Page 129 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Hypersensitivity Reactions: Mechanisms of Immune-Mediated Injury 115

Opsonization and phagocytosis

Opsonized Fc receptor Phagocytosed
cell cell
Phagocytosis
C3b

C3b Phagocyte
receptor

A Complement activation

Complement- and Fc receptor–mediated inflammation

Fc Complement Neutrophil
receptor enzymes,
by-products
B (C5a, C3a) reactive oxygen
intermediates

Complement activation Inflammation and tissue injury

Antibody-mediated cellular dysfunction Nerve
ending
Antibody TSH Antibody to Acetylcholine
against receptor ACh receptor (ACh)

TSH receptor ACh
Thyroid receptor

epithelial
cell

Muscle

Thyroid hormones Antibody inhibits binding of
neurotransmitter to receptor
C Antibody stimulates receptor without hormone

Figure 4–10 Mechanisms of antibody-mediated injury. A, Opsonization of cells by antibodies and complement components, and ingestion of opso-
nized cells by phagocytes. B, Inflammation induced by antibody binding to Fc receptors of leukocytes and by complement breakdown products.
C, Antireceptor antibodies disturb the normal function of receptors. In these examples, antibodies against the thyroid-stimulating hormone (TSH)
receptor activate thyroid cells in Graves disease, and acetylcholine (ACh) receptor antibodies impair neuromuscular transmission in myasthenia gravis.

clinical benefit in autoimmune thrombocytopenia and responses excessively. In Graves disease, antibodies
some forms of autoimmune hemolytic anemia. against the thyroid-stimulating hormone receptor stim-
• Inflammation. Antibodies bound to cellular or tissue anti- ulate thyroid epithelial cells to secrete thyroid hormones,
gens activate the complement system by the “classical” resulting in hyperthyroidism. Antibodies against hor-
pathway (Fig. 4–10, B). Products of complement activa- mones and other essential proteins can neutralize and
tion serve several functions (see Fig. 2–18, Chapter 2), block the actions of these molecules, causing functional
one of which is to recruit neutrophils and monocytes, derangements.
triggering inflammation in tissues. Leukocytes may also
be activated by engagement of Fc receptors, which rec- Immune Complex Diseases
ognize the bound antibodies. This mechanism of injury (Type III Hypersensitivity)
is exemplified by Goodpasture syndrome and pemphi-
gus vulgaris. Antigen–antibody (immune) complexes that are formed in the
• Antibody-mediated cellular dysfunction. In some cases, circulation may deposit in blood vessels, leading to complement
antibodies directed against cell surface receptors impair activation and acute inflammation. The antigens in these com-
or dysregulate cellular function without causing cell plexes may be exogenous antigens, such as microbial pro-
injury or inflammation (Fig. 4–10, C). In myasthenia teins, or endogenous antigens, such as nucleoproteins. The
gravis, antibodies against acetylcholine receptors in mere formation of immune complexes does not equate
the motor end plates of skeletal muscles inhibit with hypersensitivity disease; small amounts of antigen–
neuromuscular transmission, with resultant muscle antibody complexes may be produced during normal
weakness. Antibodies can also stimulate cellular