Kinetics of the reactive cell clones after immunosuppression and induction of tolerance: (1) Inhibition of 19 S and 7 S plaque-forming cells in the primary and secondary immune response to sheep red blood cells by cyclophosphamide and 036.5122 (Asta)

The kinetics of the reactive cell clones after primary and secondary immunization with SRBC1) modified by cyclophosphamide and a newly synthesized cyclophosphamide analogue 036.5122 (Asta), have been studied. After primary immunization, both substances caused a severe and dose dependent depletion of 19 S PFC2). The 7 S PFC in the late primary response were only slightly inhibited by cyclophosphamide in low dose ranges, indicating, that sensitization could not be prevented by this substance. In contrast, 0.36.5122 was fully able to suppress 7 S PFC. Thus, treatment with 0.36.5122 after primary immunization can fully prevent the expression of the specific response. Experiments dealing with in…

Inhibition of Granulocyte Function by Prednisolone and Non-Steroid Anti-Inflammatory Drugs. Quantitative Evaluation with NBT Test and its Correlation with Phagocytosis

The effect of prednisolone and non-steroid anti-inflammatory drugs on PMNL (polymorphonuclear leucocytes) oxidative metabolism was quantified with a newly standardized NBT test, and it was investigated whether these effects correlate with phagocytosing capacity of PMNL. Prednisolone inhibits NBT reduction in dose dependency already at concentrations, which do not interfere with phagocytosis. Thus prednisolone dissociates phagocytosis and phagocytosis-associated oxidative metabolism. High doses of prednisolone also inhibit phagocytosis. These effects of prednisolone are still demonstrable when PMNL are washed after pre-incubation with the drug. The non-steroid anti-inflammatory drugs (indome…

Third Eular Workshop on Rheumatology Research

Comparison of the immunosuppressive efficacy of 6-mercaptopurine, azathioprine, cyclophosphamide and 036.5122 (Asta) on the primary and secondary immune response of mice to sheep erythrocytes

Two alkylating (cyclophosphamide and 036.5122 Asta) and two antiproliferative agents (6-mercaptopurine and azathioprine) have been compared for their immuno-suppressive potency on the primary and secondary humoral immune response of mice. If equitoxic dosages of the respective drugs are compared, the alkylating agents proved to be of much higher immunosuppressive potency than the antiproliferative agents. In non toxic dosages alkylating agents were able to completely inhibit a primary or secondary immune response, whilst a similar effect with antiproliferative drugs could not be obtained even within toxic dose ranges. Induction of immunological tolerance was possible only by use of the alky…

Control of the production of oxygen intermediates of human polymorphonuclear leukocytes and monocytes by beta-adrenergic receptors.

The control by beta-adrenergic receptors of the production of oxygen radicals by zymosan-stimulated human polymorphonuclear leukocytes (PMN) and monocytes (M phi) was studied in vitro by means of chemiluminescence. In addition we asked whether PMN and M phi exhibit differential sensitivity to beta-adrenergic stimulation. For beta-adrenergic stimulation we applied fenoterol ranging from 10(-5) to 10(-9) M x 2.7. We found a dose-dependent suppression of the production of oxygen radicals, the ID50 being approximately 10(-6) M both for PMN and M phi. By assessment of lactic dehydrogenase release a cytotoxic effect of the drug could be ruled out. When incubated together with the beta-adrenergic …

Der Crithidia luciliae-Immunfluoreszenztest zum Nachweis von Antikörpern gegen doppelsträngige DNA

Der Crithidia luciliae-Immunfluoreszenztest (Cl-IFT) zum Nachweis von Antikorpern gegen doppelstrangige DNA (ds DNA) wurde in der Diagnostik und Verlaufsbeurteilung des systemischen Lupus erythematodes (SLE) in seiner Wertigkeit mit der radioimmunologischen Bestimmung im Farr-Test verglichen. Es zeigte sich, das der Cl-IFT lediglich bei Patienten ohne Zeichen von Krankheitsaktivitat von geringerer Sensitivitat ist, in Phasen von klinischer Krankheitssymptomatik dem Farr-Test jedoch gleichwertig ist. Eine Ubereinstimmung beider Testverfahren bestand in 76,9% der untersuchten Patienten-Seren; fehlende Ubereinstimmung war nicht nur eine Frage der Sensitivitat, in einigen Seren konnten nur mit …

Nitroblue-tetrazolium test for the functional evaluation of phagocytic cells: a critical analysis of the methodology.

The reduction of NBT to formazan has been suggested as an indicator of the reduction potential of biological systems. An increase in the amount of reduced formazan reflects the activation of the hexose monophosphate shunt of phagocytes cultivated in vitro, as a result of cellular stimulation by chemical or biological factors, or during phagocytosis. This phenomenon has been widely used for the determination of activated phagocytes by different methods. However, the technical limitations of these methods have not been evaluated carefully. In the investigations presented here three solvents for formazan, pyridine, dioxane and dimethyl-formamide, have been tested for their suitability as extra…

Immunofluorescence studies on the subcomponents of the first component of complement (C1): detection of C1q and C1s in different cells of biopsy material and on human as well as on guinea pig peritoneal macrophages.

The first component of complement (C1) is a macromolecule consisting of three distinct subcomponents, C1q, C1r, and C1s. In regard to its production site and its role in phagocytic processes it was of interest to find out whether these different subcomponents could be detected in human biopsy material only as a complex in individual cells or whether C1 subcomponents could be found on different cells. To study this question, monospecific fluorescein-labelled anti-human-C1q IgG and monospecific rhodamine-labelled anti-human C1q IgG were used. Biopsy material from human rectum was stained with fluoresceinated antisera, either by use of one antiserum or by double staining. Using this technique,…

Studies on the mechanism of PMN activation II. by triggering the alternative pathway of complement activation

By means of cobra venom factor (CVF) it is demonstrated that the stimulation of hexosemonophosphate shunt (HMPS) of human polymorphonuclear leukocytes (PMN) by zymosan (Z) and dextran sulfate (DS) is caused by at least two modes of activation: (a) via activation caused by phagocytosis, (b) via activated alternative pathway of complement activation (APC). Active factors of APC presented with phagocytizable objects strongly enhance activation of PMN. The effect of APC can be observed in serum-containing as well as in serum-free cultures. It can be demonstrated that in serum-free cultures the factors of APC participating in the activation of PMN are supplied by monocytes. By the use of synthet…

Studies on the mechanism of PMN activation III. by lymphokines.

The influence of a guinea pig lymphokine preparation on the oxidative metabolism of human and guinea pig granulocytes of various sources was investigated. A dose-dependent increase of the oxidative burst following lymphokine challenge was observed. It occurred in unstimulated guinea pig peripheral polymorphonuclear leukocytes (PMN) and in prestimulated PMN obtained from the peritoneal cavity after glycogen injection as well. The lymphokine effect on the oxidative metabolism is not species-restricted because the guinea pig lymphokine preparation elicits an oxidative burst in human PMN, too. The increase caused by lymphokines is nearly of the same order of magnitude as that obtained with zymo…

Reversible graft versus host reaction as cause of erythrophagic splenomegaly in a child?

The case history of a 9 months old infant with hepatosplenomegaly, pancytopnaenia and disturbances of clotting and cellular immune reactivity is reported. The spleen was removed and showed striking erythrophagocytosis by proliferating histiocytes, typical of "familial erythrophagocytic reticulosis" (Farquhar). A graft-versus-host reaction is discussed as a possible underlying cause. The favourable clinical course and full recovery point to an interrelation with primary hypersplenism.

Immunological investigations in two brothers with ataxia telangiectasia Louis-Bar

Two of three brothers with the classical signs of ataxia telangiectasia were investigated for their immunological disorders at the ages of 13 and 16 years, respectively. The elder brother also suffers from autoimmune hemolytic anemia, a complication which has not yet been described in the course of ataxia telangiectasia. Immunological investigations made in both brothers showed a reduction in the number and function of T lymphocytes. The number of B lymphocytes was normal, among which there were cells staining for IgA, although serum IgA was absent. It seems possible that this phenomenon is caused by a disturbance in the process of maturation of lymphoid cells with a lack of differentiation…

Untersuchungen zur Stimulierbarkeit und zur Differenzierung von Lymphocyten nach Traumen

Traumatische Gewebsschaden haben nicht nur lokale Reaktionen zur Folge, sie konnen auch Veranderungen im Gesamtorganismus hervorrufen. Postoperativ wurde ein gehauftes Auftreten von Komplikationen, die durch bekannte Mechanismen nicht voll erklart werden konnen, beobachtet. Dazu gehoren die Haufigkeit bakterieller, mykotischer und viraler Infektionen und die Beschleunigung der Metastasenbildung bei Carcinompatienten.

Studies on the mechanism of PMN activation. I. By dextran sulfates.

Evidence is presented that enhanced reduction of the dye nitroblue-tetrazolium (NBT) by polymorphonuclear leukocytes (PMN) which are stimulated by dextran sulfates (DS) is not exclusively due to the phagocytosis of particles formed by NBT and DS. Not only the size of phagocytizable particles but the degree of substitution determines the acceleration of NBT-reduction. A likely cause of this acceleration is the triggering of the alternative pathway of the complement activation.

Quantitative Untersuchungen zur Hemmung von Granulozyten- und Makrophagenfunktionen durch steroidale und nicht-steroidale Antirheumatika in vitro

Granulozyten und Makrophagen spielen eine erhebliche Rolle in der korpereigenen Abwehr und pragen grostenteils die klinische Symptomatik entzundlicher Erkrankungen. Diese Zellen zirkulieren normalerweise in einem Zustand relativer metabolischer Ruhe im peripheren Blut. Ihre Aktivitat ist sprunghaft gesteigert, wenn sie an einem entzundlichen Geschehen beteiligt sind. Hier werden sie zur Synthese und Freisetzung von Entzundungsmediatoren aktiviert und treten zum Teil in Kooperation mit T- und B-Zellen.