Page 128 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

114 C H A P T E R 4 Diseases of the Immune System Antibody-Mediated Diseases
(Type II Hypersensitivity)
IgE antibodies are produced in response to many helmin-
thic infections, and their physiologic function is to target Antibody-mediated (type II) hypersensitivity disorders are
helminths for destruction by eosinophils and mast cells. caused by antibodies directed against target antigens on the
Mast cells also are involved in defense against bacterial surface of cells or other tissue components. The antigens
infections. And snake aficionados will be relieved to hear may be normal molecules intrinsic to cell membranes or in
that their mast cells may protect them from some snake the extracellular matrix, or they may be adsorbed exoge-
venoms by releasing granule proteases that degrade the nous antigens (e.g., a drug metabolite). Antibody-mediated
toxins. Why these beneficial responses are inappropriately abnormalities are the underlying cause of many human
activated by harmless environmental antigens, giving rise diseases; examples of these are listed in Table 4–3. In all of
to allergies, remains a puzzle. these disorders, the tissue damage or functional abnormali-
ties result from a limited number of mechanisms.
S U M M A RY
Immediate (Type I) Hypersensitivity Mechanisms of Antibody-Mediated Diseases

• Also called allergic reactions, or allergies Antibodies cause disease by targeting cells for phagocyto-
• Induced by environmental antigens (allergens) that stimu- sis, by activating the complement system, and by interfer-
ing with normal cellular functions (Fig. 4–10). The
late strong TH2 responses and IgE production in geneti- antibodies that are responsible typically are high-affinity
cally susceptible individuals antibodies capable of activating complement and binding
• IgE coats mast cells by binding to Fcε receptors; reexpo- to the Fc receptors of phagocytes.
sure to the allergen leads to cross-linking of the IgE and • Opsonization and phagocytosis. When circulating cells,
FcεRI, activation of mast cells, and release of mediators.
• Principal mediators are histamine, proteases, and other such as erythrocytes or platelets, are coated (opsonized)
granule contents; prostaglandins and leukotrienes; and with autoantibodies, with or without complement pro-
cytokines. teins, the cells become targets for phagocytosis by
• Mediators are responsible for the immediate vascular and neutrophils and macrophages (Fig. 4–10, A). These
smooth muscle reactions and the late-phase reaction phagocytes express receptors for the Fc tails of IgG anti-
(inflammation). bodies and for breakdown products of the C3 comple-
• The clinical manifestations may be local or systemic, and ment protein, and use these receptors to bind and ingest
range from mildly annoying rhinitis to fatal anaphylaxis. opsonized particles. Opsonized cells are usually elimi-
nated in the spleen, and this is why splenectomy is of

Table 4–3 Examples of Antibody-Mediated Diseases (Type II Hypersensitivity)

Disease Target Antigen Mechanisms of Disease Clinicopathologic
Autoimmune hemolytic Red cell membrane proteins (Rh Opsonization and phagocytosis of Manifestations
anemia blood group antigens, I antigen) erythrocytes Hemolysis, anemia
Autoimmune Platelet membrane proteins Opsonization and phagocytosis of Bleeding
thrombocytopenic (GpIIb/IIIa integrin) platelets
purpura Skin vesicles (bullae)
Pemphigus vulgaris Proteins in intercellular junctions Antibody-mediated activation of
of epidermal cells (epidermal proteases, disruption of Vasculitis
Vasculitis caused by desmoglein) intercellular adhesions
ANCA Neutrophil granule proteins, Neutrophil degranulation and Nephritis, lung hemorrhage
Goodpasture syndrome presumably released from inflammation
activated neutrophils Myocarditis
Acute rheumatic fever Noncollagenous protein (NC1) in Complement- and Fc receptor–
basement membranes of kidney mediated inflammation Muscle weakness, paralysis
Myasthenia gravis glomeruli and lung alveoli Hyperthyroidism
Streptococcal cell wall antigen; Inflammation, macrophage Hyperglycemia, ketoacidosis
antibody cross-reacts with activation Abnormal myelopoiesis,
myocardial antigen anemia
Acetylcholine receptor Antibody inhibits acetylcholine
binding, downmodulates receptors
Graves disease TSH receptor Antibody-mediated stimulation of
(hyperthyroidism) TSH receptors
Insulin-resistant diabetes Insulin receptor Antibody inhibits binding of insulin
Pernicious anemia Intrinsic factor of gastric parietal Neutralization of intrinsic factor,
cells decreased absorption of vitamin
B12

ANCA, antineutrophil cytoplasmic antibodies; TSH, thyroid-stimulating hormone.