Immunopathology Commons^™

Novel Mechanisms Of Antigen Processing That Enhance Bcg Vaccine Efficacy, Christopher R. Singh

Dissertations and Theses (Open Access)

Mycobacterium tuberculosis, the causative agent of tuberculosis, is the most lethal single infectious agent afflicting man today causing 2 million deaths per year. The World Health Organization recommends a vaccine as the best option to prevent this disease. The current vaccine, BCG, has a variable efficacy and does not protect adults. It is known that BCG vaccine becomes sequestered in special phagosome compartments of macrophages that do not fuse with lysosomes. Since lysosome fusion is necessary for peptide production and T cell priming leading to protective T_H1 immunity, we hypothesized that vaccine efficacy is reduced and occurs perhaps …

Role Of Vitamin-D3 And Retinoic Acid In A Human Thp-1 Macrophage Model Of Mycobacterium Tuberculosis Infection, Jaymie L. Estrella

Dissertations and Theses (Open Access)

Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of Mtb. A combination of these vitamins (RAVD) enhanced the receptors on THP-1 macrophage (Mannose receptor and DC-SIGN) that increased mycobacterial uptake but inhibited the
subsequent intracellular growth of Mtb by inducing reactive oxygen species (ROS) and autophagy. RAVD also enhanced antigen presenting and homing receptors in THPs that suggested an activated phenotype for THPs following RAVD treatment. RAVD mediated activation was also associated with a marked phenotypic change in Mtb …

Role Of Pi3k-Akt Pathway In The Age Associated Decline In Tlr Mediated Activation Of Innate And Adaptive Immune Responses, Mosoka Papa Fallah

University of Kentucky Doctoral Dissertations

Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to >65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or …

Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly

Dissertations and Theses (Open Access)

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from …

Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani

Dissertations and Theses (Open Access)

Preeclampsia (PE) is a disease of late pregnancy characterized by maternal hypertension and proteinuria. It is associated with preterm delivery and significant perinatal morbidity and mortality. Despite affecting ~7% of first pregnancies, there is no effective screening method to identify women at risk, nor is there a definitive treatment other than delivery of the baby and placenta. Though the pathogenesis of PE remains unclear, an imbalance in the renin-angiotensin and immune systems are thought to be major contributors. Bridging these two concepts, it has recently been shown that women with PE harbor specific autoantibodies: the angiotensin II type 1 receptor …

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IA^s/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.

Site Directed Mutagensis Of Bacteriophage Hk639 And Identification Of Its Integration Site, Madhuri Jonnalagadda

Masters Theses & Specialist Projects

Bacteriophages affect bacterial evolution, pathogenesis and global nutrient cycling. They are also the most numerous and diverse group of biological entities on the planet [1, 2, 3, 4, 5, 6]. Members of the Lambda phage family share a similar genetic organization and control early gene expression by suppressing transcription, a process known as antitermination. Transcription antitermination in Lambda is mediated by a phage-encoded protein whereas in lambdoid phage HK022, antitermination is mediated by a phage-encoded RNA molecules. Recent results suggest that another bacteriophage called HK639 also appears to use RNA-mediated antitermination. To characterize this newly identified phage we generated site …

Pathophysiology Of Arbroviral Encephalitides In Laboratory Rodents, Aaron L. Olsen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Western equine encephalitis virus (WEEV) is an arboviral pathogen naturally found in North America. The primary disease phenotype associated with WEEV infection in susceptible hosts is a relatively long prodromal period followed by viral encephalitis. By contrast, in the current work, experimental inoculation of WEEV into the peritoneum of Syrian golden hamsters produced rapid death within approximately 96 h. It was determined that direct virus killing of lymphoid cells leads to death in WEEV-infected Syrian golden hamsters, and that inflammatory cytokines have the potential to enhance virus-induced lymphoid cell destruction. It was further concluded that WEEV retains its ability to …

T-Cell Dysfunction By Hcv Core Protein Involves Pd-1/Pd-L1 Signaling., Billy Ellis King

Electronic Theses and Dissertations

In 1989 the hepatitis C virus was identified as a significant cause of post-transfusion hepatitis. Nearly two decades later there is still no vaccine, inadequate treatment options, and limited understanding of how the virus establishes chronicity in the majority of the people it infects. Recent reports suggest that the interaction of a negative co-stimulatory pathway mediated by PD-1 and PDL-1 is associated with persistent viral infection. The role, if any, that PD-1/PDL-1 has in HCV infection is unknown. In this study we report that PD-1 is upregulated in T-cells from persons with chronic HCV infection when compared to healthy donors. …

Immunogenicity Of Terephthalate, A Constituent Of Synthetic Polymers, And Its Modulation By Adjuvants, Youssef Aachoui

All-Inclusive List of Electronic Theses and Dissertations

Objective: In this study we have focused on the potential immunotoxicity resulting from exposure to phthalate compounds which are widely present as basic constituents of many synthetic polymers.

The Defensin Gene In Dermacentor Variabilis And Ixodes Scapularis, Katherine Corbett Seguin

Biological Sciences Theses & Dissertations

In response to microbial challenge, invertebrates rely on their innate immune response to recognize and destroy harmful pathogens. One of the primary proteins produced by the response and that has been observed in many invertebrates, including insects, mussels, and ticks, is defensin. These proteins are responsible for forming pores in the membranes of invading microbes thereby destroying them. This study examined the gene coding region for defensin in two important tick disease vectors, Dermacentor variabilis and Ixodes scapularis. PCR amplification of the genes from tick chromosomal DNA resulted in the amplification of a 225 base pair amplicon. Sequencing of …

The Potential Role Of Ledgf/P75 In Prostate Cancer, Tracy Ruth Daniels

Loma Linda University Electronic Theses, Dissertations & Projects

The serum autoantibody repertoire from cancer patients is currently being exploited for the identification of tumor associated antigens (TAA) and the design of TAA arrays. Such arrays would facilitate autoantibody profiling and potentially aid in the serological diagnosis and prognosis of tumors. The goal of this study was to identify and characterize prostate-specific TAA. We observed that while the general frequency and titers of autoantibodies in PCa patients were relatively similar to those in matched controls, significant differences could be detected between the two groups in the autoantibody response to the lens epithelial-derived growth factor p75 (LEDGF/p75). LEDGF/p75 is a …

Comparison Of Tnf-A Levels Produced By Macrophages Treated With Brucella Abortus And Escherichia Coli Lps, Tajie Harris

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

Quantitative Image Analysis Of Simian Immunodeficiency Virus Replication In Macrophages Coinfected With Mycobacterium Avium Complex, Qingsheng Li, Keith G. Mansfield, Andrew Lackner, Ashley T. Haase

Qingsheng Li Publications

Mycobacterium avium is the most frequent cause of disseminated bacterial infection in patients with human immunodeficiency virus type 1 infection and in rhesus macaques with simian immunodeficiency virus (SIV) infection. This animal model of AIDS was used to test the hypothesis that this frequent association is the result of reciprocal enhancement of replication of both microorganisms. The replication of M. avium and SIV was analyzed in lymphatic tissues obtained from rhesus macaques experimentally inoculated with SIVmac who developed or remained free of overt M. avium infection. In situ hybridization, quantitative image analysis, and staining of M. avium and of macrophages …

Characterization Of P39, A Borrelia Burgdorferi Specific Protein, Jill M. Troyer

Theses and Dissertations in Biomedical Sciences

Borrelia burgdorferi, the causative agent of Lyme disease, expresses a species specific, 39 kiloDalton protein of unknown function called P39. This protein is highly immunogenic and the presence of anti-P39 antibodies in patient sera is used as an indicator of B. burgdorferi infection. P39 is also a candidate for vaccine developement due to conserved expression of P39 among B. burgdorferi isolates. Since little is presently known about this important molecule, the present study was designed to characterize P39 and was carried out in six separate investigations. First, infectious and noninfectious isolates of B. burgdorferi were established in vitro, and …

Suppressive Effects Of Transforming Factor-Β And Interleukin-10 On The Cytolytic Activity Of Murine Macrophages And Reversal By Cytokines, Chin-Hung Lin

Loma Linda University Electronic Theses, Dissertations & Projects

In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of ³H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was …

An Immunochemical Analysis Of Alcoholic Hyaline And Its Relationship To Keratin Intermediate Filaments, David L. Drexler

Loma Linda University Electronic Theses, Dissertations & Projects

Alcoholic Hyaline (AH) and keratin intermediate filaments possess ultrastructural, biochemical and immunochemical similarities. This study compares human AH, human stratum corneum keratin (HSCK) and normal human liver cytokeratin (HCK) by quantitative immunochemical means, using polyclonal as well as monoclonal antibodies. Enzyme-linked immunosorbent assays (ELISAs) were employed, as well as "immunoblotting" and immunocytochemical techniques. HCK was isolated using Triton X-100 and "high-salt” buffers and exhibited seven major polypeptide bands on SDS-PAGE (41-58 kd). Antisera were made toward HCK and the two major HCK bands. Other immunochemicals included antisera toward AH, the three major AH bands, and HSCK, as well as 3 …

Effects Of Purified Salmonella Enteritidis Endotoxin On The Immune Response Of Balb/C Mice, John B. Barnett, John W. Jutila

Journal of the Arkansas Academy of Science

Wasting disease was produced in neonatal Balb/c mice with purified Salmonella enteritidis endotoxins. The endotoxins were chemically characterized to provide the study with a potent endotoxin with constant biological activity. Neonatal mice received an initial injection of 35 μg/g body weight of endotoxin and a dose of 75 μg every third day until day 18. The degree of wasting was estimated by the runting (weight loss) index. Mortality was calculated to be 46%, with a mean survival time of approximately 15 days. The hematologic studies conducted at days 10, 20, and 30 showed an absolute neutrophilia and leukocytosis by day …

Immune Responses Of Rats To Antigens Of Moloney Leukemia Virus, Erratum, Frances B. Soderberg, Susan G. Tai, Joe M. Jones

Journal of the Arkansas Academy of Science

No abstract provided.

Immune Responses Of Rats To Antigens Of Moloney Leukemia Virus, Frances B. Soderberg, Susan G. Tai, Joe M. Jones

Journal of the Arkansas Academy of Science

No abstract provided.

Rapid Identification Of Streptococcal Infections Using Fluorescent Antibody Techniques, James H. Meadows

Biology ETDs

The use of fluorescent microscopy coupled with immunological techniques offer new methods for the demonstration of antigen-antibody reactions. The adaptation of these techniques to grouping of beta hemolytic streptococci makes feasible their further adaptation toward identification of group A streptococci in clinical material. Commercially available labeled antibodies against group A beta hemolytic streptococci were obtained for use in this study. A method for the determination of labeled antisera specificity is proposed and a technique for absorbing out any heterologous reacting antibody is described. Using this commercial labeled antisera, subsequent to specificity studies plus absorption if necessary, adaptations of basic fluorescent …

A Study Of The Relation Of Temperature To Antibody Formation In Cold-Blooded Animals, Earl C. Mcdaniel

Biology ETDs

It is an established fact that when warm-blooded animals are inoculated with foreign protein, in a great many instances they become immune, due to the formation of antibodies specific for the protein injected. In warm-blooded animals the body temperature is constant. The question naturally arises as to what the situation would be with regard to antibody formation in a cold-blooded animal where body temperature is not constant; also what part, if any, the temperature of the body would have to do with the antibody formation.

In a careful review of the literature practically nothing could be found in having direct …