PRINCIPLES OF TOXICOLOGY

194 IMMUNOTOXICITY: TOXIC EFFECTS ON THE IMMUNE SYSTEM
10.3 TYPES OF IMMUNE REACTIONS AND DISORDERS
Interactions of toxicants with the immune system may result in undesirable effects of three principal
types—those manifested as (1) a hypersensitivity reaction, (2) immunosuppression, or (3) autoimmunity.
Each is discussed below.
Allergic Reactions
Allergic reactions are divided into four classes:
Type I. Type I immune response is limited to IgE-mediated hypersensitivity (allergic) reaction.
This reaction involves an initial exposure in which immune symptoms are generally absent
(sensitization), followed by reexposure that can elicit a strong allergic reaction. In type I
immune responses, antigen interacts with IgE antibodies passively bound to mast cells. On
binding of antigen to the IgE, the mast cells release histamine and serotonin, which are
responsible for many of the immediate symptoms of an allergic reaction such as upper
respiratory tract congestion and hives. In a severe reaction, termed anaphylaxis, histamine
and serotonin release can cause vasodilation leading to vasomotor collapse, and bronchiolar
constriction making breathing difficult. This type of reaction has occurred following the
administration of a number of different drugs and diagnostic agents, hormones, and a variety
of sulfiting agents (e.g., sodium bisulfite, sodium metabisulfite, etc.).
Type II. Type II reaction is believed to be the result of the binding of a drug or chemical to a cell
surface, followed by a specific antibody-mediated cytotoxicity that is directed at the agent
(drug or chemical) or at the cell membrane that has been altered by the compound. Under
some circumstances, immune complexes may become adsorbed to a cell surface (erythrocytes,
thrombocytes or granulocytes) resulting in a complement-mediated cytotoxic response,
leading to induction of immune hemolytic anemia, thrombocytopenia or granulocytopenia.
Type III. Soluble immune complexes consisting of a drug or chemical hapten (plus carrier
molecule) and its specific antibody plus complement components are primarily responsible
for immune complex disease. A particular form of immune complex disease arising from
injection of an antigen is called serum sickness syndrome. Clinically, a type III reaction may
be characterized by the onset of fever and the occurrence of a rash that may include purpura
and/or urticaria. The immunopathology includes the activation of complement and the
deposition of immune complexes in areas such as blood vessel walls, joints, and renal
glomeruli. Some of the signs and symptoms associated with drug-related lupus may be
included under type III reactions.
Type IV. These reactions involve cell-mediated and/or delayed-type hypersensitivity responses.
The expression of type IV reactions requires prior exposure to the agent and T-cell sensitization.
A special subpopulation of T cells (TD) appear to be responsible for this reaction. The
TD cells react with antigens in tissues and release lymphokines, attracting macrophages to the
site and leading to an inflammatory response. The reaction is termed delayed because the
inflammatory reaction may not peak for 24–48 h, as opposed to responses occurring within
a few minutes to a few hours with other reaction types. These reactions are usually seen as
contact dermatitis occurring after the use of certain drugs or exposure to some chemicals.
Immunosuppression
Impairment of one or more components of the immune system from drug or chemical exposure can
lead to loss of immune function, or immunosuppression. Clinically, this is manifested primarily as
increased susceptibility to infectious disease, although diminished immune function could conceivably
increase vulnerability to cancer by impairing immune surveillance and removal of malignant cells. In