Welcome to Microbiology 130

Chapter 15Innate Immunity1Figure 15.1

The Three Lines of DefenseFirst Line of DefenseStructures, chemicals, processes that work to prevent pathogens entering the bodyNonspecific defensesIncludes the skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems3The Role of SkinTwo major layersEpidermis Outer layer composed of multiple layers of tightly packed cellsFew pathogens can penetrate these layersShedding of dead skin cells (1010 per day) removes attached microorganismsEpidermal dendritic cellsAlso termed Langerhans cells (found in skin and mucous membranes)Long, slender, multi-branched cellsPhagocytize pathogensNot WBCsInvolved with innate and adaptive immunityDermisContains protein fibers called collagenGive skin strength and pliability to resist abrasions that could introduce microorganisms4EM of Skin Surface

Dust Mite The Role of SkinPerspiration secreted by sweat glandsSalt- inhibits growth of pathogen by drawing water from their cellsLysozyme- destroys cell wall of bacteria Sebum secreted by sebaceous (oil) glandsHelps keep skin pliable and less likely to break or tearLowers the pH of the skin to a level inhibitory to many bacteriaMany are also directly toxic to bacteria6Mucous MembranesLine all body cavities open to the outside environmentComprises over 200 times more surface area than the skinTwo distinct layersEpitheliumDeeper connective layer that supports the epithelium7EpitheliumThin, outer covering of the mucous membranesUnlike skin surface epidermal cells, these epithelial cells are livingTightly packed to prevent entry of pathogensContinual shedding of cells carries attached microorganisms away8

The Ciliary Escalator9Microbial AntagonismNormal microbiota help protect the body by competing with potential pathogensVarious activities of the normal microbiota make it hard for pathogens to competeSecrete antimicrobial substances that limit pathogen growthConsumption of nutrients makes them unavailable to pathogensCreate an environment unfavorable to other microorganisms by changing pHHelps stimulate the bodys second line of defensePromote overall health by providing vitamins to host10Other First-Line DefensesMany body organs secrete chemicals with antimicrobial propertiesLacrimal glands of the eyeTears wash the eye and keep it moistLysozyme destroys bacteriaSalivaContains antibodies and lysozymeUrine flowKeeps bacteria out of the ureterStomach acidAcidity kills most pathogens11Second Line of DefensesOperates when pathogens succeed in penetrating the skin or mucous membranesNonspecific defenseComposed of cells, antimicrobial chemicals, and processes, but no physical barriersMany of these components are contained in or originate in the blood12BloodComposed of cells and portions of cells within a fluid called plasmaPlasma is mostly water containing electrolytes, dissolved gases, nutrients, and proteinsWhen the clotting factors (a group of plasma proteins) are removed from plasma, the remaining fluid is called serumOther plasma proteins include complement proteins and antibodiesThe cells and cell fragments in plasma are called formed elements13Plasma vs Serum:

14Formed ElementsThree types of formed elements:Erythrocytes- carry oxygen and carbon dioxide in the blood (4.2-6.2x109/ml)Platelets- involved in blood clotting and inflammation (1.3-4x108/ml)Leukocytes- involved in defending the body against invaders (4.5-11x106/ml)2 groups of leukocytes:GranulocytesAgranulocytes15

Human LeukocytesGranulocytes:Neutrophils: 60-70% of circulating WBCMulti-lobed nucleus>1010 neutrophils made every dayMajor phagocytes; cells of acute inflammationEosinophils: 1-3% of circulating WBCBilobed nucleus; parasite defense; red granulesBasophils: 0.5-1% of circulating WBCBilobed nucleus; contain histamine; blue granules17Granulocytes

NeutrophilEosinophilBasophilFigure 15.7

Diapedesis19AgranulocytesCytoplasm appears uniform under a light microscope2 typesLymphocytes: 20-40% of circulating WBC; most involved in specific immunityMonocytes: 1-6% of circulating WBC; leave the blood and mature into macrophages20

MonocyteLymphocyte21MacrophagesPhagocytic cells of the second line of defenseMonocytes leave the blood (via diapedesis), enter tissue, and differentiate into macrophagesSome become fixed in a particular tissue, some remain free to wander and phagocytize throughout the bodyFixed macrophages include microglial cells (central nervous system), mesangial cells (Kidney) and Kpffer cells (liver)Wandering macrophages include alveolar macs22Lab Analysis of LeukocytesThe differential white blood cell count test can signal signs of diseaseIncreased eosinophils can indicate allergies or parasitic worm infectionBacterial diseases often show increase in leukocytes, mostly neutrophilsViral infections show increase in lymphocytes23Components of the Second Line of DefensePhagocytosisExtracellular (nonphagocytic) killing by leukocytesNonspecific chemical defensesInflammationFever24PhagocytosisCells capable of phagocytosis (certain leukocytes or their derivatives) are called phagocytesPhagocytosis is performed chiefly by neutrophils (microphages) and macrophages.Can be divided into 5 stages25

Fig. 15-06Chemotaxis ofphagocyteto microbesMicrobesPseudopodia move(chemotaxis)AdherencePhagosomeIngestion of microbesby phagocytesFusion of aseries of vessicles,including lysosomesPhagolysosomeResidualbodyKilling ofmicrobesby enzymesand otherchemicalsElimination(exocytosis)PhagocyteNucleusPseudopodGolgi bodyLysosome

The Steps of Phagocytosis:26Host Cell ProtectionThe hosts cells are protected from destruction by the phagocytesSome phagocytes have receptors for bacterial surface components, such as flagellar proteins or cell wall components, that are lacking on the bodys cellsOpsonins such as certain complement split products and antibody provide a handle for the phagocyte. Opsonins are substances that enhance phagocytosis.27Extracellular (Nonphagocytic) Killing by Leukocytes3 Cell types that kill extracellularly:EosinophilsMainly attack parasitic helminths (worms) by attaching to their surfaceSecrete protein toxins that weaken or kill helminthNatural killer lymphocytes (NK cells)Secrete toxic substances onto the surface of virally-infected cells and tumor cellsDifferentiate normal body cells by recognizing type and no. of membrane proteins (MHC class I)NeutrophilsLeak antimicrobials and trapping webs (NET for neutrophil extracellular traps)A form of apoptosis to kill microbes caught in NET28Nonspecific Chemical DefensesTLRs bind to pathogen-associated molecular patterns (PAMPs).NOD proteins are intracellular receptors for sub-components of bacterial peptidoglycan.

29InterferonsProtein molecules released by host cells to nonspecifically inhibit the spread of viral infectionsParticularly effective against viruses with RNA genomesCause many symptoms typically associated with viral infections3 ClassesAlphaBetaGamma (also an important immune cytokine in activating macrophages =MAF)30InterferonsAlpha and beta interferons are called type 1 interferons and are produced early in the infectionDendritic cells produce the most type 1 interferonsGamma interferon appears later in the course of infection31Table 15.3

Fig. 15-07VirusDouble-strandedRNAIFNgeneInterferon receptorInfected cellInfected cellat a later timeVirus infects cell.Viral replicationin cell triggerstranscriptionand translationof or interferon (IFN)depending ontype of hostcell.NucleusmRNAIFNInterferon is released,diffuses to neighboringuninfected cells, andbinds to receptors.AVPgenemRNAInactiveAVPsBinding triggerstranscriptionand translation ofinactive antiviralproteins (AVPs).Uninfectedneighboring cellSameneighboringcell now protectedat the later timeRibosomeInactive AVPDouble-strandedviral RNAActive AVPsmRNAWhen the secondcell becomes infectedwith viruses, double-stranded RNA of thevirus activates AVP.Active AVPs degrade mRNAand bind to ribosomes,which stops proteinsynthesis and viralreplication.Meanwhile, theinfected cell diesand releasesthe virus.The Actions of Interferon33Interferon TherapyIt was thought that this might be a good antiviral treatmentMany viral infections dont respond to interferon therapy at allOnly a slight effect is seen with those viral infections that do respond34Complement SystemSet of serum proteins designated numerically according to the order of their discoveryComplement activation results in lysis of the foreign cellComplement can be activated in several ways:Classical PathwayAlternate PathwayLectin Pathway

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Fig. 15-08Classical pathwayAlternative pathwayLectin pathwayMannoseLectinsFactors B,D, and PEndotoxin andglycoproteinsC3bC3bAntigenAntibodyComplementproteins1, 2, 4Complement cascadeActivation(C3 C3a + C3b)C5 convertases(C5 C5a + C5b)Membrane attackcomplex and cell lysisOpsonizationInflammationInflammation36 2014 Pearson Education, Inc.

MembraneattackcomplexCytoplasmicmembraneC5b combines with C6, C7, C8,and several molecules of C9to form a membrane attackcomplex (MAC). A MAC drills acircular hole in the pathogenscytoplasmic membrane,leading to lysis of the cell.Causes chemotaxisof phagocytesand triggersinammationPathogenAntigenAntibodyC1 becomesan active enzymewhen it binds toantibody-antigencomplexes.Enzyme C1splits moleculesof C2 and of C4.C3b combineswith the remainingfragments of C2and C4 to form athird enzyme.Fragments of C2and C4 combineto form a secondenzyme thatsplits C3 intoC3a and C3b.Causes chemotaxisof phagocytesand triggersinammationThis enzyme cleavesC5 into C5a and C5b.CausesinflammationActs asopsoninEnzymatic C1H2OH2OH2OC9C9C9C9C9C9C9C9C9C9C8C7C6C5bH2OC5bC5aC4aC4bC4bC2bC3bC2bC2bC2aC4aC4bEnzymeC2aEnzymeC4bC3aC3bC3aC3bC3C3C2C2C4C4C1C5123456Figure 15.9 The classical pathway and complement cascade.37TEM of a Cell Damaged by Complement Membrane Attack Complexes

38The Classical PathwayVarious complement proteins act nonspecifically to complement the action of antibodiesFunctions:Induce inflammation (C3a, C5a)Opsonization (C3b)Chemotaxis of phagocytes (C3a, C5a)Lysis of foreign cells (MAC mostly C9)

39The Alternate (Properdin) PathwayActivation independent of antibodiesLess efficient than the classical pathwayUseful in early stages of infection before antibodies have been madeInitiated by interaction between properdin factors B, D, and P and the endotoxins and LPS from bacteria and fungiStabilizes molecules of C3b that are normally in the blood in small quantities40The Lectin PathwayMannose-binding lectin (MBL) and other serum proteins bind microbial surfaces that contain mannose sugarsMannose is found in fungi, bacteria, and virusesRarely found in mammalsLectins bound to mannose act to trigger a complement cascade by cleaving C2 and C4 just like the classical pathway41InflammationNonspecific response to tissue damage resulting from various causesCharacterized by redness (rubor), heat (calor), swelling (tumor), and pain (dolor)Two typesAcuteChronic42Acute Versus Chronic InflammationAcute inflammationDevelops quickly and is short livedIs usually beneficialImportant in the second line of defenseDilation and increased permeability of the blood vesselsMigration of phagocytesTissue repair

Chronic inflammationDevelops slowly and lasts a long timeCan cause damage to tissues43Stimulation of Inflammation by C3a & C5a

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45Figure 15.19

The Events of InflammationFigure 15.19

The Events of InflammationChemical Mediators of Inflammation

FeverA body temperature over 37CResults when chemicals called pyrogens trigger the hypothalamus to increase the bodys core temperatureVarious types of pyrogensBacterial endotoxinsCytoplasmic contents of bacteria released by lysisAntibody-antigen complexesInterleukin-1 (IL-1)49Fever ProductionIL-1 production causes the hypothalamus to secrete prostaglandin which resets the hypothalamic thermostat Communication with the brain initiates muscle contractions, increased metabolic activity, and constriction of blood vessels which raises the bodys temperatureChills associated with fever are due to the reduced blood flow of constricted vesselsDecrease in IL-1 production results in the bodys temperature returning to normal50

Fever inResponse toInfectionBenefits of FeverEnhances the effects of interferonsInhibits growth of some microorganismsMay enhance the performance of phagocytes, cells of specific immunity, and the process of tissue repair52