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At least 19 recordsLinked to original sources

Radiation-induced immune changes in patients with cancer of the cervix.

Immunological methods were used to estimate the therapeutic effect of irradiation and its influence on the immune capacity of patients with cervical cancer. Patients were examined during and following radiotherapy by means of lymphocyte counts, lymphocytic response to phytohaemagglutinin (PHA), and the depressive effect of their sera on the response of normal lymphocytes PHA stimulation. Lymphocyte counts and lymphocyte responses during radiotherapy were depressed to 20 to 50 per cent and 10 to 33 per cent respectively of the values found before treatment. Lymphopenia and depressed T-cell function persisted for years in many patients. The highest values for both lymphocyte counts and reactivities were found in those patients who had unexpectedly good responses to radiotherapy. The immunodepressive effect of patients' sera on normal lymphocyte reactivity decreased and disappeared during therapy and was not present in previously treated patients showing a good prognosis, whereas it showed no change or even increased during therapy in patients with a poor prognosis. The results suggest that not only does immune capacity influence the effect of radiation and the prognosis of the patient, but also that study of the serum-depressive effect could give important information about both the dosage and therapeutic effects of irradiation.

Adult↗

Treatment of rheumatoid arthritis with levamisole: long-term results and immune changes.

We treated 29 rheumatoid arthritis patients with levamisole. on the basis of a 25% improvement in any 3 of 6 measurements 95% of the patients had a favourable response within 20 weeks. However, 64% of the patients discontinued levamisole by 40 to 60 weeks because of rash or secondary treatment failures. Delayed skin reactivity to streptokinase-streptodornase increased significantly in the entire treatment group, but there was in inverse correlation between skin test enhancement and clinical response. There was no overall change in lymphocytes response to phytohaemagglutinin (PHA) after 4 and 16 weeks of treatment, but seven patients with enhanced lymphocyte responsiveness to PHA experienced an earlier clinical response to levamisole. Treatment with levamisole frequently results in clinical improvement in rheumatoid arthritis, but this is not clearly related to a stimulatory effect on cell-mediated immunity. Its long-term usefulness may be limited by a high incidence of relapse and rash.

Arthritis, Rheumatoid↗

[The dynamics of humoral and cellular immunity changes in patients with acute phase of trichinellosis (author's transl)].

21 patients with acute trichinellosis have been studied. The behaviour of IgG, IgA and IgM in the serum of patients as well as the percentage of lymphocytes T and B was the aim of these studies. Statistically significant increase of IgG in serum has been observed since the third week of the clinical observation. During the whole period of observation the level of IgA was lowered--though the decrease was not statistically significant--whereas the level of IgM increased considerably. Decreased percentage of lymphocyte B in the peripheral blood during the first week of the clinical observation, later on increased significantly. The percentage of T lymphocyte was lowered during the whole period of the clinical observation of patients.

Acute Disease↗

Ultrastructure of the lymph node after prolonged immunization.

Changes in the fine structure of the lymph nodes were studied after prolonged immunization with heterologous sera. Hypertrophy of the lymph node cortex and paracortex frequently occurred, as well as development of the zone lying next to the lymphatic sinuses, postcapillary venules, veins and arteries in the cortex, paracortex and medulla, which is mainly bursa-dependent. Worthy of note was the presence of germinative centers characterized by large ribosomes, rich cells and macrophages. Similar aspects were observed in splenectomized animals undergoing prolonged immunization. Particular aspects of immunologic activity in the lymph nodes were noticed in the animals which had received an immunosuppressive treatment during immunization. The significance of the morphological alterations in the fine structure of the lymph nodes is correlated with the serological findings.

Animals↗

Active specific immunization in malignant melanoma.

The effects of active specific immunization with nonirradiated autologous and irradiated cultured allogeneic melanoma tumor cells (TC) on cell-associated immunity was studied in 11 patients with widespread malignant melanoma receiving chemoimmunotherapy. Immunization with 1 X 10(6)-8 X 10(7) TC was done in the draining area of a BCG scarification on day 7 of the study. The in vitro lymphocyte blastogenic response (BR) to autologous TC was studied in terms of the stimulation index on day 1, 7, 14, and 21. The stimulation index (SI) was the counts per min (cpm) in the TC stimulated culture minus the cpm among the TC alone divided by the cpm in the unstimulated controls. A positive BR was considered as a SI equal to or greater than 3. Six out of 11 patients had a significant increase in BR lasting 7-14 days after immunization. The pre- to post-immunization changes in the SI of the 6 patients were 2.5 to 7.5; 0.7 to 3.2; 0 to 5.2; 0 to 16; 0.1 to 6.6; and 6.5 to 30.0. Nine out of 11 patients showed a delayed local inflammatory reaction at the immunization site. Five out of 11 patients mounted a cutaneous delayed hypersensitivity reaction to autologous tumor cells at a separate test site following immunization. There were no side effects. Active specific immunization in the drainage of a BCG reaction appears to be safe. Since a positive BR to autologous TC correlates with a good prognosis in patients with solid tumors, studies of the immunotherapeutic efficacy of this approach may be warranted.

Adolescent↗

Cushing's disease and autoimmune thyroid disorders in women: Impacts on fertility, pregnancy, and menopause.

Cushing's disease (CD) and autoimmune thyroid diseases (AITDs) are two distinct but interconnected endocrinopathies affecting predominantly women. A primary cause of CD is excess adrenocorticotropic hormone (ACTH) secretion, which leads to hypercortisolism and profound hormonal and immune changes. As with AITDs, Hashimoto's thyroiditis and Graves' disease are caused by a loss of immune tolerance and frequently coexist with female reproductive dysfunction. Emerging evidence suggests that chronic hypercortisolism in CD suppresses immunity as well as alters hypothalamic-pituitary-thyroid (HPT) axis activity, which may mask or exacerbate thyroid autoimmunity after disease remission. Coexisting CD and AITD has significant effects on women's reproductive health, pregnancy outcomes, and menopausal transitions, as thyroid and adrenal hormones play a crucial role in regulating ovulatory cycles, placental development, bone formation, and cardiovascular health. In this review, shared pathophysiological pathways are explored, clinical and therapeutic challenges are highlighted, and integrated management strategies are discussed. To improve early diagnosis, tailor treatment approaches, and guide future endocrine research, it is essential to understand the compounded risks of dual endocrinopathy.

Humans↗

Pre-eclampsia--a state of mother-fetus immune imbalance.

Serial lymphocyte counts and function tests were done during and after pre-eclamptic pregnancies, and in the offspring. Compared with normal pregnancies, pre-eclamptic pregnancies were associated with lower B-lymphocyte counts in the fathers; lower T-lymphocyte count, lower B-lymphocyte count, and impaired T-lymphocyte function in mothers; a low response in mixed lymphocyte culture (MLC) tests between the mother and father; and an increased B-cell count in the children. Follow-up of one pre-eclamptic woman throughout pregnancy showed important immune changes at the beginning of the second trimester. These findings suggest that pre-eclampsia is caused by a combination of maternal and paternal hyporesponsiveness together with fetal hyperresponsiveness.

B-Lymphocytes↗

An immunological approach to dementia in the elderly.

A study into the relationship of immune change in the serum and the presence of senile dementia is reported. Three groups were studied, senile dementia, cerebrovascular disease and subjects without evidence of brain disease. All were aged 65 years and over. The immunofluorescent studies showed an excess of antineuronal reactivity and a fall in antinuclear antibody in females with senile dementia. There was no significant difference between the groups in respect of immunoglobulins, slide latex and a complement fixation test, against a variety of tissues. The significance of the findings in relation to other published results is discussed.

Aged↗

Immunological comparison of HIV-1-, HIV-2- and dually-reactive women delivering in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the basic immunological changes induced by HIV-1 and HIV-2 infection and to assess the immune status of subjects serologically reactive to both HIV-1 and HIV-2 (dually-reactive). DESIGN: Immune parameters were studied cross-sectionally in women delivering in Abidjan, Côte d'Ivoire, West Africa, where HIV-1 and HIV-2 are endemic. In this area, a significant number of sera from infected individuals are reactive to both HIV-1 and HIV-2. SUBJECTS AND METHODS: Two hundred and twenty-eight women delivering in a major maternity clinic were screened for HIV-1 and HIV-2 using an enzyme-linked immunosorbent assay. Seropositivity was confirmed by Western blot. The immune parameters studied were CD4+ and CD8+ lymphocyte subsets, immunoglobulin (Ig) serum levels, neopterin and beta 2-microglobulin (beta 2M) serum levels. RESULTS: Similar but less pronounced immune changes were present in HIV-2-reactive subjects compared with HIV-1- and dually-reactive subjects. The observed differences between the HIV-seropositive groups could not be explained by differences in age or disease stage but paralleled differences in the frequency of persistent generalized lymphadenopathy (PGL). The intermediate immune profile of HIV-2-reactives (between seronegatives and HIV-1- and dually-reactives) was most clearly reflected by the number of CD8+ lymphocytes, the CD4:CD8 ratio and the IgG serum level. Median neopterin and beta 2M levels, though significantly increased in all HIV-seropositive groups, did not differ significantly between HIV-2-, HIV-1- and dually-reactives. CONCLUSIONS: HIV-2 infection is associated with typical HIV-related immunological changes. Immunologically, dually-reactives resemble HIV-1-reactives more closely than HIV-2-reactive subjects.

Adult↗

Prediction by postrevascularization biopsies of cadaveric kidney allografts of rejection, graft loss, and preservation nephropathy.

This prospective study of postrevascularization biopsies was undertaken to determine if pathological changes might be correlated with subsequent allograft rejection and loss. Such a relationship, if identified, could be used to predict graft outcome, thus permitting earlier intervention for individuals at an increased risk for rejection or graft loss. Fifty-seven biopsies were obtained, and the number of polymorphonuclear leukocytes marginating in the glomerular loops and peritubular capillaries was documented along with risk factors associated with the recipients' immunological status and with risk factors associated with ischemic preservation injury. The presence of seven PMN leukocytes in the peritubular capillaries is related to the subsequent occurrence of cellular rejection and accurately predicted in 82% of the patients studied whether or not rejection would occur. Mean glomerular PMN leukocyte count was related to cold ischemia time and subsequent graft loss, while an elevated mean glomerular PMN leukocyte count in conjunction with an elevated peritubular PMN leukocyte count was always associated with hyperacute rejection. Focal glomerular thrombosis (less than 50%) and tubular cast formation are manifestations of preservation nephropathy and had no effect on graft outcome. These findings suggest that the peritubular capillaries are a more sensitive target for immune changes and that minor donor/recipient disparities can be detected in the peritubular capillaries while preexisting sensitization to the donor is reflected by concurrent changes in the glomerular and peritubular capillaries.

Adolescent↗

Deciphering the prodrome of inflammatory bowel disease up to 10 years before disease onset by massively parallel serology.

BACKGROUND: Defining immune dysregulation during the asymptomatic prodrome of immune-mediated diseases offers opportunities for early disease detection and interception. In inflammatory bowel disease (IBD), prodromal immune changes remain poorly characterised. OBJECTIVE: To define preclinical immunological alterations by characterising longitudinal serum antibody repertoires using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq). DESIGN: We applied PhIP-Seq to profile antibody responses in 2000 longitudinal serum samples from 200 individuals who developed Crohn's disease (CD), 200 who developed ulcerative colitis (UC) and 100 matched healthy controls within the US military Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects cohort, collected up to 10 years before diagnosis. Antibody repertoires were profiled against 357 000 microbial-associated, viral-associated, food-associated and immune-associated peptides. RESULTS: Antibody repertoire variability was increased up to ~4 years prediagnosis in pre-CD and pre-UC individuals. Differential analyses revealed elevated herpesvirus-directed responses (notably Epstein-Barr virus) and anti-flagellin antibodies up to 10 years prediagnosis in CD, particularly in individuals who later developed complicated or ileal disease. In contrast, responses to encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus, Neisseria) progressively declined towards diagnosis. Pre-UC was characterised by combined antimicrobial, antiviral and autoantibody signatures, including antibodies against the MAP kinase-activating death domain protein. CONCLUSIONS: Large-scale serological profiling of archived prediagnostic samples identified disease-specific immune trajectories years before IBD onset, providing novel insights into disease pathogenesis in its prodromal phase.

ANTIGENS↗

Immune function and survival in a long-lived mouse strain subjected to undernutrition.

Functional immune changes were monitored in populations of the long-lived C57BL/6J strain of mice which were subjected to dietary restriction from time of weaning or subjected to such restriction both before and after weaning, along with the appropriate control populations. Responses to T and B cell mitogens (PHA, Con-A, pokeweed, bacterial lipopolysaccharide, and PPD), to injected sheep red blood cells, and measurement of skin allograft rejection rates were followed. Early in life, restricted mice appear immunosuppressed, as judged by all these parameters. Skin allograft rejection remained suppressed until relatively late in life. Other responses tended to reverse from the earlier pattern; by mid-life restricted mice responded better than controls. Dietary restriction profoundly affects the immune system. Mice on such regimes display anatomic and certain immune functional changes which suggest that the immune system may mature less rapidly and stay "younger" longer than in the controls. Furthermore, dietary restriction results in prolongation of life span.

Animals↗

Fecal microbiota transplantation promotes type 2 mucosal immune responses with colonic epithelium proliferation in patients with recurrent Clostridioides difficile.

BACKGROUNDFecal microbiota transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.METHODSWe report the results of a clinical trial of patients undergoing FMT therapy for rCDI (n = 16), which analyzed colon biopsies, plasma, PBMCs, and stool at the time of FMT and 2-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with patients with rCDI. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.RESULTSNo patients experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared with both pre-FMT and healthy control biopsies, inhibiting genes associated with proinflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single-cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.CONCLUSIONWe conclude that FMT promotes proliferation of the colonic epithelium in patients with rCDI, which may drive regeneration and protect against subsequent CDI.TRIAL REGISTRATIONClinicaltrials.gov NCT02797288.FUNDINGThis work was funded by grants from the NIH.

Adult↗

Laryngeal papillomatosis: immunologic and viral basis for therapy.

The distressing nature of laryngeal papillomatosis and lack of clinical progress in its treatment are reviewed. Presently accepted and investigative methods of therapy are reviewed with special attention being given to immune therapy. Support for the concept of a viral etiology is discussed and other etiologic agents considered. Known and possibly significant roles of wart virus antibodies are discussed and the importance of complex interplay between maternal and fetal immune systems explored as a possible explanation for some puzzling aspects of laryngeal papillomatosis. Finally, a proposed experimental design is outlined, the purpose of which is to provide a useful animal model to investigate immune changes in laryngeal papillomatosis, as well as effects of surgical or medical therapy.

Adult↗

CSF in 85 patients with AIDS and CNS cryptococcosis.

In an eight years time period (July 1984-June 1992) CSF samples of 40718 patients were studied, and 610 were from patients with AIDS clinically diagnosed and immunologically confirmed through HIV antibodies detection. Among opportunistic infections detected in them 85 were CNS cryptococcosis. For the purpose of this study the CSF of these 85 patients are the AIDS group of CNS cryptococcosis. For comparison, CSF data from 50 patients with CNS cryptococcosis but without AIDS were taken (non-AIDS group); in this group, 22 patients were immunosuppressed after renal transplant. In AIDS group, the more frequent CSF findings were: yeast presence at direct exam (Fuchs-Rosenthal cell counting chamber), growing of the yeast in cultures, and gamma globulins increase. In non-AIDS group were more frequent: hypercytosis, neutrophil cells presence, and total protein increase. Differences between the two groups are discussed taking into account CNS/CSF immune changes induced by HIV infection. It is concluded that in CNS cryptococcosis of patients with AIDS the CSF evidenced more extensive signs of the fungal opportunistic infection than signs of inflammatory response to the infection. The latter were more prominent among patients of the non-AIDS group of CNS cryptococcosis.

Acquired Immunodeficiency Syndrome↗

A study of cellular and humoral immune responses in owl monkeys (Aotus trivirgatus) following vaccination against Plasmodium falciparum.

VACCINATION OF ANIMALS AGAINST MALARIA PARASITES IS THOUGHT TO INDUCE TWO BASIC IMMUNOLOGICAL RESPONSES: (i) specific recognition of parasite antigens by the host, and (ii) a generalized immune enhancement due to the presence of adjuvant. Immunological techniques were used in this study to monitor cellular and humoral immune changes in owl monkeys prior to and following immunization with a vaccine consisting of merozoite-enriched schizonts of Plasmodium falciparum and one of three adjuvants: N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide), Freund's complete adjuvant, or 6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine. The results showed that most of the immunized animals responded specifically to malarial antigens as demonstrated by the fact that peripheral blood lymphocytes underwent blast transformation in vitro in the presence of parasite antigens and that substantial antibody titres were produced as detected by indirect immunofluorescence. By use of the in vitro inhibition test, it was found that sera from immunized owl monkeys collected after challenge greatly inhibited merozoite reinvasion. Generalized nonspecific immune responses observed in owl monkeys following vaccination included an increase in the number of white blood cells and the proportion of T and B cells in the peripheral blood. Responses to mitogen stimulation with phytohaemagglutinin, concanavalin A, and pokeweed mitogen, however, did not appear to be appreciably affected by immunization.

Animals↗

Immunological effects of a single evening subcutaneous injection of low-dose interleukin-2 in association with the pineal hormone melatonin in advanced cancer patients.

Recent experiments have shown that a great variety of neurohormones can interact with IL-2 in the modulation of host antitumor immune response. On the basis of these data, a study was started to evaluate the effect of the pineal hormone melatonin (MLT) on IL-2-induced immune changes in cancer. The study included 30 advanced cancer patients. They were randomized to be treated with IL-2 at a dose of 3 million IU subcutaneously twice/daily (8.00 a.m. and 8.00 p.m.) for 6 days/week for 4 weeks, with IL-2 once/daily in the evening, with IL-2 once/daily plus MLT at 10 or at 50 mg/day. MLT was given orally at 8.00 p.m. Both IL-2 given twice daily and IL-2 given once daily and IL-2 given once daily in association with MTL induced a significant increase in mean number of lymphocytes, T lymphocytes, NK cells, CD25-positive cells and eosinophils, whereas the single administration of IL-2 alone was unable to determine a significant rise in the mean number of immune cells. Soluble IL-2 receptor and neopterin increase was significantly higher during IL-2 given twice/daily than during IL-2 plus MLT, while no difference was seen in TNF rise. This study would suggest that a single daily injection of low-dose IL-2 is able to efficiently activate the lymphocyte proliferation in cancer patients when it is given in association with the pineal hormone MLT.

Adult↗