PRINCIPLES OF TOXICOLOGY

10.6 SPECIFIC CHEMICALS THAT ADVERSELY AFFECT THE IMMUNE SYSTEM 199
TABLE 10.3 Examples of Agents Used for Immune Challenge in Host Resistance Tests
Type of Agent Name Typical Exposure Route
Virus Cytomegalovirus Intraperitoneal or intratracheal administration
Herpes simplex virus type 2 Intraperitoneal, intravenous, or intravaginal
administration
Influenza virus Intranasal administration
Bacteria Corynebacterium parvum Injected intravenously
Listeria monocytogenes Injected intravenously
Pseudomonas aeruginosa Injected intravenously
Streptococcus pneumoniae Injected intravenously
Parasites Plasmodium species Intravenous or intraperitoneal injection of infected
blood
Trichinella spiralis Intragastric administration
Tumor cells B16-F10 melanoma Cells are injected intravenously
PYB6 fibrosarcoma Cells are injected subcutaneously
nitrogen species. The ability of macrophages in culture to phagocytize foreign materials is typically
examined using light microscopy, with either biological (e.g., SRBCs or bacteria) or nonbiological
materials (e.g., fluorescent beads) as targets. On activation, macrophages normally release specific
cytokines (e.g., TNF-α and IL2), as well as reactive oxygen and nitrogen. Cytokine production by
activated macrophages in culture can be measured by ELISA (enzyme-linked immunosorbent assay)
using antibodies directed to specific cytokines, or by ELISPOT, which is capable of identifying the
numbers of cells producing specific cytokines. Several techniques are available for quantitating reactive
oxygen and nitrogen species.
When immunosuppression (or, less commonly, immunostimulation) is suspected, one of the
most direct means to test overall immune competence is through a host resistance model (also
sometimes called a host susceptibility model). With this model, the ability of the animal to
withstand an immune challenge is assessed with and without exposure to the drug or chemical.
Immune challenge can take the form of an infectious microorganism or a syngeneic tumor. A
variety of types of infectious microorganisms are used for these tests, including viruses, bacteria,
yeast, fungi, and parasites. Syngeneic tumor lines are derived from the same strain and species as
the test animal, requiring their recognition as tumor cells and not simply a source of foreign
protein. Examples of microorganisms and tumor cell lines used for host resistance models are
provided in Table 10.3. Many of these agents are human pathogens, and this type of test arguably
provides the best direct evidence of the ability of a drug or chemical to produce clinically relevant
immune suppression or stimulation.
10.6 SPECIFIC CHEMICALS THAT ADVERSELY AFFECT THE IMMUNE SYSTEM
The number of drugs and chemicals associated with immunotoxicity in humans is extensive. As
discussed in Section 10.3, immunotoxicity typically occurs as a hypersensitivity reaction, immunosuppression,
or autoimmunity. Several agents commonly encountered in occupational settings are
capable of producing contact, cell-mediated hypersensitivity, with common symptoms of rash, itching,
scaling, and the appearance of redness and vesicles on the skin. Examples of these agents are shown
in Table 10.4. The respiratory tract is also a common site of allergic symptoms from drug or chemical
exposure. Inhalation of respiratory allergens can cause an immediate-type reaction (an early-phase
reaction, occurring and waning rapidly) or a delayed-type reaction (sometimes called a late-phase
reaction), which may appear 6–8 h later and require 12 to 24 hours to resolve. Both reactions are