BIOM 121 1nd Edition Lecture 7 Outline of Current Lecture 1) Innate Immunitya. Modes of defenseb. Complementsc. Pattern Recognition Receptorsd. Inflammation Current LectureInnate ImmunityPart # 2Chapter 15 Lecture 2Innate immunity up till now:… we left you at phagocytosis…to review… A pathogen can cause disease only if it can:-Gain access to the body, either by penetrating the skin or entering through an alternate portal of entry.-Attach itself to host cells.-Evade the host defense systems long enough to cause harmful changes. Innate immune responses have two basic goals:Direct action: (immediate)-Prevent the entry/proliferation of pathogens-Directly kill invading pathogens Indirect action: (immediate and delayed)-Induce inflammation-Establish/determine/regulate the type of immune responseoSo we don't bring a knife to a gun fight-Activate and recruit the appropriate adaptive immune response-Used as communication to bridge innate & adaptive immune responsesThese 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.Components of the Second Line of Defense-Phagocytic cells (neutrophils, macrophages, and eosinophils) utilize intracellular killing mechanisms after antigen capture odendritic cells capture antigens, traffic to the LN and present antigen to naive T cellsoNeutrophils are usually first, they have good half life-Specific innate leukocytes (eosinophils, natural killer (NK) cells) can kill by extracelluar mechanisms-Serum proteins including complement participates in the second line of defense:oDirectly kill pathogensoActivate inflammation Complement-Set of serum proteins designated numerically according to the order of their discovery-Complement activation has three biological effects (inflammation, opsonization/phagocytosis, and cell lysis)oInflammationoOponization/phagocytosisoCell lysisMove\/-C3BoCan bind to form final protein in cascadeoSomething elseoWithout it, kids don't live past 2-5-C3AoEnthuses chemo stasisoSomethingoSomething -C5AoCause chemo stasis and inflammationoRecruit cells to something-C5B-Complement can be activated in three waysoClassical pathwayoAlternate pathwayoLectin pathway Activation and Functions of the Complement System Classical Complement CascadeThe Alternate Pathway-Activation occurs independent of antibodies-Useful in early stages of infection before antibodies have been made-Initiated by the cleavage of C3 into C3a and C3b which occurs naturally at a slow rate in the plasma-Also initiated by components of the kinin/clotting cascade Alternate Pathway of Complement Activationthought experiment:-does the complement cascade distinguish self from non-self?oThe isn't -If yes: How?-In no: How does the body protect itself from the effects of activating the complement cascade?How do:-phagocytes and epithelial cells recognize and respond to pathogens? (self vs. non self)-Shape and direct the Adaptive Immune Response PRRs bind to PAMPs-Pattern recognition receptors: proteins expressed on innate immune cells (and most other body cells)-Pathogen associated molecular patterns: unique molecular components of microbes Pattern Recognition Receptors-Are expressed in multiple forms:oSoluble oPlasma membraneoIntracellular compartments-Bind microbial molecular patterns (PAMPs)-FunctionoTrigger phagocytic uptakeoInduce intracellular signaling pathways-Cytokines-Chemokines-Immuno-modulatory moleculesoDirectly influence both innate and adaptive immune response Examples of PRRs-Four Types of PRRsoToll-Like Receptors (TLRs)oNOD (Nucleotide Binding and Oligomerization) Domain-Like Receptors (NLRs)oRIG (Retinoic Acid Inducible Gene) 1-Like Receptors (RLRs)oC-Type Lectin Receptors (CLRs)oDon't memorizeoInsert PRRs picture PAMPs bind specific PRRs to program the nature of the immune response:Unique TLR signal=unique functionThe inflammatory process Inflammation-The body’s response to local injury, irritation, microbial invasion, or bacterial toxin is referred to as inflammation;-3 major events in acute inflammation are:oVasodilation: Histamine causes an increase in the diameter of capillaries which increases blood flow to the site.-Gets more stuff in areaoProtaglandins and word induce increased permeability of the capillaries, allowing the escape of plasma and plasma proteins.-Allows things to get out into cellsoExtravasation: Exit of leukocytes from the capillaries and their accumulation at the site of injury. (C3a & C5a and others)oResolution phase- heal tissues after warding off pathogen ooVasodilation cause more blood cells to be thereoHeat activates Triggers of Acute InflammationoInfections (bacterial, viral, parasitic) and microbial toxinsoTrauma (blunt and penetrating)oPhysical and chemical agents (burns or frostbite; irradiation)oTissue necrosisoCaused by uncontrolled death of a tissueoApoptosis, is controlledoForeign bodies (splinters, dirt, sutures)oImmune reactions Events in Inflammation: induction: an injury or invasion that results in the breakdown of the first line of defense and activates acute inflammationThis is just the dermis Events in Inflammation: resolution: activation of the healing response leads to down regulation of inflammation and the promotion of healingPeak of inflammation, resolution phase activatesMost important part of inflammationIt's induced to come to areaSomething happens to promote healing instead of killingInterferon signals neighbor cell to make antiviralsIt protects itselfYou need an address so it knows where to go Bodies relocate to cell's surfaceWhen activated they up regulate receptors & can bind more easilyBumps are inflammatory granules of actinOxygen species are very toxic to pathogens & cellsThey burn out fastThey shoot DNA out in nets & basically explodeHas numerous dendritesCan interact with a lot of T cells at onceSit & sample environmentChange if they receive activation event Extracellular Killingo2 innate immune cell types are capable of extracellular killing:oEosinophis-Mainly attack parasitic helminths (worms) by attaching to their surface-Produce proteins that weaken or kill the helminth-Eosinophilia, or elevated eosinophil levels, is often indicative of a helminth infectionoNatural killer lymphocytes (NK cells)-Sit on fence as adaptive & innate-Can distinguish normal body cells from virally