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

Type 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 reaction Type-III Wheal & flare reaction Type-I

Serum sickness

Systemic lupus erythematosus Antigen involved : DNA, nucleoproteins, others Nephritis, arthritis, vasculitis

Post-streptococcal glomerulonephritis

Chronic infection by HBV

21 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 Delayed type hypersensitivity

24 Type IV hypersensitivity ãDelayed reaction ã36 to 48 hours ãCharacterized by induration and erythema ãAlso known as cell mediated hypersensitivity ãTuberculin test is the most common example ãDelayed reaction ã36 to 48 hours ãCharacterized by induration and erythema ãAlso known as cell mediated hypersensitivity ãTuberculin 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 TH1 NK MθMθ MθMθ LAK preTc Tc IL2, TNFα IFNγ IL2 TNFα IFNγ NO2

Figure Numerous cytokines participate in the DTH reaction

The formation of a granuloma

Tuberculin test

Granuloma in a leprosy patient

contact dermatitis

Contact dermatitis reaction to mango sap

Contact dermatitis reaction to leather

Old Milwaukee helps?

No! but it makes them feel better

36 Delayed hypersensitivity reactions persistent antigen stimulus, chronic infection Mθ, giant cells, epitheloid cells, fibroblasts hardening days granuloma intradermal: tuberculin, lepromin, etc. lymphocytes, monocytes local induration hours tuberculin epidermal: heavy metals, poison ivy, rubber, latex T cells, later macrophages eczema hours contact dermatitis antigen and site histologyclinical appearance time of reaction type

37 Type IV hypersensitivity the three forms

Type-IV Type-III Type-IIType-Icharacteristic Comparison of hypersensitivity reactions TB test, poison ivy, granuloma farmers’ lung, SLE Autoimmune hemolytic anemia, Graves’ hay fever, asthma examples antibodyIgEIgG, IgM none antigen exogenouscell surface intracellular soluble response time min. Min.-hrs3-8 hours hours or longer appearance Weal & flare Lysis & necrosis Erythema & edema Erythema & induration baso- and eosinophils Ab and complement histology PMN and complement Monocytes & lymphocytes T-cells antibody transfer with

Review questions: 1.Please compare the mechanisms of 4 types of hypersensitivity. 2.Which type of hypersensitivity can penicillin cause?