The Allergic Response

Allergic reactions during anesthesia represent an important cause of perioperative complications (Levy JH. The allergic response. In: Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Ortega R, Stock MC, eds. Clinical Anesthesia. Philadelphia: Lippincott Williams & Wilkins; 2013: 287–303). Anesthesiologists routinely manage patients during the perioperative period, during which exposure to foreign substances (drugs, including injected anesthetics, antibiotics, neuromuscular blocking drugs, protamine, blood products) and environmental antigens (latex) occurs.

I. Basic Immunologic Principles

Host defense systems can be divided into cellular (T-cell lymphocytes) and humoral (antibodies, complement, cytokines) elements.

Antigens are molecules capable of stimulating an immune response (antibody production or lymphocyte stimulation) (Table 12-1).
Thymus-Derived Lymphocytes and Bursa-Derived (B-Cell) Lymphocytes
- Thymus-derived (T-cell) lymphocytes contain receptors that are activated by binding with antigens and subsequently secrete mediators that regulate the immune response (e.g., acquired immunodeficiency syndrome is caused by infection of helper T lymphocytes with a retrovirus known as the immunodeficiency virus).
- Bursa-derived (B-cell) lymphocytes differentiate into plasma cells that synthesize antibodies.
Antibodies are specific proteins (immunoglobulins) that can recognize and bind to a specific antigen (see Table 12-1). Antibodies function as specific receptor molecules for immune cells and proteins.

Effector Cells and Proteins of the Immune Response Cells (Table 12-2)

Monocytes, neutrophils (polymorphonuclear leukocytes), and eosinophils are effector cells that migrate into areas of inflammation in response to chemotactic factors.

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.

Table 12-1 Biologic Characteristics of Immunoglobulins

	IgG	IgM	IgA	IgE	IgD
Molecular weight	160,000	900,000	170,000	188,000	184,000
Serum concentration (mg/dL)	6–14	0.5–1.5	1–3	<0.5 × 10³	<0.1
Complement activation	All but IgG4	+	–	–	–
Placental transfer	+	–	–	–	–
Serum half-time (days)	23	5	6	1–5	2–8
Cell binding	Mast cells, neutrophils, lymphocytes, mononuclear cells, platelets	Lymphocytes	Mast cells, basophils, lymphocytes	Neutrophils, lymphocytes

Proteins

Cytokines and Interleukins

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).

T-cell lymphocytes produce interleukins.

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

Complement
- 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).
- 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).

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)

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