2. Opsonization is deposition of antibody or complement fragments on surfaces of foreign cells with subsequent facilitation of the process that allows the effector cells to destroy the foreign cell.

E. Proteins

1. Cytokines and Interleukins

a. Cytokines (interleukin-1, tumor necrosis factor) are inflammatory cell activators that are synthesized by macrophages to act as secondary messengers that activate endothelial cells and white blood cells (produce an inflammatory response) (Table 12-3).

TABLE 12-2 CELLS THAT PARTICIPATE IN THE IMMUNE RESPONSE

Macrophages (ingest antigens)

Polymorphonuclear leukocytes (neutrophils; first cells to appear in an acute inflammatory reaction)

Eosinophils (function unknown)

Basophils (granulocytes in blood; cell surfaces contain IgE receptors)

Mast cells (located in perivascular spaces of skin, lungs, and intestine; cell surfaces contain IgE receptors)

TABLE 12-3 SYMPTOMS PRODUCED BY RELEASE OF CYTOKINES

Fever

Hypotension

Myocardial depression

Catabolism

b. T-cell lymphocytes produce interleukins.

2. Complement

a. The primary humoral response to antigen and antibody binding is activation of the complement system (about 20 different proteins that are activated by antigen–antibody interactions, plasmin, and endotoxins).

b. A series of inhibitors regulates the complement system (e.g., angioneurotic edema, which may be activated by surgery manifesting as laryngeal obstruction, is caused by a deficiency of an inhibitor of the C1 complement system).

F. Effects of Anesthesia on Immune Function. Anesthesia and surgery depress both T- and B-cell responsiveness as well as nonspecific host resistance mechanisms, including phagocytosis. The significance, if any, of these responses is not known. (It is probably of minor importance compared with the hormonal aspects of the stress response.)

II. HYPERSENSITIVITY RESPONSES (ALLERGY) (Table 12-4 and Fig. 12-1)

A. Intraoperative Allergic Reactions

1. More than 90% of the allergic reactions evoked by drugs administered intravenously occur within 3 minutes of administration. (It is estimated that allergic reactions occur once in every 5,000–25,000 anesthetics administered.)

2. The only manifestation of an intraoperative allergic reaction may be refractory hypotension (Table 12-5 and Fig. 12-2).

III. ANAPHYLACTIC REACTIONS

A. IgE-Mediated Pathophysiology. Antigen binding to IgE antibodies, which reflects prior exposure to the antigen, initiates anaphylaxis. The antigen binds by bridging two immunospecific antibodies located on the surfaces of mast cells and basophils, resulting in the release of histamine and other chemicals.

TABLE 12-4 CLASSIFICATION OF HYPERSENSITIVITY

Type I reaction: Immediate-type hypersensitivity reaction (anaphylaxis) with release of chemical mediators (see Table 12-6) from mast cells and basophils in response to binding of IgE antibodies to the surfaces of these cells

Type II reaction: Mediated by IgG or IgM antibodies directed against antigens on surfaces of foreign cells (e.g., ABO incompatibility reactions)

Type III reaction: Antigen–antibody complexes that form insoluble complexes that deposit in the microvasculature (e.g., poststreptococcal infections)

Type IV reaction: Delayed hypersensitivity reaction of cell-mediated immunity (e.g., tissue rejection, tuberculin immunity)

B. Chemical Mediators of Anaphylaxis (Table 12-6)

C. Recognition of Anaphylaxis (see Table 12-5)

1. Individuals vary greatly in their manifestations and course of anaphylaxis. (The spectrum ranges from minor clinical significance to death.)

2. The enigma of anaphylaxis lies in the unpredictability of its occurrence, the severity of the attack, and the lack of a prior patient allergic history.

FIGURE 12-1. Type I immediate hypersensitivity reactions (anaphylaxis) involve immunoglobulin E (IgE) antibodies binding to mast cells or basophils at the Fc receptors. On encountering immunospecific antigens, the IgE becomes cross-linked, inducing degranulation, intracellular activation, and release of chemical mediators.

TABLE 12-5 RECOGNITION OF ANAPHYLAXIS DURING REGIONAL AND GENERAL ANESTHESIA

FIGURE 12-2. During a type I allergic reaction, antigen enters a patient during anesthesia via a parenteral route (intravenous [IV] or intramuscular [IM]) (A). The antigen bridges two IgE antibodies on the surface of mast cells or basophils, causing degranulation (B). The released chemical mediators produce the characteristic clinical symptoms of an allergic reaction (C). ECF = extracellular fluid.