Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.5 (urease)
 7,257 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the capacity of glutaraldehyde-fixed Helicobacter pylori to stimulate natural killer (NK) cell activity. Bacteria were incubated overnight with peripheral blood lymphocytes enriched for large granular lymphocytes (LGL), the mediators of non-major histocompatibility complex-restricted cellular cytotoxicity. Then, the cytolytic activity of LGL was tested against various tumor target cells. We observed that efficient cytolytic activity was generated against resistant and nonresistant tumor target cell lines. Nine local clinical isolates of H. pylori and the reference strain NCTC 11637 were tested, and they all were equally effective in inducing NK cell activity. However, flagellin antigen, glycine extract, urease, and lipopolysaccharide prepared from H. pylori NCTC 11637 all failed to induce significant NK cell activity. The supernatants which were collected after coincubation of bacteria with LGL contained a factor(s) which could activate resting LGL into efficient cytolytic activity. The supernatants were also analyzed for interferon (IFN) activity. We observed that high titers of IFN were produced and that IFN activity was neutralized with anti-gamma interferon (IFN-gamma) antiserum, but not with anti-IFN-alpha antiserum. Thus, contact of lymphocytes with H. pylori leads to efficient stimulation of NK cell activity and the production of IFN-gamma.
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PMID:Contact of lymphocytes with Helicobacter pylori augments natural killer cell activity and induces production of gamma interferon. 851 8

We examined the roles of cell- and antibody-mediated immunity in urease vaccine-induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [beta2-microglobulin (-/-)] but not MHC class II knockout mice [I-Ab (-/-)]. In B cell knockout mice [microMT (-/-)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4(+) cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II-restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.
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PMID:Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses. 985 14

Novel strategies are needed to control infection with Helicobacter pylori. Prophylactic and therapeutic immunization against this gastric pathogen is possible in animal models, and initial human studies in H. pylori-infected subjects showed that immunization with H. pylori urease is both safe and immunogenic. In rodents, gastric protection against Helicobacter species infection does not depend on the humoral immune response, and a prominent role of the major histocompatibility complex II-restricted CD4(+) T-cell response is recognized; however, much remains to be learned about the mechanisms of effective bactericidal response. A clear understanding of the basic mechanisms of gastric immune protection in humans is of the utmost importance for the development of an effective human vaccine. More potent vaccines are likely to be required to induce protection in humans. The availability of two complete genome sequences of H. pylori represents a unique opportunity to identify novel vaccine antigens. Multivalent vaccines delivered by recombinant attenuated bacteria or administered with nontoxic adjuvants need to be evaluated in relevant models.
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PMID:Strategies for developing a Helicobacter pylori vaccine. 1702 6