BIOM 250n 1st Edition Lecture 16Outline of Last Lecture I. Lymphatic SystemII. Phagocytosis Outline of Current Lecture I. InflammationII. FeverIII. The Complement SystemIV. Interferons Current LectureI. Inflammationa. Inflammation: a local defensive responseb. 4 signs/symptoms of inflammation: redness, pain, heat, swellingc. Functions of inflammation: i. Destruction of pathogenii. Limit damage by walling off pathogen and/or its productsiii. Ultimately promote healing/repair of tissued. Acute inflammation: short term; intensee. Chronic inflammation: long term; less intense but worsens over time; occurs when causes cannot be removedf. Activation of inflammationi. TLRs bind to ligands, become activated and release cytokinesii. The cytokine TNF is released and can activate other immune cells and cause more inflammationg. Three stages of inflammationi. Vasodilation/permeability: 1. Injury releases histamines from damaged cells2. Causes increased blood flow and leaky blood vessels3. Produces edema—excess fluid in area4. Pain is felt due to nerve damage, toxins or pressureThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.5. Blood clot forms in order to localize infection; can form an abscessii. Phagocytic migration:1. Cytokines induce neutrophils and monocytes to bind to the lining of blood vessels near the injury site2. Start migration to infection site through endothelial wall in a process denoted as diapedesis3. Activated phagocytes kill bacteria but eventually dieiii. Tissue repair:1. First all pathogens are killed/removed from the site and cell debrisis cleaned up2. Cells are regenerated and tissue is repaired if possible3. Fibrosis—scar tissue formation—heals the wound but does not form from functional cells4. Scar tissue is no longer capable of functioningII. Fevera. Fever: an abnormally high body temperature; systemic not localizedb. Release of cytokines and TNF resets the hypothalamusc. Blood vessels constrict, metabolism is increased, and shivering helps heat up the body (chills)d. Temperature reaches reset point which is determined by cytokine release—shivering stopse. As infection diminishes cytokine levels are lowered, vasodilation and sweating occurs which causes temperature to fallf. Fever aids in intensifying the immune response which possibly helps to inhibit bacterial growthg. Fever can be harmful if too high or too long lastingi. Causes dehydration, electrolyte imbalance, seizures, coma, etc.III. The Complement Systema. Serum proteins circulating in blood and in tissuesi. Acts as a cascade—each reaction triggers another until final product is formedii. Acts by lysing cells, inducing inflammation, and enhancing phagocytosisb. Starts when bacteria is recognized by the immune systemi. Either antibody or specific complement componentsii. This determines the pathway used by complementc. Classical pathway:i. Antibodies bind to bacterial surfaceii. Antibody activates cascade—starts with C3 proteiniii. Activated C3 splitsiv. One part causes histamine release from Mast cell which then causes inflammation1. Mast cells are similar to basophils but reside in the tissues not the bloodv. Second part coats bacteria to enhance phagocytosisvi. Also helps form the membrane attack complex (MAC) to lyse bacteriad. Alternative pathway:i. Other complement factors recognize and bind to surface of a pathogenii. These activate C3iii. C3 splits: causes inflammation; formation of MAC in same process as classical pathwayiv. Only difference is how C3 gets activatede. Effects of complement activation:i. Opsonization: promotes attachment of phagocytes to pathogenii. Induces inflammation by histamine release from mast cellsiii. Forms MACIV. Interferons (IFNS)a. A virus is dependent on much of the host cell machinery to reproduce itselfi. So any treatments to inhibit viruses also damage host cellsb. Virally-infected host cells can give off interferonsi. IFNs: cytokines that interfere with viral multiplicationii. IFNs can be host cell specific but are not virus specificiii. IFNs bind to neighboring host cell receptors and induce gene expressionc. IFNs induce uninfected cells to produce antiviral proteinsi. Infected cells produce very small amounts of IFNsii. Meant only to act over short distancesiii. Antiviral proteins are enzymes that disrupt viral