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Immunological defence mechanisms and viral infection of the respiratory tract

Mammalian respiratory tract is endowed with multiple mechanisms of defense. These include non specific as well as specific immunologic components operating in the peripheral blood as well as respiratory mucosal sites. Respiratory tract infections are often associated with development of specific mucosal immunity in the respiratory tract with subsequent protection against reinfection and/or clinical disease. The follicular epithelial sites which represent the common mucosal immune system include the bronchus (BALT), nasal (NALT) and gut (GALT) associated lymphoid tissues. The mucosal lymphoid follicles are replete with antigen reactive lymphoid precursors of IgA immunoglobulin, T lymphocytes and their subsets. The epithelium and lamina propria of other distant mucosal sites such as the genital tract, mammary glands, nasopharyngeal tonsils, salivary glands, and ocular tissues containing antigen-sensitized B lymphocytes and plasma cells, and T cells and their subsets represent other important elements of common mucosal immune system. Exposure to replicating or non-replicating infectious antigens and other macromolecules in the lymphoid tissue of the BALT or GALT has been shown to result in the development of specific mucosal immune responses in these sites as well as in other distant mucosal surfaces, as a result of preferential migration, systemic circulation and eventual seeding and local proliferation of antigen sensitized cells in the epithelium and lamina propria of these sites. A number of investigations have shown that Waldeyer’s ring represents the inductive component of nasal associated lymphoid tissue in man. Recent studies have shown that tonsillar germinal cells are rich in certain B cell subset phenotypes which reflect excessive somatic hypermutation. Other investigations have shown preferential migration of IgA B cells from tonsils to other segments of respiratory tract after local or intranasal immunization. Respiratory immunization has been found to be highly effective in inducing immune responses in nasopharyngeal and salivary secretions. It appears that NALT behaves as an effective inductive site in a manner similar to GALT. Recent studies have also shown that many replicating agents and vaccine antigens interact specifically with mucosal epithelium and induce synthesis of a variety of immunoregulatory and proinflammatory cytokines and chemokines. These include IL-6, IL-8, GM-CSF, IL-1, MIP-1, RANTES, IFN- and TNF-. These mediators induce expression of MHC Class 1 and Class 2, ICAM-1, E-Selectin, VCAM-1, and other adhesion molecules in the mucosal epithelium. Finally, other important cytokines and chemokines (IFN-, IL-4) are released in the mucosal surfaces during exposure to microbial antigens, secondary to the activation of T-cell subsets Th1 or Th2. Currently, most vaccines available for human use cannot be delivered or are not effective via mucosal routes, and as a result are administered systemically. Such immunizations consistently induce specific antibody responses in the circulation as well as other systemic sites. However, systemic vaccines, in particular those consisting largely of non-replicating or inactivated organisms with limited antigen mass, induce little or no mucosal responses and often provide little or no protection against mucosal reinfections. Thus, the ability to induce a balanced systemic and mucosal response following mucosal immunization is determined by a number of factors including nature of vaccine antigens, intestinal or respiratory mucosal microenvironment, concurrent use (and types) of adjuvants and delivery systems employed for vaccine administration, and the potential for induction of oral tolerance.

Immunological defence mechanisms; viral infection; respiratory tract;

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