IMMUNE RESPONSE TO INFECTIOUS DISEASES

Immune Response to Bacterial Infection

Characteris*csofBacteria

① X② X③ X④ X

⑤ X⑥ X⑦ X

AnypartofthebodycanbeinfectedbymanyInfec;ousagentsandmanybacterialdiseasesandcausingadiseasedueto:① Growthofthemicrobeina;ssue② ProduceBacterialfactorsthatareharmfultohost③ EliciteaninflammatoryresponsethatcausesdamageButalsoleadstoacquiredimmunity

BacterialDiseases

① AHachmentofbacteriumtohost;ssue•Persistenceandgrowthcalledcoloniza;on

StepsofBacterialInfec*on

StepsofBacterialInfec*on2

② Invasionintodeeperhost;ssuesandproduc;onoftoxinsandleadstoinjurytohostcelland;ssue

StepsofBacterialInfec*on3

③ Inflamma;onatsiteofinvasion•Ini;atedbyan;bodybindingtobacterium•Ini;atedbycomplementac;va;onatbacterialsurface•Ini;atedbywoundhealingmechanisms•Allcanac;vatecomplementpathwaysthataltersvascularpermeabilityandac;vateslocalmacrophageandneutrophils(PMNs)

Inflamma*onatsiteofinvasion

Thedefencemechanismsuseddependon:-

Ø  Siteofinfec;onØ  Structureoftheinvadingbacteria

Ø  Howtheycausedamage

Ø  Intracellularvs.extracellularloca;on

Immunitytobacteria

Both

Most bacteria

Mycobacteria Clostridium tetani

Toxin production Tissue invasion

HowCanBacteriaCauseDamage?

Immunitytobacteria

•  Innateandadap;veimmunesystemsworktogether.

•  Ingeneral,theinnateresponseisimportantinpreven;nganinfec;onbecomingestablished,theadap;vesubsequentlyincomba;nganestablishedinfec;on.

Innateimmunesystemcanrecogniseandrespondtocommonbacterial

components① X

② X③ X④ X⑤ X⑥ X⑦ X

InnateImmuneEffectorsandBacterialInfec*on

Adap*veImmunity:I.   An*bodymediatedresponse

Action How

Block adhesion Ab to surface proteins

Block proliferation Ab to surface receptors eg. iron

Cause phagocytosis Bind bacterial surface and allow phagocytes to bind bacteria

Lysis, phagocytosis and inflammation

Activate complement

Neutralise toxic products Bind toxins

Prevent tissue invasion and damage

Neutralise bacterial products and proteases

Immunitytoextracellularbacteriaby

an*bodies:

Immunitytoextracellularbacteriaby

an*bodies:

①  An*bodiesandcomplementresultinopsonisa;onvia FcRorCRon MØandPMN.

②  An*bodycanac;vateclassicalcomplementpathway

resul;ngMACforma;onand opsonisa;on.

③  An*bodiescanalsotriggeran;body-dependentcellmediated cytotoxicity(ADCC)byPMNwithFcRand CRandthatleadstoreleaseproteases,nucleases,lipases.

MechanismsofImmunitytointracellularbacteriabyCMI

II.   Cellmediatedimmunityvsintracellularbacteria

1.  CD8+Tcells(Tc)cytotoxicTlymphocytes(CTLs).

2.  CD4+helperTcells(TH1).

3.  NKcellsusingADCC

DoTLymphocytesHaveaRoleintheResponsetoBacteria?

①  Tcytotoxiclymphocytescankillinfectedcells(intracellularpathogensegMycobacteriumtuberculosis)

②  ThelpercellsproducecytokinesorinterleukinsA.  morean*bodyproduc*onB.   Interferonγac;vatesmacrophagesandincreasesbacterial

killing,increasesproduc;onofIgGusedbyphagocytes,increasescytotoxicityandCD8Tcellac;vity

HowbacteriaevadeHostImmunity?

① Avoidingan;body② Preventphagocytosis③ Avoidingcomplement④ Down-regulatetheexpressionofMHC-Iand

MHC-II.⑤ Impedethefunc;onoflymphocytesand

granulocytes(toxin,enzymeandproteins).⑥ Overs;mulateinflamma;on