VIRTUAL STUDENT SCHOLARS SYMPOSIUM 2020 PRESENTATIONS

Physiology and Immunology - Oral Presentations

High School Division

Analysis of White Matter Hyperintensities and Ventricular Enlargement in an Elderly Cohort
Caela Hung, Cleveland High School

White matter hyperintensities (WMH) are lesions that appear brightly on magnetic resonance images (MRI) that are commonly associated with elderly individuals and cognitive decline. There are four interconnected cavities in the brain called ventricles. Particularly large ventricles have been connected to Alzheimer’s Disease. This study explores the relationship between white matter hyperintensities and ventricular enlargement in an elderly cohort. Previous literature has suggested that ventricular enlargement is directly caused by the white matter degeneration around it, and this study sought to find out if that was true. 65 subjects were included in this study, and data was provided from a cohort of elderly individuals participating in a longitudinal study conducted by the Layton’s Aging and Alzheimer's Disease Center. A voxel-based analysis was conducted based on longitudinal MRI images. The results showed that the lateral ventricles in the brain did not grow where white matter hyperintensities previously were. This is significant because it provides insight into the validity of these as biomarkers for disease.

Undergraduate Division

Exploring the Relationship between Microglia and the Perineuronal Net during Critical Period Development of the Somatosensory Cortex
Amy Barrera, Queens College, CUNY

Sensory deprivation (SD) during the critical period of development results in behavioral and cognitive abnormalities in mammals. Previous studies from the laboratory demonstrated that SD via whisker trimming leads to activation of microglia (MG) in the primary somatosensory cortex (S1) and a reduction of Perineuronal nets (PNNs). The current study utilizes SD in conjunction with pharmacological manipulations to activate or inhibit MG throughout a developmental critical period within S1. Mice were injected with either saline (control), minocycline (MG inhibitor) or lipopolysaccharide (inflammatory agent) until post-natal day 30 while another cohort underwent SD. We hypothesized that SD and LPS will activate MG, which in turn will impact PNN density and integrity. Preliminary data shows that SD impacts MG across all injection treatments, while also resulting in qualitative changes to the PNN. This study is among the first to show correlative evidence that MG may be shaping the PNN.

Brucella abortus is Recognized by the Negative Regulator NLRX1 of the Innate Immune System
Hanna D Kiryluk, Virginia Tech

Brucella abortus is a pathogenic zoonotic bacterium that causes the disease brucellosis. Bacteria such as B. abortus contain proteins that activate immune responses, called Pathogen Associated Molecular Patterns (PAMPs). PAMPs are recognized by Pattern Recognition Receptors (PRRs) of the innate immune system. PRRs promote or inhibit immune responses by stimulating the expression of inflammatory cytokines. NLRX1 is a PRR that inhibits proinflammatory cytokine expression. This is important because chronic inflammation can lead to various diseases. However, B. abortus is unique in that it can avoid immune recognition and the inflammatory response. Removing NLRX1 could allow for increased immune response to B. abortus, therefore enhancing the innate immune system’s defense against brucellosis. This suggests that PRRs such as NLRX1 could be critical to brucellosis drug therapies. However, the activation of NLRX1 in response to B. abortus infection has yet to be determined. Thus, we used macrophages from wild type and NLRX1 knockout (Nlrx1^-/-) mice to analyze inflammatory signaling protein response to B. abortus infection. We expected Nlrx1^-/- mice to have elevated levels of inflammation over wild type mice because the absence of NLRX1 should increase inflammatory response. Our results aligned with this hypothesis, as Nlrx1^-/- macrophages had increased proinflammatory signaling proteins. This inflammatory response to B. abortus infection suggests that genomic B. abortus DNA is an effective PAMP for the immune system to recognize. Further studies focusing on the absence of NLRX1 are vital to understanding the B. abortus immune response and developing brucellosis treatments.

Cellular Adhesion Molecule Expression in Parotid Glands after MCMV Infection
Jennifer Yang, Stony Brook University

Introduction/Objectives:
Our laboratory has demonstrated that the parotid gland exhibits properties of both an inductive and effector site in the mucosal immune system. While it was demonstrated that inoculation via the parotid gland produced an effective immune response and protection against a lethal dose of murine cytomegalovirus (MCMV), little is known about the molecular mechanisms of this response. Cell-adhesion molecules (CAMs) are important to the generation of immune responses as they interact with homing receptors on antigen-specific infiltrating T-cells and B-cells. There is limited data concerning the expression of CAM in normal or inoculated parotid glands. Understanding changes in CAM expression can further elucidate the mechanisms responsible for transforming the PG into a mucosal inductive site.

Methods:
Mice were inoculated via a surgical incision of the PG with PBS (control) or MCMV (experimental). CAMs (PECAM, ICAM-1, MadCAM, VCAM) were analyzed from the PG and associated LNs 4, 7, 14, 21, and 28 days after inoculation using immunohistochemistry for protein expression and real time PCR for RNA expression. Homing receptors on infiltrating T and B cells were investigated via flow cytometry using the appropriate antibodies.

Results:
A statistically significant increase (p < 0.05.) in mRNA expression for PECAM, ICAM-1, and VCAM in MCMV inoculated mice versus control mice was demonstrated. However, differences in the kinetics of expression were observed between the PG and the associated LNs. ICAM and PeCAM mRNA were expressed earlier in the PG and later in the associated LNs. VCAM was expressed early in the PG and was maintained throughout the 21-day time course, whereas VCAM expression was expressed later in the LNs. MadCAM mRNA expression was variable (not shown). Immunohistochemistry for protein expression qualitatively verified the mRNA results. After inoculation of the parotid gland with MCMV, significant infiltration of CD4 and CD8 T cells as well as CD19 B cells was observed. Investigations of homing receptor expression on infiltrating cells demonstrated expression of the homing receptors α1 (CD49a), α4 (CD49d), and β1 (CD29) on certain subsets of lymphocytes. In addition, CD103 a marker for resident tissue memory cells was also significantly induced on CD4 T cells and CD19 B cells.

Conclusions:
Our results support the hypothesis that CAM expression is modulated after immunization and differential expression of PECAM and ICAM in the PG prior to the LNs supports the role of the PG as an inductive site. In addition, infiltrating T and B cells expressed components of homing receptors that preferentially bind to either ICAM and VCAM.

Graduate Division

Lack of Growth-space Prevents Root Completion in Impacted Maxillary Canines.
Lauren L Cardarelli, University of Connecticut

This study utilized CBCT technology to evaluate the degree of root development among unilaterally impacted canines based on the relationship between canine root development and the amount of space available between the root apex and maxillary sinus/nasal fossa floor. Unilaterally impacted maxillary canines on 54 de-identified CBCT scans were retrospectively assessed from 35 female and 19 male participants. Inclusion criteria constituted patients over the age of 15 referred for orthodontic treatment with unilaterally impacted maxillary canines. The non-impacted canines on the contralateral side served as a control in this study. Both the impacted and contralateral non-impacted sides were evaluated for key variables including but not limited to: degree of root development, proximity to closest anatomical barrier at root apex, proximity to surrounding teeth, and impaction location on Anatomage INVIVO - version 5 software. The results show that there was less space available at the root apex among maxillary impacted canines whose roots were not fully developed and this difference was statistically significant (p = 0.021). Canine length of impacted maxillary canine teeth were significantly shorter in length than their non-impacted counterparts (p = 0.001). A moderately strong negative correlation was found between the impacted canines showing closed root apex and decreased space availability between the root apex and floor of maxillary sinus/nasal fossa (r = -0.42). In conclusion, maxillary impacted canine root length and apex formation may be influenced by the lack of space between the tooth apex and either the floor of the maxillary sinus or nasal fossa floor.

MINCLE ACTIVATION DURING ORIENTIA TSUTSUGAMUSHI INFECTION: A POTENTIAL ROLE IN SCRUB TYPHUS LUNG PATHOGENESIS
James R Fisher, University of Texas Medical Branch

Lung injury and acute respiratory distress syndrome are two common severe complications of O. tsutsugamushi-induced scrub typhus. The lung is the major organ of infection, but pathogenesis and mechanisms propagating severe disease remain ill-defined. In this study, we investigated whether lung injury is immunologically mediated. Following infection with a lethal dose of O. tsutsugamushi in mice, we used a targeted shotgun approach (Nanostring technology) to determine kinetic transcriptional profiles of the lung. Of 671 genes analyzed, we found 221 differentially expressed genes (p <.05) at disease onset stage (day 6), and 312 at the terminal phase of disease (day 10). We identified Mincle (Clec4e) as one of the greatest differentially expressed genes during infection. Clec5a, along with C-type Lectin Receptor (CLR) signaling partners (Fcgr1, Fcgr2b, Fcgr3, and Fcgr4) were also significantly upregulated by day 10. To-date, CLRs have not been studied in scrub typhus. Since Mincle is expressed on myeloid cells, we performed in vitro infection of bone-marrow macrophages (BMMΦ) and BM-neutrophils and analyzed via qRT-PCR. We found Mincle highly upregulated (>100 fold increase) in MΦs at 24-48 hpi, while modestly upregulated (~3-fold increase) in neutrophils at 4-18 hpi. As Mincle can play pathogenic/protective roles during infection with other pathogenic bacteria, we are examining how Mincle/FcγR-related pathways contribute to O. tsutsugamushi infection in mouse models of severe disease. Since there are no effective vaccines for the control of Orientia infection, our study will help understand innate immune recognition of this poorly-studied bacterium and mechanisms underlying lung injury in scrub typhus.

VIRTUAL STUDENT SCHOLARS SYMPOSIUM 2020 PRESENTATIONS

Physiology and Immunology - Oral Presentations

High School Division

Undergraduate Division

Graduate Division

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