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CHAPTER 12

Immune Response to Biomaterials. CHAPTER 12. 12-1 Introduction: Overview of Acquired Immunity Innate immunity vs. Acquired immunity Immunotoxicity: adverse effects on immune system and other body systems Acquired immunity

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CHAPTER 12

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  1. Immune Response to Biomaterials CHAPTER 12 12-1 Introduction: Overview of Acquired Immunity Innate immunity vs. Acquired immunity Immunotoxicity: adverse effects on immune system and other body systems Acquired immunity specificity / diversity / self & non-self recognition / immunologic memory humoral immunity (B-cell) and cellular immunity (T-cell) Biomaterials roles hapten and adjuvant 12-2 Antigen Presentation and Lymphocyte Maturation 12.2.1 Major Histocompatibility Complex (MHC) Molecules Antigen presentation with either MHC-I and MHC-II

  2. MHC-Class I • all nucleated cells • Tc • (2) MHC-Class II • antigen-presenting cells • (macrophages, B-cells, dendritic cells) • (3) MHC molecular variation • 3 genes for each MHC-I and II • tissue rejection • tissue typing

  3. (4) Intracellular Complexation with MHC-Molecules a. endogeneous antigens --- proteolysis --- peptides --- MHC-1 in ER --- cell surface exposure b. exogeneous antigens --- phagocytosis --- proteolysis in endosome --- MHC-II binding in the endocytotic vesicles 12.2.2 Maturation of Lymphocytes 10,000 Ab/TcR (single specificity) – gene rearrangement – immunologic diversity

  4. 12.2.3 Activation and Formation of Clonal Population 12-3 B-cells and Antibodies 12.3.1 Types of B-cells plasma cells memory cells 12.3.2 Characteristics of B-cells (1) Structure of antibodies

  5. (2) Classes of antibody (3) Mechanism of Ab action agglutination precipitation neutralization lysis phagocytosis (effector function) complement activation 12-4 T Cells 12.4.1 Types of T-cells TH-cell and TC-cell

  6. 12.4.2 Helper T cells cytokines from TH-effector cells (1) B-cell growth and differentiation (IL-4, 5, 6) (2) TC-cell proliferation (IL-2) (3) TH-cell activation (IL-2) (4) Promotion of chemotaxis and activation of macrophages (MIP & IL-8) 12.4.3 Cytotoxic T cells cytotoxic T-lymphocytes (CTL) --- perforins --- cell lysis --- disengagement --- another ‘altered self’ cells (virus infected or cancer cells) 12-5 The Complement System innate immunity ~ 20 plasma proteins --- action cascade --- elimination of foreign elements via memb-attacking complex formation

  7. 12.5.1 Classical pathway / 12.5.2 Alternative pathway / 12.5.3 Memb attack complex

  8. 12.5.4 Regulation of the Complement System • localized action and preventing host cell lysis • (1) Short half-life of certain enzymes • C3b degradation by C3 convertase away of target by 40 nm • C3b and MAC regulation • C5b67 --- no membrane insertion --- leak and attack bystander cells • amplification sites • (3) Regulatory proteins • competing for key binding sites • RCA proteins (regulator of complement activation) • a. C4b + RCA (no C3 convertase) • b. C3b + RCA (no C3 convertase) • c. C8 + RCA (no poly-C9 complex) • d. DAF (decay-accelerating factor) --- C3 convertase binding • 12.5.5 Effects of the Complement System • Complement system amplifies the actions of Ab. • Complement system stimulates the inflammatory response. • mast cell and basophil binding • chemotaxis of monocytes and neutrophils / macrophage adhesion • (3) Phagocytosis • C3b --- foreign surface --- macrophage and neutrophils • uptake of the opsonized particle

  9. 12-6 Undesired Immune Responses to Biomaterials 12.6.1 Innate vs. Acquired Responses to Biomaterials no rejection / no destruction / immunocompatibility complement activation --- accumulation of inflammatory cells --- device failure 12.6.2 Hypersensitivity or Allergic reaction unusual, excessive or uncontrolled immune reaction (1) Type I: IgE mediated allergen --- IgE plasma cell --- receptors of basophils and mast cells --- Ab X-linking --- degranulation of mast cells --- histamine release --- vasodilation and smooth muscle contraction

  10. (2) Type II: Antibody mediated antibody and complement to destroy cells or platelets with foreign antigen on the surface (3) Type III: Immune complex mediated Ag + Ab complex --- ppt --- complement activation and phagocytic cell migration --- enzyme and active substance release --- tissue damage (4) Type IV: T-cell mediated (= delayed-type hypersensitivity) allergen on APC --- TDTH cell --- cytokines --- macrophage attraction --- lytic agent release --- local tissue damage (5) Hypersensitivity and the classes of biomaterials a. metals b. ceramics c. polymers d. protein coats non-self

  11. 12-7 Techniques: Assays for Immune Response materials --- lymphocytes and inflammatory cells --- stimulation 12.7.1 In vitro assays (1) cell adhesion and spreading (2) cell death (3) cell migration (4) cytokine release (5) cell surface marker expression (6) cell proliferation expansion of clonal populations LTT (lymphocyte transformation tests) migration (small scale) ELISA FACS 12.7.2 In vivo assays (1) histology/immunohistochemistry (lymphocytes) (2) immune response (blood from the animal) (3) Ag from the biomaterials skin test for localized inflammation

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