type iii and iv hypersensitivity
TRANSCRIPT
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Type III and IVhypersensitivity
Yingping Xu
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1. Characteristics
2. Mechanism of type III hepersensitivity
3. Common disease of type III hepersensitivity
Type III hypersensitivity
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1、characteristics
(immune complex hypersensitivity)
Large amounts of circulating antigen can form immune complexes
which are not easily cleared by phagocytic cells
Free Ag + Primed Ab middle immune complex
Deposit in tissue or blood vessel wall
Inflammation
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2、Mechanism of type III hypersensitivity
Formation of the intermediate immune complex
Deposition of the intermediate immune complex
Tissue injury by the immune complex
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When the complexes are deposited in tissue very near the
site of Ag entry, a localized reaction develops.
When the complexes are formed in blood, a reaction candevelop wherever the complexes are deposited.
the complex deposition is frequently observed
on the blood-vessel walls
in the synovial membrane of joints
on the glomerular basement membrane of kidney
on the choroid plexus of brain
These deposition of these complexes initiates a reaction that
result in the following mechanisms to hurt tissues.
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(1)Recruitment of neutrophi ls to the site
tissure is injuryed as consequence of granular release from neutrophils.
(2) To activate complement systems array of effector molecules
such as C3a, C4a, C5a (anaphylatoxin) cause mast-cell degranulation and
consequent increase in local valcular permeability.
such as C3a, C5a, and C5b67 are also chemotactic factors for neutrophils.
(3) Much of tissue damage in type I I I hypersensitivity stems from
release of Lytic enzymes by neutrophi ls as they attempt to phagocytose IC.
IC
C3b
neutrophil
CR1
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However, the complexes are deposited on the basement-membrane
Surface, phagocytosis is impeded to ingest the adhering IC.
(4) Fur ther activation of MAC can also contribute to the destruction
of tissue.
(5) I n addition, the activation of complement can induce aggregation
of platelets, and the resulting release of clotting factors can lead to
Fromation of microthrombi.
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3. common disease of type III hypersensitivity
(1). Local immune complex disease
Arthus reaction : Experimental local anaphylaxic reaction,
Necrotic vasculitis and Ulcer
Human local reaction(Arthus-like reaction):
insulin-dependent diabetes mellitus (IDDM)
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Vascular endothelial cell
(1) Anaphylatoxin-mediated
activation of mast cells to
degranulation
(2) Chemotactic neutrophils to
the site of tissue
(3) To release of Lytic enzymes of
neutrophils
Mechanism of type I I I hypersensitivity
Immune complex
Intradermally or subcutanenously
Edema and erythema at the site of
protein I njection or insect-bite.
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(2). Acute systemic immune complex disease
serum sickness: (To inject more antitoxin for the first time)
Anti-serum Ab+Ag systemic tissue injury,fever, arthritis, skin rash
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A Dominant Role for Mast Cell Fc Receptors in the Arthus Reaction:
Sylvestre et al, 1996,
Immunity 5:387
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A: Control -/-; B: Control +/+; C: Control W/Wv; D: W/Wv
reconstituted with -/- mast cells or E: +/+ mast cells
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Acute immune complex glomerulonephritis and
choroidmeningitis :
Streptococcus infection
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(3). Chronic immune complex disease SLE (systemic lupus erythematosus)
Rheumatoid arthritis :RF+IgG Deposit on synovial membrane
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Type IV hypersensitivity
(delayed type-hypersensitivity)
1、characteristics of type IV hepersensitivity
2、 mechanism of type IV hepersensitivity
3、
common diseases of type IV hepersensitivity
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Type IV hypersensitivity definition:
Some subpopulations of activated Th cells encounter certaintypes of Ags, they secrete cytokines that induce a localized
inflammatory reaction.
The reaction is characterized by large influxes of nonspecific
inflammatory cells, in particular, macrophages.
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1. Characteristics
Interaction of primed T cells and associated antigen
Infiltration of Mononuclear Cells, especially macrophage
induce inflammatory response
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2. Mechanism of type IV hypersensitivity
(1) Formation of effector and memory T cells (sensitization phase)
(2) Inflammation and cytotoxicity caused by effector T cells
(effector phase)
Inflammation and tissue injury mediated by CD4+Th1
Release chemokines and cytokines
Immune injury mainly caused by infiltration of mononuclear cells and
lymphocytes
Cytotoxicity of CD8+CTL
perforin and granzymes
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The development of the DTH response begins with the initial sensiti zation phase
Of 1-2 weeks after primary contact with an antigen .
A DTH ll d t b t ti l f 24h
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Recruit and activate
Macrophage and other
non-specif ic immune cells
A DTH response normally does not become apparent unti l an average of 24h
after the second contact with the antigen, the response generally peaks 48-72h
after the second contact . The delayed onset of this response ref lects the
time required for the cytokines to induce localized inf luxes of macrophages and
their activation
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Cytokines elarated by Th1 cells induce blood monocytes to
adhere to vascular endothelial cel ls and migrate from the blood
into sur rounding tissues. Dur ing the process, the monocytes
differentiate into activated macrophages.
On the one hand , activated macrophages exhibit increased levels
of phagocytosis and increased ability to kill microorganisms
through different cytotoxic mediators.
On the other hand, the heightened phagocytic activity and the
buildup of lytic enzymes from macrophages in the area of infectionlead to nonspecific destruction cells.
Double-edged nature
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In some cases, especially if the Ag is not easily cleared, a prolonged DTH response
Can itself become destructive to the host as the intense inflammatory response
Develops into a visible granulomatous reaction.
A granuloma develops when continuousactivation of macrophages induces them
to adhere closely each other, assuming
an epithelioid shape and fusing to form
multinucleated giant cells. These cells
displace normal tissue cells, forming palpable nodules, and release high
concentration of lytic enzymes which
destroy surrounding tissue.
A prolonged DTH response can lead to formation of a
granuloma, a nodule-l ike mass . Lytic enzymes released from
activated macrophages in a granuloma can cause extensive
tissue damage.
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Antigen T cell
(CD4+,CD8+)
Secondary
contact
Induce
Primed T cell
CD4+
T cell
CD8+
T cell
Release
Cytokines
IL-2
TNF-
INF-TF
MCF
MIF
MAF
SRF
Directly kill target cells
Infiltration of
monocyte and Mf
Proliferation of T cell
Exudation and edema
Cytotoxicity
Inflammation characterized by infiltration of Mf , monocyte,
And tissue injury
Mechanism of type IV hypersensitivity
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MCF:
Macrophage chemotactic factor
MIF:
Macrophage inhibitory factor
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3. Common disease of type IV hypersensitivity
(1) Infectious delayed type hypersensitivity
OT( Old Tuberculin ) test or PPD( purified protein derivative)The characteristics of Tuberculin Test
① Maximum at 48-72 hours
② Inflitration of lesion with mononuclear cells
③ First described as a reaction to the lipoprotein
antigen of tubercle bacillus
④ Responsible for lesions associated with bacterial allergy
⑤ cavitation, caseation, general toxemia seen in TB
⑥ May progress to granulomatous reaction
in unresolved infection
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Epitheloid Cell Granuloma Formation
• Large flattened cells with increased endoplasmic reticulum
• Multinucleate giant cells with little ER
•
May see necrosis• Damage due to killer T-cells recognizing antigen-coated
macrophages, cytokine-activated macrophages
• Attempt by the body to wall-off site of persistent infection
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Granuloma Formation
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(2) Contact dermatitis :
Paint, drug
red rash, papula, water blister, dermatitis