Immunology and Infectious Disease Commons^™

Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, Najwane Saïd-Sadier, Eduardo V. Padilla, Gordon Langsley, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus …

Cd1d-Dependent B-Cell Help By Nk-Like T Cells Leads To Enhanced And Sustained Production Of Bacillus Anthracis Lethal Toxin-Neutralizing Antibodies, T. Scott Devera, Lindsay M. Aye, Gillian A. Lang, Sunil K. Joshi, Jimmy D. Ballard, Mark L. Lang

Bioelectrics Publications

The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (alpha-galactosylceramide [alpha-GC]) at the time of immunization improves PA-specific Ab responses. We observed that alpha-GC enhanced …

Effects Of Mold Exposure On Immune Cells, Katrin Gorham

Honors Projects in Science and Technology

The relationship between exposure to mold spores and human disease is only beginning to be understood. While evidence exists of strong correlations between moldy environments and allergic and infectious diseases, the relationship between exposure to specific species and human immune responses to them is not fully understood. This paper seeks to clarify this relationship by analyzing the effects of exposing murine immune cells to volatile organic compounds (VOCs) produced by different mold species. Mold species studied include Stachybotrys alternans; tests performed include cell viability studies and immunoassays. Results have implications for further research and treatment of mold-related diseases.

Ecological Interactions Between Spiders And The Purple Pitcher Plant, Sarracenia Purpurea, Marc Aaron Milne

Biological Sciences Theses & Dissertations

Spiders and harvestmen are commonly captured by or reside upon the carnivorous purple pitcher plant, Sarracenia purpurea. Although spiders and harvestmen are often known to be prey of S. purpurea, other ecological interactions between these arthropods and the plant are poorly understood. Studies were undertaken at three pitcher plant populations, two in Virginia and one in North Carolina, to assess the ecological relationships between spiders and harvestmen and S. purpurea. Multiple plots containing pitcher plants (treatment) and plots lacking pitcher plants (control) were created at these locations. Spiders and harvestmen were collected through five different techniques. Spatial, …

Identity Of Diphyllobothrium Spp. (Cestoda: Diphyllobothriidae) From Sea Lions And People Along The Pacific Coast Of South America, Robert L. Rausch, Ann M. Adams, Leo Margolis

Faculty Publications from the Harold W. Manter Laboratory of Parasitology

Host specificity evidently is not expressed by various species of Diphyllobothrium that occur typically in marine mammals, and people become infected occasionally when dietary customs favor ingestion of plerocercoids. This report mainly concerns two species, Diphyllobothrium pacificum and Diphyllobothrium arctocephalinum, for which sea lions (Otariidae) are final hosts. The taxonomic status of those cestodes has not been clearly discernible because of misinterpretation of relationships; complex synonymies have resulted from misidentification(s). Stiles and Hassall in 1899 obtained, but did not describe, cestodes from the northern fur seal (Otariidae; Pribilof Islands). That taxon was subsequently studied by several investigators, with diverse …

Synlophe Structure In Pseudomarshallagia Elongata (Nematoda: Trichostrongyloidea) Abomasal Parasites Among Ethiopian Ungulates, With Consideration Of Other Morphological Attributes And Differentiation Within The Ostertagiinae, Eric P. Hoberg, Bersissa Kumsa, Patricia A. Pillit, Arthur Abrams

Faculty Publications from the Harold W. Manter Laboratory of Parasitology

The independence of Pseudomarshallagia and its placement among the medium stomach worms of ungulates, Ostertagiinae, is confirmed based on comparative morphological studies of the synlophe and genital attributes among male and female specimens. An emended description of Pseudomarshallagia elongata is presented based on a series of specimens in sheep from northern Ethiopia. Pseudomarshallagia elongata is retained among the 15 genera of the Ostertagiinae based on presence of a prominent esophageal-intestinal valve, paired "0" papillae, a modified accessory bursal membrane containing the paired "7" papillae, and configuration of the copulatory bursa. The structure of the synlophe in males and females is …

Cell-Type Specific Distribution Of Chloride Transporters In The Rat Suprachiasmatic Nucleus, Michael A. Belenky, Patricia J. Sollars, David B. Mount, Seth L. Alper, Yosef Yarom, Gary E. Pickard

Papers in Veterinary and Biomedical Science

The suprachiasmatic nucleus (SCN) is a circadian oscillator and biological clock. Cell-to-cell communication is important for synchronization among SCN neuronal oscillators and the great majority of SCN neurons use γ-aminobutyric acid (GABA) as a neurotransmitter, the principal inhibitory neurotransmitter in the adult central nervous system. Acting via the ionotropic GABAA receptor, a chloride ion channel, GABA typically evokes inhibitory responses in neurons via Cl− influx. Within the SCN GABA evokes both inhibitory and excitatory responses although the mechanism underlying GABA-evoked excitation in the SCN is unknown. GABA-evoked depolarization in immature neurons in several regions of the brain is a function …

Specificity And Signaling In The Drosophila Immune Response, Neal S. Silverman, Nicholas Paul Paquette, Kamna Aggarwal

Neal Silverman

The Drosophila immune response is characterized by the rapid and robust production of a battery of antimicrobial peptides immediately following infection. The genes encoding these antimicrobial peptides are controlled by two NF-κB signaling pathways that respond to microbial infection. The IMD pathway is triggered by DAP-type peptidoglycan, from the cell wall of most Gram-negative and certain Gram-positive bacteria, and activates the NF-κB precursor protein Relish. The Toll pathway, on the other hand, is stimulated by lysine-type peptidoglycan from many Gram-positive bacteria, β 1,3 glucans from many fungi, as well as by microbial proteases. Toll signaling leads to the activation and …

Porcine Reproductive And Respiratory Syndrome Virus Nonstructural Protein 1Β Modulates Host Innate Immune Response By Antagonizing Irf3 Activation, Lalit Beura, Saumendra Sarkar, Byungjoon Kwon, Sakthivel Subramaniam, Clinton J. Jones, Asit K. Pattnaik, Fernando A. Osorio

Papers in Veterinary and Biomedical Science

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, …

The Minor Envelope Glycoproteins Gp2a And Gp4 Of Porcine Reproductive And Respiratory Syndrome Virus Interact With The Receptor Cd163, Phani B. Das, Phat X. Dinh, Israrul H. Ansari, Marcelo De Lima, Fernando A. Osorio, Asit K. Pattnaik

Papers in Veterinary and Biomedical Science

Porcine reproductive and respiratory syndrome virus (PRRSV) contains the major glycoprotein, GP5, as well as three other minor glycoproteins, namely, GP2a, GP3, and GP4, on the virion envelope, all of which are required for generation of infectious virions. To study their interactions with each other and with the cellular receptor for PRRSV, we have cloned each of the viral glycoproteins and CD163 receptor in expression vectors and examined their expression and interaction with each other in transfected cells by coimmunoprecipitation (co-IP) assay using monospecific antibodies. Our results show that a strong interaction exists between the GP4 and GP5 proteins, although …

A New Species Of Trichostrongyloid In African Buffalo (Syncerus Caffer) (Artiodactyla: Bovinae) From Uganda, Eric P. Hoberg, Arthur Abrams, Patricia A. Pilitt

Faculty Publications from the Harold W. Manter Laboratory of Parasitology

Africanastrongylus giganticus n. sp. is described based on large ostertagiine nematodes occurring in the abomasum of African buffalo, Syncerus caffer, from Uganda; this represents the second species recognized in the genus. Specimens of A. giganticus are characterized by large size (15-19 mm in total length), a strongly tapering synlophe in the cervical region, and a great number of ridges at all levels of the body (maximum 72 attained in the third quarter); numbers of ridges exceed that reported among any known genera and species of the Ostertagiinae. We refer A. giganticus to this genus based on a strongly tapering …

Tuberculosis: An Eight Year (2000-2007) Retrospective Study At The University Of Malaya Medical Centre (Ummc), Kuala Lumpur, Malaysia, Jamaiah Ibrahim

Jamaiah Ibrahim

This was an eight year (2000-2007) retrospective study of tuberculosis in patients admitted to the UMMC. A total of 131 cases were analyzed. Malays constituted the most cases, (43%), followed by Chinese (22%), Indians (17%) and others (18%). The majority of cases were within the 21-60 year old age group, which constituted 69.5% of the total. Males were more commonly affected (65%). Most cases were reported among Malaysians (83%). The majority of patients were unemployed (39%), followed by housewives (10%), laborers (9%), students (8%), shop assistants (7%), and other occupations (27%) The most common presenting complaints were prolonged productive cough, …

Cliff Swallows, Swallow Bugs, And West Nile Virus:, Larry Clark

Larry Clark

The cliff swallow (Petrochelidon pyrrhonota) could play an important role in the transmission of West Nile virus (WNV) because of its breeding ecology, reservoir competence status, and potentially high natural exposure rates. Cliff swallows nest within colonies and their nests are occupied year-round by swallow bugs (Oeciacus vicarius), hematophagus ectoparasites that feed primarily on cliff swallows. These parasites are likely exposed to WNV while feeding on infectious blood of nesting cliff swallow adults and nestlings and thus, if competent vectors, could contribute to seasonal elevations in WNV transmission. In addition, swallow bugs remain within nests year-round and therefore could provide …

Prevalence Of Microsporidia In An Indigenous Orang Asli Community In Pahang, Malaysia, Tan Tian Chye

Tan Tian Chye

Microsporidia are ubiquitous parasites thought to be closely related to fungi. Their presence in the environment means that humans are frequently exposed to infection. Stool samples were collected from 151 indigenous villagers from the eastern state of Pahang in 2005. The samples were concentrated with water-ether sedimentation, stained with modified trichrome stain and examined under oil-immersion microscopy. Thirty-two specimens (21.2%) were positive for microsporidia. Microsporidia were observed as ovoid or rounded ovoid shapes measuring similar to 1 mu m, with a bright pink outline containing a central or posterior vacuole. PCR amplification with specific primers on microscopy-positive specimens amplified Encephalitozoon …

Memory Cd8+ T Cell Differentiation, Joshua J. Obar, Leo Lefrancois

UCHC Articles - Research

In response to infection or effective vaccination, naive antigen-specific CD8+ T cells undergo a dramatic highly orchestrated activation process. Initial encounter with an appropriately activated antigen-presenting cell leads to blastogenesis and an exponential increase in antigen-specific CD8+ T cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in formation of both primary effector and long-lived memory cells. Current findings have emphasized the heterogeneity of effector and memory cell populations with the description of multiple cellular subsets based on phenotype, function, and anatomic location. Yet, only recently have we begun to dissect the underlying factors mediating the temporal control of the …

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.

Identification Of Novel Antimalarials From Marine Natural Products For Lead Discovery, Stephenie M. Alvarado

Electronic Theses and Dissertations

An estimated 500 million cases of malaria occur each year. The increasing prevalence of drug resistant strains of Plasmodium in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. Therefore, discovery of new, inexpensive, and effective drugs are urgently needed to combat this disease. Marine biodiversity is an enormous source of novel chemical entities and has been barely investigated for antimalarial drug discovery. In an effort to discover novel therapeutics for malaria, we studied the antimalarial activities of a unique marine-derived peak fraction library provided by Harbor Branch Oceanographic …

Aging Effects On Acute Lung Inflammation After Burn Injury, Vanessa Nomellini

Dissertations

The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existant in young, healthy individuals. The studies outlined below use a murine model to determine the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals following burn injury. We hypothesized that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound. We found that neutrophils continue to accumulate in the lungs of aged …

The Im-9 Cell Line: A Model For Evaluating Tcdd-Induced Modulation Of The Polymorphic Human Hs1,2 Enhancer Within The 3' Immunoglobulin Heavy Chain Regulatory Region, Ruth C. Chambers-Turner

Browse all Theses and Dissertations

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a disrupter, of B-cell differentiation, induces binding of the aryl hydrocarbon receptor (AhR) nuclear complex to dioxin responsive elements (DRE) within the mouse immunoglobulin heavy chain regulatory region (3'IgHRR), and produces a marked inhibition of 3'IgHRR activation, IgH expression, and antibody secretion in a well-characterized mouse B-cell line (CH12.LX). The mouse 3'IgHRR consists of at least four enhancers (hs3a; hs1,2; hs3b; hs4), and is highly homologous with the three enhancers (hs3; hs1,2; hs4) of the human 3'IgHRR. A polymorphism of the human hs1,2 enhancer (resulting in varying numbers of tandem repeats containing a DRE and κB site) has …

Rev Interacts With Tubulin Heterodimers To Cause Cell Cycle Defects, Poornima Kotha Lakshmi Narayan

Browse all Theses and Dissertations

Rev is a regulatory protein that plays an important role in the replication of HIV virus by post-transcriptionally promoting expression of viral proteins late in infection. Rev expression also slows cell growth, leads to an accumulation of cells in G2/M specifically before the spindle checkpoint, and can produce changes in ploidy. Because Rev is capable of depolymerizing microtubules (MTs) in vitro, possibly by a mechanism shared with Kinesin-13 proteins, themselves potent cellular MT depolymerases, I tested the hypothesis that these cellular defects were due to an interaction between Rev and tubulin.

To this end, Rev and select Rev mutants defective …