Body DefenseAmy Warenda Czura, Ph.D.1SCCC BIO244 Chapter 16 HandoutAmy Warenda Czura, Ph.D.2SCCC BIO244 Chapter 16 Handout1. Chemotaxis and AdherenceChemotaxis = chemical attraction of phagocyte to microbe; attracted by microbial products, damagedcells, cytokines, and/or complementAdherence = attachment of plasma membrane of phagocyte to microbe; Toll-like receptors (TLRs) onphagocyte membrane bind to pathogen-associated molecular patterns (PAMPs) on microbeAdherence made easier by opsonizationOpsonization = coating of the microbe with antibodies or complement proteins2. Ingestion: phagocyte extends pseudopods around microbe3. Phagosome formation: fusion of pseudopods around the microbe encloses it in a phagocytic vesicle called a phagosome which now floats in the cytoplasm4. Phagolysosome formation: the phagosome fuses with a lysosome creating a phagolysosome putting themicrobe in contact with digestive enzymes and bacteriocidal substances5. Digestion: most microbes are killed and hydrolyzed in 10-30 minOxidative burst kills the microbe: toxic oxygen radicals (superoxide, hydrogen peroxide)Enzymes and acids hydrolyze the microbe into component organic molecules6. Formation of the residual body: useful small organic molecules are absorbed into the cytoplasm and theacids and enzymes are neutralized. Residual body = all remaining undigested material in a vesicle7. Exocytosis: residual body contents are discharged outside the cellPhagocytosisAmy Warenda Czura, Ph.D.3SCCC BIO244 Chapter 16 HandoutInflammationA. Begins with damage to the tissue:B. Vasodilation and Increased Blood Vessel Permeability 1. Damaged cells release chemicals (histamine, prostaglandins, leukotrienes) which promote vasodilation, increased permeability of vessel walls,and attraction of phagocytes 2. Blood clot forms: clotting factors solidify fibrin at theinjury site to prevent spread 3. Abscess begins to form: abscess = localized collectionof dead cells, body fluids and microbes trapped under the clotC. Phagocyte Migration and Phagocytosis 4. Margination: phagocytes attracted to the injury (by microbial molecules, leukotrienes, cytokines and/or complement) adhere to the endothelium of the local blood vessels 5. Emigration / Diapedesis: (aided by protaglandins) marginated phagocytes move into the tissues via pseudopods (ameoboid motion) exiting the vessel between the loose endothelial cells, and chemotax toward the damaged cells and microbes 6. Phagocytosis (aided by leukotrienes) Neutrophils arrive first: fast acting but short lived, phagocytose pathogens Macrophages arrive second: engulf necrotic tissue, dead neutrophils, and remaining pathogensActivated macrophages secrete cytokines that increase vasodilation & vessel permeability, andattract more phagocytesD. Tissue repair 7. Repair: begins only after all harmful substances and microbes have been neutralized & removedTissue = parenchyma (cells) + stroma (CT) parenchyma growth = reconstruction stroma growth = scarAmy Warenda Czura, Ph.D.4SCCC BIO244 Chapter 16 HandoutComplement SystemComplement FixationActivated by:1. Antibody binding to microbe2. Complement proteins binding to microbe3. Lectins binding to microbeThree Antimicrobial Results ofComplement Fixation:1. MAC formation = CytolysisC5-C9 form the Membrane Attack Complex: the proteins assembleinto a pore on the microbe membraneresulting in cell lysis2. Opsonization = PhagocytosisC3b opsonizes bacteria to enhance phagocytosis3. Inflammation = PhagocytosisC3a + C5a triggers histamine release fromMast cells thus triggering inflammationC3C3C3bC3bC3aC3aCascade is triggered in blood: onecomplement protein turns on the nextAmy Warenda Czura, Ph.D.5SCCC BIO244 Chapter 16