CHAPTER10 Biomaterial Implantation and Acute Inflammation 10.1 Introduction: Overview of Innate and Acquired Immunity Wound healing Implantation --- assault on the body’s homeostais Body’s defense mechanism innate immunity (inflammation) acquired immunity (antibody production) Infection Characteristics of Leukocytes (1)Leukocyte types Granulocytes Monocytes Lymphocytes/plasma cells Megakaryocytes

(2) Leukocyte formation: pluripotent hematopoietic stem cell (3) Life span of leukocytes granulocytes / monocytes /lymphocytes Sources of Innate Immunity anatomic barrier / physiologic barriers / phagocytic cells / inflammation 10.2 Clinical Signs of Inflammation and Their Causes redness (rubor) / swelling (tumor) / heating (calore) / pain (dolore) - Acute inflammation and Chronic inflammation mediators of acute inflammation (Table 10-1) - Process: Injury – Vasodilation – Capillary Permeability – Fibrinogen and Chemotaxis of granulocytes and monocytes – Tissue cell swelling Kinin release from the blood clotting cascade

10.3 Role of Tissue Macrophages and Neutrophils Extravasation of neutrophils Influx of phagocytes Migration of Neutrophils Extravasation process rolling / activation / arrest and adhesion / migration via diapedesis Actions of Neutrophils (1) phagocytosis (2) respiratory burst (3) secretion of chemical mediators

10.4 Role of Other Leukocytes Monocytes / Macrophages Actions of Macrophages (1) phagocytosis and biomaterials - bacteria and particles (ex. silicosis) - frustrated phagocytosis (2) secretion of chemical mediators (IL-1, IL-6, TNF-  ) - inflammatory effects, acquired immunity, systemic effects (ex) IL-1 and TNF-  cell migration / CAM and integrins / IL-8 / neutrophils and macrophages / acquired immunity / systemic effects (body temp and blood clotting cascade) (3) role as antigen presenting cells (APC) Other Granulocytes (1) Eosinophils chemotaxis / small cytotoxic capacity / parasite destruction / detoxification (2) Basophils mast cells / heparin, histamine, bradykinin, and serotonin release allergic reaction

10.5 Termination of Acute Inflammation (1) IL-1 receptor agonist (IL-1ra) from macrophage relative amount of IL-1 and IL-1ra (2) TGF-b (transforming growth factor) from macrophage and lymphocytes (3) destruction of chemical mediators - Acute to either chronic or granulation tissue/a foreign body reaction 10.6 Techniques: In Vitro Assays for Inflammatory Response Leukocyte Assays (Neutrophils or Macrophages) (1) cell adhesion and spreading (2) cell death (3) cell migration (direct observation and population assay) (4) cytokine release (IL and TNF-  ) (5) cell surface marker expression FACS analysis Other assays - endothelial cells (selectin and CAM) - in vitro model system (skin replacement) cytokine release and ELISA

[1] Innate and Acquired Immunity

Innate Immunity (1)Physiologic and Chemical Barrier (Skin and Mucous Membranes) (2)Cellular Defenses (neutrophil, basophil, eosinophil, monocyte) (3)Phagocytosis and Extracellular Killing (a) Endocytosis and Phagocytosis

Endocytosis (pinocytosis and receptor-mediated endocytosis) Phagocytosis (opsonin-mediated engulfing of microorganism) a) Polymorphonuclear Leukocytes (PMN) b) Macrophages Kupffer cells, Alveolar macrophages, Splenic macrophages Peritoneal macrophages, Microglial cells c) Reticuloendothelial System (RES) Macrophages in blood Dendritic cells, Interdigitating cells, Langerhans cells

(b) Extracellular Killing (Tc cell and NK cell) NK cell via Killer cell inhibitory receptors (KIR) NK cell activated by IL-2, IL-12, interferons (4) Fever pyrogens (IL-1 & IFN) from monocytes and macrophages (5) Biologically Active Substances degradative enzymes, toxic free radicals, acids, inhibitors of growth acute-phase proteins, interferons

(6) Inflammation swelling, redness, heat, pain, loss of function of the inflamed area Injury – acute responses a) localized inflammatory response activation of the clotting, kinin-forming, and fibrolytic pathways kinin ----[smooth muscle contraction, distal muscle relaxation vascular permeability, leukocyte extravasation, pain (itching) perception] b) systemic inflammatory response fever, WBC, hydrocortisone and ACTH, acute-phase proteins c) cytokines IL-1, IL-6, TNF-  [extravasation, coagulation, vascular permeability] IL-8, IFN-  [chemotaxis, phagocytosis] Accumulation of fluid (edema) and leukocytes d) polymorphonuclear leukocytes and mononuclear cells e) persisted infection Ab and cell-mediated immunity f) repairing the injury [macrophage-mediated] g) chronic inflammation [tuberculosis, rheumatoid arthritis, glomerulonephritis]

Acquired Immunity humoral immunity: Ab from B-cell cell-mediated immunity: T-cell and macrophage immunization: active immunization passive immunization adoptive immunization characteristics of the immune response 1. specificity 2. adaptiveness 3. discrimination between self and non-self 4. memory: anamnestic response