Subacute (de Quervain's) thyroiditis: association with HLA-Bw35 antigen and abnormalities of the complement system, immunoglobulins and other serum proteins.

The HLA antigens in 40 patients with subacute thyroiditis were investigated. An association between subacute thyroiditis and HLA-Bw35 antigen as previously reported, was confirmed. Further immunological observations included a decrease in Serum Clq, C4 and C3 activator levels; conversely, there was an increase in serum C3, IgM, alpha1-acid glycoprotein and alpha1-antitrypsin levels. Serum IgA levels were decreased in those patients who were Bw35 negative, but were normal in the patients who were Bw-35 positive, with serum alpha2-macroglobulin levels the opposite was found. These studies support the view that a genetic factor(s), viz., the major histocompatibility system, plays a role in the pathogenesis of subacute thyroiditis. A "nosological clustering" around the Bw35 antigen as a marker for viral susceptibility is suggested.

Quantification of proliferative and suppressive responses of human T lymphocytes following ConA stimulation.

The mitogenic response of human T lymphocytes to graded doses of concanavalin A (ConA) has been measured by means of an MTT tetrazolium dye metabolic assay. Three groups of healthy subjects, representing children, younger adults and elderly persons, were investigated. It was shown that a typical bell-shaped course of the ConA dose-response curve is the result of a proliferative response to suboptimal concentrations of ConA and a toxic action of ConA at supraoptimal concentrations. The ascending part of the response curve reflects in its shape the regulatory interaction of responding cells. A decrease in suppressive functions is accompanied by a shift of this part of the curve to lower concentrations of ConA. By means of a mathematical model derived from enzyme kinetics, an attempt was made to quantify the suppressive functions from the course of the individual dose-response curve. It was found that after suitable data processing, suppression-related shape changes can be assigned to a single parameter. The value of this parameter as a diagnostic tool was tested in a study of the age dependence of human T lymphocyte responses to ConA. While the proliferative response decreased with age, the suppressive functions exhibited their maximum effect in the group of adults. Thus it could be demonstrated that ConA induced proliferative and suppressive responses are due to two different pathways which can be independently extracted from the dose-response curve.

A standard microcytotoxicity technique for quantitative analysis of lymphocyte subsets. A comparison with indirect immunofluorescence, evaluated by microscopy or flow cytometry.

A standard complement-dependent microcytotoxicity (CDC) technique was used for quantitative analysis of T-lymphocyte subsets in human peripheral blood and the results compared to those obtained by indirect immunofluorescence microscopy and flow cytometry. The monoclonal antibodies OKT3, OKT4 and OKT8 were used in the CDC method for detection of total-T cells, T-helper and T-suppressor cells respectively. The CDC technique provided reproducible results (CV, 3-7%) correlating well with both immunofluorescence techniques. This observation was valid both for healthy persons (n = 21) and for patients (n = 10) with immunological disorders. The correct antibody dilution, correction for background and the use of eosin staining are considered critical for the usefulness of this technique. The method has several advantages: it is widely used for histocompatibility testing, only simple equipment is necessary, and the amount of monoclonal antibody required per test is small.

Family study of natural killer cell activity in C1q-deficient patients with systemic lupus erythematosus-like syndrome: association between impaired natural killer cell function and C1q deficiency.

Impaired natural killer (NK) cell activity has been found in patients with systemic lupus erythematosus (SLE)-like syndrome. The mechanism by which NK cell function is impaired in SLE patients is not quite clear. We report here a family study of NK cell activity in C1q-deficient patients with SLE-like syndrome. In both SLE-active and SLE-inactive stages of the disease, NK cell function was significantly impaired when compared with the healthy controls (10.6 +/- 2.3% and 16.9 +/- 4.8% to 34.7 +/- 9.6%, p less than 0.025). On the other hand, differences in NK cell cytotoxicity between SLE-active and SLE-inactive members of the family were not statistically relevant (p less than 0.1). Further, we found no correlation between NK cell activity and clinical or laboratory values, except for a positive correlation between function of NK cells and C1q and CH50 values, respectively (rs = 0.93, 0.01 less than p less than 0.02). To our knowledge, this is the first report on a notable association between impaired NK cell activity and C1q deficiency. The type of inheritance of C1q deficiency in this family is also discussed.

Vaginal leukocyte characteristics in urogenital trichomoniasis.

Morphological and functional characteristics of vaginal exudate leukocytes were examined in 47 patients with urogenital trichomoniasis. Electron microscopic morphology, viability, phagocytosis of Candida albicans blastospores and ability to undergo respiratory burst in the iodonitrotetrazolium reductase test were evaluated in these cells. Vaginal inflammatory leukocytes were almost exclusively polymorphonuclear neutrophils, and their concentration was positively correlated (r = 0.58; p less than 0.001) with the number of trichomonads in the exudate. Median leukocyte viability reached 39% and both phagocytic and tetrazolium reductase activities of these cells were significantly reduced in comparison with those of circulating polymorphonuclear leukocytes. Patients with a clinical picture of severe mucosal inflammation had significantly higher vaginal exudate leukocyte concentrations and viability than those without inflammatory signs. The possible role of vaginal leukocytes in the pathogenesis of urogenital trichomoniasis is discussed.

The HLA class II antigens determined by cellular techniques. A review.

The D region of the HLA system is very complex. Three loci, HLA-DR, DQ and DP, are now very well established. However, the question of the independence of the first known locus of this region remains elusive--it is not yet known if HLA-D antigens are really independent or if they represent some epitopes on the molecules of HLA-DR/DQ antigens. The HLA-DP antigens represent an independent series in the HLA system recognized by the PLT technique. On the other hand, the HLA-PL antigens also detected by PLT correlate with both HLA-D and HLA-DR antigens, and it seems that they do not constitute an independent group of HLA antigens.

Genetic determination of phagocytic activity of polymorphonuclear leucocytes.

Sixty-three persons with the known HLA-A, -B, -C, -DR and -Dw antigens were investigated for phagocytic ability, candidacidal activity, respiratory burst values, and the levels of circulating immune complexes, C2, C4, IgG, IgM, and IgA. The investigated persons were divided into the HLA-DR2/Dw2, the HLA-DR3/Dw3 and a control group, members of which possessed neither antigen in question. The phagocytic activity of polymorphonuclear leucocytes ingesting dead cells of C. albicans and the candidacidal activity were found to be significantly lower (P less than 0.02) in the HLA-DR3/Dw3 compared to the control group. The respiratory burst values did not considerably differ in all three groups under study. The levels of circulating immune complexes were higher in both the HLA-DR2/Dw2 and HLA-DR3/Dw3 in comparison with the control group.

HLA-D/DR identity results in a positive CML reaction.

Investigating HLA-A, HLA-B, HLA-C, and HLA-DR antigens, MLR, CML, and PLT reactivity in two unrelated persons it was found that despite their HLA-D/DR identity cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the necessary proliferative impetus for the generation of CTL.

Modulatory effect of glucans on the functional and biochemical activities of guinea-pig macrophages.

The particulate and soluble glucan preparations isolated from Saccharomyces cerevisiae and Candida albicans affected various activities of guinea-pig macrophages. The stimulation of INT reduction and superoxide production were observed in the presence of all insoluble and some soluble glucans in vitro, but most of the preparations under study had an inhibitory effect on phagocytic activity. On the other hand, the stimulation of both metabolic and functional activities was obtained in vivo. Macrophages from guinea-pigs treated with glucans exerted an increased ability to reduce INT and to produce superoxide. Their candidacidal capacity was rapidly elevated, and peritoneal macrophages had raised phagocytic activity as well. A more pronounced stimulatory effect was observed in the presence of insoluble rather than soluble glucans, and this was more expressive in vitro than in vivo.

Effect of cyclophosphamide on the candidacidal activity of rabbit peritoneal macrophages.

Single and repeated intravenous administration of cyclophosphamide significantly decreased the candidacidal activity of rabbit peritoneal macrophages. Using higher doses of the drug, a more pronounced decrease, persisting up to 10 d, was observed. The phagocytic index has not changed significantly 10 d after cyclophosphamide injection as compared with controls. No changes in the phagocytic activity were recorded. The decreased candidacidal activity may be one of the causes of serious microbial infections in cyclophosphamide-treated patients.

Lysosomal enzyme activities in polymorphonuclear leukocytes, macrophages, serum, and spleen of conventional, germ-free, and antigen-free Minnesota miniature swine.

The activities of lysozyme, myeloperoxidase, and elastase were lower in PMNs and AMs from GF and AF Minnesota miniature piglets than in the leukocytes from their CONV counterparts. In the spleen and serum of gnotobiotic piglets only the levels of lysozyme were slightly reduced. Substantially depressed activities of these LEs were found also in PMNs from precolostral piglets in comparison with PMNs from their CONV mother. The bisassociation of GF piglets with Enterococcus liquefaciens and Escherichia coli caused an increase of LE activities in their AMs, spleens, and sera. Fewer LEs were released after phygocytic stimulation with zymosan from PMNs of GF, AF, and precolostral piglets than from PMNs of CONV animals of the same age. These data suggest that the antigenic-microbial stimulation is important for the development of normal lysosomal enzyme activities in PMNs and AMs from gnotobiotic animals.

Effect of Coxiella burnetii on the stimulation of hexose monophosphate shunt and on superoxide anion production in human polymorphonuclear leukocytes.

Killed Coxiella burnetii (C.b.) cells in phase II but not in phase I had a mild stimulatory effect on hexose monophosphate shunt (HMPS) and superoxide anion production by human polymorphonuclear (PMN) leukocytes. Preincubation of C.b. cells of either phase with serum of a leukocyte donor lacking detectable antibodies to C.b. did not affect the studied activities of PMN leukocytes. In contrast, both HMPS stimulation and superoxide production were enhanced by specific opsonization of C.b. cells with rabbit immune sera containing corresponding phase I and/or phase II antibodies. Stimulatory effect was observed also with lipopolysaccharide-protein-phospholipid (LPS-Pr-Pl) complex but not with lipopolysaccharide-protein (LPS-Pr) complex and with purified lipopolysaccharide (LPS) isolated from phase I C.b. cells. Possible consequences of these findings for explanation of C.b. resistance to intracellular killing by professional phagocytes are discussed.

[Inflammation, immunity and surgery]. / Zápal, imunita a chirurgia.

The activation of endothelial and phagocytic cells, with concomitant formation of a range of adhesive molecules and inflammatory mediators, are integral parts of the host response to injurious agents (trauma, infection, altered antigens, toxins, chemicals etc.). The excessive mediator responses are associated with increased morbidity and lethality. Cytokines, soluble mediators secreted by cells, play an integral role in the metabolic and immune responses to the injurious agents. Widespread tissue damage, when associated with fulminant sepsis may induce massive release of cytokines (TNF, IL-1, IL-6), triggering certain steps of reactions involving multiple organs and culminating in the systemic inflammatory response syndrome, sepsis syndrome or multiple organ failure syndrome. (Fig. 2, Ref. 21.)

[Trichomonas in girls during the period of hormonal inactivity]. / Trichomoniáza dievcat v období hormonálneho pokoja.

Trichomoniasis occurs also in childhood in the period of hormonal inactivity, though its rate is not so high as in women of childbearing age and full sexual activity. In our series of children in the period of sexual inactivity, established by functional cytology, trichomoniasis was diagnosed in 3.8% of the total number of 1,562 children. Preparations of imidazol proved to be fully effective in the treatment of trichomoniasis in girls. In diagnosis the semisolid Szenes's culture medium in Valent's modification was used to advantage. Its standard use provides a basic precondition for good recovery of the protozoon. Trichomoniasis as such does not present so serious a problem as do the consequences of the unrecognized and untreated disease when the proliferated secondary flora potentiates the severity of the infection. This condition may lead to salpingitis and peritonitis causing sterility, and it may also spread into the uropoietic system.

[Antiphagocytic activity of sera treated with organic solvents (chloroform, ether)]. / Antifagocytárna aktivita sér opracovaných organickými rozpúst'adlami (chloroform, éter).

The opsonization of C. albicans by means of sera treated with chloroform and ethyl ether resulted in significantly decreased values of PMN leucocyte phagocytic activity. In contrast to ethyl ether treated sera (decrease of phagocytic activity about 45%), chloroform processed sera possessed increased antiphagocytic activity (decrease of phagocytic activity about 63%). Significant changes were observed in the candidacidal capacity to C. albicans (decrease about 50%) and in the capacity of NBT (INT) reduction measured spectrophotometrically (decrease about 66% in chloroform treated sera and about 42% in ethyl ether treated sera). (Fig. 1, Ref. 22.)

[Antiphagocytic activity of human amniotic fluid]. / Antifagocytárna aktivita l'udskej plodovej vody.

The preincubation of PMN leukocytes in amniotic fluid obtained at the end of the gestation period resulted in decreased values of phagocytic activity (about 37%), phagocytic index (about 21.5%) and mainly of the candidacidal capacity to C. albicans (about 72%). The level of lysozyme (11.8 +/- 7.2 mg.l-1) and the level of alpha 1-antitrypsin (0.745 +/- 0.53 g.l-1) were also determined in amniotic fluid. The level of alpha 2-macroglobulin and the proteolytic activity at acidic and mildly alkaline pH could not be established by the methods applied. (Fig. 1, Ref. 23.)

[The development of cytotoxic T lymphocytes in HLA-D/DR identity]. / Vznik cytotoxických lymfocytov T pri identite HLA-D/DR.

The development of cytotoxic T-lymphocytes is controlled by genes of the HLA complex and occurs, in the majority of cases, when the responding and stimulating subjects differ both in HLA-A, -B and HLA-D/DR antigens. We examined a married couple for kidney transplantation and found that they differed in HLA-A, -B antigens and were identical in HLA-DR antigens. The negative results of the MLC test confirmed the serological findings. Nevertheless, cytotoxic T-lymphocytes developed despite HLA-D/DR identity. The presented case is one of the few published exceptions to the rule governing the development of cytotoxic T-lymphocytes.