Transcript Local Type III Hypersensitivity Arthus reaction

Veterinary Immunology
Type III
Hypersensitivity
Dr. Chi-Young Wang

Two major forms of reactions
dependent on the amount and site
of deposition of immune complexes

Local reactions: immune
complexes form within tissue

Large quantities of immune
complexes within the bloodstream
which are deposited in glomeruli in
the kidney (glomerulonephritis),
bound to blood cells (anemia,
leukopenia, and deposited in blood
walls) or joints (vasculitis or
arthritis)
Local Type III Hypersensitivity

Arthus reaction: antigen is injected
subcutaneously into animals that
already have precipitating
antibodies

Red, edematous swelling, local
hemorrhage, thrombosis, and local
tissue destruction (if severe)
Local Type III Hypersensitivity

Histology: neutrophils adhere to
vascular endothelium (6-8 hours at
peak), mononuclear cells appear at
24 hours or later, depending on the
amount of antigen injected

Antigen diffuses into the vessel
walls and encounters antibodies
Local Type III Hypersensitivity
and complement

Mast cells and neutrophils were
activated by the immune complexes
Local Type III Hypersensitivity

Immune complexes can be removed
after binding with Fcγ RIIa on
sentinel cells

Nitric oxide, leukotrienes,
prostaglandins, cytokines, and
chemokines released by
macrophages bound with immune
complexes
Local Type III Hypersensitivity

Neutrophil chemotactic factors and
proteases which activates kinins,
lipid mediators, and complement by
mast cells
Local Type III Hypersensitivity

The immune complexes activate
complex to generate the chemotactic
peptide C5a which attracts neutrophils

Neutrophils emigrate from the blood
vessels and eliminates complexes by
phagocytosis

Neutrophils degranulate proteases and
oxidants (OCl-)
Local Type III Hypersensitivity

A reverse Arthus reaction-if
antibodies are administrated
intradermally to an animal with a
high level of circulating antigen

Blue eye: infected or vaccinated
with canine adenovirus type I; an
anterior uveitis leading to edema
and opacity; the cornea is infiltrated
by neutrophils and virus-antibody
complexes (develops about 1-3 weeks)
Generalized Type III
Hypersensitivity Reaction

Serum sickness: a generalized vasculitis
with erythema, edema, and urticaria of
the skin, neutropenia, lympho node
enlargement, joint swelling, and
proteinuria

Administration of intravenous dose of
antigen
Generalized Type III
Hypersensitivity Reaction

Acute if a single, large injection of an
antigen or chronic, if caused by multiple
small injections; glomerulonephritis and
arteritis

Glomerulonephritis: complexes are
deposited in the glomeruli leading to
basement membrane thickening and
proliferation of glomerular cells

MPGN (membranoproliferative
glomerulonephritis): epithelial cells,
endothelial cells, and mesangial cells

MPGN lesions are classified into three
major types based on their
histopathology
Type I Membranoproliferative
Glomerulonephritis

Type I MPGN: immune complexes
deposited in glomerular vessels

Usually trapped on the endothelial
side, which stimulates endothelial
cell swelling and proliferation

Animals are given small doses of
an antigen for a long time
Type I Membranoproliferative
Glomerulonephritis
TGF-β production which stimulate
nearby cells to yield fibronectin,
collagen, and proteoglycans

Wire loop lesions: a thickening of
the basement membrane

Alternatively, complex may be
Type I Membranoproliferative
Glomerulonephritis
deposited in the mesangial region
(a smooth muscle cells) which
proliferate and release IL-6 and
TGF-β…eventually produce
extracellular matrix

Lumpy aggregates of immune
complexes deposited in capillary
Type I Membranoproliferative
Glomerulonephritis
walls on the epithelial side of the
glomerular basement membrane
Type II Membranoproliferative
Glomerulonephritis

There is endothelial and mesangial
proliferation as well as the
presence of homogenous, dense
deposits within the glomerular
basement membrane rather than its
surface

The deposits contain C3 not
immunoglobulin
Type III Membranoproliferative
Glomerulonephritis
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Type III contains the presence of immune
complexes on both the endothelial and
epithelial sides of the basement
membrane

Very small immune complexes penetrate
the basement membrane

Epithelial cell swelling and proliferationepithelial crescents
Type III Membranoproliferative
Glomerulonephritis

Type III contains the presence of immune
complexes on both the endothelial and
epithelial sides of the basement
membrane

Very small immune complexes penetrate
the basement membrane
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Epithelial cell swelling and proliferationepithelial crescents
Clinical Features of MPGN
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Equine anemia virus, ICH, African swine
fever, Lyme disease, FLV, pyometra,
distemper encephalitis, and ehrlichiosisproteinuria: Type I MPGN with
proteinuria
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Glomeruli lesions by neutrophils,
mesangial cells, macrophages, and
platelets
Clinical Features of MPGN

Plasma proteins (albumin) in the urine,
edematous and ascitic animals
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Low RGF, retention of urea and
creatinine, azotemia, and
hypercholesterolemia

Nephrotic syndrome-anorexia, weight
loss, vomiting, polyuria, polydipsia, and
azotemia
Polyarthritis
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Immune complexes found in the blood and
synovial fluid of animals with rheumatoid
arthritis and osteoarthritis-local trauma
(not clear)
Dirofilariasis
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The heartworm Dirofilaria imitis develops
glomerular lesions and proteinuria
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Thickening of the glomerular basement
membrane with minimal endothelial or
mesangial proliferation
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IgG1-containing deposits found on
Dirofilariasis
the epithelial side of the basement
membrane (type III MPGN) and it has
been suggested that immune complexes
formed by antibodies to heartworm
antigens provoke these lesions