Type II. Antibody-mediated cytotoxic hypersensitivity

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1 Type II Antibody-mediated cytotoxic hypersensitivity

2 The four types of hypersensitive responses Kuby J et al., Immunology 2003

3 Type II hypersensitivity reactions (1) - Caused by antibody to cell surface antigens and components of the extracellular matrix. - These antibodies can sensitize the cells for antibody-dependent cytotoxic attack by K cells or for complement-mediated lysis. - Type II hypersensitivity is seen in the destruction of red cells in transfusion reactions and in haemolytic disease of the newborn.

- These antibodies can sensitize the cells for antibody-dependent cytotoxic attack by K cells or

4 Type II hypersensitivity reactions (2) - Innocuous antigens can cause Type II hypersensitivity reactions in susceptible individuals by binding to the surfaces of circulating blood cells. - IgG antibodies against cell-surface receptors that disrupt the normal functions of the receptor, either by causing uncontrollable activation or by blocking receptor function.

7 Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) Kuby J et al., Immunology 2003

8 ABO blood group Kuby J et al., Immunology 2003

9 Development of erythroblastosis fetalis (hemolytic disease of the newborn) caused when an RH- mother carries an RH+ fetus, and effect of treatment with anti-rh antibody, or Rhogam Kuby J et al., Immunology 2003

carries an RH+ fetus, and effect of treatment with

10 Effector mechanisms of antibody-mediated disease C Graves disease: Hyperthyroidism Myasthenia gravis : Muscle weakness (hormones) (neurotransmitter)

11 Type III Immune complex-mediated hypersensitivity

12 The four types of hypersensitive responses Kuby J et al., Immunology 2003

13 Type III hypersensitivity reactions (1) - Directed against soluble antigens - Caused by the deposition of antigen/antibody complexes in tissue and blood vessels. - The complexes activate complement and attract ploymorphs and macrophages to the site. - These cells may exocytose their granule contents and release reactive oxygen and nitrogen intermediates to cause local tissue damage.

- The complexes activate complement and attract ploymorphs and macrophages to the site.

14 Type III hypersensitivity reactions (2) - The deposition of immune complexes in tissues causes a local inflammatory response known as an Arthus reaction. - Serum sickness is a classic example of a transient immune complex-mediated syndrome. - In situations in which antigen persists subacute bacterial endocarditis chronic viral hepatitis systemic lupus erythematosus (SLE)

- Serum sickness is a classic example of a transient immune complex-mediated syndrome.

15 Development of a localized Arthus reaction Immunology (Fig ), 5th edn 2003 Kuby J

17 The multiple activities of the complement system.

18 Immune complex disease - The immune complexes produced may bind to vascular endothelium and kidney glomeruli and activate complement (MAC generation). - It initiates the acute inflammatory responses that destroy the vessel walls or glomeruli and lead to thrombosis, ischemic damage to tissues, and scarring. - Some of the late complement proteins may activate prothrombinases in the circulation that initiate thrombosis.

- It initiates the acute inflammatory responses that destroy the vessel walls or glomeruli and lead to

19 Serum sickness is a classic example of a transient immune Figure complex-mediated 12-23syndrome

20 Type IV Delayed-type hypersensitivity (DTH) (Cell-mediated hypersensitivity)

21 The four types of hypersensitive responses Kuby J et al., Immunology 2003

22 Type IV hypersensitivity reactions - T-cell mediated - 1st group: Tissue damage is caused by the activation of macrophages by TH1 cells, which results in an inflammatory response. - 2nd group: Damage is caused by the activation by TH2 cells of inflammatory responses in which eosinophils predominate. - 3rd group: Damage is caused directly by cytotoxic T cells (CTL).

23 Type IV hypersensitivity responses Figure 12-24

25 Overview of the DTH response Kuby J et al., Immunology 2003

26 Figure part 1 of 2 The delayed-type (type IV) hypersensitivity response is directed by chemokines and cytokines released by TH1 cells stimulated by antigen (1)

27 Figure part 2 of 2 The delayed-type (type IV) hypersensitivity response is directed by chemokines and cytokines released by TH1 cells stimulated by antigen (2)

28 A prolonged DTH response can lead to formation of a granuloma Lytic enzymes released from activated macrophages in a granuloma can cause extensive tissue damage. Kuby J et al., Immunology 2003

29 A Second Exposure to Poison Oak May Result in Delayed-Type Hypersensitivity Kuby J et al., Immunology 2003

30 Development of delayed-type hypersensitvity reaction after a second exposure to poison oak Secrete INF-γ and other cytokines Activated macrophages Secrete mediators of inflammation Immunology (Fig ), 5th edn 2003 Kuby J

32 Blistering skin lesions on hand of patient with poison ivy contact dermatitis Figure 12-28

33 There are four types of hypersensitivity reaction mediated by immunological mechanisms that cause tissue damage

34 Kuby J et al., Immunology 2003

Hypersensitivity. TYPE I Hypersensitivity Classic allergy. Allergens. Characteristics of allergens. Allergens. Mediated by IgE attached to Mast cells.

Hypersensitivity. TYPE I Hypersensitivity Classic allergy. Allergens. Characteristics of allergens. Allergens. Mediated by IgE attached to Mast cells. Gel and Coombs classification of hypersensitivities. Hypersensitivity Robert Beatty Type I Type II Type III Type IV MCB150 IgE Mediated IgG/IgM Mediated IgG Mediated T cell Classic Allergy rbc lysis Immune