Models of respiratory immunotoxicology and host resistance.

The immune system consists of a vast network of lymphoid and nonlymphoid cells, communicating via messenger molecules to create a functional immune system to protect against disease. This network, while interconnected via mediator molecules, contains compartmentalized units especially equipped to defend against insults to the integrity of the immune system. The pulmonary immune system is an example of such a specialized and compartmentalized system, that, while capable of performing all immunological functions locally, is also capable of interacting with the systemic immune system, as Ž . reviewed by Burleson 1987, 1995, 1996 and LeŽ . brec and Burleson 1994 . Resistance to infectious and neoplastic disease is the raison d’ etre of the immunological armamentarˆ ium. Host resistance models reflect an aggregate, integral, intact, and functional immune system consisting of both local and systemic, as well as the innate and acquired immunity. Animal host resistance models of human pulmonary disease have been Ž . instrumental a in better understanding the infecŽ . tious and neoplastic diseases of the lungs, b as probes to better understand the pulmonary immune Ž . system, c to assess the efficacy of new therapeutic Ž . agents, and d to detect inhaled compounds exhibiting pulmonary immunotoxicity. Exposure to chemicals, pharmaceuticals, recombinant biologicals, or environmental and occupational pollutants may enhance susceptibility or severity of viral, bacterial, andror neoplastic diseases. Upper and lower respiratory diseases may also potentiate and modulate xenobiotic-induced hypersensitivity Ž . reactions Lebrec et al., 1996 . This enhanced susceptibility or severity may be a direct or indirect consequence of the impaired immune function of an individual exposed to an environmental or occupational air pollutant. Some of the numerous host resistance models used to study the immunotoxicity of inhaled xenobiotics and the efficacy of therapeutics include influenza virus in mice, rats, and ferrets; respiratory syncytial virus in mice and rats; and streptococcus in mice and rats. Host resistance studies have utilized different strategies, such as in vivo exposure and in Ž . vivo infection in vivo host resistance models with mortality or disease symptomatology as an endpoint. Other approaches have utilized pulmonary cells that Ž are exposed and infected in vitro in vitro host . resistance models . Studies have also used a combination approach of in vivorin vitro exposure and Ž . infection ex vivo host resistance models . For example, many studies have used ex vivo host resistance models, where animals are exposed and infected prior to evaluation of the respiratory tract for immune function and clearance or progression of infectious agent or neoplastic lesion. Host resistance models provide an opportunity to Ž measure antigen-driven or microorganism infectious . agent -augmented immune functions that are associ-