Dr. Fadwa Alghalib
Hypersensitivity
3rd Year 2009
Type III Hypersensitivity
Type III hypersensitivity is also known as immune complex hypersensitivity.
It is mediated by soluble immune complexes. They are mostly of the IgG class,
although IgM may also be involved.
This form of hypersensitivity has a lot in common with type I except that the
antibody involved is IgG and therefore not prebound to mast cells, so that only
preformed complexes can bind to the low affinity Fcgamma RIII.
The antigen is soluble and not attached to the organ involved.
The primary components are soluble immune complexes and complement (C3a,
4a. And C5a)
The Antigen may be exogenous (chronic bacterial, viral parasitic infections). Or
endogenous (non-organ specific autoimmunity).The damage is caused by platelets
and neutrophils. The reaction is Initiated within 2 – 8 hours of exposure.
Mechanism of Type III
A. Formation of soluble Ag-Ab complexes ( IgG- IgM) (which are able to fix
complement)
B. These soluble Immune complexes escape pagocytosis
C. Tissue damage then occurs due to:
i.
Complement fixation
ii.
Attraction of neutrophils by C3a & C5a
iii.
Platelets aggregation
Formation of immune complexes:
Immune complexes usually form when Ag is in excess of antibody, and more likely to
enter the circulation.
Small immune complexes can escape phagocytosis, penetrates the endothelium of
blood vessels and are deposited on the vascular basement membrane. That is how they
are capable of causing tissue damage.
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Dr. Fadwa Alghalib
Hypersensitivity
3rd Year 2009
Mechanism of Tissue Damage:
1) Large quantities of soluble antigen-antibody complexes form in the blood and
are not completely removed by macrophages.
2) These antigen-antibody complexes lodge in the capillaries between the
endothelial cells and the basement membrane.
3) The antigen-antibody complexes activate the classical complement pathway
and complement proteins and antigen-antibody complexes attract leukocytes
to the area.
4) The leukocytes then discharge their killing agents and promote massive
inflammation. This leads to tissue death and hemorrhage.
Deposition of immune complexes (IC) in blood vessels
 Vascular permeability IC deposit in blood vessel wall
 Induce platelet aggregation and complement activation
 Platelets form microthrombi on basement membrane
 Neutrophils are attracted
 Fail to ingest the complexes
 Release their lysosomal enzymes
 Causing further damage to vessel wall
There are 3 examples of type III reactions:
1. Arthus reaction (Local Deposition)
2. Serum sickness (Generalized Deposition)
3. Immune complex disease
i.
auto immune disease
ii.
Glomerulonephritis
iii.
pneumonitis
Mechanism of Immune-Complex Deposition:
1) Local Deposition--- Arthus Reaction:
Immune complexes are deposited in vessel walls. These complexes are due to
receiving high amounts of antigen, which cause huge amounts of antibodies to be
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Dr. Fadwa Alghalib
Hypersensitivity
3rd Year 2009
produced, then receiving the antigen subcutaneously. This causes edema and
hemorrhage.
Repeated subcutanious injection of an Ag results in local formation of immune
complexes. Erythema, oedema and necrosis due to accumulation of neutrophils.
E.g: rabies vaccine, insulin injection
Development of Arthus reaction.:
Exposure to an antigen > immune complex (Ag-Ab) formation > complement
activation (C3a, C4a, and C5a,) > release of small complement subunits > C5a induce
mast cell degranulation, chemotaxis of neutrophils > lytic enzyme release during
neutrophil attempts at phagocytosis.
2) Generalized Deposition---- Serum Sickness:
This term originated when serum from immunized animals was used to treat
diphtheria and tetanus. immune complexes form and circulate or precipitate. They
cause fever, itching, arthralgia, arthritis, lymphadenopathy, and splenomegaly.
Develops after 7-10 days from first exposure within 2-3days for secondary
immune response.
3- Immune complex diseases
They are three groups:
1. Persistent infections
2. Autoimmune diseases
3. Inhalation of antigenic material
a- Persistent Infections:
 continued infection and continual production of antigen & plasma cells
continue producing Abs.
 Immune complexes continually generated
 Deposition of Immune complexes
 Stimulate inflammation
E.g. Poststreptococcal glomerulonephritis (PSGN), (streptococci, some
viruses (Chronic Viral Hepatitis), malaria)
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Dr. Fadwa Alghalib
Hypersensitivity
3rd Year 2009
b- Autoimmune diseases
A. Continued production of Autoantibody to a self-antigen
B. Leads to prolonged immune complex formation
E.g:
1. Rheumatoid arthritis (RA is an autoimmune disorder that causes joint
inflammation).
2. SLE: Accumulation of DNA complexed with anti-DNA Ab in synovial
membranes or kidney basement membranes yielding arthritic symptoms or
kidney damage.
3. hyperthyroidism is occasionally caused by long acting thyroid stimulators
(LATS) as a result of an autoimmune reaction.
c- Inhalation of antigenic material
1. Some common inhaled Ags provoke IgG rather than IgE response Type III
2. Repeated inhalation of hay dust, mold, spores,  formation of immune
complexes deposit in lungs
E.g: Farmer’s Lung Disease
Diagnosis :
Detection of immune Complexes:
1) In Tissues
Tissue biopsies for deposits of Ig and complement by immunofluorescence
2) In Serum
A- Measurement of serum level of C3 and C4 ( usually decreased)
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