Medical Immunology Commons^™

T-Cell Responses To The M3 Immune Evasion Protein Of Murid Gammaherpesvirus 68 Are Partially Protective And Induced With Lytic Antigen Kinetics, Joshua J. Obar, Douglas C. Donovan, Sarah G. Crist, Ondine Silvia, James P. Stewart, Edward J. Usherwood

Dartmouth Scholarship

DNA vaccination with the M3 gene, encoding an immune evasion molecule expressed during both the acute lytic and persistent phases of murid gammaherpesvirus 68 infection, yielded a significantly lower titer of virus in the lung than controls. The protection seen was dependent on T cells, and we mapped an epitope recognized by CD8 T cells. The immune response to this epitope follows the same kinetics as lytic cycle antigens, despite the fact that this gene is expressed in both lytic and persistent stages of infection. This has important implications for our understanding of T-cell responses to putative latency-associated gammaherpesvirus proteins …

Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper

Dartmouth Scholarship

Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50 % lethal dose (LD₅₀) of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J) or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD₅₀ of CBA/J mice) died post infection, whereas CBA/J mice that received 15 …

Amelioration Of Proteolipid Protein 139–151-Induced Encephalomyelitis In Sjl Mice By Modified Amino Acid Copolymers And Their Mechanisms, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Eric Sheu, Masha Fridkis-Hareli, Hiroyuki Nishimura, Celia F. Brosnan, Laura Santambrogio, Vijay K. Kuchroo, Jack L. Strominger

Jay Reddy Publications

Copolymer 1 [Cop1, glatiramer acetate, Copaxone, poly(Y,E,A,K)n] is widely used in the treatment of relapsing/remitting multiple sclerosis in which it reduces the frequency of relapses by ≈30%. In the present study, copolymers with modified amino acid compositions (based on the binding motif of myelin basic protein 85–99 to HLA-DR2) have been developed with the aim of suppressing multiple sclerosis more effectively. The enhanced efficacy of these copolymers in experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with proteolipid protein 139–151 was demonstrated by using three protocols: (i) simultaneous administration of autoantigen and copolymer (termed prevention), (ii) …

The Cd154/Cd40 Interaction Required For Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated By Upregulation Of The Cd80/Cd86 Costimulatory Molecules, Kathy A. Green, W. James Cook, Arlene H. Sharpe, William R. Green

Dartmouth Scholarship

C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40^−/− and CD154^−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4⁺ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86^−/− B6 mice develop MAIDS after LP-BM5 infection.

Characterization Of Host-Bacteria Interactions Contributing To Group B Streptococcus Colonization, Jennifer Marie Smith

Theses, Dissertations and Capstones

Group B streptococcus (GBS) is the leading cause of life-threatening bacterial infections during the first three months of life. GBS is also a frequent cause of maternal postpartum infections. Both types of infections stem from maternal vaginal and/or rectal colonization with GBS in the perinatal period. Limited information is available concerning how the colonization process occurs and what role the host immune system may play in the establishment of persistent colonization by GBS. The complex interactions between the immune system and GBS normally should end in clearance of the bacteria. However, since colonization by GBS occurs in a large number …

Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green

Dartmouth Scholarship

Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or …

Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel

Dartmouth Scholarship

No abstract provided.

Lack Of Cd4+ T Cells Does Not Affect Induction Of Cd8+ T-Cell Immunity Against Encephalitozoon Cuniculi Infection, Magali Moretto, Lori Casciotti, Brigit Durell, Imtiaz A. Khan

Dartmouth Scholarship

Cell-mediated immunity has been reported to play an important role in defense against Encephalitozoon cuniculi infection. Previous studies from our laboratory have underlined the importance of cytotoxic CD8⁺ T lymphocytes (CTL) in survival of mice infected with E. cuniculi. In the present study, immune response against E. cuniculi infection in CD4⁺T-cell-deficient mice was evaluated. Similar to resistant wild-type animals, CD4^−/− mice were able to resolve E. cuniculi infection even at a very high challenge dose (5 × 10⁷ spores/mouse). Tissues from infected CD4^−/−mice did not exhibit higher parasite loads in comparison to …

Anti-Gag Cytolytic T Lymphocytes Specific For An Alternative Translational Reading Frame-Derived Epitope And Resistance Versus Susceptibility To Retrovirus-Induced Murine Aids In F1 Mice, Shawn-Marie Mayrand, Patricia A. Healy, Bruce E. Torbett, William R. Green

Dartmouth Scholarship

Murine AIDS (MAIDS) develops in susceptible mouse strains after infection with the LP-BM5 murine leukemia virus complex that contains causative defective, and ecotropic helper, retroviruses. We previously demonstrated that the MAIDSresistant H-2d strains BALB/cByJ and C57BL/KsJ generate MHC class I (Kd ) restricted virus-specific CD81 cytolytic T lymphocytes (CTLs) that lyse cells expressing either defective or ecotropic gag proteins. In contrast, the congenic BALB.B and closely related C57BL/6J MAIDS-susceptible H-2b strains were unable to serve as a source of gag-specific CTLs (Schwarz and Green, 1994), suggesting that anti-gag CTLs might provide a basis for resistance to MAIDS. Although its susceptibility …

Naturally Occurring Tap-Dependent Specific T-Cell Tolerance For A Variant Of An Immunodominant Retroviral Cytotoxic T-Lymphocyte Epitope, Victor Kim, Jonathan W. Yewdell, William R. Green

Dartmouth Scholarship

Upon immunization and restimulation with tumors induced by the endogenous AKR/Gross murine leukemia virus (MuLV), C57BL/6 mice generate vigorous H-2K(b)-restricted cytotoxic T-lymphocyte (CTL) responses to a determinant (KSPWFTTL) derived from the p15E transmembrane portion of the viral envelope glycoprotein. By contrast, the highly homologous determinant RSPWFTTL, expressed by tumor cells induced by Friend/Moloney/Rauscher (FMR) MuLV, is not immunogenic, even when presented to the immune system as vaccinia virus-encoded cytosolic or endoplasmic reticulum (ER)-targeted minigene products. Such minigene products are usually highly immunogenic since they bypass the need for cells to liberate the peptide or transport the peptide into the ER …

Immune Responses Induced By Gene Gun Or Intramuscular Injection Of Dna Vaccines That Express Immunogenic Regions Of The Serine Repeat Antigen From Plasmodium Falciparum, Alexia A. Belperron, David Feltquate, Barbara A. Fox, Toshihiro Horii, David J. Bzik

Dartmouth Scholarship

The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110) of SERA. Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic …

Attachment Ligands Of Viable Toxoplasma Gondii Induce Soluble Immunosuppressive Factors In Human Monocytes, Jacqueline Y. Channon, Edward I. Suh, Rosanne M. Seguin, Lloyd H. Kasper

Dartmouth Scholarship

Previous studies have demonstrated that surface antigen proteins, in particular SAG-1, of Toxoplasma gondii are important to this parasite as attachment ligands for the host cell. An in vitro assay was developed to test whether these ligands and other secretory proteins are involved in the immune response of human cells to toxoplasma. Human monocytes were infected with tachyzoites in the presence of antiparasite antibodies, and their effect on mitogen-induced lymphoproliferation was examined. The presence of antibody to either parasite-excreted proteins (MIC-1 and MIC-2) or surface proteins (SAG-1 and SAG-2) during infection neutralized the marked decrease seen in mitogen-induced lymphoproliferation in …

Role Of Gamma Interferon In Cellular Immune Response Against Murine Encephalitozoon Cuniculi Infection, Imtiaz A. Khan, Magali Moretto

Dartmouth Scholarship

Microsporidia are obligate intracellular protozoan parasites that cause a wide variety of opportunistic infection in patients with AIDS. Because it is able to grow in vitro, Encephalitozoon cuniculi is currently the best-studied microsporidian. T cells mediate protective immunity against this parasite. Splenocytes obtained from infected mice proliferate in vitro in response to irradiated parasites. A transient state of hyporesponsiveness to parasite antigen and mitogen was observed at day 17 postinfection. This downregulatory response could be partially reversed by addition of nitric oxide (NO) antagonist to the culture. Mice infected withE. cuniculi secrete significant levels of gamma interferon (IFN-γ). Treatment …

Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan

Dartmouth Scholarship

Neospora caninum is a coccidial protozoan parasite that appears morphologically indistinguishable from Toxoplasma gondii and that infects a large range of mammals. Both inbred and outbred strains of mice exhibit a high degree of resistance to infection with N. caninum. Three inbred strains of mice (A/J, BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were protected against a lethal challenge from T. gondii. Vaccine-induced protection was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that had been vaccinated with N. caninum and challenged with T. gondii was observed. Adoptive transfer of CD8+ T-cell splenocytes …

Cryptococcus Neoformans Serotype Groups Found In Clinical And Environmental Isolates, John Clauson

Masters Theses & Specialist Projects

Cryptococcus neoformans is an encapsulated yeast responsible for severe meningoencephalitis. The importance of epidemiological studies on cryptococcosis has increased since the beginning of the AIDS epidemic. C. neoformans exists in two varieties containing four serotypes, C. neoformans var. neoformans (serotypes A and D) and C. neoformans var. gattii (serotypes B and C). Locally C. neoformans var. neoformans has been associated with pigeon feces during those months having an average temperature of 64.2°F j(17.8°C) and above. Clinical and environmental isolates of C. neoformans obtained from regional hospitals and environmental samplings, respectively, have been grouped into their variety status utilizing canavanine-glycine-bromthymol blue …

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.

Murine Gamma Interferon Fails To Inhibit Toxoplasma Gondii Growth In Murine Fibroblasts., Joseph D. Schwartzman, Steven L. Gonias, E R. Pfefferkorn

Dartmouth Scholarship

Although treatment of human macrophages or fibroblasts with human gamma interferon results in the inhibition of intracellular Toxoplasma gondii, murine gamma interferon stimulated only murine macrophages, not murine fibroblasts, to inhibit T. gondii. This species difference may be important in understanding the control of acute and chronic toxoplasmosis.

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 …

Lethatlity Of And Elicitation Of Protective Antibody By Vibrio Parahaemolyticus Attc 17803, Richard Carlucci

Masters Theses & Specialist Projects

The LD₅₀ of Vibrio parahaemolyticus ATCC 17803 for 13- to 18-g male mice, strain ICR, as determined by the 50% endpoint method, was found to be an estimated 7 x 10⁷ CFU, when administered intraperitoneally in 0.5 ml of 24-h broth culture, O. D. 0.5 at 650 nm, diluted to 10^-0.72.

The elicitation of protective antibody by this bacterium in male New Zealand White rabbits was demonstrated by testing control, baseline, and hyperimmune rabbit sera for their protective effect against 2 LD₅₀ of the bacterium administered intraperitoneally in 13- to 18-g male mice, strain ICR. …