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[Acute-phase reaction after inflammatory aggression. Experimental study].

It is well known that inflammatory aggression makes important changes in plasma proteins levels. Among all of these proteins, C3 fragment of the complement system and haptoglobin, Acute Phase Reactants Proteins, are considered important mediators of the inflammatory response although their specific behaviour is not completely understood. In this work we have studied the modification of both proteins after an inflammatory aggression, which was experimentally induced in rats, trying to connect their behaviour with the lesion stages. Our data show that the plasmatic level of both proteins is increased during the inflammatory aggression, although haptoglobin level gives a more accurate approach to the local phenomenons which occur in the inflammatory focus. This fact suggests that each acute phase reactant has a certain specificity depending on the kind of aggression suffered by a patient.

Acute-Phase Reaction↗

Clinical applications of crossed immunoelectrophoresis to the study of complement activation.

The purpose of our study was to set up a reliable method for the measurement of complement activation by adapting the method of crossed immunoelectrophoresis. We utilised anti C3 antiserum and barbitone buffer, containing sufficient EDTA to prevent in vitro activation of complement. We studied 44 patients undergoing open heart surgery, with cardiopulmonary bypass (CPB) by the analysis of plasma samples taken during the operation, and also samples of plasma and dialysate effluent from patients with end stage renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD). Measurements were also carried out on stored blood, aged serum and serum treated with varying doses of lipopolysaccharide (LPS). Complement activation occurs in 95% of patients during CPB with levels ranging from less than 4.5% to 11.3% of total C3, but there was no detectable activation in any pre-bypass sample. Negligible complement activation occurs in the plasma of CAPD patients, but the dialysate effluent gave results from undetectable levels to 31.7%, in the absence of clinical peritonitis. Variable in vitro complement activation occurs in aged serum, but it was not detectable in stored blood. Serum treated with LPS showed levels of activation directly proportional to the dose of LPS and measurable at a level of 0.1 microgram/ml of serum. The method had a coefficient of variation of 4.5%, and provides a reliable way of measuring complement activation in clinical situations such as cardiopulmonary bypass and peritoneal dialysis.

Cardiopulmonary Bypass↗

Increased serum IgE antibodies in institutionalized asthmatic children after a transient return home. The role of house dust mite allergens in the home as a trigger of asthmatic attacks in mite-sensitive patients.

Increased serum IgE antibodies to Dermatophagoides pteronyssinus, a house dust mite, were observed in 12 of 13 institutionalized mite-sensitive asthmatic children after returning for four days to their own homes. These results implicate the house dust mite as a trigger of asthmatic attacks in these patients.

Adolescent↗

Restriction of immunoglobulin heterogeneity, autoimmunity and serum protein levels in aged people.

Ninety-one sera of persons above 80 years of age were screened for autoantibody activity against lipoproteins (anti-LDL 7, anti-HDL 6 positive), for rheumatoid factor activity (Latex 14, Waaler-Rose 7 positive) and for antinuclear factors (11 positive). Among the sera with autoantibody activity 29 percent showed deviations of the normal kappa/lambda ratio of immunoglobulins, as opposed to 22 percent of the sera without detected autoantibody activity. In 3 percent of the sera an M component was detected. Determination of the alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, haemopexin, complement component C3c and C4, IgG, IgA and IgM levels showed significant increases in alpha-, and beta-globulins as well as in IgG and IgA in sera of the aged persons as compared to a normal population between 20 and 60 years old. No significant difference was noted between the gamma-globulin concentration in sera of aged persons with or without autoantibody activity. The evaluation of the relationship between serum protein levels and alterations of the kappa/lambda ratio indicated that the alpha- and the beta-globulins were significantly raised in sera with altered kappa/lambda ratios, whereas, with the exception of M component containing sera the gamma-globulin levels seemed not significantly affected by changes in this ratio.

Aged↗

Chemotactic factor generation by asbestos. Fibre type differences and the effects of leaching.

The generation of chemotactic factors in normal human serum by treatment with chrysotile and crocidolite asbestos was investigated using the Boyden chamber method. Both types of asbestos produced chemotactic activity but not to the same extent. The two fibre types also produced different levels of complement activation as measured by C3 conversion using two dimensional immunoelectrophoresis. While there was a simple correlation between fibre concentration and C3 conversion the production of chemotactic activity declined at high doses of chrysotile. Phosphate buffer treatment reduced the differences between fibre types. The possible role of these phenomena in asbestos-associated disease is discussed.

Asbestos↗

[Facial eosinophilic granuloma].

We report on a patient with the diagnosis granuloma eosinophilicum faciale (GEF). Clinical and histological findings are described with special emphasis on immunhistological characteristics in lesional skin. A review on the literature is given.

Adult↗

Autoimmune phenomena in infertile patients with endometriosis.

To assess the presence of autoimmune factors in patients with endometriosis, endometrial homogenates, peritoneal fluid, and serum were evaluated in 23 patients with endometriosis and 22 control subjects. The methods used were Ouchterlony immunodiffusion, immunoelectrophoresis, polyacrylamide gel electrophoresis, and radial immunodiffusion. The study demonstrated precipitation lines between endometrial homogenates and serum from some endometriosis patients but not from the control subjects. Immunoelectrophoresis demonstrated precipitation lines at beta-globulin position when endometrial homogenates were used against serum of patients with endometriosis and with goat antihuman serum. It is suggested that an antigen, possibly a glycoprotein, is present in the endometrial homogenates. Radial immunodiffusion studies for immunoglobulins (Ig) G, A, and M and complement components C3c and C4 showed significantly higher concentrations of C3c and C4 in serum and peritoneal fluid of patients with endometriosis than the control subjects (P less than .05). There was no significant difference in concentration of IgG, A, M, factor B, and properdin.

Adolescent↗

Association of rheumatoid factor with complement activation in rheumatoid arthritis and other diseases.

Rheumatoid factor (RF) is a complement activating autoantibody. In rheumatoid arthritis (RA) the rate of catabolism of complement is closely related to the titre of RF. Therefore, we have examined whether these relationships are unique to RA or will be found in non-RA disorders in which RF may be found in the circulation. We studied patients with subacute bacterial endocarditis, leprosy, tuberculosis, and a variety of other rheumatic and vasculitic disorders. We found that in all the disorders examined the RF had a complement activating potential which was equivalent to that of the RF of RA patients. Furthermore in vivo activation of complement, as exhibited by the appearance of C3 degradation products, was significantly related to higher titres of haemolytically active RF in non-RA as well as the RA group. In these respects, therefore, the RF in RA and non-RA patients is indistinguishable. A possible survival value for RF is discussed.

Adolescent↗

Humoral and cellular immunity in extrinsic pulmonary granulomatoses.

In the present study the AA. analyse the immunological behaviour of patients taken from a group of 309 cases of Extrinsic Pulmonary Granulomatoses (E.P.G.). Humoral immunological changes were studied by assessing serum immunoglobulins, various complement fractions and, when possible, circulating precipitating antibodies. Immunoglobulins A and G values were significantly higher than control values. On the contrary there was no significant difference between IgM values, in patients and controls. The complement fractions (C3c, C4 and C3 activator) showed values within normal limits. Specific circulating antibodies were detected both in bird fanciers and in cork workers. Cellular immunity was evaluated by comparing the results of various tests. Eighty percent of all cases of E.P.G. had negative tuberculin tests, while eighty percent of the general population, in Portugal, has positive tuberculin tests. The Kveim-Siltzbach test was positive in one of 19 cases of E.P.G., and this was considered a false positive result. In vitro lymphocyte blastic transformation in presence of pigeon antigen showed a significant increase in pigeon breeders as compared with controls. The migration of leucocytes from affected and non-affected corkworkers, affected and non-affected pigeon fanciers and controls, in the presence of the specific antigens, showed significant results. Finally, similarities and differences in immunological behaviour of these patients are discussed.

Antibody Formation↗

[Mechanisms and implications of the adhesion phenomenon in Aspergillus fumigatus].

During the last few years, several works have demonstrated the fixation of different host proteins on Aspergillus fumigatus conidia. Thus, after incubation in the presence of normal human plasma, the C3 component of complement is detected at the surface of conidia. In fact, most of the C3 deposited on conidia is converted in C3b or iC3b which would facilitate their phagocytosis by the macrophages. In the non immune host, the activation of the alternative pathway seems to be the main mechanism of the activation of the complement system by the conidia, but the participation of the classical pathway initiated by the fixation of the C-reactive protein has also been suggested. Aspergillus fumigatus conidia interact also with fibrinogen and laminin. These interactions which are mediated by the D domains of fibrinogen and by the fragment P1 of laminin, are specific. The number of fibrinogen binding sites at the surface of conidia has been calculated to be 1200 by cell, and the dissociation constant 2.2 x 10(-7) M. These interactions could determine the adhesion of conidia to the host tissues as suggested by adherence assays of conidia to proteins immobilized onto wells of microtiter plates. Conidia would bind to the fibrin deposits formed on damaged epithelia in response to the inflammatory reaction, or directly to laminin of the subepithelial basement membrane. Finally, different experiments suggested the identity of the binding sites for C3, fibrinogen and laminin at the surface of A. fumigatus conidia.

Aspergillus fumigatus↗

The time courses of intracellular transport of some secretory proteins of rat liver are not affected by an induced acute phase response.

To study the effects of changed synthesis on intracellular transport of secretory proteins, an acute phase response was induced in rats. The synthesis and secretion of haptoglobin, complement C3, transferrin and albumin were then investigated by pulse labeling with [3H]leucine. Maximal increase in the syntheses of the positive acute phase proteins was observed after 24 h, amounting to an increase of nine, three and twofold for haptoglobin, C3 and transferrin, respectively. The synthesis of albumin decreased to a minimum after 48 h, reaching approximately one fourth of normal synthesis. The time courses for transit through rough endoplasmic reticulum and for secretion were determined after 36 h, and were found to be roughly unchanged for all four proteins despite the different changes in synthesis. The fraction of haptoglobin associated with the microsomal membrane was reduced during the acute phase response, but there was no significant change in membrane association as a function of time after labeling with [3H]leucine. It is concluded that the altered protein synthesis during an acute phase response in vivo has little effect on the time course of secretion of the proteins studied. Furthermore, the basal mechanisms for intracellular transport appear relatively unchanged during this condition.

Acute-Phase Reaction↗

Some immunological aspects on human Schistosoma mansoni infection in Egypt.

Human Schistosomiasis mansoni is a chronic disease, which ranges from subclinical infection to huge hepatosplenomegaly. Reducing the risk of infection remains the aim of many control measures. So the present study was designed to evaluate the interaction between S. mansoni infection and immunological system of the host. The study included 3 groups of 50 adult males each. The first group was control group, the second group was early S. mansoni infection and third group was advanced schistosomiasis with hepatosplenomegaly. The results showed some changes in both humoral and cellular immune response during the course of infection.

Adolescent↗

[The effects of occupational exposure to nitrogen dioxide (NO2) on the immunological parameters in workers].

The study of T-cell subpopulation: T CD3+, T CD4+, T CD8+; NK CD16+ and B CD19+ cells as well as of serum concentrations of immunoglobulins G, A, M, E, complement components C3c and C4, total circulating immune complexes (CIC), CRP, haptoglobin, ceruloplasmin and transferin, was carried out in 16 males, smokers and non-smokers. The control group of smokers and non-smokers comprised 36 males not exposed to any chemical compound. The study was performed also in two groups of non-smokers: 5 workers occupationally exposed and 7 non-exposed controls. For the determination of T-cells, NK- and B CD19+ cells populations monoclonal antibodies were used in indirect immunofluorescence tests. Passive sampling spectrophotometric method was employed to determine NO2 and NO concentrations in the work environment air. Their mean values were 0.0867 +/- 0,0585 mg x m-3 (from 0.0165 to 0.1960) and 0.0614 +/- 0.0263 mg x m-3 (from 0.0220 to 0.1090), respectively. The number of total leucocytes and lymphocytes in the group of 16 smokers and non-smokers exposed to NO2 and NO was increased. Stimulation T-cells line in the men exposed to NO2 and NO was evidenced by an increased number of T CD3+ cells, about two-fold increase in absolute number of T CD4+ cells (p < 0.001), an increased number of T CD8+ cells (p < 0.001) and by an enhanced value (by 24.7%) of the T CD4+/T CD8+ ratio. In the group of 16 persons exposed to NO2 and NO serum IgG concentration was elevated (p < 0.01), C3c C4 decreased (p < 0.001), and serum CIC enhanced by about two times (p < 0.001). Stimulation T-cells line in the groups of 5 non-smoking workers exposed to NO2 and NO was evidenced by an increased number of T CD3+ (p < 0.05), T CD4+ (p < 0.05) and T CD8+ cells but without any change in the value of the T CD4+/T CD8+ ratio. In addition, decreased serum C3c and C4 levels together with serum CIC elevated by 76.7% (p < 0.05) were evidenced in this group on non-smokers. Moreover, significant positive correlations between NO2 concentrations in the air and the numbers of total lymphocytes, T CD3+, TCD4+, T CD8+ cells or IgG: (magnitude of r in the range between 0.31 and 0.71), as well as significant negative correlations between NO2 concentrations in the air and C3c (r = 0.44) in the group of 16 smoking and non-smoking workers were calculated. In this group significant positive correlation between NO concentrations in the air of the workplace and counts of T CD3+, T CD8+, B CD19+ (magnitude of r in the range between 0.51 and 0.63), haptoglobin and ceruloplasmin (magnitude of r from 0.37 to 0.58), as well as significant negative correlation between NO concentrations in the air and serum levels of IgG, IgA and IgM (magnitude of r from -0.67 to -0.47) and CIC (magnitude of r = -0.39) were also observed. In the group of 5 exposed non-smoking workers, the values of correlation coefficients magnitude of r between NO2 and NO concentrations in the work environment air and immunological parameters were similar to those in the whole group. The results obtained suggest that during occupational exposure NO2 may play a more important role mainly in the process of inflammation but exogenous NO seems to act as modulating factor of this proinflammatory NO2 effect through a greater and exposure-dependent influence mainly on B CD19+ cells and other parameters of humoral immunity.

Adult↗

Activation and fragmentation of the third (C3) and the fourth (C4) components of complement: generation and isolation of physiologically relevant fragments C3c and C4c.

The degree of the activation and fragmentation of C4 and C3, including chain structure of the activation products, was evaluated by SDS-PAGE analysis of the C4 or C3 antigens that were withdrawn from the reaction media with appropriate immunoadsorbent beads. Full activation of C4 and C3, and subsequent quantitative conversion of C4b into C4c, and C3b into iC3b took place in fresh NHS after the activation of complement with both aggIgG and CVF. For complete conversion of iC3b to C3c erythrocytes carrying the C3b receptor were added to the already activated serum. Both C4c and C3c were isolated by a 2-step procedure involving (i) an adsorption to and (ii) electrophoretic desorption from the respective immunoadsorbent beads.

Complement Activation↗