GRAHAM B; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. 656.
Vanderbilt Univ., Nashville, TN
RSV infects bronchiolar epithelium and Type I alveolar pneumocytes causing bronchiolitis and interstitial pneumonitis, and leading to distinct disease syndromes in infants, immunocompromised adults and the elderly. The pathology of primary infection includes neutrophils, mucus, and sloughed epithelial cells in the airway, and T lymphocyte infiltration into peribronchiolar and interstitial spaces. The pattern of clinical disease is determined by the balance between virus-induced cytopathology and immune-mediated pathology, and by the composition of the immune effectors responding to infection. Co-existing factors that influence T cell differentiation can affect the cytokine milieu and determine the profile of CD4+ T cell phenotypes in the immune response. The consequent mix of cytokines, chemokines, and other inflammatory mediators dictate the clinical manifestations of infection. The patterns of immune response can be influenced by prior immunity or concurrent allergen exposure. For example, preexisting IL-4 can modify mechanisms of CD8+ T cell killing and promote Th2 CD4+ responses leading to delayed virus clearance and enhanced immune-mediated pathology. RSV can also directly influence immune responses through unique antigenic and functional qualities of the RSV G glycoprotein. RSV G is produced as both a membrane-anchored surface glycoprotein and is also secreted. G has recently been shown to bind the fractalkine receptor as well as heparan sulfate. This may allow the secreted form of G to influence signaling and other cellular activities in neighboring, uninfected cells, as well as infected cells. The RSV G glycoprotein also has unique antigenic properties, and in selected genetic backgrounds, can induce an oligoclonal CD4+ Th2 epitope-specific response that is responsible for subsequent induction of eosinophilia and immunopathology. Understanding how the local cytokine milieu and the RSV G glycoprotein influence the immune response to RSV is critical for discovering interventions that will reduce RSV.
Publication Types:
Keywords:
- Adult
- Aged
- Bronchiolitis
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Cytokines
- Eosinophilia
- Humans
- Infant
- Interleukin-4
- Lung
- Lymphocyte Activation
- Respiratory Syncytial Virus Infections
- T-Lymphocytes
- immunology
Other ID:
UI: 102270478
From Meeting Abstracts