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
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