Implantation & Inflammation Types of Immunity Innate Immune response Host Defense

Implantation & Inflammation Types of Immunity Innate Immune response Host Defense

Implantation & Inflammation Types of Immunity Innate Immune response Host Defense

Thompson, Michele, Health/Wellness Channel Editor has reference to this Academic Journal, PHwiki organized this Journal Implantation & Inflammation Topics Innate in addition to Acquired Immunity Physiological Response to Acute Inflammation Signs of Inflammation in addition to their Cause Actions of Neutrophils Actions of Macrophages Host Response to Material Implantation Implantation of a biomaterial is an invasive procedure that initiates a series of events whose outcome ultimately determine the biocompatibility of the material. In vivo response to a biodegradable, polymeric biomaterial implanted in a rat as long as 12 weeks. (a) 4 days (b) 3 weeks (c) 12 weeks. P indicates polymer, or space left by polymer; N: neutrophils, FC: fibrous capsule, M: macrophages, PF: polymer fragments embedded in fibrous capsule. Infiltration of neutrophils into implantation area is seen within a few days, followed by slower development of fibrous capsule surrounding implant. Because material is biodegradable, polymer fragmentation is present at later times.

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Types of Immunity Innate (nonspecific) – 1st line of defense Anatomic barriers (e.g, skin in addition to mucous membranes) Physiologic barriers (body temp., low pH in stomach) Phagocytic cells (granulocytes) Inflammation Acquired (specific): Activation of white blood cells (lymphocytes) Develops following exposure to certain pathogens Innate Immune response If a pathogen breaches the epithelium, then the innate immune response begins. The cells of the immune system determine “self” from “non-self” by recognizing molecules on the microbe surface. Macrophages are immune cells (phagocytes) that reside within the tissue. Neutrophils are phagocytes that reside in the blood but can extravasate into tissue during inflammation. There are circulating proteins, called complement, that either kill microbes or mark them as long as effective phagocytization. Host Defense The body is under constant attack by microorganisms in the environment. pathogen : an infectious agent that causes disease Infectious disease occurs when a microorganism succeeds in evading or overwhelming host defenses to establish a local site of infection in addition to replication. In order as long as a pathogen to enter the body it must first overcome the epithelium in addition to then the innate immune response.

First Line of Defense Epithelial Tissue covers the whole surface of the body made up of closely packed cells can be divided into simple or stratified interior epithelium covered with a mucus layer Types of Leukocytes Granulocytes: Includes neutrophils, eosinophils in addition to basophils: Granular appearance Nuclei have multiple lobes Phagocytose as long as eign invaders Aid in inflammatory response Phagocytosis: the cellular process of engulfing solid particles by the cell membrane to as long as m an internal phagosome, which is a food vacuole, or pteroid. The phagosome is usually delivered to the lysosome, an organelle involved in the breakdown of cellular components, which fuses with the phagosome. The contents are subsequently degraded in addition to either released extracellularly via exocytosis, or released intracellularly to undergo further processing. Types of Leukocytes, Continued Monocytes: Large phagocytic capability Play key roll in inflammation response Lymphocytes/plasma cells: Includes T- in addition to B-cells Part of acquired immune response Lymphocytes have memory cells, give rapid response when exposed to same pathogen Lymphocytes also have effector cells, producing antibodies in addition to try to remove as long as eign invaders Megakaryocytes: Found only in bone marrow Produces platelets that participate in clotting

Intravascular Cells white blood cells neutrophil eosinophil basophil monocyte lymphocyte Granulocytes Leukocyte Formation Leukocytes as long as med in pluripotent hematopoietic cells in bone marrow Granulocytes, monocytes, megakaryocytic as long as m in bone marrow Lymphocytes as long as m in bone marrow in addition to mature in lymphoid tissues (lymph gl in addition to s, spleen, thymus, tonsils) Life Span of Leukocytes Only present in blood as needed Granulocytes: 4-8 hrs. in blood 4-5 days in tissue Monocytes: 10-20 hrs. in blood Migrate to tissue, becoming “tissue macrophages” Tissue macrophages Longer lasting in addition to more powerful than monocytes Can live months to years Provide continual resident defense against infection Lymphocytes Resident in lymphoid tissue Enter blood stream as long as only a few hours Re-enter the lymph system Can continue in this loop as long as months to years

Inflammatory Response Pathogen recognition in addition to tissue damage begin an inflammation response. This is characterized by : swelling pain redness heat Inflammation allows as long as neutrophil in addition to plasma protein extravasation. Both of these effects aids the immune response. Role of Macrophages in addition to Neutrophils Macrophages: 1st line of defense, followed by granulocytes, neutrophils Move from blood vessels to tissue: extravasation Migration of neutrophils: Neutrophil extravasation takes 4 steps: Rolling Activation Arrest Adhesion

Rolling: neutrophils bind briefly to endothelium through weak selectin-carbohydrate interactions Activation: neutrophils activated by chemoattractants, substances that cause neutrophils to migrate toward site of injury Definition: Selectins are receptors on endothelial cells that have a carbohydrate-like portion that binds with proteoglycans (mucins) on neutrophil surface Definition: chemotaxis is the movement of cells in response to chemical stiuli Arrest/adhesion: neutrophils stop rolling in addition to attach to endothelial cells Transendothelial migration: diapedesis, or the squeezing of parts of the cell at a time through the endothelial cells Actions of Neutrophils Killing via phagocytosis Respiratory Burst Release of signaling molecules Phagocytosis Phagocytosis: Engulfing in addition to degradation or digestion of fragments of tissue or material long membrane evaginations, called pseudopodia. Ingestion as long as ming a “phagosome,” which moves toward the lysosome. Fusion of the lysosome in addition to phagosome (phagolysosome), releasing lysosomal enzymes Digestion of the ingested material. Release of digestion products from the cell.

Respiratory Burst Glucose metabolism increased 10-fold Oxygen consumption increased 2-3 fold Formation of reactive oxygen in addition to nitrogen species (radicals in addition to oxidizers) to kill as long as eign invaders These substances promote corrosion of biomaterials in addition to may cause unwanted tissue damage Secretion of Chemical Mediators Neutrophils secrete cytokines Definition: cytokines are a category of signaling proteins in addition to glycoproteins that, like hormones in addition to neurotransmitters, are used extensively in cellular communication. Role of other Leukocytes Monocytes/macrophages Monocytes arrive at injury ~6 hrs after inflammatory response begins They enlarge to as long as m macrophages. Macrophages take up to 8 hours to mature in addition to as long as m a large quantity of lysosomes, or digestive enzymes. Macrophage then becomes the dominant type of cell. They are similar to neutrophils, but with greater killing capacity. Macrophages: Phagocytose as long as eign invaders Secrete chemical mediators Coordinate response of other body systems Act as intermediary between innate in addition to acquired immune response systems

Phagocytosis in Biomaterials If phagocytosed material resists degradation it can remain in a macrophage until it dies in addition to undergoes lysis (disintegration) in addition to is released If macrophages cannot digest particles, fibroblasts can as long as m to encapsulate particles Objects too big to be ingested result in frustrated phagocytosis. Neutrophils in addition to macrophages release lysosomal materials (digestive enzymes) Secretion of Chemical Mediators Macrophages secrete chemical mediators to stimulate Inflammatory response Acquired immune response Systemic effects Examples of chemical mediators include: Interlukin 1 (IL-1) Interlukin 6 (IL-6) Tumor Necrosis Factor a (TNF-a) IL-1 in addition to TNF-a Promote cell migration by expressing CAMs on endothelial wall Increase expression of CAMs that bind integrin to granulocytes Increase production of IL-8 Activate migration of lymphocytes Promote production of acute-phase proteins by liver leading to fever Activate blood clotting cascade Activated macrophages present antigens ( as long as eign proteins) to lymphocytes, triggering activation of acquired immune response.

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Other Granulocytes Eosinophils Respond as neutrophil, but have less phagocytic ability Attach in addition to destroy parasites Prevent spread of inflammation Basophils: Release heparin, histamine, bradykinin, serotonin (soluble mediators of inflammation) Termination of Inflammation Inflammation ends with release of IL-1ra, a receptor antagonist to IL-1. IL-1ra binds to receptors as IL-1 but does not stimulate them. TGF-a: trans as long as ming growth factor a, inhibits certain cell types involved in inflammatory response IL-1ra in addition to TGF-a must act within a small radius of where they are produced The End

Foreign Body Reaction The presence of the implant changes the healing response, in addition to this is called the Foreign Body Reaction. FBR consists of: protein adsorption macrophages multinucleated as long as eign body giant cells fibroblasts angiogenesis Fibrosis in addition to Fibrous Encapsulation End stage of healing response Usually four or more weeks after implantation A relatively acellular fibrous capsule spindle shaped fibroblasts small number of macrophages Presence of neutrophils suggests persisting inflammatory challenge Presence of as long as eign body giant cell suggests production of small particles by corrosion, depolymerization, dissolution or wear Foreign Body Response – Resolution continuing presence of an implant may result in the attainment of a final steady-state condition called resolution there are 3 possible outcomes as long as the implant : resorption integration encapsulation (fibrosis)

Cell Regeneration After Injury Possible outcomes as long as the injured tissue: replacement of injured tissue with parenchymal cells of the same type replacement by connective tissue that constitutes the fibrous capsule The regeneration of cells in the body is tightly controlled There are essentially 3 categories of cell populations Renewing or labile Exp in addition to ing or stable Static or permanent

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