PRINCIPLES OF TOXICOLOGY

192 IMMUNOTOXICITY: TOXIC EFFECTS ON THE IMMUNE SYSTEM
TABLE 10.1 Cytokines and their Functions
CytokineProduced by Function(s)
IL1
(IL1-α and
IL1-β)
Several cell types, including
neutrophils and
macrophages
Variety of effects, including neutrophil and macrophage
activation, T- and B-cell chemotaxis, and increased IL2
and IL6 production
IL2 T cells Stimulates replication of T cells, NK cells, and B cells
IL3 T cells Involved in regulation of progenitor cells for several
different cell types, including granulocytes, macrophages,
T cells, and B cells
IL4 Activated T cells Activates T and B cells; suppresses synthesis of IL1 and
TNF
IL5 T cells and activated B cells Increases secretion of immune globulins by B cells
IL6 Several cell types, including T Important in inflammatory reactions and in differentiation
and B cells
of B cells into Ig-secreting cells
IL7 Bone marrow stromal cells Important in regulating lymphocyte growth and
differentiation
IL8 Activated monocytes and Activates neutrophils; important for chemotaxis of
macrophages
neutrophils and lymphocytes
IL9 TH cells Stimulates growth of TH cells
IL10 B cells Stimulates growth of T cells in the presence of IL2 and IL4
TNF-α Variety of cells, primarily
activated macrophages
Important in inflammatory responses; effects similar to IL1
TGF-β Variety of cells Inhibits T-cell proliferation and suppresses inflammatory
responses
TNF-β Activated CD4+ cells (TH) Important in mediating cytotoxic immune responses, cell
lysis
Interferons Leukocytes (INF-α),
fibroblasts (INF-β), and
lymphocytes and NK cells
(INF-γ)
(INF): Neoplastic growth inhibitor; activates macrophages;
protects against viral infections by interfering with viral
protein synthesis
is afforded by long-lived cells that become activated only following repeat exposure to the antigen or
immunization. While it has been assumed that “ memory cells” last indefinitely following a single
antigen contact, recent evidence suggests the life-span of memory cells may be related to repeat contact
with antigen.
In order to be recognized by the immune system, antigens must be of appreciable size. Some
of the smallest antigens, for example, are natural substances with molecular weights in the low
thousands. There are circumstances where much smaller molecules can elicit an immune response,
but this requires the participation of a large molecule to serve as a carrier. For example, some
metals, drugs, and organic environmental and occupational chemicals too small to be recognized
by the immune system can become antigenic when bound to a macromolecule such as a protein.
Once the immune response has been initiated, antibodies will recognize and bind the small
molecule even when it is not bound to the carrier molecule. In situations such as this, the small
molecule is called a hapten.
The antibodies themselves are glycoproteins, the basic unit of which consists of two pairs of
peptide chains (see Figure 10.1) connected by disulfide bonds. The longer peptide chain is termed
the heavy (or H) chain and the shorter is the light (or L) chain. There are five main types of
antibodies, or immunoglobulins (Ig): IgG, IgM, IgA, IgE, and IgD. They differ both in structure
and function. IgG is present in the greatest concentration in serum, has a molecular weight of
around 150,000 (there are four subtypes of somewhat different sizes), and is important in
secondary immune responses. IgM is a primary response antibody, meaning that it is increased