Medical Immunology Commons^™

Toxoplasma Gondii-Induced Immune Suppression By Human Peripheral Blood Monocytes: Role Of Gamma Interferon., Jacqueline Y. Channon, Lloyd H. Kasper

Dartmouth Scholarship

The ability of Toxoplasma gondii to evade the host immune response during primary infection in humans is poorly understood. In murine toxoplasmosis, infected spleen macrophages release soluble factors that mediate a transient immunosuppression, which may allow the parasite to become established. When an enriched population of human monocytes from seronegative individuals was incubated with toxoplasmas in vitro, soluble factors that mediated market suppression of mitogen-induced lymphocyte DNA synthesis were released. Irradiated tachyzoites that do not undergo replication were sufficient stimuli for near-maximal soluble factor release. Up to 50% of the soluble factor-mediated suppression is attributable to a gamma interferon (IFN-gamma)-dependent …

Survival Of Immunoglobulin G-Opsonized Toxoplasma Gondii In Nonadherent Human Monocytes., Camilo E. Fadul, Jacqueline Y. Channon, Lloyd H. Kasper

Dartmouth Scholarship

Toxoplasma gondii is a protozoan parasite that is able to penetrate human monocytes by either passive uptake during phagocytosis or active penetration. It is expected that immunoglobulin G (IgG) opsonization will target the parasite to macrophage Fc gamma receptors for phagocytic processing and subsequent degradation. Antibody-opsonized T. gondii tachyzoites were used to infect nonadherent and adherent human monocytes obtained from the peripheral blood of seronegative individuals. The infected monocytes were evaluated for the presence of intracellular parasites and the degree of parasiticidal activity. A marked difference in both the numbers of infected macrophages and numbers of parasites per 100 macrophages …

Biochemical And Molecular Characterization Of The Prostate-Specific Membrane Antigen (Psma), John Karl Troyer

Theses and Dissertations in Biomedical Sciences

Prostate cancer is the most common malignancy and the second leading cause of cancer death in males in the United States. Additionally, the number of deaths attributed to prostate cancer is increasing at a rate of approximately 8% a year. Development of new diagnostic and therapy strategies are needed in order to improve the life expectancy of patients with this disease. One tool which may allow for improvements in prostate cancer diagnosis and therapy is the monoclonal antibody (MAb) 7E11-C5.3 which was first described in 1987. Since then, the antigen recognized by MAb 7E11-C5.3 has been named the prostate specific …

Identification Of An Idiotypic Peptide Recognized By Autoantibodies In Human Immunodeficiency Virus-1-Infected Individuals, Q. L. Wang, H.-T. Wang, Edwin Blalock, Sybille Müller, Heinz Köhler

Markey Cancer Center Faculty Publications

Antibodies against HIV-1 proteins in HIV-1-infected individuals share a cross-reactive idiotype defined by the monoclonal antiidiotypic antibody 1F7 (5). Using a computer algorithm based on the molecular recognition theory, regions of inverse hydropathy between the variable sequence of 1F7 and human monoclonal anti-HIV-1 antibodies were identified, which are assumed to be involved in idiotype-antiidiotype contacts. A peptide was designed from the proposed contact in the variable heavy chain framework 3-complementarity determining region 3 (FR3-CDR3) of human antibodies and was synthesized. This peptide is recognized by the antiidiotype 1F7 and inhibits the binding of 1F7 to human anti-HIV-1 antibodies which express …

Immune Response To The Carcinoembryonic Antigen In Patients Treated With An Anti-Idiotype Antibody Vaccine, Kenneth A. Foon, Mala Chakraborty, William J. John, Amanda Sherratt, Heinz Köhler, Malaya Bhattacharya-Chatterjee

Markey Cancer Center Faculty Publications

We have generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) designated 3H1, which mimics a specific epitope on the carcinoembryonic antigen (CEA). Patients with CEA positive tumors are immunologically "tolerant" to CEA. We used 3H1 as a surrogate for CEA for vaccine therapy of 12 patients with advanced colorectal cancer. Each of the patients received a minimum of four intracutaneous injections of aluminum hydroxide precipitated 3H1 at either 1, 2, or 4 mg dosage per injection. 9 of 12 patients demonstrated anti-anti-idiotypic (Ab3) response to 3H1. All nine patients generated specific anti-CEA antibody demonstrated by reactivity with radiolabeled purified CEA; …

A Model Of Cytomegalovirus Association With The Development Of Heart Graft Atherosclerosis, Evan Skowronski

Loma Linda University Electronic Theses, Dissertations & Projects

The development of graft atherosclerosis in heart transplant recipients has been associated with the development of post-transplant cytomegalovirus infection. The mechanism of this involvement, however, remains unclear. I undertook a study to determine the role of cytomegalovirus in the development of graft atherosclerosis. First, a rapid method of detecting cytomegalovirus based on capillary polymerase chain reaction and gel electrophoresis was employed to determine the presence of cytomegalovirus in a wide variety of clinical samples. Detection of cytomegalovirus is a lengthy procedure under normal conditions, and timely detection of cytomegalovirus in transplant recipients may allow intervention early enough to block the …

Media Components Influence Viral Gene Expression Assays In Human Fetal Astrocyte Cultures, Micheline Mccarthy, Charles Wood, Larisa Fedoseyeva, Scott R. Whittemore

Nebraska Center for Virology: Faculty Publications

In vitro neurovirological studies of viral infectivity or viral gene expression may be confounded by the mulHple neural cell types and/or fibrob last contamination present in early passage cultures prepared from dissociated human central nervous system (eNS) tissue. We have developed highly enriched astrocyte cultures for neurovirological study by culturing in a serum-free defined medium, 816, supplemented with basic fibroblast growth factor (FGF-2). Subculture in this medium selects against fibroblast proliferation and favors sustained proliferation of a highly enriched glial fibrillary acidic protein (GFAP)-positive cell population. These astrocytes support productive replication of cytomegalovirus (CMV) and transient expression of transfected CMVand …

Impairment Of The Cellular Immune Response In Acute Murine Toxoplasmosis: Regulation Of Interleukin 2 Production And Macrophage-Mediated Inhibitory Effects., Sakhina Haque, Imtiaz Khan, Azizul Haque, Lloyd Kasper

Dartmouth Scholarship

Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-1). Spleen cells from infected A/J mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg- and PTgB-infected A/J mice exhibited …

Comparison Of Cytotoxic Properties Of Neonatal And Adult Neutrophils And Monocytes And Enhancement By Cytokines., E . R. Stiehm, R. L. Roberts, B. J. Ank, S. Plaeger-Marshall, N. Salman, L. Shen, M. W. Fanger

Dartmouth Scholarship

We studied cytotoxic capabilities of newborn polymorphonuclear leukocytes (PMNs) and monocytes and their enhancement by cytokines and antibodies. Umbilical cord PMNs were assessed for their ability to kill various target cells spontaneously, after activation with phorbol myristate acetate, in the presence of antiserum (antibody-dependent cellular cytotoxicity), and in the presence of dually specific antibody (heteroantibody-mediated cytotoxicity). Target cells included the K562 cell line (natural killer cell target), chicken erythrocytes (CRBCs), and herpes simplex virus-infected CEM cell lines. Newborn PMNs were equivalent to adult PMNs in their cytotoxic capacity in several cytotoxicity assays. Neither adult nor newborn PMNs lyse tumor cell …

Interleukin-12 Enhances Murine Survival Against Acute Toxoplasmosis., Imtiaz A. Khan, Tadashi Matsuura, Lloyd H. Kasper

Dartmouth Scholarship

Protective immunity against Toxoplasma gondii is mediated by the host cellular immune response. Interleukin-12 (IL-12), a recently described cytokine that stimulates NK cells to produce gamma interferon (IFN-gamma), is able to enhance host protection against this parasite in SCID mice. Administration of IL-12 to A/J mice significantly increased survival over that of control mice when IL-12 was delivered early in the course of acute infection. If it was administered at day 3 or thereafter, there was no observed difference in mortality between treated and control mice. Antibody depletion of IL-12 increased susceptibility to infection, as measured by mortality, only when …

Immunologic Evaluation Of Ectopic Gestation, Tawfig Amin Nasser

Health Services Research Dissertations

Ectopic gestation is an error in the implantation site of the blastocyst. Extrauterine implantation presents a unique environment since the protective features of the uterus are absent. This study is an investigation into the immunoregulatory differences that may develop as a result of a change in the feto-maternal junction.

The effects of female plasma on one-way mixed lymphocyte cultures and mitogen-stimulated cultures, anti-paternal lymphocytotoxicity, and lymphocyte phenotypes were determined on normal, ectopic and non-pregnant females. The results indicated that pregnant female plasma enhanced the response of autologous lymphocytes to spouse and male control lymphocytes. Enhancement was not seen in the …

Book Review: The Baculovirus Expression System: A Laboratory Guide (1992) King, L. A. & Possee, R. D., David D. Dunigan

Nebraska Center for Virology: Faculty Publications

The power of molecular biology is unleashed with the ability to clone and sequence genes, and then express these genes in heterologous systems. This sets the stage for the full analysis of proteins that are otherwise difficult to isolate and/or purify, especially when present at very low copy number per cell or when isolated from relatively precious materials. Overexpression of protein is now possible in a number of systems including prokaryotes (e.g., E. coli) and various eukaryotes (yeast, insects, and plants). The issue then becomes, which system (1) most closely reflects the homologous expression with respect to posttranslational modifications, …

Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green

Dartmouth Scholarship

LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors.

Altered Expression Of Adenovirus 12 Dna-Binding Protein But Not Dna Polymerase During Abortive Infection Of Hamster Cells, Lynne A. Lucher, Benjawan Khuntirat, Jiansheng Zhao, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Replication of human adenovirus type 12 DNA is blocked in abortively infected baby hamster kidney cells. The activity and accumulation of adenovirus 12 DNA polymerase is equivalent in infected hamster and human cell extracts. However, the accumulation of adenovirus type 12 DNA-binding protein is approximately 120-fold lower in extracts from infected hamster cells when compared to infected permissive human cells. This difference in accumulation is not because of replication of viral DNA during productive infection, since this difference is observed in the presence of hydroxyurea. The DNA-binding protein from infected hamster cells retains the ability to bind denatured DNA-cellulose. An …

Cell Mediated Immunity By Cytotoxicity Assay And The Effect Of Corynebacterium Parvum And Radiation On Mice Bearing Herpes-Induced Tumors, Robert B. Stagg

Loma Linda University Electronic Theses, Dissertations & Projects

Cell mediated immune (CMI) cytotoxic reactivity of Balb/c mice against H238 cells, a Herpes simplex virus (HSV) Type 2 - induced sarcoma, was measured by the ¹²⁵IUdR release assay. The Balb/c mouse response to the growing HSV-induced tumor, treated with radiation and , was measured by survival rate, tumor growth and immune cytotoxicity of spleen and peritoneal exudate cells (PEC) as determined by ¹²⁵IUdR release assay. Subcutaneous (s.c.) inoculation of 1 x 10⁶ H238 cells (high dose) produced progressive tumor growth while s.c. inoculation of 1 x 10⁴ H238 cells (low dose) produced no tumors. A …

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses, Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R. Pease, Richard J. Webby, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed “single-cycle” adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors …