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PubMed1978

Atopic dermatitis, impaired cellular immunity, and molluscum contagiosum.

A substantial elevation in the level of serum IgE (7,000 to 19,000 ng/ml) was noted in a man with atopic dermatitis and chronic molluscum contagiosum. Cell-mediated immunity (CMI) was depressed in vivo (cutaneous anergy), whereas in vitro tests showed normal numbers of "T" rosette-forming lymphocytes, a normal phytohemagglutinin-P-elicited lymphocyte transformation response, and lymphocyte transformation reactivity to the antigens streptokinase-streptodornase and purified protein derivative. Accumulated evidence suggests that patients with atopic dermatitis may have, associated with an elevated serum IgE level, a functional defect(s) in CMI that is greater in vivo than in vitro. This functional defect may impair host defense and account for the chronic molluscum contagiosum infection present in this patient.

Adult↗

PubMed1983

Differentiation-associated alteration in human monocyte-macrophage accessory cell function.

Human monocyte (Mo) to macrophage (Mx) differentiation is associated with marked and well studied changes in morphology, biochemical parameters, and effector cell function. Nevertheless, the comparative accessory cell (AC) function of blood Mo and differentiated Mx has not been carefully studied. We, therefore, examined the kinetics and mechanisms of change in AC function during in vitro Mo to Mx differentiation. The system utilized has two distinctive features: blood Mo and resultant cultured Mx represent a cohort of cells derived from the bone marrow within a 12-hr period. Moreover, the in vitro derived Mx utilized herein have been characterized extensively and are functionally and biochemically similar to pulmonary macrophages (PMx). In the experiments reported, AC functions of blood Mo, Mx derived from Mo after 1 to 6 days of culture, and PMx was compared. AC were cultured with nylon wool column-purified autologous T cells and were stimulated with concanavalin A (Con A) or streptokinase-streptodornase (SKSD). Blood T cell proliferation to Con A or SKSD was inhibited greater than 90% by the removal of Mo and was reconstituted by 20% Mo. Mx derived from Mo by culture for 1 to 3 days exhibited the same (or better) AC function as Mo when T cells were stimulated with either SKSD or Con A. In marked contrast, Mx derived from 6-day cultures exhibited less than or equal to 15% of Mo (i.e., control) capacity to support T cell proliferative response to SKSD. Six-day Mx support T cell proliferation to Con A was somewhat variable. Similar to 6-day cultured Mx, PMx failed to function as AC. The mechanism of loss of AC function was examined: a) cultured Mx maintained Ia antigen positivity for greater than 8 days; b) mixing experiments with Mo + 6-day cultured Mx or Mo + PMx demonstrated no T cell suppression; c) the normal capacity of most 6-day cultured Mx to support Con A but not SKSD induced T cell proliferation, apparently ruled out the loss of the ability to deliver a nonspecific "second signal" as the involved mechanism; d) inhibition of Mo to Mx differentiation by dexamethasone preserved AC activity. Thus, human culture-derived Mx and PMx exhibit deficit AC function through loss of an undefined mechanism. However, loss of AC antigen processing or presentation may occur.

5'-Nucleotidase↗

PubMed1983

Coccidioidomycosis: early immunologic findings.

T and B lymphocyte number and lymphocyte response to phytohemagglutinin, pokeweed mitogen, concanavalin A, coccidioidin and streptokinase-streptodornase (SKSD), plus monocyte ingestion of coccidioidin- and IgG-coated chicken erythrocytes were measured in 5 patients with coccidioidal meningitis, 11 with nonmeningeal extrapulmonary cocidioidomycosis and 5 with localized pulmonary infections. These cases were evaluated within six months of the onset of infection. Lymphocytic responses to phytohemagglutinin, pokeweed mitogen, concanavalin A, SKSD and coccidioidin and monocytic ingestion of coccidioidin- and IgG-coated chicken erythrocytes were severely decreased in patients with meningeal and nonmeningeal, extrapulmonary coccidioidomycosis but not in patients with localized pulmonary infections. T and B cell numbers, however, were normal in all groups. Thus, defects in cellular immunity are involved in the pathogenesis of extrapulmonary coccidioidomycosis and measurements of lymphocytic and monocytic function may identify patients prone to extrapulmonary infection.

Adult↗

PubMed1983

Immunosuppression in Kenyan visceral leishmaniasis.

Cell-mediated immune responses were evaluated in 15 patients with active visceral leishmaniasis from Masinga location in eastern Kenya where the disease is endemic. Age and sex matched controls were selected from a village school in the same area. In vivo studies were carried out by skin testing with leishmanin, tuberculin, streptococcal and candida antigens. Lymphocyte blastogenic transformation to the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) and the antigens purified protein derivative (PPD), streptokinase-streptodornase (SKSD) and leishmanial antigen (LA) was studied in vitro. The results showed that immunosuppression in visceral leishmaniasis in Kenya was both specific and non-specific. In the majority of patients there was complete anergy to all antigens in vivo and in vitro. The suppression of responses to mitogens was less marked. Recovery of non-specific responses preceded the development of specific immunity. In a small number of patients (23%) immune unresponsiveness to leishmanial antigens persisted 1 year after parasitological cure.

Adolescent↗

PubMed1983

Delayed hypersensitivity skin testing: response rates in a surgical population.

The results of this study indicate that skin test responses should be measured at both 24 and 48 hours post-injection and considered reactive or positive if induration of greater than or equal to 5 mm. is noted at either time. The practice of measuring responses at 48 hours only is neither appropriate nor recommended as it may produce a large percentage of false negative results. Erythema without induration was noted in a small percentage of patients. Future studies should evaluate the efficacy of erythema greater than or equal to 15 mm. in the absence of induration as a reactive response to mumps antigen. The validity of data interpretation must ultimately be based on correlations with morbidity and mortality. Streptokinase-streptodornase, mumps, and trichophyton were the three antigens with highest response rates, and this battery detected 94% of the reactive or positive responses to the five-antigen battery.

Adolescent↗

PubMed1980

Suppression splenic T lymphocytes in human hepatosplenic Schistosomiasis mansoni.

Splenic suppressor cell activity was evaluated in 10 patients with advanced hepatosplenic Schistosomiasis mansoni undergoing elective splenectomy. We used cell mixing experiments to assess the effect of mitomycin-C-treated spleen cells on antigen and mitogen-induced 3H-thymidine incorporation of responder cells. The suppressor to responder ratio was 1.0. Spleen cells from 7 of 10 patients caused at least 20% suppression of phytohemagglutinin-induced 3H-thymidine incorporation of one or more populations of responder cells (spleen cells, autologous and allogeneic peripheral blood mononuclear cells)Responses of peripheral blood mononuclear cells to streptokinase-streptodornase and schistosome soluble egg and worm antigen preparations also were inhibited by co-cultured spleen cells. An inverse correlation was apparent between the spleen cell response to PHA and the suppressor activity of that spleen cell population (r = -0.74, p less than 0.05). Cell purification procedures showed that the active suppressor splenic cell was non-adherent and rosetted neuraminidase-treated sheep erythrocytes. This splenic suppressor T lymphocyte may modulate splenic and peripheral blood lymphocyte responses in patients with hepatosplenic schistosomiasis.

Adolescent↗

PubMed1982

[Immunity in hypothyroid children (author's transl)].

For a long time investigators have focused attention on the relationship between specific immunity and hormones. In the present paper, authors investigated on 26 children, 9 males and 17 females, from 9 months to 14 and 10/12 years old, with primary hypothyroidism. All patients were in substitutive treatment. The following studies were done to all the patients: serum IgG, IgA, IgM and complement. Blood lymphocyte counts, percentages of B and T lymphocytes, as well as the response of lymphocytes to PHA. Skin tests were also carried out: tuberculin, candidin and streptokinase-streptodornase. All results obtained in both, hypothyroid and control groups fell within the range of normal age-matched values for our laboratory, and by results of statistics studies carried out they were considered of little significance, except the percentage of circulating B lymphocytes that was lower in hypothyroid group (p less than or equal to 0.01).

Adolescent↗

PubMed1980

Skin test reactivity and in vitro responses to microbes and microbial antigens.

In the present study the relationships between skin reactivity, leucocyte migration inhibitory factor (LIF) production and lymphocyte transformation in healthy volunteers and newborns were investigated. LIF synthesis was assessed by the two-step agarose migration method and cellular proliferation by the incorporation of iododeoxyuridine. The following soluble antigens and whole microbes were used: purified protein derivative of tuberculin (PPD), bacille Calmette-Guérin (BCG), streptokinase-streptodornase (SK-SD), Streptococcus Beta-haemolyticus, group A, Dermatophytin O (DO) and Candida albicans. The results indicated a significant correlation between skin reactivity and in vitro tests with soluble antigens and that, of the in vitro tests used, lymphocyte transformation correlated better with skin test than LIF production. Furthermore, soluble antigens gave better correlations with skin tests than whole microbes. Experiments with cord blood cells demonstrated that they did not respond to antigens but were activated by whole microbes. Thus the whole microbes appear to contain mitogenic components.

Adult↗

PubMed1978

Abnormalities of lymphocyte transformations in women with intraepithelial carcinoma of the vulva.

Cellular immunity of the delayed type in women with intraepithelial carcinoma (carcinoma is situ) of the vulva was investigated by an in vitro assay of mitogen-induced lymphocyte transformations. Test results from 9 patients were compared to those of 23 age-matched control subjects. Lymphocyte transformation responses in counts per minute were significantly lower for women with carcinoma in situ of the vulva than for control subjects for phytohemagglutinin-P (at 50 microgram/ml) 6238 and 28,102 (P less than 0.0001); for phytohemagglutinin-P (at 165 microgram/ml 7222 and 21,417 (P less than 0.001); for concanavallin A, 14,988 and 41,888 (P less than 0.0001); and pokeweed mitogen, 20,861 and 49,601 (P less than 0.001). No significant differences in lymphocyte transformations were noted between these two groups to the specific antigens, Candida or streptokinase-streptodornase. Four patients with carcinoma in situ of the vulva were also found to have intraepithelial carcinoma of the cervix and/or vegina. The occurrence and clinical course of carcinoma in situ of the vulva in some women may be related to an underlying defect in cellular immunity. Immunosuppression may also explain the frequent association noted between carcinoma of the vulva and the development of other malignant neoplasms.

Adolescent↗

PubMed1982

In vivo and in vitro cell-mediated immunity in tuberculous meningitis.

This study assessed in vivo and in vitro parameters of cell-mediated immunity in 45 tuberculous meningitis patients. Delayed-type hypersensitivity responses to purified protein derivative of tuberculin (PPD), Candida albicans and streptokinase-streptodornase antigens were lacking in 34 patients compared to 2 of 54 normal volunteers. Circulating T lymphocyte subpopulations (E-rosetting active and total T cells) were diminished in 41 patients studied compared to 41 normal donors (p less than 0.001). Lymphocyte blast responses to PPD (25 micrograms-500 micrograms/ml) were positive but quantitatively depressed in all 34 patients studied compared to PPD positive normal donors (p less than 0.001). Phytohemagglutinin responses were significantly depressed (p less than 0.001). Repeat studies in 20 patients 4-5 months post-therapy resulted in reversals of all parameters to control values with heightened blastogenic responses to all PPD concentrations.

Adolescent↗

PubMedDate not supplied

Cellular and humoral responses following one year of hyposensitization with aqueous and tyrosine adsorbed Dermatophagoides pteronyssinus extracts.

The present study compared the influence of hyposensitization treatment with a tyrosine adsorbed house dust mite solution (Migen) and an aqueous house dust mite (HDM) solution on the immunological parameters in 41 adult asthma and rhinitis patients. The immunological parameters included total IgE, spec. IgE and spec. IgG antibody determination, circulating immune complexes (CIC), lymphocyte response to Dermatophagoides pteronyssinus and to candidin and streptokinase-streptodornase (SKD). The two groups were compared to a control group of 123 non-allergic subjects. An increase in spec. IgG antibodies was found, with no change in the total and spec. IgE antibodies. The one year hyposensitization treatments had no influence on the appearance and level of CIC. A positive lymphocyte test to HDM antigen was found in 62% of the controls and in 70% of the treated patients. The response was significantly greater in the allergic patients than in the controls. Under the influence of hyposensitization, an early increase of the lymphocyte response to HDM, followed by a decrease, was noticed, whereas the response to candidin and to SKD remained unchanged. The present study demonstrated that the tyrosine adsorbed HDM extract had the same immunological consequences as the aqueous solution.

Adolescent↗

PubMed1981

[Reabsorption of standardised intramuscular haematomas in rabbits treated with streptokinase per os (author's transl)].

Standardised i.m. haematomas in rabbits were studied with and without oral administration of Varidase (containing streptokinase and streptodornase). 125I-fibrinogen was mixed with 2 ml of rabbit blood and reinjected i.m. The standardised haematomas were reabsorbed after 12 to 14 days. During the 3-day administration period of streptokinase the counts measured over the haematoma were even higher than in control animals. As during the therapy a high fibrinolytic activity was found, additional spontaneous bleeding into the haematomas may be suspected. When oral administration of streptokinase was stopped the decrease of counts detected in those animals was significantly accelerated as compared to non-treated animals. This indicates an accelerated reabsorption of those haematomas treated with streptokinase in a low concentration. These results were confirmed by microscopic findings.

Absorption↗

PubMed1981

[Influence of physical parameters on the production of streptococcal extracellular proteins in cultures with stabilized pH. I. Communication: pH-dependence of extracellular protein production (author's transl)].

The influence of the pH of the medium on growth and production of extracellular proteins was examined in a group C streptococcus (SA. equisimilis strain H 46 A). The pH values employed ranged from 5.0 to 8.5 and the analytical methods used included the determination of enzyme activities, isoelectric focusing, crossed-immunoelectrophoresis, and SDS electrophoresis. The strain is able to grow in the entire pH range used, with maximum growth occurring at pH 6.5. The amount of extracellular proteins elaborated depended on both the pH of the medium and the biomass produced. A specific pH range was defined for optimum production of all enzymes examined. With the exception of streptodornase and NAD-glycohydrolase, the pH optimum for product formation was generally in the neutral and weakly alkaline range. Active proteinase was formed only a pH 6.0, leading to gross degradation of most of the other proteins in the culture medium. At pH values ranging from 6.5 to 7.5, isoelectric focusing revealed the production of 28 different extracellular proteins, and crossed immunoelectrophoresis demonstrated 30 to 32 antigens. The number of extracellular products produced greatly declined at pH values above and below this range. Under optimum conditions, the main extracellular product at H 46 A was streptokinase, followed by deoxyribonuclease A.

Antigens, Bacterial↗

PubMedDate not supplied

In vitro lymphocyte response in early rheumatoid arthritis.

Streptokinase-streptodornase (SK-SD) skin tests and peripheral blood mononuclear stimulation to purified SK-SD delayed skin reactor (DSR) and phytohemagglutinin (PHA) was assessed in 41 patients with rheumatoid arthritis (RA) and 17 controls. Lymphocyte response to DSR correlated directly with the diameter of SK-SD-induced erythema, and PHA stimulation decreased with age. RA patients did not show significant depression by either test or did hyporesponsiveness predict rheumatoid disease activity or prognosis. Six patients without medication demonstrated increased PHA responsiveness and a direct rather than inverse correlation with age.

Adult↗

PubMed1981

[Role of the delayed hypersensitivity skin test in surgery].

The correlation between state of preoperative immunity assessed by in vitro test and the onset of postoperative septic complications has been evaluated. 153 patients subjected to surgery of choice have been examined. Before the operation cutaneous delayed hypersensitivity tests with recall antigens (streptokinase-streptodornase, purified tuberculoprotein and candidine) were carried out. 111 patients were classed as immunologically normal (at least one positive test) and 42 were anergic (no positive test) Among the former, 12 cases (10.8%) showed post-surgical septic complications, while among the latter, fully 24 (57%) suffered from infectious processes. It is concluded that, although numerous factors make patients prone to infection during the postoperative course, immunitary conditions play a very important part. Prophylactic measures are therefore suggested for anergic patient prior to surgery, measures that are essentially represented by parenteral support feeding and immunostimulation.

Adult↗

PubMed1977

[Immune deficiences during pyoderma gangrenosum associated with a polycythemia vera].

A deficiency in cellular immunity was demonstrated in a patient suffering from polycythaemia rubra vera in the myelofibrosis stage. Intradermal reactions to classical antigens (candidine, trichophytine, streptokinase, streptodornase, tuberculine) were negative, as was the di-nitrofluorobenzene test. However, the T lymphocyte count was normal. There was no disturbance in humoral immunity. Phagocytosis was normal but leucocyte migration, studied in vitro, was nil. The possibility of an intrinsic abnormality in the polynuclear neutrophil is evoked.

Adrenal Cortex Hormones↗

PubMed1997

Is psoriasis induced by streptococcal superantigens and maintained by M-protein-specific T cells that cross-react with keratin?

The evidence that T lymphocytes play a key role in the pathogenesis of psoriasis is now compelling. Eruption of psoriatic skin lesions coincides with epidermal infiltration and activation of T cells, and spontaneous or treatment-induced resolution of the lesions is preceded by the reduction or disappearance of epidermal T cells. An upregulation has also been demonstrated for various molecules associated with T-cell mediated inflammation, and treatments selectively directed against T cells have proved very effective. Infections with group A beta-haemolytic streptococci have been associated with onset of acute psoriasis and exacerbation of chronic psoriasis. Such infections are also frequently accompanied by erythematous skin rashes. Also, recent reports indicate that streptococcal superantigens can induce expression of cutaneous lymphocyte antigens (CLA), believed to play a major role in enabling T cells to migrate to the skin. Furthermore, T-cell lines isolated from psoriatic lesions may show strong reactivity to streptococcal antigens. We have postulated that psoriasis is an autoimmune disease mediated by T cells reacting to epitopes that are common to streptococcal M-proteins and keratins. To investigate this possibility, circulating T cells from 12 patients with active psoriasis, paired controls, and six patients with atopic dermatitis were challenged in vitro with five synthetic 20aa (amino acid) M-peptides: production of IFN-gamma and IL-4 was analysed by ELISPOT and RT-PCR techniques. Four of these peptides shared five to six aa sequences with several type I keratins and one did not. In 10 of the 12 psoriasis patients, measurable IFN-gamma production could be induced by one or more of the four peptides that share sequences with keratins. A borderline response was observed in only four of the 18 controls: the dermatitis patients were all negative. The only peptide that shared 6aa with keratins was the one that induced a response in the psoriatic patients most frequently, and four of them showed the strongest response to this peptide while none of the controls reacted to it. In all instances negligible responses were observed to the control peptide that did not share sequences with keratins. Except for PHA-stimulated controls, IL-4 responses could not be detected by either ELISPOT or RT-PCR and there was generally good agreement between the two techniques. A marked reduction in the M-peptide-induced IFN-gamma responses was observed in the psoriasis patients during remission induced by UVB treatment, while their responses to streptokinase-streptodornase were not affected. Thus, active psoriasis is associated with a Th1 type response to short peptides with epitopes shared by streptococcal M-protein and keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein-specific Th1-like cells that cross-react with human epidermal keratin.

Animals↗

PubMed1979

Dual response of lymphocytes from multiple sclerosis patients to myelin basic protein.

Peripheral blood lymphocytes from forty-nine patients with multiple sclerosis (MS), twelve patients with other neurological diseases and twenty-seven healthy individuals were examined by a two-stage procedure based on the Con A stimulation of the basic protein (BP) pre-treated lymphocytes. Enhanced BP-induced blastogenic stimulation (BS) (90--220% was observed in MS individual classified as active (A-MS), whereas suppressed BS (27--120%) was observed in MS patients classified as non-active (NA-MS). The difference was statistically significant (P less than 0.01). The results obtained with the MS patients' lymphocytes also differed significantly (P less than 0.05) from those of the two control groups. Either response obtained with MS lymphocytes could be elicited with a similar concentration of BP. The enhanced or suppressed response to BP did not correlate with the cellular response to common antigens such as candida and streptokinase-streptodornase. Most lymphocytes of individuals from the two control groups showed BS values of 100 +/- 20% in response to BP. However, some degree of stimulation or suppression was also obtained with lymphocytes from a few individuals of both control groups. The potential value and application of the two-stage procedure is discussed.

Adult↗