scholarly journals PATHOMORPHOLOGY OF EXPERIMENTAL INFECTION CAUSED BY DORMANT YERSINIA PSEUDOTUBERCULOSIS STRAINS

2021 ◽  
Author(s):  
L. Somova ◽  
B. Andryukov ◽  
I. Lyapun ◽  
E. Drobot ◽  
O. Ryazanova ◽  
...  
Keyword(s):  
Experimental Infection ◽  
Persistent Infection ◽  
Yersinia Pseudotuberculosis ◽  
Granulomatous Inflammation ◽  
Delayed Type Hypersensitivity ◽  
Hypersensitivity Reactions ◽  
Dormant State ◽  
Local Tissue ◽  
Target Organs

In the 2000s, with the development of scientific research on the uncultivated (dormant) state of pathogenic bacteria, the ideas about persistent, chronically recurrent infections, difficult to respond to antibiotic therapy have begun to shape. However, regarding human pseudotuberculosis (Far Eastern scarlet-like fever, FESLF), this question remains open. While analyzing the pathology of pseudotuberculosis, its clinical and epidemic manifestation as FESLF, we identified the etiopathogenetic prerequisites for the disease recurrence and development of persistent infection [3]. In this study, it was found that the strains of Yersinia pseudotuberculosis, which were in a dormant state, caused the development of a peculiar granulomatous inflammation in target organs with pronounced delayed-type hypersensitivity reactions in vivo. To reproduce the experimental infection, sexually mature white mice were inoculated with the strain 512 Y. pseudotuberculosis, serotype I sored for 10 years at the Museum of the Research Somov Institute of Epidemiology and Microbiology and transformed into a dormant state. For comparative studies, a dormant form from vegetative bacteria of the strain 512 Y. pseudotuberculosis was obtained by exposure to a large dose of kanamycin (the minimum antibiotic dose was exceeded 25 times). The infecting dose of both forms of bacteria was 108 µ/mouse. Samples of target organs (lung, liver, spleen) were collected for histological examination on days 3, 7, 10, 14, 21 and 32 after infection. Histological sections with 3-5 µm thickness were stained with hematoxylin and eosin according to standard techniques. It was established that strains of Y. pseudotuberculosis in dormant state caused in vivo development of a peculiar granulomatous inflammation due to delayed-type hypersensitivity reactions (DHR), which characterizes the protective reaction in infected host and reflects formation of local, tissue immunity in target organs. The peculiarities of granulomatous inflammation were revealed, in comparison with that of found during infection with vegetative ("wild") Y. pseudotuberculosis bacteria, namely: the granulomas were predominantly small in size, clearly delimited from the surrounding tissue, without destruction of central zone cells and formation of the so-called "granulomas with central karyorrhexis" (terminology proposed by A.P. Avtsyn) [4]; perivascular infiltrates and vasculitis consisted mainly of lymphocytes and often had a follicle-like appearance, resembling the follicles in lymphoid organs; in the lungs, a well-marked reaction of the bronchial-associated lymphoid tissue was observed, and in the spleen, a follicular hyperplasia, indicating a T-cell defense reaction, was observed. Thus, the causative agent of Y.pseudotuberculosis infection / FESLF, being in a dormant state, initiates the development of immunomorphological changes of a protective nature such as productive granulomatous inflammation with reactions of local tissue immunity in target organs and can contribute to the formation of persistent infection.

Molecular weight determines the frequency of delayed type hypersensitivity reactions to heparin and synthetic oligosaccharides

2005 ◽  
Vol 94 (12) ◽  
pp. 1265-1269 ◽  
Author(s):  
Susanne Alban ◽  
Roland Kaufmann ◽  
Edelgard Lindhoff-Last ◽  
Wolf-Henning Boehncke ◽  
Ralf J. Ludwig ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Heparin Therapy ◽  
Delayed Type Hypersensitivity ◽  
Published Data ◽  
Low Molecular Weight ◽  
Hypersensitivity Reactions ◽  
Type Iv ◽  
Total Data ◽  
The Individual

SummaryEczematous lesions, resulting from type IV sensitizations are well-known and relatively frequent cutaneous adverse effects of s.c. heparin therapy. If anticoagulation is further required intravenous heparin, heparinoids or lepirudin may be used as a substitute. However, these alternatives are not optimal in terms of practicability and/or safety-profiles. As molecular weight of different heparin preparations has repetitively been implied to determine the frequency of sensitization, we hypothesized, that due to its low molecular weight the pentasaccharide fondaparinux may provide a practicable and safe anticoagulant therapy in patients with delayed type hypersensitivity reactions (DTH) to heparin and other oligosaccharides. To test this concept, patients referred for diagnosis of cutaneous reactions after s.c. anticoagulant treatment underwent a series of in vivo skin allergyand challenge-tests with unfractionated heparin, a series of low molecular weight heparins (nadroparin, dalteparin, tinzaparin, enoxaparin and certoparin), the heparinoid danaparoid and the synthetic pentasaccharide fondaparinux. In total, data from twelve patients was evaluated. In accordance with previously published data, we report a high crossreactivity among heparins and heparinoids. In contrast – and in support of our initial hypothesis – sensitization towards the synthetic pentasaccharide fondaparinux was rarely observed. Plotting the cumulative incidence against the determined molecular weight of the individual anticoagulant preparations, shows that molecular weight generally is a key determinant of sensitization towards heparins and other oligosaccharides (r2=0.842, p=0.009). Hence, fondaparinux may be used as a therapeutic alternative in patients with cutaneous DTH relations towards heparin and other polysaccharides.

scholarly journals The 130-kDa Glycoform of CD43 Functions as an E-Selectin Ligand for Activated Th1 Cells In Vitro and in Delayed-Type Hypersensitivity Reactions In Vivo

2007 ◽  
Vol 127 (8) ◽  
pp. 1964-1972 ◽  
Author(s):  
Pilar Alcaide ◽  
Sandra L. King ◽  
Charles J. Dimitroff ◽  
Yaw-Chyn Lim ◽  
Robert C. Fuhlbrigge ◽  
...  
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Th1 Cells ◽  
Hypersensitivity Reactions ◽  
Selectin Ligand

In Vivo Effects of Interleukin-10 on Contact Hypersensitivity and Delayed-Type Hypersensitivity Reactions

1994 ◽  
Vol 103 (2) ◽  
pp. 211-216 ◽  
Author(s):  
Agatha Schwarz ◽  
Stephan Grabbe ◽  
Helge Riemann ◽  
Yoshinori Aragane ◽  
Manuel Simon ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Contact Hypersensitivity ◽  
Delayed Type Hypersensitivity ◽  
Hypersensitivity Reactions ◽  
In Vivo Effects

scholarly journals Immune-Mediated Tissue Injury (Hypersensitivity Reactions)

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Gerald J Prud'homme
Keyword(s):  
Tissue Injury ◽  
Granulomatous Inflammation ◽  
Delayed Type Hypersensitivity ◽  
Target Cells ◽  
Type I ◽  
Hypersensitivity Reactions ◽  
Fixed Tissue ◽  
Type Iv ◽  
Immune Mediated ◽  
Type V

Hypersensitivity is synonymous with immune-mediated tissue injury. Hypersensitivity reactions occur in several forms and give rise to numerous conditions including allergies, autoimmune disease, allograft rejection, granulomatous inflammation, and a variety of acute or chronic inflammatory disorders (vasculitis, glomerulonephritis, arthritis, pneumonitis, encephalitis, etc.). While hypersensitivity is usually detrimental, in some cases it represents a normal response to a pathogen (e.g., the granulomatous inflammation of tuberculosis). Several years ago, Gell and Coombs divided hypersensitivity states into four basic types (1), and this classification remains useful today (Table 1). Type I hypersensitivity reactions result from IgE-dependent degranulation of mast cells or basophils. Type II, or "cytotoxic" hypersensitivity, results from the binding of IgG or IgM antibodies to cell membranes or fixed tissue antigens, causing activation of the complement system. Type III, or "immune-complex" hypersensitivity, results from the formation of immune complexes that precipitate in tissues (or form in situ), also with activation of complement. Type IV, or "cell-mediated" reactions, can be subdivided into two basic types: type IV-A is synonymous with delayed-type hypersensitivity (DTH) and usually occurs in response to soluble antigens; type IV-B results from the direct killing of target cells by cytotoxic T lymphocytes (CTL). Stimulation of cells by anti-receptor autoantibodies (such as the anti-TSH receptor antibodies of Graves' disease) has been designated as type V hypersensitivity by some authors. In addition, there are syndromes caused by massive cytokine release that are not usually referred to as hypersensitivity reactions, although (in accord with the definition) they should be included in that category. Examples are anti-CD3 mAb therapy, superantigen- (superAg) induced diseases (toxic shock syndrome, scalded skin syndrome), and shock caused by endotoxins (gram negative septicemia). Despite the occurrence of tissue injury, it should be understood that hypersensitivity mechanisms evolved as a means of fighting infectious agents. The mechanisms underlying these hypersensitivity states will be described and some clinical examples will be mentioned. In particular, the important role of cytokines, which is an area where considerable progress has occurred in recent years, will be emphasized.

scholarly journals Effects of Interleukin-1 Receptor Antagonist Overexpression on Infection by Listeria monocytogenes

1999 ◽  
Vol 67 (4) ◽  
pp. 1901-1909 ◽  
Author(s):  
Vera M. Irikura ◽  
Emmet Hirsch ◽  
David Hirsh
Keyword(s):  
Receptor Antagonist ◽  
Gene Dosage ◽  
Interleukin 1 ◽  
Delayed Type Hypersensitivity ◽  
Interleukin 1 Receptor Antagonist ◽  
Histocompatibility Complex ◽  
Target Organs ◽  
Ifn Γ

ABSTRACT Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring cytokine whose only known function is the inhibition of interleukin-1 (IL-1). Using a reverse genetic approach in mice, we previously showed that increasing IL-1ra gene dosage leads to reduced survival of a primary listerial infection. In this study, we characterize further the role of endogenously produced IL-1ra and, by inference, IL-1 in murine listeriosis. IL-1ra overexpression inhibits, but does not eliminate, primary immune responses, reducing survival and increasing bacterial loads in the target organs. We demonstrate that IL-1ra functions in the innate immune response to regulate the peak leukocyte levels in the blood, the accumulation of leukocytes at sites of infection, and the activation of macrophages during a primary infection. Reduced macrophage class II major histocompatibility complex expression was observed despite increased gamma interferon (IFN-γ) levels, suggesting that IL-1 activity is essential along with IFN-γ for macrophage activation in vivo. We also show that IL-1ra plays a more limited role during secondary listeriosis, blunting the strength of the delayed-type hypersensitivity response to listerial antigen while not significantly altering cellular immunity to a second infectious challenge. When these results are compared to those for other mutant mice, IL-1ra appears to be unique among the cytokines studied to date in its regulation of leukocyte migration during primary listeriosis.

68Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with 68Ga-NODAGA-AE105

2019 ◽  
Vol 18 (9) ◽  
pp. 1289-1294 ◽  
Author(s):  
Kusum Vats ◽  
Rohit Sharma ◽  
Haladhar D. Sarma ◽  
Drishty Satpati ◽  
Ashutosh Dash
Keyword(s):  
Solid Phase ◽  
Evaluation Studies ◽  
Radiochemical Yield ◽  
In Vivo Evaluation ◽  
Peptide Conjugates ◽  
Biodistribution Studies ◽  
Target Organs ◽  
U87mg Tumor

Aims: The urokinase Plasminogen Activator Receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPARexpressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes. Method: The peptide conjugates, HBED-CC-AE105-NH2 and NODAGA-AE105-NH2 were manually synthesized by standard Fmoc solid phase strategy and subsequently radiolabeled with 68Ga eluted from a commercial 68Ge/68Ga generator. In vitro cell studies for the two radiotracers were performed with uPAR positive U87MG cells. Biodistribution studies were carried out in mouse xenografts with the subcutaneously induced U87MG tumor. Results: The two radiotracers, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 that were prepared in >95% radiochemical yield and >96% radiochemical purity, exhibited excellent in vitro stability. In vivo evaluation studies revealed higher uptake of 68Ga-HBED-CC-AE105 in U87MG tumor as compared to 68Ga-NODAGAAE105; however, increased lipophilicity of 68Ga-HBED-CC-AE105 resulted in slower clearance from blood and other non-target organs. The uPAR specificity of the two radiotracers was ascertained by significant (p<0.05) reduction in the tumor uptake with a co-injected blocking dose of unlabeled AE-105 peptide. Conclusion: Amongst the two radiotracers studied, the neutral 68Ga-NODAGA-AE105 with more hydrophilic chelator exhibited faster clearance from non-target organs. The conjugation of HBED-CC chelator (less hydrophilic) resulted in negatively charged 68Ga-HBED-CC-AE105 which was observed to have high retention in blood that decreased target to non-target ratios.

scholarly journals Techniques for the Assessment of In Vitro and In Vivo Antifungal Combinations

2021 ◽  
Vol 7 (2) ◽  
pp. 113
Author(s):  
Anne-Laure Bidaud ◽  
Patrick Schwarz ◽  
Guillaume Herbreteau ◽  
Eric Dannaoui
Keyword(s):  
Animal Models ◽  
Fungal Infections ◽  
Acquired Resistance ◽  
Adequate Treatment ◽  
Combination Treatments ◽  
Target Organs ◽  
Fungal Load ◽  
Time Kill

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs.

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