Immunologic Aspects of Human Endometriosis

ABSTRACT: General and specific immune function were examined in women with endometriosis. Nonspecific parameters included total leukocyte and differential counts, quantitative immunoglobulin (IgG, IgA, and IgM) determinations, total hemolytic complement, C₃, C₄, mitogen-induced lymphocyte stimulation, and human leukocyte antigen (HLA) typing; no differences were observed when data were compared to age-matched controls without endometriosis. In contrast, the specific immune response T-lymphocyte-mediated cytotoxicity to autologous endometrial cells was significantly reduced (P <0.01) in women with endometriosis. When results from patients were analyzed according to clinical severity of endometriosis, even more striking immunologic alterations were delineated. In addition, lymphocyte stimulation responses to autologous endometrial antigen were lower in patients with severe or moderate disease, approaching statistical significance (P = 0.18 and 0.12, respectively). These studies suggest an immunologic basis for development of endometriosis.     

Physiologic and Morphologic Natural History of a Model of Intrahepatic Cholestasis (Manganese-Bilirubin Overload)

Study of the morphologic and physiologic features of the biliary excretory apparatus at 24 and 48 hours after the induction of intrahepatic cholestasis by manganese-bilirubin overload shows that at the same time that physiologic cholestasis is rapidly waning, morphologic features of cholestasis are, in fact, increasing. These observations therefore provide the first direct proof of the proposal that such features are not, in fact, causes of cholestasis, at least at its outset. Although morphologic and physiologic features do not parallel one another in time, they do seem to parallel one another in severity. Morphologic features in manganese-bilirubin cholestasis closely resemble those in human cholestasis, and so reaffirm the validity and potential value of manganese-bilirubin overload as a model for the study of cholestasis. However, a review of information available about these features, reveals little conclusive evidence as to their pathogenesis and biochemical connotations.     

Immunologic Mimicry Between Mouse Tissue and Enterobacterial Common Antigen

Organs of Swiss white albino and C57BL/6Ha mice were assessed for an antigen (CRA) which cross-reacts with common enterobacterial antigen (CA) of To this end, supernatant fluids (HKS) and ethanol-soluble fractions (ES) of heated homogenates of spleens, kidneys, and livers were examined for their capacities to react with CA hemagglutinins and to engender humoral and cellular events in the rabbit. The immunogenicity of CRA in the rabbit can not be predicted on the basis of CA hemagglutinin neutralization studies alone; although CRA was identified in the liver extracts of both mouse strains, according to this parameter, only the liver fraction of Swiss white albino mice elicited significant numbers of rosette-forming cells (RFC) in the spleens of rabbits. Also, kidney fractions, which primed the rabbits for booster with CA, were less effective in stimulating RFC in the spleens of the identical animals. Moreover, although extracts of mouse spleens failed to inhibit CA hemagglutination and did not prime rabbits for a CA hemagglutinin response, these same preparations clearly evoked RFC in rabbit spleens. Thus, the antigenicity and immunogenicity of CRA in target organs of mice reflect the mouse strain, extraction procedure, and testing method employed.     

Etiopathogenesis of Recurrent Aphthous Stomatitis and the Role of Immunologic Aspects: Literature Review

Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers; canker sores) belongs to the group of chronic, inflammatory, ulcerative diseases of the oral mucosa. Up to now, the etiopathogenesis of this condition remains unclear; it is, however, considered to be multifactorial. The results of currently performed studies indicate that genetically mediated disturbances of the innate and acquired immunity play an important role in the disease development. Factors that modify the immunologic response in RAS include: food allergies, vitamin and microelement deficiencies, hormonal and gastrointestinal disorders (e.g., celiac disease, Crohn’s disease, ulcerative colitis), some viral and bacterial infections, mechanical injuries and stress. In this paper, we presented the main etiopathogenetic factors of RAS with a special emphasis on the mechanisms of the immune response modification. Moreover, we discussed the crucial clinical symptoms and types of RAS together with epidemiologic data based on the current medical literature reports and our own observations.     

In Vitro Cytotoxicity of Mouse Macrophages Activated by Coculture with Syngeneic Sarcoma Cells

Normal resident peritoneal macrophages from C₃D² (C3H/Tif × DBA/2) F₁ mice were activated in vitro by culturing with semisyngcneic tumour celts. The tumour cells originated from a methylcholanthrene-induced sarcoma (MCIM) growing in vivo in ascites form. Macrophagc-mediated cytotoxicity was evaluated after 5 days of in vitro culture, using five different target cells. Semisyngencic (L 929), allogeneic (B16 melanoma), and xcnogeneic (HeLa) tumour cell lines and normal allogencic tibroblast cell lines (3T3, 3T6) were tested. The morphology and kinetics of the cytotoxicity reaction were studied by scanning electron microscopy and compared with release of radioactivity from ¹⁴C-thymidine-labelled target cells. The activated macrophages were able to kill the semisyngeneic, allogeneic, and xenogeneic tumour cell lines tested under conditions that did not affect normal fibroblasis. The requirement for T cells during activation of the macrophages was also tested. The cyioioxicity decreased markedly when T cells were removed from the macrophage cultures before activation or when macrophages from nude mice were used in the experiments.     

Humokal and Cellulaa Immunologic Aspects of Adjuvant and Collagfn Arthritis in Rats

Systemic and local immunological responses of rats sensitized with either M. butyricumor native type II collagen have been evaloatod. In rats exhibiting adjuvant-induced arthritis no antibodies to collagen could be detected. In animals exhibiting collagen-induced arthritis, high antibody titsrs developed by day 14, and could be correlated with the severity of the arthritis.

Delayed type hypersensitivity (DTH) responses were measured by a 5-iodo-2'-deoxyuridine 125-I (125-IUdR) uptake assay. Arthritic scores in rats immunized with collagen were not accompanied by a positive DTFt response, where as adjuvant arthritic rats showed a positive response. T-lymphocyte cellular responses in both adjuvant- and collagen-induced arthritic rats were measured. In neither syndrome were major alterations observed in T-lymphocytz subpopulations. These results provide evidence that adjuvant-induced arthritis and type II collagen-induced arthritis are distinct entities, and that they may be discriminated by the nature of the humoral response.     

Aspects of B-Cell Non-Hodgkin's Lymphoma Development: A Transition from Immune-Reactivity to Malignancy

The development of B-cell lymphomas is an intricate interplay among various pathogenic factors, leading to a multi-step process, encompassing various stages of B-cell maturation. Besides genetic abnormalities, a variety of environmental and microbial factors, as well as disproportional immune-regulatory processes lead to the malignant transformation. Yet, little is known about the exact chain of events, which lead from the physiological polyclonal B-cell activation as a response to exogenous antigens through oligoclonality to a monoclonal, uncontrolled, malignant B-cell proliferation. The aim of the present review was to summarize the potential harmful steps in the development of B-cell lymphomas, according to conventional and novel theories, and to depict therapeutic regimens presently in use as well as to envision future drug developments, beneficial in the battle against this lymphoid malignancy.     

Role of Levamisole as Immunomodulant in Mouse Lymphoma Model

Levamisole (LMS) has been considered an immunorestorative agent capable of enhancing host's antitumor immune responses. Clinical studies showed that LMS plays a significant role in adjuvant chemotherapy of colorectal cancer. Therefore studies were performed to test whether LMS would be able to restore graft responsiveness in mice with drug-dependent, age-dependent or virus-dependent immunodeficiency. the results show that LMS has little or no influence on the limited antitumor effects of Dacarbazine or Ara-C in mice bearing allogeneic leukemias (i.e. in a host-tumor model in which immuno-chemotherapy synergism occurs with less immunodepressive anticancer drugs) Moreover LMS does not alleviate allograft response inhibition produced by high-dose Dacarbazine or by a mouse RNA virus. However the agent restored graft responsiveness in aged animals. the limited immunoenhancing effects of LMS, as detected in the present study, suggest that the clinical efficacy of the agent could be due to mechanisms not entirely related to its immunopharmacological properties.     

Morphologic and Antigenic Maturation of Lymphocytes in the Mouse Thymus In Vitro

A simple technique for organ culture of the thymus of 14-day-old mouse embryos is decribed. It allowed a characteristic time-dependent development of the immature thymus into a lymphoid thymus with large numbers of nondividing small lymphocytes. Most of these cells carried the T-lymphocyte antigenic markers Thy-1 and TL, and all expressed H-2 antigens as determined in cytotoxicity assays. They probably developed from precursor cells without detectable Thy-1 and TL. This development appeared to be dependent on the thymic microenvironment, since it also occurred in serum-free organ cultures and in cultures with medium supplemented with serum from nude mice.     

Characterization of Non-Hodgkin''s Lymphomas Using Multiple Cell Markers: Immunologic, Morphologic, and Cytochemical Studies of 72 Cases

Tissues from 72 cases (87 specimens) of various non-Hodgkin's lymphomas were analyzed for cell markers using multiple techniques. Cell suspensions were evaluated for E, EAC, and IgGEA rosette forming cells; Fc receptor cells; and surface immunoglobulin bearing cells. Cryostat section studies topographically defined EAC binding cells. Cytochemical determinations and immunoperoxidase methods for detection of intracellular immunoglobulin and lysozyme complemented other techniques in evaluating infiltrates containing large neoplastic cells. B-cell malignancies comprised 58 cases (80%) of this series and included well and moderately well differentiated lymphocytic lymphomas (10/10); nodular (23/23) and diffuse (10/18) poorly differentiated lymphocytic lymphomas; and lymphomas of mixed lymphocytic-“histiocytic” (3/3), “undifferentiated” (3/3), and “histiocytic” (9/13) types. Nodular lymphomas were characterized as B-cell neoplasms but also revealed a prominent population of T lymphocytes (39 ± 12%). Alkaline phosphatase activity, a cytochemical marker for lymphoid cells of follicular cuffs, was most consistently observed in B-cell lymphomas of moderately well differentiated lymphocytic type (4/6 cases). In some diffuse lymphomas, cryostat section studies (EAC rosettes) suggested a pre-existing nodular proliferation. One unusual B-cell lymphoma of large cell type exhibited IgGEA rosette formation and a strong receptor for the Fc portion of IgG. Ten lymphomas (14%) were of T-cell type and were represented by cases of diffuse poorly differentiated lymphocytic lymphoma (5/18, including 3 lymphoblastic lymphomas), Sézary syndrome (1), mycosis fungoides (1), and a cytologically distinctive large cell (“histiocytic”) lymphoma (3/13). Acid phosphatase activity was a consistent marker for the T-cell malignancies, some of which also revealed α-naphthyl butyrate esterase activity. No true histiocytic lymphomas were detected. Three cases of diffuse poorly differentiated lymphocytic lymphoma and one “histiocytic” lymphoma were null.     

Production of Immune Interferon (Type II) in Cocultures of Mouse Peritoneal Macrophages and Syngeneic Tumour Cells

Mouse peritoneal macrophages were activated by coculture with syngeneic methylcholanthrene-induced sarcoma cells [7], which grow as an ascites tumour in C3D2 mice [3]. During 4-5 days of cocultivation tumour cells progressively died, leaving highly activated macrophages. Cell-free supernatant harvested from the cultures contained larger amounts of interferon than either macrophages or tumour cells cultivated alone. Peak activity of interferon occurred on day 2. Non-adherent cells cultivated together with tumour cells did not produce interferon. Removal of all non-adherent cells from macrophage cultures and host cells from tumour cell suspension did not abolish interferon production. The macrophages thus seem to be the interferon-producing cells, but the possibility that the very few remaining lymphocytes may cooperate with the macrophages in interferon production cannot be totally ruled out. The interferon produced could not be inactivated by antibodies against virus-induced interferon and was destroyed by treatment at pH 2, indicating that the interferon was not of the alpha or beta type.