Type II Hypersensitivity:
Antibody-mediated cytotoxicity
• Results when Ig or IgM bind to cell surface Ag’s
– Activating Complement
– Binding Fc receptors on Tc cells promoting ADCC
• Both processes result in lysis of the Ab-coated cell
• Clinical examples of Type II responses include:
– Certain autoimmune diseases where Ab’s produced vs membrane Ag’s
• Grave’s Disease – Ab’s produced vs thyroid hormone receptor
• Myasthenia Gravis – Ab’s produced vs acetylcholine recpetors
• Autoimmune hemolytic anemia – Ab’s produced vs RBC membrane Ag’s
– Hemolytic Disease of the Newborn
– Hyperacute graft rejection
• Blood Transfusion rxns
• Graft rejection
Type II Hypersensitivity:
Transfusion reactions
• Produced by mismatched blood types
– Destroys foreign RBC by complementmediated lysis triggered by IgG
• Produces fever, intravascular clots,
lower back pain, Hgb in urine
– Free Hgb produced has 2 fates:
• passes to the kidneys – hemoglobinuria
• Breaks down to bilirubin..can be toxic
Type II Hypersensitivity:
Hemolytic Disease of the Newborn
• Occurs via maternal IgG Ab’s crossing the placenta
• In severe cases causes erythroblastosis fetalis
– Most commonly develops in Rh- mother with Rh+ fetus
– Exposure to Rh+ fetal RBC’s stimualtes prod of memory/plasma
– Activation of memory cells in subsequent pregnancy stim IgG Ab’s which
can cross the placenta
– mild-severe hemolytic anemia ensues along with bilirubin which affects
the brain/CNS
• Treatment centers on anti-Rh antibodies (Rhogam)
• Mothers can be tested for anti-Rh antibodies to check for a rise in titre
• Isolated fetal RBC’s can be checked for anti-Rh IgG w/ Coombs test
Hemolytic Disease of the Newborn
Type II Hypersensitivity:
Drug-induced hemolytic anemia
• Drugs such as aspirin and antibiotics can bind to the
surfaces of RBC’s
• These interactions act similar to hapten-carrier conj.
• Such complexes can trigger Ab-mediated cell lysis
by complement activation
Type III Hypersensitivity:
Immune Complex-mediated cytotoxicity
• Caused by immune complex deposition in tissues
– Small amts cleared by phagocytic cells
– Activates complement which attracts neutrophils and
stim Mast cell degranulation
– Depending on location, rxn can be localized or systemic
• Most damage stems from activity of Neutrophils
– Immune complexes can adhere to tissue making it
difficult for Neutrophils to phagocytize
– Neutrophils continue releasing lytic enzymes, etc.
Type III Hypersensitivity:
Localized reactions
• Arthus rxns:
– Exposure to an Ag for
which there already is a
high [c] of Ab
– Produces edema/erythema
from damage to bv and tiss
• Insect bites
• Inhalation of bacteria, fungi,
dried fecal matter
Type III Hypersensitivity:
Systemic (generalized) reactions
• Produced when large amounts of Ag
enter the bloodstream
– The sites of deposition vary; usually
in tissues where plasma is filtered
– Esp. in kidneys, blood vessels, and
joints
• Can cause tissue damaging rxns:
• Serum sickness
• Autoimmune diseases
• Drug reactions
• Infectious diseases
Type IV Hypersensitivity:
Delayed-Type Hypersensitivity
• Occurs 48-72 hrs after Ag contact and is mediated
by Ag-specific TH1 cells and activated MØ
• TH1 cells secrete:
– IFN-γ activates MØ
– TNF-α and β upregulate CAM’s on local b.v’s
– Il-3 and GM-CSF stim bone marrow monocyte output
Initial contact with Ag (sensitization) may induce
memory TH1 cells without symptoms
Phases of the DTH Response
• Sensitization – TH1 cells triggered by contact with APC
• Effector response – produces huge influx of activated MØ
– Activated MØ is more efficient at antigen-presentation
– Release of lytic enzymes lead to non-specific destruction of cells
– Works well vs intra-cellular pathogens
– If pathogen/particle lingers -> can lead to granuloma formation
• Ex: Mycobacterial pathogens in TB and Leprosy
DTH Response
Cytokines released include: TNF-β, GM-CSF, and IFN – γ
DTH Response
Type IV rxns marked by time delay and recruitment of
MØ instead of Neut’s and Eosino’s
Contact Dermatitis
Produced by a variety of substances
Mostly small molecules attach to a
protein in the skin
The Ag-protein complex is processed
and presented  sensitize TH1 cells
Subsequent exposure activates TH1
cells  48-72 hrs later MØ infiltrate
Activation of MØ causes the
inflammation that characterizes the
disorder