Immunitat und Infektion最新文献

Sarcoidosis is a frequent, systemic, granulomatous disorder with predominant involvement of the hilar lymph nodes and the pulmonary parenchyma. By bronchoalveolar lavage an activation of alveolar immune cells has been observed yielding a detailed concept of the immunopathogenesis of the disease from which new, clinically applicable staging parameters are delineated.

Autoantibodies, immune complexes and autoreactive lymphocytes represent the initial steps in the pathogenic events leading to interstitial pulmonary manifestations of collagen vascular diseases. Vascular damage caused by deposition of immune complexes in the vascular wall and chemotactic factors result in an influx of neutrophils and mononuclear cells leading to inflammatory phenomena like vasculitis and alveolitis. Finally, persistent activation of lung fibroblasts may result in interstitial pulmonary fibrosis characterized by nearly identical histopathological findings independent of the underlying disease. Several inflammatory mediators, e.g. cytokines, are markedly involved in the regulation of different pathogenic mechanisms. Furthermore, different pathogenic mechanisms exert variable roles depending on the specificity of the underlying disease. Therefore, disease-specific effective pharmacotherapy, which in most cases will be a combination therapy, has to take into consideration not only the predominant pathogenic mechanisms but also drug-specific efficacy.

Classic polyarteritis nodosa is a necrotizing vasculitis affecting medium- and small-sized arteries. Renal involvement from aneurysm formation is common and can result in perirenal or intrarenal bleeding. The gold standard of diagnostic procedures is the arteriography. Treatment of choice is a combination of steroids and cyclophosphamide, but in the case of severe hemorrhage surgery is mandatory. Patients with PAN need at least 2 years of long-term therapy; repeated arteriography will establish the efficacy of therapy.

The phagocytic abilities of human monocytes/macrophages have been investigated in people with chronic alcohol abuse. The blood monocytes of the patients were tested in three functional systems: Fc-receptor-mediated phagocytosis, phagocytosis via complement receptor interaction and the so-called lectinophagocytosis. In a group of 57 alcoholics, the values for the phagocytic ability were distributed over a wide range by using all three tests in comparison with a group of 23 non-drinking control persons. However, a significant change in the monocytic function by ethanol could not be observed. Also a correlation between age, liver damage or abstinent periods with respect for these forms of phagocytosis could not be evaluated. As a result of our investigations we discuss our hypothesis, that in chronic alcoholics the so-called "unspecific defense mechanisms" are not altered at all: on the contrary, sometimes they have been up-regulated. A functional defect of specific defense mechanisms, however, has been observed by other investigators. Accordingly, we assume a compensatory up-regulation of "unspecific" immune reactions in long-term alcoholics.

Immunological complications of insulin therapy are extremely rare, since highly purified insulins, especially human semi- or biosynthetic insulin preparations became available for treatment of diabetes mellitus. Insulin antibodies of the immunoglobulin G or immunoglobulin E class can develop in 10-60%, however, in low titers in patients treated exclusively with human insulin. In rare cases these antibodies assume clinical significance, if the antigenic potential of the insulin used is high enough and if genetic predisposition exists. Two case reports presented here confirm this concept.

Hyperacute graft rejection triggered by the activation of the recipient's complement system represents the major obstacle to a successful xenotransplantation. Inhibition of complement activation is, therefore, considered as a prerequisite for xenograft survival. Support of the physiological regulation of the complement system appears to be the most promising strategy as indicated by first results from animal xenograft experiments. The transfer of human membrane-bound complement regulatory proteins offers new chances to protect the xenograft against the cytolytic complement attack. Another approach aims at interfering with receptor/ligand interaction of the adhesion molecules CR3 and CR4 (CD11b,c/CD18). All strategies of complement intervention have to consider the important function of complement within the immunological defense.

Paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia are associated either as a PNH-aplasia syndrome or the emergence of glycosylphosphatidylinositol-(GPI)deficient blood cells in patients with severe aplastic anemia (SAA). It could be demonstrated that SAA patients with GPI-deficient cells in comparison to those without have a worse response to classical immunosuppressive therapy. Therefore, we treated a female PNH patient with severe thrombocytopenia, anemia and granulopenia with G-CSF and cyclosporine. Within 8 weeks, a trilineage response of hematopoiesis was observed. In addition, the proportion of normal to GPI-deficient granulocytes and monocytes increased significantly.

Although the involvement of complement in hyperacute renal allograft rejection is well established, its possible implication in acute reversible and chronic graft rejection remains uncertain. In recent clinical studies with a total of 83 patients undergoing renal transplantation, plasma levels of complement activation products were elevated 4-7 days before clinical diagnosis of graft rejection. Immunohistochemical analysis of biopsies revealed local complement activation with glomerular deposition of the terminal C5b-9 complex within 1 h after organ reperfusion. Increasing levels of complement activation products, preceding the clinical manifestation of renal graft rejections may be of diagnostic value in recognizing patients at risk.

The presented results show that renal cell carcinomas (RCC) have partial immunomodulatory capacity (production of cytokines as IL-6, -10, -11; modulation of mitogen-induced transformation of T lymphocytes). The production of IL-10 shows a tendency to correlate with higher staging and grading of RCC. The cytokine production does not correlate with specific types of RCC. Direct immunosuppression of T lymphocytes in lymphocyte transformation tests (LTT) was not detectable.

Two post mortem examinations from the Institute of Pathology, Albert-Ludwigs-University of Freiburg, will be presented. In both cases diagnosis of a T-cell-rich B-cell-lymphoma was first established after necropsy and evaluation of the immunohistochemical results. In the first case a peripheral T-cell-lymphoma was diagnosed after a peripheral T-cell-marker test. A liver biopsy showed suspicion of a Hodgkin-lymphoma. In the second case a biopsy of an extended retroperitoneal tumor showed a centroblastic non-Hodgkin-lymphoma 3 weeks before death. By autopsy we found in both cases a wide infiltration with small monomorphic lymphocytes. Less than 20% of the infiltrate consisted of polymorphous blasts with a wide morphologic range and prominent nucleoli. Immunohistochemistry showed the blasts to be CD20-positive, while the small monomorphic lymphocytes expressed the CD3 marker. In the first case kappa-light-chain-restriction was shown in the blasts by immunohistochemistry. Differential diagnosis difficulties, diagnostic criteria, prognosis and classification of these cases in the common non-Hodgkin-lymphoma classification will be discussed in view of the current literature.