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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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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

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


Chapter 12

  • 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


Chapter 12

(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


Chapter 12

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


Chapter 12

(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


Chapter 12

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


Chapter 12

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


Chapter 12

  • 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


Chapter 12

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


Chapter 12

(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


Chapter 12

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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