chapter12 immune response to biomaterials 12-1 introduction: overview of acquired immunity innate...
TRANSCRIPT
CHAPTER
1212Immune Responseto Biomaterials
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 memoryhumoral 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
(1) 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 rejectiontissue typing
(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
12.2.3 Activation and Formation of Clonal Population
12-3 B-cells and Antibodies 12.3.1 Types of B-cells
plasma cellsmemory cells
12.3.2 Characteristics of B-cells(1) Structure of antibodies
(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
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
12.5.1 Classical pathway / 12.5.2 Alternative pathway / 12.5.3 Memb attack complex
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 (2) 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 (1)Complement system amplifies the actions of Ab. (2)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
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 --- vasodilationand smooth muscle contraction
(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
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