01Intro and Innate Immunity.ppt

8/8/2019 01Intro and Innate Immunity.ppt

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Microbiology 532:Microbiology 532:

ImmunologyImmunologyDennis E. Lopatin, Ph.D.Dennis E. Lopatin, Ph.D.Dept. of iologic an! Materials "ciencesDept. of iologic an! Materials "ciences

#2$% Dental uil!ing#2$% Dental uil!ing

&'ce (ours by )ppointment&'ce (ours by )ppointment

Phone: *#+3%-2Phone: *#+3%-2

Electronic mail: lopatinumich.e!uElectronic mail: lopatinumich.e!u


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(elpful (ints(elpful (ints

/ea!ings in te0t are bene1cial/ea!ings in te0t are bene1cial II e0pecte

0pect you to rea! the releant chapters in ester.you to rea! the releant chapters in ester. 4n!erstan!ing the4n!erstan!ing the conceptsconce

pts is not optionalis not optional hin6 hin6, rather than memori7e, rather than memori7e

est 8uestions are base! on est 8uestions are base! on conceptsconcepts )s6 8uestions)s6 8uestions Don9t ait until the last minute to stu!yDon9t ait until the last minute to stu!y ;hec6 the ebsite;hec6 the ebsite


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Lecture 1Lecture 1

ImmunologyImmunology

Introduction & Innate immunityIntroduction & Innate immunity


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o types of immunity o types of immunity Innate immunity Cnot antigenspeci1cInnate immunity Cnot antigenspeci1c

)natomical barriers)natomical barriers MechanicalMechanical iochemicaliochemical

onspeci1c Ceg. Lo p( in stomachonspeci1c Ceg. Lo p( in stomach /eceptor!rien Ceg. P)MPrecognition/eceptor!rien Ceg. P)MPrecognition

)!aptie immunity Cantigenspeci1c)!aptie immunity Cantigenspeci1c /eceptor!rien/eceptor!rien Pree0isting clones programme! to ma6e a speci1cPree0isting clones programme! to ma6e a speci1c

immune response Chumoralcellularimmune response Chumoralcellular


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)ntigen)ntigen

) substance Cantigen that is capable of) substance Cantigen that is capable ofreactingreacting ith the pro!ucts of a speci1cith the pro!ucts of a speci1cimmune response, e.g., antibo!y orimmune response, e.g., antibo!y or

speci1c sensiti7e! lymphocytes.speci1c sensiti7e! lymphocytes. ) AselfB component may be consi!ere! an) AselfB component may be consi!ere! an

antigen een though one !oes notantigen een though one !oes notgenerally ma6e immune responsesgenerally ma6e immune responses

against those components.against those components.


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;haracteristics of )!aptie;haracteristics of )!aptie

ImmunityImmunity Immune response is highly speci1c for the antigen thatImmune response is highly speci1c for the antigen that

triggere! it.triggere! it. /eceptors on surface of immune cells hae same speci1city as the/eceptors on surface of immune cells hae same speci1city as the

antibo!ye@ector actiity that ill be generate!antibo!ye@ector actiity that ill be generate! E0posure to antigen creates an immunologic Amemory.BE0posure to antigen creates an immunologic Amemory.B

Due to clonal e0pansion an! creation of a large pool of cellsDue to clonal e0pansion an! creation of a large pool of cells

committe! to that antigencommitte! to that antigen

"ubse8uent e0posure to the same antigen results in a rapi! an!"ubse8uent e0posure to the same antigen results in a rapi! an!

igorous responseigorous response


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;omponents of the;omponents of the

immune systemimmune system


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CellsCells

involvedinvolvedinin

immunityimmunity

plateletsplatelets

megakaryocytemegakaryocyteeosinophileosinophil

neutrophilneutrophil

basophilbasophil

mast cellmast cell

commoncommonmyeloidmyeloidprogenitorprogenitor

monocytemonocyte

macrophagemacrophage

NaturalNatural

Killer cellKiller cell

plasma cellplasma cell

B LymphocyteB Lymphocyte

T LymphocyteT Lymphocyte

commoncommonlymphoidlymphoidprogenitorprogenitor

PluripotentPluripotenthematopoietichematopoietic

stem cellstem cell


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BloodBloodSerum orSerum or

PlasmaPlasma

Leukocytes,Leukocytes,

Platelets and RBCPlatelets and RBC

Serum ProteinsSerum ProteinsMononuclearMononuclear

CellsCells

PolymorphonuclearPolymorphonuclear

leukocytes (orleukocytes (orGranulocytes)Granulocytes)

•ImmunoglobulinsImmunoglobulins

•ComplementComplement•Clotting factorsClotting factors•Many othersMany others

•NeutrophilsNeutrophils

•EosinophilsEosinophils•BasophilsBasophils

•LymphocytesLymphocytes

(T cells, B cells(T cells, B cells& NK cells)& NK cells)•MonocytesMonocytes


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Lymphoi! &rgansLymphoi! &rgans

Primary or central lymphoi! organsPrimary or central lymphoi! organs bone marro an! thymusbone marro an! thymus

here lymphocytes are generate!here lymphocytes are generate!

"econ!ary or peripheral lymphoi! organs"econ!ary or peripheral lymphoi! organs here a!aptie immune responses arehere a!aptie immune responses are

initiate!initiate!


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Distribution of Lymphoi! issuesDistribution of Lymphoi! issues


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Response to Initial InfectionResponse to Initial Infection


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Stages of Response to InfectionStages of Response to Infection


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CourseCourse

of Typicalof Typical

AcuteAcuteInfectionInfection


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Innate Host Defense MechanismsInnate Host Defense Mechanisms

Anatomic FactorsAnatomic Factors Mechanical FactorsMechanical Factors

Biochemical FactorsBiochemical Factors


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SkinSkin

Stratified and cornified epithelium provides aStratified and cornified epithelium provides a

mechanical barriermechanical barrier

Indigenous microbiota competes with pathogensIndigenous microbiota competes with pathogens

Acid pH inhibits growth of disease producingAcid pH inhibits growth of disease producing

bacteriabacteria

Bactericidal long chain fatty acids in sebaceousBactericidal long chain fatty acids in sebaceous

gland secretionsgland secretions


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Respiratory TractRespiratory Tract

Upper Respiratory TractUpper Respiratory Tract Nasal hairs induce turbulenceNasal hairs induce turbulence

Mucous secretions trap particlesMucous secretions trap particles

Mucous stream to the base of tongue where material is swallowedMucous stream to the base of tongue where material is swallowed

Nasal secretions contain antimicrobial substancesNasal secretions contain antimicrobial substances

Upper respiratory tract contains large resident floraUpper respiratory tract contains large resident flora

Lower Respiratory TractLower Respiratory Tract Particles trapped on mucous membranes of bronchi and bronchiolesParticles trapped on mucous membranes of bronchi and bronchioles

Beating action of cilia causes mucociliary stream to flow up into the pharynxBeating action of cilia causes mucociliary stream to flow up into the pharynx

where it is swallowedwhere it is swallowed

90% of particles removed this way. Only smallest particles (


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Alimentary TractAlimentary Tract General defense mechanismsGeneral defense mechanisms

Mucous secretionsMucous secretions

Integrity of of mucosal epitheliumIntegrity of of mucosal epithelium

Peristaltic motions of the gut propel contents downwardPeristaltic motions of the gut propel contents downward

Secretory antibody and phagocytic cellsSecretory antibody and phagocytic cells

StomachStomach Generally sterile due to low pHGenerally sterile due to low pH

Small IntestineSmall Intestine Upper portion contains few bacteriaUpper portion contains few bacteria

As distal end of ilieum is reached flora increasesAs distal end of ilieum is reached flora increases

ColonColon

Enormous numbers of microorganismsEnormous numbers of microorganisms 50-60% of fecal dry weight is bacteria50-60% of fecal dry weight is bacteria


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Genitourinary TractGenitourinary Tract

MaleMale No bacteria above urethrovesicular junctionNo bacteria above urethrovesicular junction

Frequent flushing action of urineFrequent flushing action of urine

Bactericidal substances from prostatic fluidBactericidal substances from prostatic fluid

pH of urinepH of urine

Bladder mucosal cells may be phagocyticBladder mucosal cells may be phagocytic

Urinary sIgAUrinary sIgA

Female (Vagina)Female (Vagina) Large microbial population (lactobacilli)Large microbial population (lactobacilli)

Microorganisms produce low pH due to breakdown of glycogen produced byMicroorganisms produce low pH due to breakdown of glycogen produced by

mucosal cellsmucosal cells


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EyeEye

Flushing action of tears which drain through theFlushing action of tears which drain through the

lacrimal duct and deposit bacteria in nasopharynxlacrimal duct and deposit bacteria in nasopharynx

Tears contain a high concentration of lysozymeTears contain a high concentration of lysozyme(effective against gram positive microorganisms(effective against gram positive microorganisms


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/eceptors/eceptors

)lmost all of biology occurs because)lmost all of biology occurs because

recognitionrecognition En7ymatic actionEn7ymatic action

Interactions beteen cellsInteractions beteen cells

CcooperationactiationCcooperationactiation

;ommunication beteen cells;ommunication beteen cells

Innate an! a!aptie immunity re8uires itInnate an! a!aptie immunity re8uires it


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Innate Immune /ecognitionInnate Immune /ecognition

)ll multicellular organisms are able to)ll multicellular organisms are able torecogni7e an! eliminate pathogensrecogni7e an! eliminate pathogens Despite their e0treme heterogeneity,Despite their e0treme heterogeneity,

pathogens share highly consere! molecules,pathogens share highly consere! molecules,

calle! Apathogenassociate! molecularcalle! Apathogenassociate! molecularpatternsB CpatternsB CP)MPsP)MPs (ost cells !o not share P)MPs ith pathogens(ost cells !o not share P)MPs ith pathogens P)MPs are recogni7e! by innate immuneP)MPs are recogni7e! by innate immune

recognition receptors calle! patternrecognition receptors calle! patternrecognition moleculesreceptors Crecognition moleculesreceptors CP/MsP//sP/MsP//s


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ypical P)MPs ypical P)MPs

Lipopolysacchari!esLipopolysacchari!es

Pepti!oglycansPepti!oglycans

;ertain nucleoti!e se8uences uni8ue to;ertain nucleoti!e se8uences uni8ue to

bacteriabacteria

&ther bacterial components&ther bacterial components


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En!ogenous "ignals In!uce! by P)MPsEn!ogenous "ignals In!uce! by P)MPs

Me!iate inFammatory cyto6inesMe!iate inFammatory cyto6ines )ntigenpresenting cells recogni7e)ntigenpresenting cells recogni7e

P)MPsP)MPs "ame )P; processes pathogens into speci1c"ame )P; processes pathogens into speci1c

pathogen!erie! antigens an! presents thempathogen!erie! antigens an! presents themith M(; enco!e! receptors to cellsith M(; enco!e! receptors to cells

cell respon!s only hen presente! ith both cell respon!s only hen presente! ith bothsignalssignals

Di@erent E@ector ;yto6ines in /esponse to Di@erentDi@erent E@ector ;yto6ines in /esponse to Di@erentPathogens Ch- s. h2Pathogens Ch- s. h2


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)ntimicrobial)ntimicrobial

Pepti!esDefensinsPepti!esDefensins Gour hun!re! pepti!es !escribe! to !ateGour hun!re! pepti!es !escribe! to !ate Defensins C3 56D, four families in eu6aryotesDefensins C3 56D, four families in eu6aryotes

αα!efensins Cneutrophils an! intestinal Paneth cells!efensins Cneutrophils an! intestinal Paneth cells ββ!efensins Cepithelial cells!efensins Cepithelial cells

Insect !efensinsInsect !efensins Plant !efensinsPlant !efensins

Defensins appear to act by bin!ing to outerDefensins appear to act by bin!ing to outermembrane of bacteria, resulting in increase!membrane of bacteria, resulting in increase!membrane permeability.membrane permeability.

May also play a role in inFammation an! oun!May also play a role in inFammation an! oun!repairrepair


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;omplement "ystem;omplement "ystem

hree pathays no 6non hree pathays no 6non ;lassical;lassical

)lternatie)lternatie

Lectin or ML pathay Cbin!ing to mannoseLectin or ML pathay Cbin!ing to mannosecontaining carbohy!ratescontaining carbohy!rates

(ost cells hae complement regulatory(ost cells hae complement regulatory

proteins on their surface that protect themproteins on their surface that protect them

from spontaneous actiation of ;3 moleculesfrom spontaneous actiation of ;3 molecules


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InFammatory Me!iators in InnateInFammatory Me!iators in Innate

ImmunityImmunity ;yto6ines secrete! by phagocytes in response to;yto6ines secrete! by phagocytes in response to

infection inclu!e:infection inclu!e: IL-IL-

actiates ascular en!othelium an! lymphocytesactiates ascular en!othelium an! lymphocytes Increases a!hesieness of leu6ocytesIncreases a!hesieness of leu6ocytes

IL*IL* In!uces cell terminal maturation into Igpro!ucing plasma cellsIn!uces cell terminal maturation into Igpro!ucing plasma cells

ILHILH In!uces e0pression of b2 integrin a!hesion molecules on neutrophils,In!uces e0pression of b2 integrin a!hesion molecules on neutrophils,

lea!ing to neutrophil migration to infection sitelea!ing to neutrophil migration to infection site IL-2IL-2

)ctiates cells an! in!uces h-cell !i@erentiation)ctiates cells an! in!uces h-cell !i@erentiation IL-HIL-H G G

αα

)ctiates ascular en!othelium an! increases ascular permeability,)ctiates ascular en!othelium an! increases ascular permeability,lea!ing to accumulation of Ig an! complement in infecte! tissueslea!ing to accumulation of Ig an! complement in infecte! tissues


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&ther Me!iators an! Molecules&ther Me!iators an! Molecules

PhagocytesPhagocytes o0ic o0ygen ra!icals o0ic o0ygen ra!icals Pero0i!esPero0i!es itric o0i!e C&itric o0i!e C& Lipi! me!iators of inFammationLipi! me!iators of inFammation

Prostaglan!insProstaglan!ins L#L# Platelet actiating factorPlatelet actiating factor

;omplement component ;5a;omplement component ;5a "timulates mast cells to release histamine, serotonin an! L#"timulates mast cells to release histamine, serotonin an! L#

IL-, IL* an! GIL-, IL* an! Gαα In!uce acutephase response in lierIn!uce acutephase response in lier In!uce feerIn!uce feer

IL- an! IL-H signaling pathays actiate GIL- an! IL-H signaling pathays actiate Gκ κ , important in, important ininnate immunityinnate immunity

ll ! i


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Immune ;ells an! Innate ImmunityImmune ;ells an! Innate Immunity

PhagocytesPhagocytes

eutrophilseutrophils MoncytemacrophageMoncytemacrophage Eosinophils Cto a lesser e0tentEosinophils Cto a lesser e0tent

cells cells Clarge granular lymphocytesClarge granular lymphocytes )ntibo!y!epen!ent cellme!iate! cytoto0icity)ntibo!y!epen!ent cellme!iate! cytoto0icity

C)D;;C)D;;

(ae to ma>or functions(ae to ma>or functions Lysis of target cellsLysis of target cells Pro!uction of cyto6ines CIGPro!uction of cyto6ines CIGγ γ an! Gan! Gαα

)ct against intracellular pathogens)ct against intracellular pathogens (erpesiruses(erpesiruses LeishmaniaLeishmania

Listeria monocytogenesListeria monocytogenes )ct against proto7oa)ct against proto7oa

ToxoplasmaToxoplasma TrypanasomaTrypanasoma


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Immune ;ells an! Innate Immunity Ccont9!Immune ;ells an! Innate Immunity Ccont9!

γ γ δδ cells cells

o types of cell receptors o types of cell receptors &ne compose! of&ne compose! of αα an!an! ββ chains Cbasic cell antigen receptorchains Cbasic cell antigen receptor &ne compose! of&ne compose! of γ γ an!an! δδ chains Cminor population of cellschains Cminor population of cells

o groups of o groups of γ γ δδ cells cells &ne group foun! in lymphoi! tissues&ne group foun! in lymphoi! tissues &ne group locate! in paracellular space beteen epithelial cells&ne group locate! in paracellular space beteen epithelial cells

/ecogni7es unprocesse! target antigen in absence of )P; help/ecogni7es unprocesse! target antigen in absence of )P; help

- cells Cminor fraction of cells, !o not re8uire cell help- cells Cminor fraction of cells, !o not re8uire cell help Mast cellsMast cells

Locate! in serosa, un!er epithelial surfaces an! a!>acent to bloo!Locate! in serosa, un!er epithelial surfaces an! a!>acent to bloo!essels, neres an! glan!sessels, neres an! glan!s

;apable of phagocytosis;apable of phagocytosis Process an! present antigen using M(; class I or II receptorsProcess an! present antigen using M(; class I or II receptors LP" can !irectly in!uce release of mast cell me!iatorsLP" can !irectly in!uce release of mast cell me!iators ;omplement C;3a an! ;5a in!uce mast cells to release me!iators;omplement C;3a an! ;5a in!uce mast cells to release me!iators

;hemota0is, complement actiation, inFammation;hemota0is, complement actiation, inFammation G Gαα secrete! by mast cells results in neutrophil inFu0 into infecte!secrete! by mast cells results in neutrophil inFu0 into infecte!

sitesite


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"ummary of Innate Immunity"ummary of Innate Immunity

E0ternal an! mechanical barriersE0ternal an! mechanical barriers

/eceptors for pathogen motifs/eceptors for pathogen motifs

"oluble antimicrobial proteins"oluble antimicrobial proteins Pattern of cyto6ines pro!uce!Pattern of cyto6ines pro!uce!

inFuences a!aptie responseinFuences a!aptie response

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01Intro and Innate Immunity.ppt