ABSTRACT
The induction of immunity and pathology during viral infection of the lung depends on a number of factors. These include one or more of the following: the age of the host, the presence of an efficient immune system, host genetic makeup, the presence of coinfecting pathogens, underlying congenital abnormalities and maternal antibody, and the extent of previous infections. In this chapter we review a number of these variables in relation to the immunopathology induced by viral infection of the lung and the subsequent development of asthma and atopy
A. The Lung as a Mucosal Organ
To understand why problems arise in the lung during infection we first need to appreciate how the lung maintains homeostasis in an immunocompetent individual. The lung is an integral part of mucosal-associated lymphoid tissue (MALT). Such MALT structures separate the external environment from the body’s interior at most sites by a single layer of epithelium. Mucosal surfaces are constantly bombarded with antigenic material. The induction of immune responses to all foreign particles we eat and breathe would be inappropriate. Large inflammatory reactions in delicate sites such as the lung would likewise lead to bystander tissue damage and a state
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of immunological exhaustion. The mucosal tissues (including the respiratory, gastrointestinal, and urogenital tracts and the ducts of all exocrine glands) have therefore evolved a specialized immune network that seeks to exclude, eliminate, or tolerate antigen rather than reacting to it. One of the hallmarks of mucosal immunity is the selective production of dimeric immunoglobulin A (IgA). The joining chain present in dimeric IgA selectively binds to secretory component on the basolateral surface of mucosal epithelium. IgA is then actively transported through the epithelium and secreted into the lumen where complexes with antigen form. This effectively prevents the absorption of antigen by a process called immune exclusion. IgA therefore functions to exclude antigens from the body without causing overt inflammation. IgA is particularly appropriate for mucosal surfaces since it is more resistant to degradation by luminal proteases than other antibody isotypes and it does not fix complement. The impact of this mechanism on antigen control at mucosal surfaces is highlighted by the recurrent lung infections that occur in patients with a selective IgA deficiency. It can be difficult to diagnose such a deficiency because induction of other antibody isotypes such as pentameric IgM often compensate. For example, IgA-deficient mice seem equally efficient at controlling sublethal influenza virus infection via the production of other antibody isotypes (1). Dimeric IgA can also complex antigen within the submucosa itself and transport it into the lumen of the lung or gut via the secretory component: joining chain interaction. Even agents that infect the mucosal epithelium can be mopped up during the transition of IgA through the epithelial cell (2).
