type iii and iv hypersensitivity

8/13/2019 Type III and IV Hypersensitivity

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Type III and IVhypersensitivity

Yingping Xu

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mailto:[email protected]

mailto:[email protected]



1. Characteristics

2. Mechanism of type III hepersensitivity

3. Common disease of type III hepersensitivity

Type III hypersensitivity



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



2、Mechanism of type III hypersensitivity

Formation of the intermediate immune complex

Deposition of the intermediate immune complex

Tissue injury by the immune complex



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.



(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



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.



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)



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.



(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



A Dominant Role for Mast Cell Fc Receptors in the Arthus Reaction:

Sylvestre et al, 1996,

Immunity 5:387



A: Control -/-; B: Control +/+; C: Control W/Wv; D: W/Wv

reconstituted with -/- mast cells or E: +/+ mast cells



Acute immune complex glomerulonephritis and

choroidmeningitis :

Streptococcus infection



(3). Chronic immune complex disease SLE (systemic lupus erythematosus)

Rheumatoid arthritis ：RF+IgG Deposit on synovial membrane



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



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.



1. Characteristics

Interaction of primed T cells and associated antigen

Infiltration of Mononuclear Cells, especially macrophage

induce inflammatory response



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



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



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



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



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.



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



MCF:

Macrophage chemotactic factor

MIF:

Macrophage inhibitory factor



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



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



Granuloma Formation



(2) Contact dermatitis :

Paint, drug

red rash, papula, water blister, dermatitis

type iii and iv hypersensitivity

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