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At least 811 records · Page 45Linked to original sources
PubMed2004

Distinct profiles of human B cell effector cytokines: a role in immune regulation?

There is growing interest in the fundamental roles that B cells may play in regulating immune responses. Emerging animal studies point to an important contribution of B cell effector cytokines to immune modulation, yet little is known about the factors regulating such cytokine production. We report that the profile of human B cell cytokine production is context dependent, being critically influenced by the balance of signals through the B cell receptor and CD40. B cells appropriately stimulated by sequential B cell receptor and CD40 stimulation proliferate and secrete TNF-alpha, lymphotoxin, and IL-6, which can act not only as autocrine growth and differentiation factors, but also serve to amplify the ongoing immune response. In contrast, CD40 stimulation alone, a mimic of a B cell receiving bystander T cell help in the absence of specific Ag recognition, induces negligible proinflammatory cytokines, but significant production of IL-10 that serves to suppress inappropriate immune responses. We thus describe a novel paradigm of reciprocal regulation of B cell effector cytokines, and ascribe active roles for human B cells in either promoting or suppressing local immune responses through context-dependent cytokine production.

Adjuvants, Immunologic↗
PubMed1987

Isotypic pattern of the polyclonal B cell response during primary infection by Plasmodium chabaudi and in immune-protected mice.

The primary infection by P. chabaudi induces an increase of the numbers of splenic immunoglobulin (Ig)-secreting B cells in both athymic and euthymic BALB/c mice. The isotypic pattern of the polyclonal response is restricted only in euthymic mice where IgG2a, IgG2b and IgM plaque-forming cells (PFC) predominate. In immunized animals, protected against a parasite challenge, the isotypic pattern of splenic PFC is completely different, the IgG1 and IgM isotypes constituting the main part of the response. Reinoculation of immune-protected animals induces a PFC response which is dose dependent and accentuates the characteristic isotypic profile of the immune-protected mice.

Animals↗
PubMed1989

Distinct IL-3 activation profile induced by intravenous versus subcutaneous routes of immunization.

Lymphoid cells from mice immunized i.v. or s.c. with Leishmania major antigens were analyzed for their capacity to produce lymphokines when stimulated with specific antigens in vitro. Spleen cells from BALB/c mice immunized by the s.c. route produced significantly higher levels of IL-3 and IL-3 mRNA than those from mice immunized by the i.v. route. The differential production of IL-3 was maintained at a wide range of antigen concentrations tested in vitro and for different culturing times. T cell enrichment procedures and treatment with CD4+ mAb in vitro confirmed the T cell nature of the IL-3 producer population. However, the IL-3 production in the two populations of spleen cells was equally high after Con A stimulation in vitro. The IL-2 production by the two populations of cells was also not significantly different after antigen or mitogen stimulation in vitro. To our knowledge, this is the first report of a differential synthesis of IL-3 mRNA and secretion of IL-3 induced by different routes of immunization followed by specific-antigen stimulation in vitro. These findings may also explain earlier observations that i.v. immunization with leishmanial antigen induces protection, whereas s.c. immunization leads to exacerbation of L. major infection, since IL-3 has been previously shown to promote leishmanial infection. The fact that the phenomenon also extends to other antigen systems suggests that this finding may have a broader implication in immune regulation and vaccine development.

Animals↗
PubMed2000

Phenotype, immunological reactivity and cytokine production profile of Peyer's patch cells from mice immunized orally with allogeneic cells.

Mice of inbred strain BALB/c were immunized orally for 10 consecutive days with fresh spleen cells from allogeneic C57BL/10 (B10) donors. The immunized mice displayed significant allotransplantation immunity in vivo as demonstrated by resistance to the growth of allogeneic tumours induced by high doses of tumour cells. No significant changes in the proportion of the major T cell subsets in PP of immunized mice were found 1 or 7 days after the last immunization dose. However, PP cells from orally immunized mice displayed stronger proliferative response after stimulation with cells used for oral immunization than the cells from control animals. Similarly, after stimulation in vitro with specific alloantigens, PP cells from orally immunized mice produced more IFN-gamma than the cells from control recipients. On the contrary, the production of IL-4 was significantly decreased in the immunized mice. The production of IL-2 by PP cells after oral immunization was not significantly changed and IL-10 was only slightly increased. The results thus show that oral immunization with allogeneic cells induces systemic transplantation immunity which can be demonstrated already in Peyer's patches by increased cell proliferation after immunization with specific alloantigens and by changes in cytokine production.

Administration, Oral↗
PubMedDate not supplied

[The protective role of postvaccinal immunity in mumps in children].

The immunological study of children with infectious parotitis (IP) without complications and with such complications as pancreatitis, meningitis or orchitis in the glandular form was carried out. In accordance with the previously proposed principle, 4 types of immune response (IR) were established on the basis of differences in initial resistance and the IR profile: cell-mediated immunity (types I and III) and humoral immunity (types II and IV). The patients included nonvaccinated children, as well as children vaccinated on epidemic indications, 3-6, 7-9, 10 and more years before infection. The comparative analysis of the number of IP cases with and without complications in the groups of children, divided according to their immunization history and the type of IR, revealed that postvaccinal immunity in children vaccinated on epidemic indications (less than a month ago) or 3-6 years before infection had protective potential, sufficient for the prevention of complicated forms of IP. Immunity obtained 7-9 years ago was effective for the protection from IP complications only in cell-mediated, but not humoral IR. Postvaccinal immunity obtained more than 10 years ago did not ensure the decrease in the occurrence of complicated forms of IP (in comparison with that in nonvaccinated patients) in children with any type of IR.

Adolescent↗
PubMedDate not supplied

Serum complement profile in human leprosy and its comparison with immune complex diseases.

In the present study we have estimated the serum levels of early, middle, and distal complement components, e.g., Clq, C3, C4, C5, C8, and C9 along with C1-inactivator and CH50 in patients with tuberculoid and lepromatous leprosy and have compared these results with the levels in healthy subjects as well as with levels in patients with other immune complex diseases. We have also analyzed the cryoglobulins present in the sera of these patients; they consisted of either a single or mixed IgG, IgA, IgM or fibrinogen in most instances. The component C3 was found in only one sample. It appears that unlike lupus nephritis, in which complement is activated by direct path in which complement is activated by direct path in about 30% to 50% of leprosy patients, significant C3 complement consumption takes place primarily via the alternate pathway and is probably initiated by the aggregated immunoglobulins represented in cryoprecipitates. This is further supported by the study of serum factor B and its breakdown product (Ba) in these patients. The question of the role of the middle and distal complement components, such as C5, C8 and C9, during total hemolytic complement and C3 consumption in leprosy remains unanswered.

Complement C1 Inactivator Proteins↗
PubMed2000

Immune activation in africa is environmentally-driven and is associated with upregulation of CCR5. Italian-Ugandan AIDS Project.

BACKGROUND: HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population. METHODS: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity. FINDINGS: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains. CONCLUSIONS: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.

Africa↗
PubMed1986

[Possibility of using the etiological factor and the function of the immune system in assessing the pathogenetic treatment of chronic suppurative sinusitis].

The etiologic profile and state of the immune system of the patients with different forms of sinusitis treated at the Moscow Research Institute of the Ear, Throat and Nose in 1983-1985 were studied. The treatment of the patients with a combination of penicillin and dimexide was shown to be efficient. Differences between the humoral factors of the nonspecific defence and between the indices of the cell reactivity of the patients before and after the treatment were revealed.

Adolescent↗
PubMed1997

Effectiveness of a short-term group psychotherapy program on endocrine and immune function in breast cancer patients: an exploratory study.

Cancer patients who had been treated for early stage breast cancer and were diagnosed with either positive axillary lymph nodes or distant metastases were randomly assigned to either a 13-week experiential-existential group psychotherapy (EEGP) program or a waiting list control (WLC) condition. Endocrine and immune measures were obtained before and after the intervention period. The findings of this study are that, after the 13 weeks of the experiment, patients in the EEGP group showed lower levels of plasma cortisol and lower levels of prolactin as well as lower percentages of natural killer cells, CD8 cells, and CD4 cells in addition to a lower proliferative response to pokeweed mitogen than patients in the WLC group. Importantly, this was only found in those breast cancer patients presenting relatively high endocrine and immune baseline levels, suggesting that the patients' profile with regard to endocrine and immune function at the start of a program can have an important effect. If replicated on a larger scale, the current results may be relevant for the treatment of breast cancer.

Adrenocorticotropic Hormone↗
PubMed1998

Rubella serology in mentally retarded adults.

BACKGROUND: Rubella and congenital rubella syndrome remain a problem in the United States; institutionalized individuals are at higher risk. We assessed demographic variables and rubella serology in a population of institutionalized adults with mental retardation. METHODS: Subjects were 181 institutionalized adults with mental retardation. We reviewed charts to determine patient's age, sex, race, and fertility status (if female), cause of mental retardation, and rubella history. Serologic testing to determine rubella immunity was done. RESULTS: We found that 26.4% of subjects were nonimmune. Sex, cause of mental retardation, and history of rubella vaccination were not related to serologic immunity status. Of the 29 fertile female subjects, 8 (27.6%) were nonimmune to rubella. CONCLUSION: Subjects with unknown immunization status had a similar serologic profile to those whose medical records indicated immunization. Neither history of infection nor immunization was predictive of serology status.

Adult↗
PubMed2001

Protection against woodchuck hepatitis virus (WHV) infection by gene gun coimmunization with WHV core and interleukin-12.

Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar with respect to genomic organization, host antiviral responses, and pathobiology of the infection. T-cell immunity against viral nucleocapsid (HBcAg or WHcAg) has been shown to play a critical role in viral clearance and protection against infection. Here we show that vaccination of healthy woodchucks by gene gun bombardment with a plasmid coding for WHcAg (pCw) stimulates proliferation of WHcAg-specific T cells but that these cells do not produce significant levels of gamma interferon (IFN-gamma) upon antigen stimulation. In addition, animals vaccinated with pCw alone were not protected against WHV inoculation. In order to induce a Th1 cytokine response, another group of woodchucks was immunized with pCw together with another plasmid coding for woodchuck interleukin-12 (IL-12). These animals exhibited WHcAg-specific T-cell proliferation with high IFN-gamma production and were protected against challenge with WHV, showing no viremia or low-level transient viremia after WHV inoculation. In conclusion, gene gun immunization with WHV core generates a non-Th1 type of response which does not protect against experimental infection. However, steering the immune response to a Th1 cytokine profile by IL-12 coadministration achieves protective immunity. These data demonstrate a crucial role of Th1 responses in the control of hepadnavirus replication and suggest new approaches to inducing protection against HBV infection.

Animals↗
PubMed2003

[Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome].

Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients. One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis. Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile. It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms. Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome. Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.

Aluminum↗
PubMed2006

Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcepsilonRI-aggregation reveals a complex network of genes involved in inflammatory responses.

BACKGROUND: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcepsilonRI aggregation. RESULTS: Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation. CONCLUSION: This report represents a substantial advance in our understanding of the genome wide effects triggered by "passive sensitization" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.

Gene Expression Profiling↗
PubMed1996

T helper cell activation and human retroviral pathogenesis.

T helper (Th) cells are of central importance in regulating many critical immune effector mechanisms. The profile of cytokines produced by Th cells correlates with the type of effector cells induced during the immune response to foreign antigen. Th1 cells induce the cell-mediated immune response, while Th2 cells drive antibody production. Th cells are the preferential targets of human retroviruses. Infections with human T-cell leukemia virus (HTLV) or human immunodeficiency virus (HIV) result in the expansion of Th cells by the action of HTLV (adult T-cell leukemia) or the progressive loss of T cells by the action of HIV (AIDS). Both retrovirus infections impart a high-level activation state in the host immune cells as well as systemically. However, diverging responses to this activation state have contrasting effects on the Th-cell population. In HIV infection, Th-cell loss has been attributed to several mechanisms, including a selective elimination of cells by apoptosis. The induction of apoptosis in HIV infection is complex, with many different pathways able to induce cell death. In contrast, infection of Th cells with HTLV-1 affords the cell a protective advantage against apoptosis. This advantage may allow the cell to escape immune surveillance, providing the opportunity for the development of Th-cell cancer. In this review, we will discuss the impact of Th-cell activation and general immune activation on human retrovirus expression with a focus upon Th-cell function and the progression to disease.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Cetirizine decreases interleukin-4, interleukin-5, and interferon-gamma gene expressions in nasal-associated lymphoid tissue of sensitized mice.

Although the action of cetirizine dihydrochloride (cetirizine), a potent histamine H1 receptor antagonist, has been well known, its effect on the cytokine profiles in the nasal immune inductive site has not been elucidated yet. We studied the effect of cetirizine on the cytokine profiles in the nasal-associated lymphoid tissue (NALT), which is a principal mucosal lymphoid tissue of the respiratory tract in rodents. Two different doses of cetirizine were given intraorally for 5 days before the nasal challenge of ovalbumin in sensitized mice. The sensitized group was given normal saline instead of cetirizine, and the nonsensitized group had no sensitization or medication. The cytokine gene expressions in the NALT taken from the mice were investigated with real-time quantitative reverse-transcription polymerase chain reaction. The effect of cetirizine on the allergic symptom score, histamine threshold, and the eosinophil count in the nasal septal mucosa were examined also. Compared with the normal mice, the sensitized mice showed significantly increased levels of interleukin (IL)-4 and IL-5 gene expression although the increase of interferon (INF)-gamma gene expression was not significant. In the cetirizine groups, the levels of expression of IL-4, IL-5, and INF-gamma in the NALT were significantly decreased compared with the sensitized group. The cetirizine groups also showed decreased allergic symptom score, histamine threshold, and eosinophil count in the nasal septal mucosa compared with the sensitized group. In conclusion, cetirizine reduced the levels of expression of IL-4, IL-5, and INF-gamma in the NALT of ovalbumin-sensitized mice. Cetirizine also reduced the acute allergic symptom, histamine sensitivity, and eosinophil count in the nasal septal mucosa.

Airway Resistance↗
PubMed1991

Streptokinase immunogenicity in thrombolytic therapy for acute myocardial infarction.

The major drawback in implementing thrombolytic therapy with streptokinase in cases of acute myocardial infarction (AMI) stems from its antigenicity. To evaluate the dimensions of this problem, the immune response following thrombolytic therapy with streptokinase was prospectively studied in 16 patients with AMI. Streptokinase was given to 12 patients once and to 4 patients twice within 4-14 days. No clinical immune responses were observed following treatment. The specific antistreptokinase immune responses subsequent to streptokinase administration were monitored. The cellular immune response, reflected by the 3H-thymidine uptake of streptokinase-stimulated peripheral blood mononuclear cells, was three times higher than that of the controls. The antistreptokinase circulating IgG antibody level, measured by an enzyme-linked immunosorbent assay, was 8 times higher than that of the controls. No antistreptokinase circulating IgE antibodies could be detected and no decrease in complement concentration was noted. The profile and magnitude of the immune response of patients who had received two treatments were similar to those of patients who had received a single treatment only. Our data suggest that thrombolytic therapy with streptokinase in AMI elicits a characteristic profile of antistreptokinase immune responses, in vitro, not necessarily associated with parallel clinical immune responses. An early repeat treatment with streptokinase was not accompanied by clinical or exacerbated in vitro immune responses.

Antibody Formation↗
PubMed2026

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals↗