Exam 3 Review Guide PART ONE NONSPECIFIC RESISTANCE SPECIFIC IMMUNITY Defense Mechanisms 1 First Line External barriers skin mucous membranes 2 Second Line Nonspecific defense mechanisms phagocytic cells leukocytes macrophages antimicrobial proteins immune surveillance inflammation fever 3 Third Line Specific immunity Phagocytic Cells 5 Neutrophils fight bacteria by phagocytosis respiratory burst Eosinophils fight parasites allergens secrete antihistamines toxic proteins Basophils secrete histamine increases blood flow to attract WBCs heparin anticoagulant Lymphocytes mostly NK cells immune surveillance Monocytes transform into macrophages in the connective tissues Antimicrobial Proteins short term resistance Interferons proteins secreted by cells when they re infected w a virus a cell s dying words prevent multiplication of virus activate NK cells macrophages Complement System completes the action of the antibody group of 30 globulins that contribute to nonspecific resistance specific immunity they are synthesized in the liver and circulate in inactive form until they are activated by the presence of a pathogen inactive vs active inactive C a number ex C1 C2 etc active C a number a lowercase letter ex C1a C1b etc Complement System Activation Pathways 1 Classical Pathway Antibody Dependent part of specific immunity Ag Ab complexes form on pathogen surface Reaction cascade complement fixation because a chain of complements attaches to antibody antibody bind to an antigen on surface of a microbe changes shape which exposes complement binding sites C1 binds to these sites sets off reaction cascade which is similar to blood clotting reactions because each step is an amplifying process 2 Alternative Pathway Antibody Independent nonspecific defense C3 dissociates into C3a C3b C3b binds directly to targets tumor cells viruses bacteria which also triggers a reaction cascade with an autocatalytic effect which is a feedback cycle autocatalytic effect the C3b that is present leads to accelerated splitting of more C3 and increased production of more C3b 3 Lectin Pathway Antibody Independent part of nonspecific defense Lectins plasma proteins that bind to carbs a lectin binds to certain sugars of a microbial cell surface sets off a reaction cascade yielding more C3b ALL pathways converge at the splitting of C3 into C3a C3b C3a inflammation C3b immune clearance phagocytosis cytolysis Four Mechanisms of Pathogen Destruction in Complement System 1 Inflammation C3a stimulates mast cells basophils to secrete histamine other inflammatory chemicals which activates and attracts neutrophils macrophages key cells of pathogen destruction in inflammation 2 Immune Clearance principle means for cku8learing antigens from the blood C3b binds Ag Ab complexes to RBCs as RBCs circulate through liver spleen macrophages destroy the Ag Ab complexes without harming the RBCs 3 Phagocytosis neutrophils macrophages C3b digestion of bacteria viruses other pathogens through C3b opsonization opsonization butters up foreign cells coats microbial cells serves as binding sites for phagocyte attachment 4 Cytolysis C3b C5 C5a C5b C3b splits C5 into C5a and C5b C5a helps C3a in proinflammatory actions C5b binds to the enemy cell attracts complements C6 C7 C8 which is now called C5b678 membrane attack complex C5b678 binds up to 17 molecules of C9 which forms a ring called membrane attack complex which forms a hole in the target cell which causes it to rupture Immune Surveillance 4 steps NK Cells Kiss of death 1 Releases perforins which form a hole in the enemy cell membrane 2 granzymes enter perforin hole degrade enemy cell enzymes 3 Enemy cell dies by apoptosis 4 macrophage engulfs digests dying cell Inflammation itis local defense response to tissue injury 4 cardinal signs redness heat swelling pain regulated by cytokines have paracrine autocrine effects 3 major processes 1 Mobilization of defenses immediately vasodilates surrounding vessels for local hyperemia increased blood flow to bring WBCs to the site Cytokines secrete vasoactive chemicals to remain vasodilated and increase capillary permeability Margination occurs endothelial cells recruit WBCs by producing selectins cell adhesion molecules which loosely attach to WBCs cause them to adhere to vessel wall Diapedesis occurs WBCs crawl through gaps between ECs to the site now considered extravasated 2 Containment destruction of pathogens containment fibrinogen filters into tissue fluid and clots in areas adjacent to injury forms sticky mesh that isolates bacteria Heparin prevents clotting in injury area to trap the bacteria in a fluid pocket surrounded by clotted fluid which prevents them from escaping they are attacked by antibodies Chemotaxis attraction to chemicals leukotrienes etc experienced by neutrophils when they leave the bloodstream guides them to the site of injury 3 Tissue cleanup repair monocytes emigrate from the blood and turn into macrophages arrive within 8 12 hours They engulf destroy bacteria dead cells They are also an APC in specific immunity Edema swelling compresses the veins allows for lymphatic drainage which can remove bacteria dead cells debris better than the blood can Fever pyrexia febrile adaptive defense mechanism does more good than harm how it s initiated 1 exogenous pyrogens produce fever 2 attacked by neutrophils macrophages which secrete endogenous pyrogens 3 endogenous pyrogens stimulate anterior hypothalamus to increase body temperature 4 prostaglandin E2 PGE2 from the anterior pituitary enhances the increase in temperature course of a fever 6 steps Infection pyrogen secretion hypothalamic thermostat reset to a higher set point onset body temp rises stadium body temp oscillates around new set pt infection ends set point returns to normal defervescence body temp returns to normal SPECFIC IMMUNITY 3rd line of defense Immunity vs Nonspecific Resistance 1 Specificity immunity is directed against a particular pathogen Immunity to one is NOT immunity to all 2 Memory when reexposed to same pathogen body reacts so quick there are no symptoms of illness whereas time for inflammation other nonspecific defenses is just as long as it took for the first exposure 4 classes of immunity natural active artificial active natural passive artificial passive Passive acquire antibodies from someone else animal Active make own antibodies Natural acquire antibodies due to natural exposure Artificial acquire Ab s artificially usually through injection