in the spleen, lung and MLN. In contrast, the site of IgA and IgG production is restricted to the lung and lymph nodes draining the site of infection. In these organs IgA, IgG2a and IgG1 ASC are found as a result of primary virus infection while viral challenge induces mostly activation of IgA-producing cells and secretion of IgA to the lung lavage. In contrast, the majority (80-90%) of Ab detected in the serum belong to the IgG2a subclass and their serum level is maintained at a high level during the whole period of the response. The relative level of virus-specific serum IgG2a in correlation with the production of IgG2a Ab found predominantly in MLN and lung is highly dependent on the viral dose used for priming or challenge. As IgG2a ASC can be detected at relatively low numbers in the spleen and BM these results suggest that the production of the dominant IgG2a isotype of serum Ab occurs close to the viral challenge site. These data, however, point to distinct isotypic regulation in systemic versus local virus-specific Ab responses.

Animals↗
PubMed2004

Vitamin E and gene expression in immune cells.

Aging is associated with dysregulation of immune cells, particularly T cells. Previous studies indicated that vitamin E improves T cell function, in part by a direct effect on T cells. We studied gene expression profile of T cells to better understand the underlying mechanisms of aging- and vitamin E-induced changes in T cell function. Young and old C57BL mice were fed diets containing 30 (control) or 500 (E) ppm of vitamin E for 4 weeks. T cells were purified from splenocytes by negative selection using magnetic beads (anti-Mac-1 and anti-MHC class II), then cultured with media or stimulated with anti-CD3 and anti-CD28. Gene expression profile was assessed using microarray analysis. Genes showing more than two-fold changes, P < 0.05 by ANOVA, and with at least one present call were selected. Aging had significant effects on genes involved in signal transduction, transcriptional regulation, and apoptosis pathways in T cells, while vitamin E had a significant effect on genes associated with the regulation of cell cycle.

Aging↗
PubMed2000

[Hepatitis C virus infection in renal diseases: state of knowledge, therapeutic problems and perspectives].

Chronic infection with hepatitis C virus (HCV) is estimated to affect almost 170 million individuals worldwide. 20-30% of these individuals develop cirrhosis and its sequelae. Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response to interferon monotherapy. The prevalence of anti-HCV antibodies in dialysis patients varies between 1% and 29% in Western Europe. In patients with ESRD on maintenance HD therapy, in whom a blunted immune response per se is observed, the usefulness of IFN-alpha therapy is usually discussed in the context of subsequent transplantation associated with intensive immunosuppressive treatment regimens. A recent study has shown that in this patient group renal transplantation is associated with a fivefold increase in posttransplantation liver disease as well as a relative risk of death of 3.3 compared to HCV-negative patients. Thus, eradication of HCV infection in patients with ESRD may substantially reduce morbidity and mortality in renal allograft recipients. The imbalance of T-helper (Th) lymphocyte cytokine production may play an important role in the immunopathogenesis of chronic HCV infection. Little is known about the effects of IFN-alpha therapy on Th1/Th2 activity in HD patients. The type of immune response against infectious agents is determined in part by the pattern of cytokines secreted by T lymphocytes. Th1 cells promote cellular immunity against infectious agents, while Th2 cells induce humoral immune response and immune tolerance activity. The measurement of Th1/Th2 profile should increase our understanding of the immune status of patients with HCV infection. Therefore, the recently presented studies were undertaken to evaluate the influence of IFN-a therapy on Th1/Th2 balance in HD patients with chronic HCV infection.

Antiviral Agents↗
PubMed1982

The immunological profile of mycosis fungoides.

The immune reactivity of 25 patients with mycosis fungoides was studied twice with a 6 month interval using a panel of T lymphocyte surface markers and functional tests. Patients with clinically inactive disease (stage I + II) had normal T lymphocyte biology. Patients with clinically active disease (stage II-IV) had T lymphopenia, alterations in T cell subpopulations (T gamma and T mu) and a reduced lymphocyte reactivity in vitro following mitogen (PHA, Con A, PWM) and antigen (PPD) stimulation. They also had a reduced secretion of immunoglobulin in vitro after PWM stimulation, apparently due to the alterations in their T lymphocyte subpopulations. The observed changes in the peripheral blood T lymphocyte population and the in vitro function of lymphocytes were not shared by lymphocytes from histologically affected lymph nodes. The natural killer cell activity in blood lymphocytes was found to be normal in all patients.

Adult↗
PubMed2006

Cytokine detection by multiplex technology useful for assessing antigen specific cytokine profiles and kinetics in whole blood cultured up to seven days.

Cytokine profile assessment is important to characterize immune responses to pathogens. To identify optimal time points for determination of cytokine profiles, we diluted whole blood 1:10, to enable daily cytokine measurements during one week. Cultures for 10 blood donors were set up in the presence of phytohemagglutinin (PHA), cytomegalovirus (CMV) or Candida. Supernatant levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, interferon-gamma (IFN-gamma), granulocyte/macrophage colony-stimulating factor, and tumor necrosis factor-alpha (TNF-alpha), were determined by multiplex technique, and intracellular cytokine staining (ICS) was employed to detect IFN-gamma, IL-2, IL-4 and IL-13 in CD3+ cells. The multiplex analysis detected representative cytokine profiles for the majority of the cytokines on day 7 by identifying peak levels or good correlation with peak levels, with the exception of IL-2 and TNF-alpha in PHA and CMV cultures and IL-10 in PHA cultures. For these cytokines an extracellular measurement on day 2-3 would be appropriate. The intracellular cytokines showed distinct kinetics for IFN-gamma and IL-2, while IL-4 and IL-13 were not detected at all with ICS. In conclusion, the combination of whole blood cultures with multiplex analysis is a simple and powerful tool that can be used to identify detailed cytokine profiles of specific cell-mediated immune responses.

Adult↗
PubMed2002

Assessment of protein allergenicity: studies in brown norway rats.

For the safety evaluation of genetically engineered crops, the potential allergenicity of the newly introduced protein(s) has become an important issue. There is, however, no universal and reliable test system for the evaluation of the allergic sensitizing ability of food proteins. Therefore, there is a growing interest in the development of animal models. This paper summarizes the results of a promising food allergy model developed in Brown Norway (BN) rats. The results demonstrate that BN rats can be sensitized via the relevant oral route of exposure. Daily gavage dosing of the animals with several food proteins, without the use of adjuvants, resulted in significant antigen-specific IgE responses. In addition, the profile of allergens recognized by the immune system of the BN rat, appeared comparable to the profile of allergens recognized by allergic humans. Besides oral sensitization, local and systemic immune-mediated effects, such as increased gastrointestinal permeability, decreased breathing frequency, and decreased blood pressure, could also be observed in the sensitized animals after an oral challenge. All together, these observations suggest that this BN rat model might provide a suitable animal model to study the allergenicity of food proteins in humans.

Allergens↗
PubMed2006

Classical Hodgkin's lymphoma: molecular evidence for specific alterations in circulating T lymphocytes.

OBJECTIVE: Impairment in cell-mediated immunity has long been recognized in classical Hodgkin's lymphoma (cHL). The immunosuppressive environment at the tumor site and/or a primary T-cell defect may contribute to an ineffective immune clearance of Hodgkin/Reed-Sternberg (H/R-S) cells. Here, we analyzed whether circulating T lymphocytes of cHL patients show specific alterations in gene expression with possible impact on anti-tumor immunity. MATERIAL AND METHODS: Gene expression profiles were performed from CD3+ T cells isolated from peripheral blood samples of untreated patients with cHL versus two control groups consisting of healthy donors and patients with sarcoidosis. The regulation of gene expression was confirmed in additional patients for selected genes by real-time RT-PCR. RESULTS AND CONCLUSION: Circulating T cells of cHL show a Th1 immune response likely supporting anti-tumor immunity. However, the molecular profile reveals an association between cell cycle transition/proliferation and induction of immune regulatory genes which may limit an effective anti-tumor immune response of differentiated Th1 cells.

Adult↗
PubMed2001

Changes in plasma inhibin A levels during sexual maturation in the female chicken and the effects of active immunization against inhibin alpha-subunit on reproductive hormone profiles and ovarian function.

Inhibins and activins are firmly implicated in the control of pituitary FSH secretion and ovarian follicular development in mammals. As in mammals, inhibin A and activin A are expressed in the preovulatory follicles of birds, and a defined ovulation cycle for inhibin A has recently been demonstrated in the laying hen. To investigate further the role of inhibin-related proteins in developing pullets, circulating concentrations of inhibin A, inhibin B, total immunoreactive inhibin alpha-subunit (ir-alpha), activin A, LH, FSH, and progesterone were measured from the juvenile state through to sexual maturity in 22 birds. In the 11 birds assigned to control groups, plasma inhibin A levels were low from 7 to 13 wk of age rising about threefold to a peak at Week 19 after which levels fell slightly to a plateau level characteristic of adult hens. Plasma inhibin A levels were negatively correlated with FSH (r = -0. 33; P: < 0.001) and positively correlated with progesterone (r = 0. 67; P: < 0.001) and ir-alpha (r = 0.53; P: < 0.001). Plasma ir-alpha levels were much higher than inhibin A levels although the relative differences varied with age. Plasma levels of inhibin B and activin A were below assay detection limits at all times. The remaining group of 11 birds was actively immunized (IMM) against a synthetic chicken inhibin alpha-subunit peptide (amino acids 1-26). The IMM generated circulating antibodies that bound native bovine inhibin A but altered neither plasma FSH nor progesterone levels relative to control birds at any stage of development nor the timing of first oviposition in week 19. Apart from a transient decline 1 wk after primary IMM, plasma LH concentrations did not differ from controls. Comparison of the numbers and size-class distribution of ovarian follicles at 29 wk showed an approximate twofold increase in the number of 8- to 9.9-mm-diameter follicles (control; 1.82 +/- 0.44 vs. IMM; 3.91 +/- 0.89; P: < 0.05), a size class that corresponds to follicles that have just joined the preovulatory hierarchy. The numbers of growing follicles in other size-classes and the sizes of hierarchical F(1)-F(7) follicles were not altered by IMM. However, the number of postovulatory follicles increased (control 3.73 +/- 0. 20 vs. IMM 5.55 +/- 0.28; P: < 0.01), and significantly more (P: < 0. 02) immunized hens laid two eggs within a 24-h period on at least one occasion (control 1 of 11 vs. IMM 9 of 11). The IMM increased (P: < 0.05) activin A content of F(1) and F(2) theca layers and decreased (P: < 0.05) activin A content in F(3) and F(4) granulosa layers, raising the possibility of a local intraovarian role of activin in mediating the response to IMM. These findings support a role for inhibin A in regulating the entry of follicles into the preovulatory hierarchy in the chicken, although further studies are required to establish the mechanism by which inhibin IMM increases the rate of follicle selection and ovulation without raising plasma FSH.

Activins↗
PubMed2004

Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10.

A lymphocytic enterocolitis has been reported in a cohort of children with autistic spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory cytokine production is present in these ASD children. Comparison was made with developmentally normal children with, and without, mucosal inflammation. Duodenal and colonic biopsies were obtained from 21 ASD children, and 65 developmentally normal paediatric controls, of which 38 had signs of histological inflammation. Detection of CD3+ lymphocyte staining for spontaneous intracellular TNFalpha, IL-2, IL-4, IFNgamma, and IL-10, was performed by multicolor flow cytometry. Duodenal and colonic mucosal CD3+ lymphocyte counts were elevated in ASD children compared with noninflamed controls (p<0.03). In the duodenum, the proportion of lamina propria (LP) and epithelial CD3(+)TNFalpha+ cells in ASD children was significantly greater compared with noninflamed controls (p<0.002) but not coeliac disease controls. In addition, LP and epithelial CD3(+)IL-2+ and CD3(+)IFNgamma+, and epithelial CD3(+)IL-4+ cells were more numerous in ASD children than in noninflamed controls (p<0.04). In contrast, CD3(+)IL-10+ cells were fewer in ASD children than in noninflamed controls (p<0.05). In the colon, LP CD3(+)TNFalpha+ and CD3(+)IFNgamma+ were more frequent in ASD children than in noninflamed controls (p<0.01). In contrast with Crohn's disease and non-Crohn's colitis, LP and epithelial CD3(+)IL-10+ cells were fewer in ASD children than in nondisease controls (p<0.01). There was a significantly greater proportion of CD3(+)TNFalpha+ cells in colonic mucosa in those ASD children who had no dietary exclusion compared with those on a gluten and/or casein free diet (p<0.05). There is a consistent profile of CD3+ lymphocyte cytokines in the small and large intestinal mucosa of these ASD children, involving increased pro-inflammatory and decreased regulatory activities. The data provide further evidence of a diffuse mucosal immunopathology in some ASD children and the potential for benefit of dietary and immunomodulatory therapies.

Adolescent↗
PubMed2000

Seasonal variations in cytokine expression and cell-mediated immunity in male rhesus monkeys.

Our objectives in this study were to examine seasonal changes in immune responses including cytokine profiles of male rhesus monkeys housed under natural lighting conditions. We also monitored circannual changes in the secretion of several immunomodulatory hormones as potential mediators of the seasonal shifts in immune status. Retrospectively, the medical records of a large group of rhesus monkeys were examined to determine whether a common disease (campylobacteriosis) in this species shows a seasonal pattern of prevalence. Results of the study showed that there was a seasonal shift in the frequency of cells expressing TH1 cytokines (interleukin-2 and interferon-gamma) versus the TH2 prototype cytokine (interleukin-4) by peripheral blood mononuclear cells (PBMC) collected during the winter and summer. The frequency of TH1-type cytokine synthesis in the summer was markedly greater than in the winter whereas TH2-type cytokine expression did not vary between the two seasons. The proliferative response of PBMC to mitogens and natural killer cell activity of PBMC also varied with the season. Several hormones (testosterone, leptin, and prolactin) that modulate immune function exhibited circannual patterns of secretion. The prevalence of Campylobacter infections was higher in the spring than during the summer, fall, or winter. The data suggest that seasonal fluctuations in immune system status may alter the ability of primates to successfully respond to pathogens, and this may be related to circannual patterns of secretion of immunomodulatory hormones.

Animals↗
PubMed2004

Restricted changes in major surface protein-2 (msp2) transcription after prolonged in vitro passage of Anaplasma phagocytophilum.

BACKGROUND: Anaplasma phagocytophilum strains often vary in Msp2 expression, a situation assumed to be related to immune evasion. However, Msp2 is also an adhesin, and little is known about the role of endogenous msp2 transcriptional changes in the absence of immune selection. Thus, Msp2 profiles and msp2 transcripts of low passage A. phagocytophilum Webster strain, initially comprised of a single abundant msp2 transcript, were re-examined after > or = 20 in vitro passages without immune selection. RESULTS: Using an Msp2 monoclonal antibody, immunoblots revealed an unchanged dominant band and several weak bands that appeared with passage. Similarly, msp2 transcript diversity changed, with a decrease in the initially abundant low passage transcript and appearance of a newly abundant and several minor msp2 transcripts with high passage. BLASTN search of the A. phagocytophilum HZ strain genome revealed > or = 52 msp2 paralogs. CONCLUSIONS: Msp2 expression and msp2 transcription modulate even without immune selective pressures. However, the limited diversity of msp2 transcripts in the absence of immune pressure suggests selection for Msp2 by specific functions beyond that of immune evasion, in spite of a large genomic reservoir for Msp2 diversity.

Amino Acid Sequence↗
PubMed2003

Transcutaneous immunization and immunostimulant strategies: capitalizing on the immunocompetence of the skin.

The skin is an attractive target for vaccine delivery. Topical application of adjuvants results in potent immune responses and good safety profiles. Adjuvants can be coadministered in a patch with vaccine antigens (transcutaneous immunization) or similar delivery format, or administered separately with an injection or IS patch (Iomai), leading to enhanced immune responses. These observations have moved into the clinic, highlighting the likelihood that skin delivery of vaccines will play an important future role in vaccine applications.

Adjuvants, Immunologic↗
PubMedDate not supplied

Depressed host immunity in a case of metachronous primary uterine papillary serous carcinoma and non-Hodgkin's lymphoma.

Metachronous primary malignant tumors of uterine papillary serous carcinoma (UPSC) and non-Hodgkin's lymphoma (NHL) are rare. UPSC is a clinically aggressive and morphologically distinctive variant of endometrial carcinoma. We describe the clinical features of a 63-year-old patient with UPSC that was found 2 years after chemotherapy for malignant lymphoma of neck, stage IV and 5 months after radiation therapy for recurrence. This patient had undergone staging surgery and postoperative radiation for UPSC. One month after completion of radiotherapy, the patient expired due to persistence of the disease. The association between host immunity and UPSC is rarely described in the literature. Immunological profiles of this patient, with compositional changes of natural killer, B, and T cell, dramatically altered the percentage of CD4(+) T cell, CD8(+) T cell, and CD4/CD8 ratio, signifying depressed host immunity. Immunological profile of this patient stressed the issue of depressed host immunity and associated malignancies.

Carcinoma, Papillary↗
PubMed1996

Immunoglobulin G subclass responses of children during infection with Onchocerca volvulus.

To characterize the patterns of immunoglobulin G (IgG) subclass and IgE reactivity during the early stages of onchocerciasis, sera were collected from 224 children (age groups, 2 to 5, 6 to 10, and 11 to 15 years) residing in a region of Sierra Leone where Onchocerca volvulus is endemic, and these samples were tested by enzyme-linked immunosorbent assay for their reactivity to adult antigens (OvAg) and against four recombinant proteins (OV11, OV27, OV29, and OV16). Over 88% of the samples contained detectable levels of anti-OvAg IgG. In samples from microfilaria (MF)-positive children, IgG4 responses were significantly elevated and constituted on average 39, 35 and 28% of the total IgG responses for the age groups of 2 to 5, 6 to 10, and 11 to 15 years, respectively. For MF-negative individuals, the mean contributions of IgG4 to the total IgG response were 11% (2 to 5 years), 27% (6 to 10 years), and 56% (11 to 15 years). OvAg-specific IgE was detectable in the sera from both MF-negative and MF-positive individuals. To increase the specificity of the response, recombinant antigens OV11, OV27, and OV29 were tested individually or as a cocktail. Nearly 50% of the MF-negative children and 85% of the MF-positive children had detectable levels of IgG against at least one of the recombinant antigens. Only a small portion of the IgG against the recombinant peptides was IgG4. The prevalence of IgG against OV16 in samples from MF-negative children was 51%, and that for MF-positive children was 75%. The general profile of the humoral immune responses mounted by both MF-positive and a large percentage of the MF-negative children during the initial phases of infection with O. volvulus is similar to the profile reported for adults harboring chronic O. volvulus infections. These results suggest that very quickly after infection, the interactions between parasite and host result in an immunological environment that may contribute to the maintenance of a long-term, chronic infection.

Adolescent↗