The Immune System

AtifHassanKhirelsied,B.Sc.,M.Sc.,Ph.D. DepartmentofBiochemistry f i h i FacultyofMedicine UniversityofKordofan

Immunity I it
Immune(Latin immunus)=tobefree,exempt It is the bodies ability to resist infection Itisthebodiesabilitytoresistinfection I Immunitycanbenatural oracquired it b t l i d

Theimmunesystem:

Theimmunesystemisacomplexnetworkof Th i t i l t k f molecules,cellsandorganswhichprotectthebody molecules, cells and organs which protect the body againstinvadingpathogensandtheirtoxins

Thepathogens =diseasecausingmicroorganisms di i i i
bacteria virus fungi, protozoa, t parasite, prion

Theantigen Th ti
Antigenswereoriginallydefinedasnonselfmolecules whichboundspecificallytoantibodies. which bound specifically to antibodies

Inpractice,thetermantigenisusedtomeanany moleculerecognizedbytheimmunesystem.

Theantigen Th ti
Antigenswhichinduceadaptiveimmunityarecalled immunogens. Allimmunogensareantigens,butsomeantigensarenot necessarilyimmunogensandareknownashapten. Haptens,arenotimmunogenicunlesstheyarecovalently linkedtoimmunogeniccarrierscalledadjuvant(usually proteins).

Thehapten
Asubstancethatisnonimmunogenicbutwhichcanreact withtheproductsofaspecificimmuneresponse.Haptens aresmallmoleculeswhichcouldneverinduceanimmune are small molecules which could never induce an immune responsewhenadministeredbythemselvesbutwhichcan whencoupledtoacarriermolecule.

Theepitopeandparatope ofanantibody
A. EpitopeorAntigenicDeterminant Thatportionofanantigenthatcombineswiththeproductsof aspecificimmuneresponse.

B. Paratope i th B P t isthecomplementarypartoftheantibodythat l t t f th tib d th t recognizestheepitope

Thepathogens
Invadingmicroorganismsenterthebodiesthrough differentroutesandhavedifferenthabitatsinthe d ff dh d ff h b h body.

Theorgansoftheimmunesystemarestrategically positionedthroughoutthebody.

Theorgansofthe The organs of the immunesystem.

Levels of Protection

Figure 17.7

Theimmunesystem:
Innateimmunityispresentcontinuously,itisa defensemechanismthatispresentfrombirth. d f h i th t i tf bi th

Acquiredimmunityisinducedbythepresenceof foreignmaterialandisusuallyquitespecific

Thecomponentsoftheimmunesystem: The components of the immune system:

Innate
Non-specific Immunity Antigen-independent Immediate response Not antigen-specific No immunologic memory

Adaptive
Specific Immunity Antigen-dependent Delayed response Antigen-specific Immunologic memory

Thebodydefenselines

 Theelementsoftheinnate(natural)immune systeminclude;
Anatomicalbarriers. Secretorymolecules. Cellularcomponents. p

Naturalresistanceisthefirstlinesofdefence Naturalresistanceisthefirstlinesofdefence
Saliva antibacterial enzymes
Skin prevents entry

Tears antibacterial ib i l enzymes Mucus liningstraps dirtandmicrobes

Stomachacid lowpHkills harmfulmicrobes

goodgut bacteria out out competebad

Thenaturalresistance
Physicochemicalbarrierstoinfections y
System/Organ Skin GItract Lung Nasopharynx y andeye Activecomponent Squamous cells; Sweat Columnarcells Trachealcilia Mucus,saliva,tears EffectorMechanism Desquamation;flushing, organicacids organic acids Peristalsis,lowpH,bileacid, flushing,thiocyanate flushing thiocyanate Mucocialiary surface Flushing,lysozyme

Thenaturalresistance
Innatesystembarrierstoinfections Innate system barriers to infections
System/Organ Circulationand lymphoidorgans y p g Active component Phagocytic cells NKcellsand LAK EffectorMechanism Phagocytosis and intracellularkilling g Directandantibody dependentcytolysis IL2activatedcytolysis

LAK:lymphokine activatedkillercells y p

Thenaturalresistance
Humoralinnatebarrierstoinfections
System/ Organ Serum Activecomponent Lactoferrinand Transferrin Interferons TNFalpha Lysozyme Fibronectin Complement EffectorMechanism Ironbinding Antiviralproteins antiviral,phagocyteactivation Peptidoglycanhydrolysis Opsonizationandphagocytosis Opsonization,enhanced phagocytosis,inflammation

Theinflammation
Is characterized by raised temperature, swelling and Ischaracterizedbyraisedtemperature,swellingand therecruitmentofphagocytic cells.

Humoralfactorsintheserumorformedatthesiteof infectionplayanimportantroleininflammation. i f ti l i t t l i i fl ti

Thecomplementsystem
Isacomplementtoantibodymediatedimmunity.

Consistsofthirtyfiveinteractingplasmaand membraneassociatedproteinswhichcontributeto hostdefenseandinitiateandamplifyinflammation. hostdefense and initiate and amplify inflammation

Itisthemajorhumoralnonspecificdefense mechanism. mechanism

Thecomplementsystem

Onceactivatedcomplementcanleadtoincreased vascularpermeability,recruitmentofphagocytic cells, andlysis andopsonizationofantigens. and lysis and opsonization of antigens.

Thecomplementsystem

Thecoagulationsystem
Someproductsofthecoagulationsystemcan Some products of the coagulation system can contributetothenonspecificdefensesbecauseof theirabilitytoincreasevascularpermeability and actaschemotactic agentsforphagocytic cells. h i f h i ll

Thecoagulationsystem

Some products of the coagulation system are directly Someproductsofthecoagulationsystemaredirectly antimicrobial.Forexample,betalysin,aprotein producedbyplateletsduringcoagulationcanlyse manyGrampositivebacteriabyactingasacationic detergent. detergent

Thecellularcomponentsoftheinnate immunityinclude; i i i l d
1. Phagocytes (monocytes,macrophages) 2. PMNCs(neutophils,eosinophils,basophils). 3. Naturalkiller (NK)cells. 4. 4 Dendritic cells cells.

Cellularbarrierstoinfection Cellular barriers to infection

Partoftheinflammatoryresponseistherecruitment ofneutrophils andmacrophages tositesof f hl d h f infection. infection.

Thesecellsarethemainlineofdefenseinthenon specificimmunesystem.

Neutrophils. Neutrophils
PMNsrecruitedtothesiteofinfection phagocytose i di h t invadingorganismsandkillthem i d kill th intracellularly. y

PMNscontributetocollateraltissuedamagethat occursduringinflammation.

Macrophages.
Functioninphagocytosis andintracellularkillingof F n tion in phagoc tosis and intra ell lar killin of microorganisms. g

Actasantigenpresentingcells,induceadaptive responses.

Naturalkillercells. Natural killer cells.

Naturalkiller(NK)cellsarelymphocytesthatcan recognizeanddestroyviralorcancerouscells. NKcellscontactothercells.Iftheothercellappears NK cells contact other cells If the other cell appears tobeabnormal(i.e.virallyinfectedorcancerous) thentheNKcellreleasescytotoxic moleculesthat then the NK cell releases cytotoxic molecules that causetheabnormalcelltoundergoapoptosis.

Phagocytosis

Macrophages.

Oxygendependentmechanismsofintracellular killing
Reaction
H2O2 + Cl- --> OCl- + H2O OCl- + H2O --> 1O2 +Cl- + H2O > 2O2 + 2H+ --> O2- + H2O2 H2O2 --> H2O + O2 Superoxide dismutatse Catalase

Enzyme
Myeloperoxidase

Oxygenindependentmechanismsofintracellular killing killi

EffectorMolecule Eff t M l l
Cationicproteins(including p ( g cathepsin) Lysozyme Lactoferrin Proteolyticandhydrolytic y y y enzymes

Function F ti
Damagetomicrobialmembranes g

Splitsmucopeptide inbacterialcell wall Deprivesproliferatingbacteriaof Deprives proliferating bacteria of iron g g Digestionofkilledorganisms

Themajorfunctionsoftheinnateimmune The major functions of the innate immune systeminclude:

Recognitionandremovalofantigens. Activationofthecomplementsystem. Recruitmentofimmunecellstositesofinfectionand inflammation.. Inductionoftheadaptivesystemwhennecessary.

Comparison between innate and adaptive immunity.

Attribute Response time Specificity Innate Immunity y Minutes/hours Specific for molecules and molecular patterns A limited number of germline encoded receptors None Perfect, no microbe specific patterns in host Many antimicrobial peptides and proteins Phagocytes (monocytes (monocytes, macrophages, neutrophils) NK cells, dendritic cells Adaptive Immunity p y Days Highly specific, discriminate minor differences in molecular structures Highly diverse, very large number of receptors arising by genetic recombination Persistent memory Very good, occasional failure of discrimination Antibodies T cells, B cells, antigen presenting cells cells cells

Diversity

Memory responses Self/nonself discrimination Soluble components Major cell types