Biologic Markers in Pulmonary Toxicology (1989) / Chapter Skim
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5 Markers of Inflammatory and Immune Response
5 Markers of Inflammatory and Immune Response
Pages 91-104
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From page 91... ...
Finally, a major portion of the chapter is devoted to a 91 discussion of the immune response of the lung, markers of this type of response and the use of memory cells of the immune system as markers of both exposure and adverse health effects in the respiratory tract. INFLAMMATORY RESPONSE TO INHALED TOXINS Epithelial cells and resident macrophages in the respiratory tract are the points of first contact of the body with inhaled toxicants.
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From page 92... ...
. MARKERS OF PULMONARY TOXICOLOGY INFLAMMATORY RESPONSE TO MICROBIAL INFECTIONS The respiratory tract constitutes the primary mammalian portal of entry for many pathogens.
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From page 93... ...
IMMUNE RESPONSE The human respiratory tract contains a complex array of host defenses-anatomic barriers, mucociliary clearance, phagocytic cells, and various components of cellular and humoral immunity-that collectively cleanse inhaled air and inactivate infectious and other injurious
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From page 94... ...
That includes degradation of foreign substances and exposure of lymphocytes to antigens, which stimulates the production of antibody, sensitized cells, or both (Figure 51~. Interactions of macrophages stimulated by antigens with cells in lymphoid tissue result predominantly in a cellular or humoral immune response.
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From page 95... ...
of cell-surface markers, in the cytolytic capacity of T cells or natural killer cells, and in the ability of phagocytes to ingest particles. Various components of lung fluid that are associated with the inflammatory response can serve as markers.
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From page 96... ...
AMs participate further in the regulation of the inflammatory and immune process in the lungs by secreting a variety of soluble mediators, including products of the arachidonic acid pathway, which seem to play an important role in inflammation (Hunninghake et al., 1980a; Slauson, 1982~. AMs secrete chemotactic factors for neutrophils that cause influx of these cells into the lung parenchyma and alveolar space, where they can participate actively in the inflammatory response.
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From page 97... ...
With respect to local immune system as a generator of markers, two underlying possibilities or conditions need to be considered: the presence of antigen-specific antibodies or cells indicates that the host has been exposed to an antigen at some time, even if no longer harboring it; and specific immune responses might indicate the presence and persistence of an antigen that produces a chronic inflammatory response that leads to tissue injury. Thus, the products of the immune system can be used as markers of a host's exposure to an antigen that might or might not be responsible for tissue injury and disease.
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From page 98... ...
Perhaps equally or more important are the unique genetic properties of the host, especially the immune responses that are linked and controlled by the immune-response genes. The latter consideration is particularly relevant for two immunologic diseases, hypersensitivity pneumonitis and chronic berylliosis, that are discussed below.
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From page 99... ...
With further sophistication, a challenge might be graded not only by the amount of visible inflammation present, but by other factors, such as the influx of inflammatory cells and the presence of inflammatory mediators, including histamine, immunoglobulins, and immune complexes. Skin Testing A standard method for testing for reaction to a possible pollutant is skin test TABLE 5-1 Immunologic Mechanisms of Tissue Injury Type Manifestations Mediators II III IV Immediate hypersensitivity reactions Antibody-directed reactions Formation of antigen-antibody complexes Mainly IgG IgE and other immunoglobulins IgG and IgM Delayed hypersensitivity (cell-mediated)
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From page 100... ...
MARKERS OF PULMONARY TOXICOLOGY Another difficulty with skin testing has involved the need to relate the findings with the pulmonary symptoms of the subjects. A positive skin prick test in platinum refiners is a more specific and sensitive index of disease than are some clinical symptoms (Dally et al., 1980~.
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From page 101... ...
In summary, nasal challenge has distinct advantages over skin testing, because it uses a mucosal surface. Direct observation can be used to assess inflammatory response, so it might be appropriate for screening large populations.
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From page 102... ...
With the current system, including close observation, studies are expensive and require highly trained medical and technical assistants. In conclusion, the utility of intrabronchial challenge as a screening tool for identifying patients sensitive to pulmonary toxicants seems limited.
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From page 103... ...
Although proliferation of lymphocytes from peripheral blood has been studied most extensively, there is preliminary evidence that bronchoalveolar lymphocytes from a patient with berylliosis also proliferate when exposed to beryllium (Epstein et al., 1982~. In summary, lymphocyte proliferation seems to be an index of exposure to environmental agents and in some instances a marker of disease.
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