Immuniteit: De noodzaak van zelfherkenning voor zelfbescherming

REDE uitgesproken bij de openbare aanvaarding van het ambt van gewoon hoogleraar in de celbiologie, histologie en microscopische anatomie, in het bijzonder de histofysiologie van het immuunsysteem, aan de Erasmus Universiteit te Rotterdam op woensdag 25 november 198

Antibody formation in mouse bone marrow

lymphoid organs are generally subdivided into two groups according to their contribution to antibody formation: 'primary 1 and 'secondari lymphoid organs. In mammals bone marrow and thymus are considered to be 'primar/ because these organs are involved in the generation of lymphocytes: B cells and T cells respectively. These lymphocytes can ieave t·heir place of origin and provide for antibody formation in secondary lymphoid organs: sp!een, lymph nodesr Peyer1s patches and other gut-associated lymphoid tissue. After antigenic stimulation B cells can potentialfy differentiate into antibody producing plasma cells. T cells play a principal role in cell-mediated immune responses, which include delayed hypersensitivity, contact sensitivity, graft rejection, graft-versus-host responses and acquired resistance to some microbes. In addition to be involved in cell-mediated immunity T cells cooperate with B cells in antibody formation to most antigens. Thereby T cells can enhance and suppress the response of the B cells to the antigen. Antigens which reguire cooperation of B cells and T celfs to evoke antibody formation are called 1thymus-dependent1 antigens in contrast to 1thymus-independent1 antigens which do not require T cells for antibody formation. There are suggestions in the I iterature that antibody formation in mammals can take place not only in secondary lymphoid organs but also in bone marrow

Substantially increased sensitivity of the spot-ELISA for the detection of anti-insulin antibody-secreting cells using a capture antibody and enzyme-conjugated insulin

This paper describes an antibody capture spot-ELISA for the detection of anti-insulin antibody-secreting cells. The assay is based on the binding of secreted antibodies by immobilised isotype-specific capture antibodies and subsequent detection of insulin-specific antibodies with a conjugate of human insulin and alkaline phosphatase (HI-AP). Compared with the conventional approach, using antigen for coating and employing an enzyme-linked detecting antibody, this technique improved the detection of murine cells secreting anti-insulin antibodies of different IgG subclasses

Enhanced production of biologically active interleukin-1α and interleukin-1β by psoriatic epidermal cells ex vivo: Evidence of increased cytosolic interleukin-1β levels and facilitated interleukin-1 release

The expression of interleukin (IL)-1 is altered in psoriatic lesions. However, little is known about the actual production of IL-1α and IL-1β by psoriatic epidermal cells (EC). We monitored IL-1 in the extracellular, the membrane and the intracellular compartment of freshly isolated EC from untreated lesional psoriatic (PP) and normal healthy (NN) skin during non-stimulated short-term cultures, representing a psoriasis model ex vivo. Cytokines were measured using bioassays combined with neutralizing antibodies and enzyme-linked immunosorbent assay in parallel. PP EC released significantly increased amounts of biologically active IL-1α and IL-1β in a ratio of 3:1, whereas NN EC only released IL-1α. Also, the release of IL-6, but not of TNF-α, by PP EC was significantly increased. Membrane-associated IL-1 activity, analyzed using glutaraldehydefixed EC, was low and not unique to PP EC. The cytosol of PP EC contained significantly increased levels of immunoreactive IL-1β. Furthermore, PP EC displayed loss of membrane integrity, as determined by trypan blue exclusion and release of cytosolic lactate dehydrogenase. This facilitated release of intracellular IL-1. Depletion of CD45+ cells showed that intraepidermal leukocytes did not contribute to the production of IL-1. Our observations show that resident PP EC express enhanced IL-1 production ex vivo, which is due to an increased cytosolic IL-1β content and facilitated IL-1 release. This study provides the first evidence that PP EC can produce bioactive IL-1β

Chronologic Change and Clinicopatiologic Characteristics of Gastric Cancer Patients Over 70 Years of Age

Chronologic change and clinicopathology of 299 gastric cancer patients over 70 years of age (old group) were examined by comparing with those of 307 patients under 50 years of age (young group), and the histogenesis was discussed. The patients of the old group increased significantly in frequency from 9.9 % in the 1960's to 33.9 % in the 1990's, and the patients of the young group decreased clearly from 23.5 % in the 1960's to 9.4 % in the 1990's. However, no significant difference was found in the frequency of patients between 50 and 69 among 4 periods from the 1960's to the 1990's. In 6 out of 12 clinicopathologic factors, significant difference were found between both groups; male, tumor of lower 3rd of the stomach, macroscopic localized type in advanced cancer and protruded and elevated types in early cancer, liver metastasis, differntiated adenocarcinoma and venous invasion were significantly more in the old group than in the young group. From the results, it is suggested that the frequency of gastric cancer in Japan increases recently in the old group and decreases in the young group. Histogenetically, differentiated adenocarcinoma originating from intestinal metaplasia is suggested to arise more frequently in the former than in the latter

Histological and immunohistochemical characterization of joint inflammation and flare-up reactions induced by cloned MT4+, Lyt-2-T cells

Abstract This report describes the histological and immunohistochemical characterization of joint inflammations and flare-up reactions in mice induced by cloned MT4+, Lyt-2− T cells. The T-cell clone used was specific for the antigen methylated bonne serum albumin (mBSA) and was inoculated locally into a joint together with the antigen. The histological examination was performed in methylmethacrylate sections, and the various cell types were quantified m distinct regions of the knee joint. The infiltrates consisted predominantly or granulocytes admixed with small numbers of histiocytes. Few lymphocytes were present, while plasma cells were not found. Fibrosis was prominent in the later stages of the inflammation. Immunohistochemical analysis of total unfixed, non-decalcified sections using monoclonal antibodies revealed the presence of T cells which were predominantly of the helper phenotype. sporadic B cells, and a considerable number of la-positive cells. Macrophages were scattered throughout the infiltrate. The synovial lining was shown to express Ia antigens and to contain cells that stained with macrophage markers Cell clusters were found including helper T (Th) cells, some B cells, and Ia-positive cells. These results are in line with immunohistological examinations in other arthritis models and resemble the early events in human rheumatoid arthritis. The data indicate that activated helper T cells are required and sufficient to give rise to the inflammatory infiltrates that are characteristic of the inflammations and exacerbations in human rheumatoid arthritis

Fc receptor binding of anti-CD3 monoclonal antibodies is not essential for immunosuppression, but triggers cytokine-related side effects

A major drawback to the use of OKT3, a mouse anti-CD3 monoclonal antibody (mAb), as an immunosuppressive agent is the associated cytokine release syndrome. We used a mouse model to elucidate the properties of anti-CD3 mAb responsible for these cytokine-related side effects. We have previously demonstrated that the hamster anti-CD3 mAb 145-2C11 induced strong cytokine release and morbidity in vivo, whereas two rat anti-CD3 mAb 17A2 and KT3 did not. In the current study, we show that the mitogenic capacity of soluble anti-CD3 mAb in vitro correlates with their induction of side effects in vivo. Mitogenesis in vitro and tumor necrosis factor-α (TNF-α) release in vivo induced by anti-CD3 mAb could be inhibited by the anti-FcγR mAb 2.4G2, indicating that FcγR binding of anti-CD3 mAb is responsible for their mitogenic properties and for their induction of side effects. Importantly, the two non-mitogenic rat anti-CD3 mAb were equally capable of suppressing skin allograft rejection as the mitogenic hamster anti-CD3 mAb, suggesting FcγR binding of anti-CD3 mAb is not essential for their immunosuppressive properties. This suggestion is reinforced by our demonstration that administration of 2.4G2 in vivo did not interfere with immunosuppression of skin allograft rejection by 145-2C11. These findings suggest that clinical use of non-mitogenic anti-CD3 mAb will result in effective immunosuppression without cytokine-related side effects