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J Immunol. 2002 Nov 1;169(9):5202-8.
Perforin-mediated CTL cytolysis counteracts direct cell-cell spread of Listeria monocytogenes.
San Mateo LR, Chua MM, Weiss SR, Shen H.
Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
The immune system has evolved various effector cells and functions to combat diverse infectious agents equipped with different virulence strategies. CD8 T cells play a critical role in protective immunity to Listeria monocytogenes (Lm), a bacterium that grows within the host cell cytosol and spreads directly into neighboring cells. The importance of CD8 T cells during Lm infection is currently attributed to the cytosolic niche of this organism, which allows it to evade many aspects of immune surveillance. CTL lysis of infected cells is believed to be an essential protective mechanism, presumably functioning to release intracellular bacteria, although its precise role remains to be fully defined. In this study, we examined the contribution of perforin-mediated CTL cytolysis to protective immunity against recombinant Lm capable of or defective in cell-cell spread. We found that CTL cytolysis is critical for protective immunity to Lm capable of cell-cell spread while protective immunity against spread-defective Lm is largely independent of CTL cytolysis. These results demonstrate that an important function of CTL cytolysis is to counter the microbial virulence strategy of direct cell-cell spread. We propose a model that advances the current view of the role of CTL cytolysis in immunity to intracellular pathogens.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12391238&dopt=Abstract
J Immunol. 2002 Nov 1;169(9):5308-14.
Down-regulation of intestinal lymphocyte activation and Th1 cytokine production by antibiotic therapy in a murine model of Crohn's disease.
Bamias G, Marini M, Moskaluk CA, Odashima M, Ross WG, Rivera-Nieves J, Cominelli F.
Digestive Health Center of Excellence, University of Virginia, Charlottesville 22908, USA.
Resident intestinal bacteria likely play an important role in the pathogenesis of Crohn's disease through their interaction with the gut immune system. SAMP1/YitFc mice spontaneously develop chronic, discontinuous, transmural ileitis with many features similar to Crohn's disease. The aim of this study was to determine the effects and elucidate the mechanisms of action of antibiotic treatment in the SAMP1/YitFc mouse model of ileitis. Mice were treated orally with ciprofloxacin and metronidazole before the development of ileitis (prevention protocol) or after ileitis was fully established (treatment protocol). Terminal ilea were harvested for histological scoring, and lamina propria and mesenteric lymph node cells were isolated for analysis of activation markers and cytokine production. Antibiotic therapy significantly decreased the severity of ileitis both in the prevention (40% reduction, p < 0.05) and the treatment (25% reduction, p < 0.01) protocols, compared with untreated, control mice. These effects were associated with a decreased percentage of CD4(+)/CD45RB(high) lymphocytes in mesenteric lymph nodes of antibiotic-treated mice, as well as decreased production of IFN-gamma (prevention: 0.53 +/- 0.21 vs 1.84 +/- 0.04 ng/ml, p < 0.05; treatment: 8.4 +/- 0.4 vs 12.4 +/- 0.7 ng/ml, p < 0.005) and TNF (prevention: 61.5 +/- 13 vs 134 +/- 19 pg/ml, p < 0.01; treatment: 333.5 +/- 11 vs 496 +/- 20 pg/ml, p < 0.001). The number of activated lamina propria lymphocytes was also reduced after antibiotic treatment. In conclusion, antibiotic therapy significantly ameliorates the severity of ileitis in SAMP1/YitFc mice by a mechanism involving down-regulation of activated gut lymphocytes and inhibition of intestinal Th1 cytokine production.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12391251&dopt=Abstract
Mol Pharmacol. 2002 Nov;62(5):1011-26.
Haptenation of sulfonamide reactive metabolites to cellular proteins.
Manchanda T, Hess D, Dale L, Ferguson SG, Rieder MJ.
Section of Paediatric Clinical Pharmacology, Toxicology & Experimental Therapeutics, Department of Paediatrics, Faculty of Medicine & Dentistry, University of Western Ontario, Ontario, Canada.
Adverse drug reactions are a major problem complicating medical therapy. The pathogenesis of many severe adverse drug reactions, notably hypersensitivity reactions, is poorly understood. The sulfonamides are associated with severe hypersensitivity reactions. The initial pathogenesis seems to be caused by bioactivation of the parent drug to a reactive intermediate and subsequent propagation by the immune system. The determinants of the immune response are not known. We explored the formation of sulfonamide haptens in Molt-3 and HEPA 1C1C7 cells after incubation with sulfamethoxazole (SMX), the hydroxylamine of sulfamethoxazole (SMX-HA), or the nitroso of sulfamethoxazole (SMX-NO). Haptenation was demonstrated with SMX-HA and SMX-NO but not SMX; this occurred at concentrations below that associated with toxicity (significant haptenation was seen at 25 to 50 microM). Thus, haptenation occurred presumably onto viable cells. Haptenation occurred rapidly; haptenation of cell surface proteins was demonstrated within 5 min. This did not occur indiscriminately; confocal microscopy demonstrated haptenation onto specific sites on the cell membrane. We found that haptenation was significantly inhibited by thiols and other antioxidants (p < 0.05). Sulfonamide-specific haptens were rapidly internalized by what seemed to be a caveolae-dependent process. It seems that sulfonamide reactive metabolites haptenated specific cell surface proteins that are rapidly internalized. Understanding the specific protein target(s) for haptenation and how these haptens are processed will be important in understanding the immune mediation of sulfonamide hypersensitivity adverse drug reactions.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12391263&dopt=Abstract
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14356-61. Epub 2002 Oct 21.
Lamprey lymphocyte-like cells express homologs of genes involved in immunologically relevant activities of mammalian lymphocytes.
Uinuk-Ool T, Mayer WE, Sato A, Dongak R, Cooper MD, Klein J.
Max-Planck-Institut fur Biologie, Abteilung Immungenetik, Corrensstrasse 42, D-72076 Tubingen, Germany.
To shed light on the origin of adaptive immunity, a cDNA library was prepared from purified lymphocyte-like cells of a jawless vertebrate, the sea lamprey (Petromyzon marinus). Randomly selected cDNA clones were sequenced, and their homologies to proteins in the databases were determined. Of the sequences homologous to proteins involved in immune responses, five were selected for further characterization. Their encoding genes corresponded to loci that in jawed vertebrates are essential for activities of lymphocytes. These activities include regulation of T and B cell stimulation and proliferation (CD45); stabilization of molecular complexes involved in lymphocyte activation, adhesion, migration, and differentiation (CD9/CD81); adaptor functions in signaling leading to the activation of B lymphocytes (BCAP) and T lymphocytes (CAST); and amino acid transport associated with cell activation (CD98). The presence of these genes in the lamprey genome and their expression in lymphocyte-like cells support the notion that these cells perform many of the functions of gnathostome lymphocytes. It reopens the question of the stage jawless fishes reached in the evolution of their immune system.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12391333&dopt=Abstract
Prikl Biokhim Mikrobiol. 2002 Sep-Oct;38(5):578-84.
[Development of quantitative immunoenzyme and radioimmunologic analysis of lambda-free immunoglobulin light chains]
[Article in Russian]
Piven' NV, Goncharik AV, Reznikov IuP, Shkumatova GA, Kul'bakova AI.
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, 220141 Belarus. pives.iboch.ac.by
New quantitative techniques of radioimmunoassay (RIA) and enzyme immunoassay (EIA) were developed for determination of free light lambda-chains of immunoglobulins (immunometric sandwich-like variants) in biological fluids using two types of monoclonal specific antibodies (MAB-1 and MAB-2) to different epitopes of the antigen molecule: MAB-1 were immobilized on a solid phase (polystyrene beads), whereas MAB-2 were labeled with iodine or with the enzyme. The test systems prepared can be used for determination of concentrations from 25 to 1000 ng/ml, are very sensitive (25 ng/ml), and the analysis time is 5 h. The two methods were compared, and their clinical and diagnostic validity was evaluated in patients with various diseases associated with disorders in the antibody synthesis by the immune system.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12391762&dopt=Abstract
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