Immunomodulatory effect of a newly synthesized compound, TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5, 6-dihydroimidazo [2,1-b]thiazole-2-carboxamide) on antibody production in in vivo and delayed-type hypersensitivity in mice

1990 ◽  
Vol 12 (5) ◽  
pp. 497-502 ◽  
Author(s):  
Kensuke Shibata ◽  
Toyokazu Kobayashi ◽  
Noriyasu Takayanagi ◽  
Masami Fujiwara ◽  
Itaru Yamamoto
Keyword(s):  
Antibody Production ◽  
Immunomodulatory Effect ◽  
Delayed Type Hypersensitivity

scholarly journals H-2 restriction of virus-specific T-cell-mediated effector functions in vivo. II. Adoptive transfer of delayed-type hypersensitivity to murine lymphocytic choriomeningits virus is restriced by the K and D region of H-2.

1976 ◽  
Vol 144 (3) ◽  
pp. 776-787 ◽  
Author(s):  
R M Zinkernagel
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Gamma Globulin ◽  
Effector T Cells ◽  
Delayed Type Hypersensitivity ◽  
T Effector Cells ◽  
Immune Lymphocytes ◽  
D Region

In mice, primary footpad swelling after local infection with lymphocytic choriomeningitis virus (LCMV) and delayed-type hypersensitivity (DTH) adoptively transferred by LCMV immune lymphocytes are T-cell dependent. Nude mice do not develop primary footpad swelling, and T-cell depletion abrogates the capacity to transfer LCMV-specific DTH. Effector T cells involved in eliciting dose-dependent DTH are virus specific in that vaccinia virus-immune lymphocytes could not elicit DTH in LCMV-infected mice. The adoptive transfer of DTH is restricted to H-2K or H-2D compatible donor-recipient combinations. Distinct from the fowl-gamma-globulin DTH model, I-region compatibility is neither necessary nor alone sufficient. Whatever the mechanisms involved in this K- or D-region associated restriction in vivo, it most likely operates at the level of T-cell recognition of "altered self" coded in K or D. T cells associated with the I region (helper T cells and DTH-T cells to fowl-gamma-globulin) are specific for soluble, defined, and inert antigens. T cells associated with the K and D region (T cells cytotoxic in vitro and in vivo for acute LCMV-infected cells, DTH effector T cells, and anti-viral T cells) are specific for infectious, multiplying virus. The fact that T-cell specificity is differentially linked with the I region or with the K and D regions of H-2 may reflect the fundamental biological differences of these antigens. Although it cannot be excluded that separate functional subclasses of T-effector cells could have self-recognizers for different cell surface structures coded in I or K and D, it is more likely that the antigen parameters determine whether T cells are specific for "altered" I or "altered" K- or D-coded structures.

In vivo Antibody Production by Spleen Cells after Incubation in vitro with Heterologous Antilymphocyte Plasma

Nature ◽  
1968 ◽  
Vol 220 (5174) ◽  
pp. 1350-1352 ◽  
Author(s):  
H. F. JEEJEEBHOY ◽  
A. G. RABBAT
Keyword(s):  
Antibody Production ◽  
Spleen Cells

scholarly journals A Critical Role for Fas Ligand in the Active Suppression of Systemic Immune Responses by Ultraviolet Radiation

1999 ◽  
Vol 189 (8) ◽  
pp. 1285-1294 ◽  
Author(s):  
Laurie L. Hill ◽  
Vijay K. Shreedhar ◽  
Margaret L. Kripke ◽  
Laurie B. Owen-Schaub
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Immune Suppression ◽  
Fas Ligand ◽  
Critical Role ◽  
Cell Activity ◽  
Contact Hypersensitivity ◽  
Delayed Type Hypersensitivity ◽  
Intact Cells

Induction of antigen-specific suppression elicited by environmental insults, such as ultraviolet (UV)-B radiation in sunlight, can inhibit an effective immune response in vivo and may contribute to the outgrowth of UV-induced skin cancer. Although UV-induced DNA damage is known to be an initiating event in the immune suppression of most antigen responses, the underlying mechanism(s) of such suppression remain undefined. In this report, we document that Fas ligand (FasL) is critical for UV-induced systemic immune suppression. Normal mice acutely exposed to UV exhibit a profound suppression of both contact hypersensitivity and delayed type hypersensitivity (DTH) reactions and the development of transferable antigen-specific suppressor cells. FasL-deficient mice exposed to UV lack both transferable suppressor cell activity and primary suppression to all antigens tested, with the exception of the DTH response to allogeneic spleen cells. Interestingly, suppression of this response is also known to occur independently of UV-induced DNA damage. Delivery of alloantigen as protein, rather than intact cells, restored the requirement for FasL in UV-induced immune suppression of this response. These results substantiate that FasL/Fas interactions are essential for systemic UV-induced suppression of immune responses that involve host antigen presentation and suggest an interrelationship between UV-induced DNA damage and FasL in this phenomenon. Collectively, our results suggest a model whereby UV-induced DNA damage disarms the immune system in a manner similar to that observed in immunologically privileged sites.

Host-Etiological Agent Interactions in Intranasally and Intraperitoneally Induced Cryptococcosis in Mice

1980 ◽  
Vol 29 (2) ◽  
pp. 633-641 ◽  
Author(s):  
Thuang S. Lim ◽  
Juneann W. Murphy ◽  
Larry K. Cauley
Keyword(s):  
Etiological Agent ◽  
Delayed Type Hypersensitivity ◽  
In Vivo Model ◽  
Spleen Cells ◽  
Polysaccharide Antigen ◽  
Cryptococcal Antigen ◽  
Agent Interactions ◽  
Growth Profiles ◽  
Host Parasite

Inbred CBA/J mice were used in developing a defined in vivo model for studying host-parasite relationships in cryptococcosis. Mice were infected either intranasally or intraperitoneally with 10 3 viable Cryptococcus neoformans cells. At weekly intervals over a 92-day period, C. neoformans growth profiles in the lungs, spleens, livers, and brains of the infected animals were determined. In addition, humoral and delayed-type hypersensitivity responses and cryptococcal antigen levels were assayed in these mice. Intranasally infected mice developed strong delayed-type hypersensitivity reactions in response to cryptococcal culture filtrate (CneF) antigen, and there was good correlation between acquisition of delayed-type hypersensitivity and the reduction of C. neoformans cell numbers in infected tissues. In contrast, intraperitoneally infected mice displayed greater numbers of C. neoformans cells in tissues and had somewhat suppressed delayed-type hypersensitivity responses to CneF antigen. Anticryptococcal antibodies were not detected in intranasally or intraperitoneally infected mice, but cryptococcal polysaccharide antigen titers were relatively high in both groups. The transfer of sensitized spleen cells from intranasally infected mice to syngeneic naive recipient mice resulted in the transfer of delayed-type hypersensitivity responsiveness to cryptococcal antigen in the recipients. The intranasally induced infection in mice was similar to the naturally acquired infection in humans; therefore we are proposing that this murine-cryptococcosis model would be useful in gaining a greater understanding of host-etiological agent relationships in this disease.

scholarly journals A Signal Transducer and Activator of  Transcription (Stat)4-independent Pathway for the Development of  T Helper Type 1 Cells

1998 ◽  
Vol 188 (6) ◽  
pp. 1191-1196 ◽  
Author(s):  
Mark H. Kaplan ◽  
Andrea L. Wurster ◽  
Michael J. Grusby
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Th2 Cells ◽  
Signal Transducer ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th Cell ◽  
Ifn Γ

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6−/− lymphocytes fail to differentiate into interleukin (IL)-4–secreting Th2 cells. However, in contrast to Stat4−/− lymphocytes, T cells from Stat4, Stat6−/− mice produce significant amounts of interferon (IFN)-γ when activated in vitro. Although Stat4, Stat6−/− lymphocytes produce less IFN-γ than IL-12–stimulated control lymphocytes, equivalent numbers of IFN-γ–secreting cells can be generated from cultures of Stat4, Stat6−/− lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell–promoting conditions. Moreover, Stat4, Stat6−/− mice are able to mount an in vivo Th1 cell–mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.

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 Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis.

1993 ◽  
Vol 178 (5) ◽  
pp. 1541-1554 ◽  
Author(s):  
K Ando ◽  
T Moriyama ◽  
L G Guidotti ◽  
S Wirth ◽  
R D Schreiber ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Cytotoxic T Lymphocyte ◽  
Hepatitis B Surface Antigen ◽  
Cell Interaction ◽  
Class I ◽  
Delayed Type Hypersensitivity ◽  
Cellular Mechanisms ◽  
Multistep Process ◽  
Necroinflammatory Liver Disease

The molecular and cellular mechanisms responsible for cytotoxic T lymphocyte (CTL)-induced immunopathology are not well defined. Using a model in which hepatitis B surface antigen (HBsAg)-specific CTL cause an acute necroinflammatory liver disease in HBsAg transgenic mice, we demonstrate that class I-restricted disease pathogenesis is an orderly, multistep process that involves direct as well as indirect consequences of CTL activation. It begins (step 1) almost immediately as a direct antigen-specific CTL-target cell interaction that triggers the HBsAg-positive hepatocyte to undergo programmed cell death (apoptosis). It progresses (step 2) within hours to a focal inflammatory response in which antigen-nonspecific lymphocytes and neutrophils amplify the local cytopathic effect of the CTL. The most destructive pathogenetic function of the CTL, however, is to secrete interferon gamma when they encounter antigen in vivo, thereby activating the intrahepatic macrophage and inducing a delayed-type hypersensitivity response (step 3) that destroys the liver and kills the mouse. We propose that the principles illustrated in this study are generally applicable to other models of class I-restricted, CTL-induced immunopathology, and we suggest that they contribute to the immunopathogenesis of viral hepatitis during hepatitis B virus infection in humans.

scholarly journals Simple Nanoparticles from the Assembly of Cationic Polymer and Antigen as Immunoadjuvants

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 105 ◽  
Author(s):  
Yunys Pérez-Betancourt ◽  
Bianca de Carvalho Lins Fernandes Távora ◽  
Mônica Colombini ◽  
Eliana L. Faquim-Mauro ◽  
Ana Maria Carmona-Ribeiro
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Hydrodynamic Diameter ◽  
Spherical Nanoparticles ◽  
Diallyldimethylammonium Chloride ◽  
The One ◽  
Antigen Presenting ◽  
Th 1 ◽  
Positively Charged ◽  
Stimulation Of

Since antigens are negatively charged, they combine well with positively charged adjuvants. Here, ovalbumin (OVA) (0.1 mg·mL−1) and poly (diallyldimethylammonium chloride) (PDDA) (0.01 mg·mL−1) yielded PDDA/OVA assemblies characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM) as spherical nanoparticles (NPs) of 170 ± 4 nm hydrodynamic diameter, 30 ± 2 mV of zeta-potential and 0.11 ± 0.01 of polydispersity. Mice immunization with the NPs elicited high OVA-specific IgG1 and low OVA-specific IgG2a production, indicating a Th-2 response. Delayed-type hypersensitivity reaction (DTH) was low and comparable to the one elicited by Al(OH)3/OVA, suggesting again a Th-2 response. PDDA advantages as an adjuvant were simplicity (a single-component adjuvant), low concentration needed (0.01 mg·mL−1 PDDA) combined with antigen yielding neglectable cytotoxicity, and high stability of PDDA/OVA dispersions. The NPs elicited much higher OVA-specific antibodies production than Al(OH)3/OVA. In vivo, the nano-metric size possibly assured antigen presentation by antigen-presenting cells (APC) at the lymph nodes, in contrast to the location of Al(OH)3/OVA microparticles at the site of injection for longer periods with stimulation of local dendritic cells. In the future, it will be interesting to evaluate combinations of the antigen with NPs carrying both PDDA and elicitors of the Th-1 response.

scholarly journals Immunologic Mechanisms in Heavily Irradiated Mice Treated with Bone Marrow

Blood ◽  
1959 ◽  
Vol 14 (5) ◽  
pp. 548-557 ◽  
Author(s):  
J. W. HOLLINGSWORTH ◽  
Mary C. Perfetto
Keyword(s):  
Bone Marrow ◽  
Antibody Production ◽  
Treated Mouse ◽  
Rat Erythrocytes ◽  
End Points ◽  
Humoral Antibody ◽  
Conflicting Evidence ◽  
Donor Bone Marrow

Abstract 1. Humoral antibody production has been studied in severely irradiated mice treated with isologous (same strain) or homologous (different strain) bone marrow. 2. The two methods of study involved functional end points of humoral antibody production as evidenced by in vivo lysis of rat erythrocytes or by regression of mouse leukosis E.L. 4 in histoincompatible mouse recipients. 3. Humoral antibody production was lost after irradiation and isologous marrow treatment, but recovered partially in two weeks and almost completely in four weeks. 4. Established immunity was not abruptly terminated after irradiation and treatment with either isologous or homologous marrow, although there was premature loss of immunity to rat erythrocytes by the irradiated, isologous marrow-treated mouse. 5. Permanent immunity could not be transferred by isologous marrow or spleen from immunized donors to irradiated recipients. 6. Treatment of mice histoincompatible to E.L. 4 leukosis with histocompatible donor bone marrow failed to establish rejection of the tumor. 7. These studies support the concept that humoral antibody production in irradiated, marrow-treated mice remains a function of the host rather than of the transplanted tissues. 8. These studies failed to clarify the conflicting evidence concerning the mechanism of the late illness that occurs after treatment of the irradiated mouse with bone marrow from a different strain or species.

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