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Biomedical subjects

H Arvilommi

Publications and source records attributed to H Arvilommi.

At least 55 records · Page 3Linked to original sources

Cow's milk provocation induces an immune response to unrelated dietary antigens.

The activation of immune mechanisms was evaluated by the solid phase enzyme linked immunoassay of immunoglobulin and specific antibody secreting cells in 27 patients (aged from nine to 69 months), subjected to a diagnostic cow's milk challenge or a rechallenge. A significant rise in the total number of immunoglobulin secreting cells was associated with clinically positive (n = 17), but not a negative (n = 10) cow's milk challenge in all immunoglobulin isotypes. The number of specific antibody secreting cells against beta lactoglobulin, mean (95% confidence interval), increased from 4.8 (1.4, 15.8) to 16.9 (5.5, 52.7) specific antibody secreting cells/10(6) cells, p = 0.02, and against casein from 2.2 (0.8, 6.1) to 7.5 (2.5, 22.5) specific antibody secreting cells/10(6) cells, p = 0.01, in patients positive to challenge in the IgM class only, indicating defective immune elimination of milk antigens. In addition to the specific immune response to cow's milk antigens, an increase in IgM specific antibody secreting cells against an unrelated dietary antigen, gliadin, from 8.2 (2.1, 31.1) to 31.0 (14.2, 67.6) specific antibody secreting cells/10(6) cells, p = 0.01, was observed. These results indicate that cow's milk challenge, in patients who have cow's milk allergy, induces a strong non-antigen specific immune response that includes a response against unrelated antigens concomitantly present in the intestinal lumen. Activation of such immune mechanisms may hence reflect increased antigenic load caused by the immune mediated lesion in the gut mucosa.

Antibody Specificity↗

Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain.

Human Lactobacillus sp strain GG (Lactobacillus GG) administered during acute rotavirus diarrhea has been shown to promote clinical recovery. To elucidate the immune mechanisms behind such a favorable outcome, the ELISPOT (solid phase enzyme-linked immunospot) assay of Ig- and specific antibody-secreting cells among circulating lymphocytes was used, giving indirect evidence of the immunologic events in the gut. After rehydration, 39 children with acute rotavirus diarrhea, mean age 16 (SD 6) mo, randomly received either a Lactobacillus GG fermented milk product (study group) or a pasteurized yogurt (placebo group). The duration of diarrhea was significantly shorter in the study group than in the placebo group [mean 1.1 (SD 0.6) versus 2.5 (SD 1.4)d, p = 0.001]. Lactobacillus GG therapy was associated with a significantly enhanced nonspecific humoral response during the acute phase of the infection, reflected in the IgG, IgA, and IgM Ig-secreting cell numbers. At convalescence, 90% of the study group versus 46% of the placebo group had developed an IgA specific antibody-secreting cell response to rotavirus (p = 0.006). The results indicate that Lactobacillus GG promotes recovery from rotavirus diarrhea via augmentation of the local immune defense. Furthermore, specific IgA response to rotavirus is endorsed, which is possibly relevant in protection against reinfections.

Animals↗

Immediate and delayed hypersensitivity reactions to birch pollen in patients with atopic dermatitis.

We investigated immediate and delayed hypersensitivity to birch pollen in 10 patients with atopic dermatitis (AD) who had experienced a worsening of their eczema during the birch pollen season. The patients were prick- and patch-tested and antigen-induced basophil histamine release and lymphocyte proliferation were measured. 9/10 birch pollen-allergic patients proved positive in the histamine release test and the results correlated with specific IgE levels measured by RAST. Birch pollen antigen induced lymphocyte proliferation in 6/10 patients, but a positive patch test result was obtained in only one case. Both peripheral blood monocytes and purified epidermal Langerhans' cells were able to present birch pollen antigen to T cells, although Langerhans' s cells seemed to function less efficiently in this respect.

Allergens↗

Active immunity is seen as a reduction in the cell response to oral live vaccine.

Oral immunization elicits a response of antibody-secreting cells (ASC) in the peripheral blood; these cells are believed to originate in the mucosa and hence give information on the mucosal immune response. We have shown earlier that oral booster immunization is followed by an elevated ASC response reflecting an immunologic memory. In the present study we show that a booster dose of a live bacterial vaccine given at a time of active mucosal immunity elicits a low ASC response only. This is probably because the multiplication of the live vaccine is inhibited in the gut, resulting in a low actual dose of the antigen. This situation may be an example of the protective immunity manifested when an orally immunized person encounters the pathogen in nature, and could be used to assess the protective immunity.

Administration, Oral↗

Comparison of the human immune response to live oral, killed oral or killed parenteral Salmonella typhi TY21A vaccines.

The live oral typhoid vaccine Ty21a has proved to confer protection against the disease at least as effectively as killed parenteral vaccines, whereas killed oral vaccines have not been protective in field trials. This prompted us to compare the immune response of subjects vaccinated either with live oral, killed oral or killed parenteral Salmonella typhi Ty21a vaccine. The immune responses were studied by analysis of peripheral blood antibody-secreting cells (ASC), believed to reflect the mucosal immune response. Live and killed bacteria administered by the oral route elicited immune responses of similar specificity and Ig class profile (IgA dominating), but the response to the live vaccine was significantly stronger and lasted longer. The administration route, on the other hand, influenced the antigenic specificity of the ASC response suggesting different processing of the antigen by the systemic and local immune systems. Thus, the response after oral vaccination was almost exclusively directed to the surface O-antigen, whereas after parenteral vaccination an equally strong response was seen to the O-antigen, to lipopolysaccharide core and to flagella.

Administration, Oral↗

Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate.

The mean dietary selenium intake in Finland increased from 40 to 100 micrograms/d in 1987 because of the addition in 1985 of selenium to fertilizers. A selenium-supplementation study was performed in 1987 on the same men as were followed in a 1981 study that had a similar design (200 micrograms Se/d). Selenite and selenate, but not selenium yeast increased platelet glutathione peroxidase (GSHPx) activity by 30% compared with placebo, much less than the 70% found in the previous study. Selenium yeast and selenite increased plasma selenium after 11 wk from 1.39 mumol/L to peak values of 2.15 and 1.58 mumol/L, respectively. Only yeast selenium was incorporated into red cells. From a regression plot based on present and literature data, it was estimated that the plasma selenium concentration needed to achieve maximal platelet GSHPx activity was 1.25-1.45 mumol/L. At the present selenium intake in Finland, 100 micrograms/d, GSHPx activity is saturated in plasma and red cells and almost saturated in platelets.

Analysis of Variance↗

HLA-DR antigens and HLA-DQ beta chain polymorphism in susceptibility to rheumatoid arthritis.

Forty four patients with rheumatoid arthritis (RA) were studied for HLA-DR antigens and for HLA-DQ beta chain gene restriction fragment length polymorphism using DNA hybridisation. A significant increase in the prevalence of the DR4 antigen and a tendency towards an increase of DR1 was found in patients with RA. No allelic form of HLA-DQ restriction fragment length polymorphism patterns was increased, but the prevalence of an allele characterised by a combination of 7.5 and 3 kb fragments was decreased among patients with RA. The DQw8 subtype represented by a 12 kb fragment was the most common DR4 associated allele, and a 3.7 kb fragment related to DQw7 was found in only 5/25 (20%) DR4 positive patients and 2/12 (17%) controls. The results support the hypothesis that RA susceptibility factors are primarily located within HLA-DR genes but HLA-DQ genes may have a role in protection from the disease.

Arthritis, Rheumatoid↗

Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.

Adolescent↗

Local immune response measured in blood lymphocytes reflects the clinical reactivity of children with cow's milk allergy.

Study was made of immune responses in cow's milk allergy by a new immunoassay that measures total Ig-secreting cells and specific antibody-secreting cells during their maturation cycle in peripheral blood. These primed gut-associated lymphoid tissue-derived lymphocytes are assumed to reflect the intestinal immune responses. During diagnostic milk provocation, 15 patients had acute urticarial skin eruptions, eight patients had slow onset of eczema, and 15 showed symptoms from the gastrointestinal tract. A significant increase in IgM-secreting cells (means with 95% confidence intervals) from 382.2 (265, 552) to 621.4 (381, 1013)/10(6) cells, p less than 0.01, but not IgA- and IgG-secreting cells was associated with acute urticaria. In patients with eczematous skin eruptions and gastrointestinal symptoms, the response involved all these Ig isotypes. The magnitude of the postchallenge Ig-secreting cell responses in patients with gastrointestinal symptoms in the IgM class [from 657.9 (428, 1012) to 3544.0 (1696, 7406)/10(6) cells, p less than 0.001] and the IgA class [from 974.6 (590, 1610) to 2482.4 (1528, 4028)/10(6) cells, p = 0.001] significantly exceeded that of the patients with cutaneous symptoms. Notwithstanding the distinct increase in the total number of Ig-secreting cells, the specific antibody-secreting cell response specifically directed against beta-lactoglobulin and alpha-casein was small and inconsistent. These findings indicate that immune exclusion of milk antigens is defective in cow's milk allergy. The quality and extent of the response varied in the three reaction types, suggesting that different immunopathogenic mechanisms are operative in cow's milk allergy.

Animals↗

Antibodies against native type II collagen do not precede the clinical onset of rheumatoid arthritis.

Serum levels of IgG and IgM antibodies to native human type II collagen were determined in 22 pre-illness sera from subjects who developed seropositive rheumatoid arthritis (RA) 4 months to 5 years after sera were obtained, in 51 specimens from 35 healthy controls, and in 4-5 specimens from 58 patients with recent-onset RA. The antibody levels in all pre-illness serum specimens fell within the range seen for the healthy controls. Four RA patients had an IgG class antibody level and 4 had an IgM class antibody level that was above the highest level observed for controls, in at least 1 serum sample. No significant difference in the mean level of anticollagen antibodies was observed in the followup specimens from RA patients.

Adolescent↗

Immune response to acute diarrhea seen as circulating antibody-secreting cells.

We studied the immune response to acute diarrhea by examining antibody-secreting cells among peripheral blood lymphocytes, which are believed to be derived from the intestinal mucosa and to be on their way back there. In 23 of 24 patients, a dramatic increase in the total number of cells actively secreting immunoglobulins was detected one week after onset of diarrhea, and most of the cells were secreting IgA. Cells secreting antibody specific to the pathogen (Campylobacter jejuni or Salmonella spp.) also appeared at this time but accounted for only a part of the total response. The data suggest that diarrhea induces a vigorous, apparently polyclonal response, including antibodies to normal intestinal flora. The response to the infective agent was outstanding and suggests that this method can be used to identify the causative agent of an infection.

Acute Disease↗

Specific immunoglobulin-secreting human blood cells after peroral vaccination against Salmonella typhi.

Studies on intestinal immunity in animals have suggested that lymphocytes, after sensitization in Peyer's patches and maturation in regional lymph nodes, home via the circulation to the intestinal wall, where they secrete antibodies into the lumen. To detect such homing cells in the blood of human volunteers given oral, attenuated Salmonella typhi vaccine, we used the solid-phase enzyme-linked immunospot assay for S. typhi-specific antibody-secreting cells (ASCs). ASCs were found in eight of 10 individuals after the third postvaccination day, peaked in level on day 7, and were undetectable on day 14. Of the cells secreting specific immunoglobulin, approximately 62% produced IgA, 32% IgM, and 6% IgG. Antibodies could not be demonstrated in serum, saliva, or feces. This technique might give an opportunity to follow the response to antigens entering the body via mucous membranes. It will be of interest to correlate these findings with protection against diseases after peroral vaccination.

Administration, Oral↗

Suppressor factors generated from human mononuclear cells by means of purified myeloma proteins.

Peripheral blood mononuclear cells (PBMC) from normal human donors were cultured in Marbrook flasks in the presence of purified IgG or IgA myeloma proteins. The culture supernatants were tested for their ability to suppress pokeweed mitogen (PWM)- or Epstein-Barr virus (EBV)-driven Ig synthesis by normal PBMC. Two supernatants from PBMC cultured with IgG and one from PBMC cultured with IgA were tested and suppressed PWM-driven Ig synthesis as measured by a reverse haemolytic plaque assay and by quantitation of the Ig secreted into the culture medium of the PWM-driven cells. This suppression was not restricted to the Ig isotype of the 'inducing' myeloma protein, but was extended to IgG, IgA, and IgM. The suppressive effect could be absorbed out with human IgG.

Antibody Formation↗

Bacteria are polyclonal T-dependent stimulants of immunoglobulin formation.

Various gram-positive and gram-negative bacteria were tested for their ability to induce antibody secretion in human blood cell cultures. Total and specific immunoglobulin levels in the culture supernatants were quantitated with enzyme-linked immunosorbent assays (ELISA). All the twelve strains used stimulated IgM and IgG secretion in adult mononuclear cell cultures. With the four strains tested, also umbilical cord blood cells produced IgM. Specific antibodies directed against two bacteria were sought in adult and newborn cell culture but none were found. Bacterium-induced antibody synthesis thus seemed to be polyclonal. Experiments with purified T and B lymphocytes showed that bacterium-driven antibody formation was T-cell dependent.

Antibodies, Bacterial↗

Effect of elevated temperature on human immunoglobulin synthesis, lymphokine production and lymphocyte proliferation in vitro.

Fever in infections is mediated by endogenous pyrogen, a protein inseparable from interleukin 1 (IL-1). It remains unclear what the role of fever in host defence is. We studied the effect of elevated temperature on mitogen-induced human lymphocyte stimulation in vitro. Lymphocyte proliferation, elaboration of leukocyte migration inhibiting factor (LIF) and immunoglobulin production were measured at normal and elevated temperatures. Pokeweed mitogen-(PWM) driven responses were quantitated with a plaque-forming cell assay and by measuring secreted immunoglobulins in culture medium. The responses at 38, 39 or 40 degrees C were, if anything, lower than those at 37 degrees C. The production of LIF after stimulation with PWM was not augmented at elevated temperatures. In contrast, the proliferative responses to PWM, phytohaemagglutinin (PHA) and concanavalin A (ConA) were increased at 38 degrees C. These results indicated that elevated temperature has diverse effects on mitogen-induced lymphocyte functions in vitro.

Cells, Cultured↗

The effect of phenytoin in vitro on normal human mononuclear cells and on human lymphoblastoid B cell lines of different Ig isotype specificities.

The anticonvulsant drug phenytoin, in less than cytotoxic concentrations, caused significant reductions in Ig secretion by unstimulated or EBV-stimulated normal MNC, as measured by PFC or secretion of Ig into the culture medium. Isotype-specific LBL varied in their sensitivity, the secretion of IgA (1 line) and IgG (3 lines) being reduced by phenytoin near therapeutic concentrations, whereas that of IgM (1 line) was resistant. Six-day exposure of MNC to phenytoin caused no selective depletion of or enrichment for B cells, monocytes or T cell subsets. The results suggest that the reduction in serum Ig levels reported in phenytoin-treated epileptic patients is, at least in part, due to a direct effect of the drug on the B lymphocyte. However, among EBV-activated normal MNC, those secreting IgA were no more sensitive to the drug than those secreting IgG or IgM, and other factors may, therefore, operate to cause the preferential reduction in serum IgA in phenytoin-treated patients.

Antibody-Producing Cells↗