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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.
  • 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.
  • 5. Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) Kuby J et al., Immunology 2003
  • 6. ABO blood group Kuby J et al., Immunology 2003
  • 7. 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
  • 8. Effector mechanisms of antibody-mediated disease C Graves’ disease: Hyperthyroidism Myasthenia gravis : Muscle weakness (hormones) (neurotransmitter)
  • 9. Type III Immune complex-mediated hypersensitivity
  • 10. The four types of hypersensitive responses Kuby J et al., Immunology 2003
  • 11. 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.
  • 12. 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)
  • 13. Development of a localized Arthus reaction Immunology (Fig. 16-15), 5th edn 2003 Kuby J
  • 14. The multiple activities of the complement system.
  • 15. 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.
  • 16. Serum sickness is a classic example of a transient Figure 12-23 immune complex-mediated syndrome
  • 17. Type IV Delayed-type hypersensitivity (DTH) (Cell-mediated hypersensitivity)
  • 18. The four types of hypersensitive responses Kuby J et al., Immunology 2003
  • 19. 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).
  • 20. Type IV hypersensitivity responses Figure 12-24
  • 21. Overview of the DTH response Kuby J et al., Immunology 2003
  • 22. The delayed-type (type IV) hypersensitivity response is directed by Figure 12-26 part 1 of 2 chemokines and cytokines released by TH1 cells stimulated by antigen (1)
  • 23. Figure 12-26 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)
  • 24. 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
  • 25. A Second Exposure to Poison Oak May Result in Delayed-Type Hypersensitivity Kuby J et al., Immunology 2003
  • 26. 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. 16-20), 5th edn 2003 Kuby J
  • 27. Blistering skin lesions on hand of patient with poison ivy contact dermatitis Figure 12-28
  • 28. There are four types of hypersensitivity reaction mediated by immunological mechanisms that cause tissue damage
  • 29. Kuby J et al., Immunology 2003