Type III hypersensitivity

(immune complex)

Introduction

Large amounts of immune complexes can

lead to tissue damage, either in local sites or

systemically, which mediated by activation of

complements, neutrophils, basophils, and

platelets.

APC

TH2

B cell

Sensitization for Type III hypersensitivity

Sensitization for Type III hypersensitivity

Type III hypersensitivity mechanismType III hypersensitivity mechanism

Antigen:

Soluble antigens

Antibodies:

IgG, IgM, IgA

Intermediate size immune complex

Effectors:

1. Complement

2. Neutrophils

3. Platelet

4. Mast cells

Conditions of immune complex formation

1. Size of immune complex

2. Tissue structures such as blood vessel walls, synovial membrane of joints, glomerular basement membrane.

not

Figure 10-32

Clinical diseases：Localized：

Arthus reaction ， Arthus-like reaction

Systemic：

Serum sickness ， streptococcal nephritis ， polyarteritis nodosa ， SLE

Development of a localized Arthus reaction

Arthus reactionArthus reaction

Arthus reactionType-III

Wheal & flare reactionType-I

Serum sicknessSerum sickness

Serum sickness

Systemic lupus erythematosusSystemic lupus erythematosus

Antigen involved : DNA, nucleoproteins, others

Nephritis, arthritis, vasculitis

Post-streptococcal glomerulonephritis

Chronic infection by HBV

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Detection of immune complexes in tissue

Detection of immune complexes in tissue

Features of type III sensitivity

① Mediated by immune complexes

② Complement activation

③ Infiltrated by neutrophils, platelets, and basophils.

④ Tissue injury directly cause by lytic enzymes

Type IV hypersensitivity

Type IV hypersensitivity

Delayed type hypersensitivity

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Type IV hypersensitivityType IV hypersensitivity

Delayed reaction 36 to 48 hours Characterized by induration

and erythema Also known as cell

mediated hypersensitivity Tuberculin test is the most

common example

Delayed reaction 36 to 48 hours Characterized by induration

and erythema Also known as cell

mediated hypersensitivity Tuberculin test is the most

common example

Introduction

This occurs from 24 hour after contact with an antigen and is mediated by T cells together with dendritic cells, macrophages and cytokines characterized by induration and erythema.

The persistent presence of the antigen e.g. chronic mycobacterial infections, results in granulomas.

Skin contact with a number of small molecules (chemicals and plant molecules) can also result in delayed hypersensitivity.

APC

Mechanism of damage in contact hypersensitivity

Mechanism of damage in contact hypersensitivity

TH1

NK

Mθ Mθ

LAK

preTc

Tc

IL2, TNFαIFNγ

IL2 TNFαIFNγ

NO2

Figure 10-35Numerous cytokines participate in the DTH reaction

The formation of a granuloma

Tuberculin testTuberculin test

Granuloma in a leprosy patientGranuloma in a leprosy patient

contact dermatitis

Contact dermatitis reaction to mango sap

Contact dermatitis reaction to mango sap

Contact dermatitis reaction to leather

Contact dermatitis reaction to leather

Old Milwaukee helps?Old Milwaukee helps?

No! but it makes them feel betterNo! but it makes them feel better

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Delayed hypersensitivity reactionsDelayed hypersensitivity reactions

persistent antigen stimulus, chronic infection

Mθ, giant cells, epitheloid cells, fibroblasts

hardening21-28 days

granuloma

intradermal: tuberculin, lepromin, etc.

lymphocytes, monocytes

local induration

48-72 hourstuberculin

epidermal: heavy metals, poison ivy, rubber, latex

T cells, later macrophageseczema

48-72 hours

contactdermatitis

antigen and sitehistologyclinical appearance

time of reaction

type

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Type IV hypersensitivitythe three forms

Type IV hypersensitivitythe three forms

Type-IVType-IIIType-IIType-Icharacteristic

Comparison of hypersensitivity reactions

Comparison of hypersensitivity reactions

TB test, poison ivy, granuloma

farmers’ lung, SLE

Autoimmune hemolytic anemia, Graves’

hay fever, asthma

examples

antibody IgE IgG, IgM IgG, IgM none

antigen exogenous cell surface intracellularsoluble

response time

15-30 min. Min.-hrs 3-8 hours 48-72 hoursor longer

appearance Weal & flare Lysis & necrosis

Erythema & edema

Erythema & induration

baso- and eosinophils

Ab and complement

histology PMN andcomplement

Monocytes & lymphocytes

T-cellsantibodyantibodyantibodytransfer with

Review questions:

1. Please compare the mechanisms of 4 types of hypersensitivity.

2. Which type of hypersensitivity can penicillin cause?