Download type II

Hypersensitivity reactions:
Antibody-mediated (type II) cytotoxic reactions
and immune complex (type III) reactions
Type II
• Tissue/cell damage due to direct action of
antibody or complement
• Antibody dependent cell-mediated cytotoxicity
(ADCC)
• Examples
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Transfusion reactions (Rhesus incompatibility)
Organ transplants
Autoimmune type II reactions - ‘cold’ agglutinins
Type II drug reactions - ‘penicillin’
Figure 15.1
Schematic illustration of three different mechanisms of antibody-mediated injury in type II
hypersensitivity. (A) Complement-dependent reactions that lead to lysis of cells or render them
susceptible to phagocytosis. (B) Antibody-dependent cell-mediated cytotoxicity (ADCC). IgGcoated target cells are killed by cells that bear Fc receptors for IgG (e.g., NK cells, macrophages).
(C) Antireceptor antibodies disturb the normal function of receptors. In this example, acetylcholine
receptor antibodies impair neuromuscular transmission in myasthenia gravis.
ABO blood grouping system
Transfusion reaction caused by ABO
blood types
• IgM activates complement --- RBC lysis, and later
phagocytosis by anti-RBC IgG
• Kidney and other tissue damage
• Toxicity due to released heme complex
Rhesus imcompatibility
• Rabbit antisera to rhesus RBC react with 85% of
human population
– Positive = Rh+
– Negative = Rh-
• Hemolytic disease of newborn (HDN)
(erythroblastosis fetalis) in Rh- mothers
Drug-induced hemolytic anemia
Drugs act as haptens, combine with cells &
other constituents
Type III : Immune complexmediated hypersentivity
Body exposed to Ag in various situations
(persistent infection, autoimmunity or
repeated contact with environmental agents)
Ag-Ab complex at fixed sites
Acute inflammatory reaction
(Localized or systemic)
Figure 15.3
Type III hypersensitivity Arthus reaction. (A) Gross appearance, showing
hemorrhagic appearance (purpura); (B) Histologic features of Arthus reaction
showing neutrophil infiltrate (courtesy of Dr. M. Stadecker, Tufts University
Medical School).
Arthus reaction
Hypersensitive pneumonitis
Named after Ag source
‘Farmer’s lung’
‘Pigeon-breeder’s lung’
‘Mushroom grower’s lung’
Reactions to inhaled Ag
‘Farmer’s lung’ : pneumonitis due to Actinomyces spp.
Histology
Alveolus filled with fluid
Spore-Ab
complex
Serum sickness
Caused by side effect of passive immunization
Figure 15.2
Schematic
illustration of the
three sequential
phases in the
induction of
systemic type III
(immune complex)
hypersensitivity.
Contribution of immune complex to the pathogenesis
of diseases other than serum sickness
• Autoimmune diseases
– Systemic lupus erythematosus
– Rheumatoid arthritis
– Goodpasture’s syndrome
• Drug reactions
– Allergies to penicillin and sulfonamides
• Infectious diseases
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Poststreptococcal glomerulonephritis
Meningitis
Hepatitis
Malaria
Trypanosomiasis
Figure 15.4
Ribbon-like deposit of antibody along the basement membrane revealed
by fluorescent antibodies to human Ig. [Courtesy of Dr. A. Ucci, Tufts
University Medical School.]