CHAPTER

1010BiomaterialImplantation and AcuteInflammation

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 10.1.1 Characteristics of Leukocytes (1)Leukocyte types

GranulocytesMonocytesLymphocytes/plasma cells Megakaryocytes

(2) Leukocyte formation: pluripotent hematopoietic stem cell (3) Life span of leukocytes

granulocytes / monocytes / lymphocytes

10.1.2 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

10.3.1 Migration of Neutrophils Extravasation process rolling / activation / arrest and adhesion / migration via diapedesis

10.3.2 Actions of Neutrophils (1) phagocytosis (2) respiratory burst (3) secretion of chemical mediators

10.4 Role of Other Leukocytes 10.4.1 Monocytes / Macrophages

10.4.2 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)

10.4.3 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 10.6.1 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

10.6.2 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 macrophagesPeritoneal 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 growthacute-phase proteins, interferons

(6) Inflammation swelling, redness, heat, pain, loss of function of the inflamed area

Injury – acute responsesa) 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 responsefever, 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-cellcell-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-self4. memory: anamnestic response