C h a p t e r 1 6
Disorders of the Immune Response
349
Complement- and Antibody-Mediated Cell
Destruction
The deletion of antibody-targeted cells can occur by way
of the complement system or by antibody-dependent cell-
mediated cytotoxicity (ADCC), which does not require
complement.
2,3
Complement-mediated cell destruction
can occur because the cells are coated with molecules
(opsonized; see Fig. 16-2A) that make them attractive
to phagocytes or because of the formation of mem-
brane attack proteins that disrupt the integrity of the
cell membrane and cause cell lysis (see Chapter 15,
Understanding the Complement System). With ADCC
destruction, cells that are coated with low levels of IgG
antibody are killed by a variety of effector cells that bind
to their target by their receptors for IgG, and cell lysis
occurs without phagocytosis.
Examples of antibody-mediated cell destruction
include mismatched blood transfusion reactions, hemo-
lytic disease of the newborn due to ABO or Rh incom-
patibility (see Chapter 13), and certain drug reactions.
In the latter, the binding of certain drugs or drug metab-
olites to the surface of red or white blood cells elicits an
antibody response that lyses the drug-coated cell. Lytic
drug reactions can produce transient anemia, leukope-
nia, or thrombocytopenia, which often are corrected by
the removal of the offending drug.
Complement- and Antibody-Mediated
Inflammation
When antibodies are deposited in extracellular tissue
components, such as basement membranes and matrix,
injury results from inflammation rather than phago-
cytosis or cell lysis (see Fig. 16-2B).
2,3
In this case, the
deposited antibodies activate complement, generating
chemotactic by-products that recruit and activate neu-
trophils and monocytes. The activated leukocytes release
injurious substances, such as enzymes and reactive oxy-
gen intermediates, that cause inflammation and tissue
damage. Antibody-mediated inflammation is responsible
for the tissue injury seen in some forms of glomerulone-
phritis, vascular rejection of organ grafts, and other dis-
eases. In Goodpasture syndrome, for example, antibody
binds to a major structural component of pulmonary and
glomerular basement membranes, causing pulmonary
hemorrhage and glomerulonephritis
3
(see Chapter 25).
Antibody-Mediated Cellular Dysfunction
In some type II reactions, antibody binding to specific
target cell receptors does not lead to cell death, but to a
change in cell function (see Figs. 16-2C, D). In Graves
disease, for example, autoantibodies directed against
thyroid-stimulating hormone (TSH) receptors on thy-
roid cells stimulates thyroxine production, leading to
hyperthyroidism
2,3
(see Chapter 32). In myasthenia
gravis, autoantibodies to acetylcholine receptors on the
neuromuscular endplates either block the action of ace-
tylcholine or mediate internalization or destruction of
receptors, leading to decreased neuromuscular function
(see Chapter 36).
Type III, Immune Complex–Mediated
Disorders
Immune complex allergic disorders are mediated by the
formation of insoluble antigen–antibody complexes,
complement fixation, and localized inflammation
2,3
(Fig. 16-3). Immune complexes formed in the circula-
tion produce damage when they come in contact with
the vessel lining or are deposited in tissues, such as the
renal glomerulus, skin venules, lung tissue, and joint
synovium. Once deposited, the immune complexes elicit
an inflammatory response by activating complement,
thereby leading to chemotactic recruitment of neutro-
phils and other inflammatory cells. Activation of these
inflammatory cells by immune complexes and comple-
ment, accompanied by the release of potent inflamma-
tory mediators, is directly responsible for the injury.
Type III reactions are responsible for the vasculitis seen
in certain autoimmune diseases such as systemic lupus
erythematosus (SLE) or the kidney damage seen with
acute glomerulonephritis. As with type I hypersensitivity
reactions, type III immune complex disorders may pres-
ent with systemic manifestations or as a local reaction.
Systemic Immune Complex Disorders
Serum sickness is a type III systemic immune complex
disorder that is triggered by the deposition of insolu-
ble antigen–antibody (IgM, IgG, and occasionally IgA)
Vessel endothelium
Antibody
Antigens
Formation of
antigen–antibody
complexes
Deposition of
immune complexes
Complement
activation
Attraction of
inflammatory cells
Tissue-damaging
mediators
Fibrinoid
necrosis
1
2
3
FIGURE 16-3.
Type III, immune complex reactions involving
complement-activating IgG or IgM immunoglobulins with
(1) formation of blood-borne immune complexes that are
(2) deposited in tissues. Complement activation at the site
of immune complex deposition (3) leads to attraction of
leukocytes that are responsible for vessel and tissue injury.
