L1 The_Immune_Response immune system is clearly essential for survival. .ppt

It also detects and responds to abnormal cells and molecules that periodically develop in the body so that diseases such as cancers do not occur.
An essential aspect of the immune response is the ability to recognize almost limitless numbers of foreign cells and nonself substances, distinguishing them from self molecules that are native to the body – it distinguishes self from nonself.

1. PRINCIPLES OF
IMMUNOLOGY (ECH 855)
DR. (MRS.) H. A AMEEN
(MB;BS, MPH, FWACP)
DEPARTMENT OF
EPIDEMIOLOGY & COMMUNITY
HEALTH, UNIVERSITY OF ILORIN

2. COURSE OUTLINE
The immune response
Hypersensitivity reactions
Immunology of tissue transplant
Immunology of vaccines
Immunology of parasitic infections
Immunology of cancers

3. The immune response

4. The importance of immune system
Theimmunesystemisclearlyessentialforsurvival.
Itconstantlydefendsthebodyagainstbacteria,viruses,andother
foreignsubstancesitencounters.
Italsodetectsandrespondstoabnormalcellsandmoleculesthat
periodicallydevelopinthebodysothatdiseasessuchascancers
donotoccur.
Anessentialaspectoftheimmuneresponseistheabilityto
recognizealmostlimitlessnumbersofforeigncellsandnonself
substances,distinguishingthemfromselfmoleculesthatarenative
tothebody–itdistinguishesselffromnonself.

5. Definitions
Theimmunesystemconsistsofthecentralandperipherallymphoid
tissues.
Theindividualcomponentsofthesubstancethattheimmune
systemrecognizesasforeignarecalledantigens.
Theinteractionofthecollectiveandcoordinatedcomponentsofthe
immunesystemandtheantigensofaforeignagentiscalledthe
immuneresponse.

6. The immune
system
Thecentrallymphoidorgans
the bone marrow and the
thymus
provide the environment for
immune cell production and
maturation
Theperipherallymphoidorgans
Lymph nodes, spleen, tonsils,
appendix, Peyer’s patches in
the intestine, and mucosa-
associated lymphoid tissues in
the respiratory,
gastrointestinal, and
reproductive systems
function to trap and process
antigen and promote its
interaction with mature
immune cells

7. The immune system -classification
The immune system
Nonspecific or innate defense system
Cellular
Humoral
Specific or acquired immune system
Cellular
Humoral

8. Nonspecific or innate defense system
Firstlineofdefensesystem
Itdistinguishesselffromnon-selfbutdoesnotdistinguishonetype
ofpathogenfromanother.
Components:
skinandmucousmembranes
inflammatoryresponse
phagocyticandnonphagocyticleukocytescells

9. Nonspecific defense system
1. Mechanical factors
The epithelial surfaces form a physical barrier that is very
impermeable to most infectious agents.
The skin acts as our first line of defense against invading
organisms. The desquamation of skin epithelium also helps
remove bacteria and other infectious agents that have adhered to
the epithelial surfaces.
Movement due to cilia or peristalsis helps to keep air passages
and the gastrointestinal tract free from microorganisms.
The flushing action of tears and saliva helps prevent infection of
the eyes and mouth.
The trapping effect of mucus that lines the respiratory and
gastrointestinal tract helps protect the lungs and digestive
systems from infection.

10. Nonspecific defense system
2.Chemical factors
Fattyacidsinsweatinhibitthegrowthofbacteria.
Lysozymeandphospholipasefoundintears,salivaandnasal
secretionscanbreakdownthecellwallofbacteriaanddestabilize
bacterialmembranes.
ThelowpHofsweatandgastricsecretionspreventsgrowthof
bacteria.
Defensins(lowmolecularweightproteins)foundinthelungand
gastrointestinaltracthaveantimicrobialactivity.
Surfactantsinthelungactasopsonins(substancesthatpromote
phagocytosisofparticlesbyphagocyticcells).
3. Biological factors
Thenormalfloraoftheskinandinthegastrointestinaltractcan
preventthecolonizationofpathogenicbacteriabysecretingtoxic
substancesorbycompetingwithpathogenicbacteriafor
nutrientsorattachmenttocellsurfaces.

11. Nonspecific defense system
Theanatomicalbarriersareveryeffectiveinpreventingcolonization
oftissuesbymicroorganisms.
However,whenthereisdamagetotissuestheanatomicalbarriers
arebreachedandinfectionmayoccur.Onceinfectiousagentshave
penetratedtissues,anotherinnatedefensemechanismcomesinto
play,namelyacuteinflammation.
Humoralfactorsplayanimportantroleininflammation,whichis
characterizedbyedemaandtherecruitmentofphagocyticcells.

12. Nonspecific humoral immune system
Thecomplementsystem
Thecomplementsystemisaprimarymediatorofthehumoral
immuneresponsethatenablesthebodytoproducean
inflammatoryresponse,lyseforeigncells,andincrease
phagocytosis.
Thecomplementsystem,likethebloodcoagulationsystem,
consistsofagroupofproteinsthatnormallyarepresentinthe
circulationasfunctionallyinactiveprecursors.Theseproteins
makeup10%to15%oftheplasmaproteinfraction.
Foracomplementreactiontooccur,thecomplement
componentsmustbeactivatedinthepropersequence.
Uncontrolledactivationofthecomplementsystemisprevented
byinhibitorproteins.

13. Complement activation
Theclassicpathwayofcomplementactivationisinitiatedby
antibodyboundtoantigensonthesurfaceofmicrobesorthrough
solubleimmunecomplexes.
Thealternateandthelectinpathwaysdonotuseantibodiesandare
partoftheinnateimmunedefenses.
Thealternatepathwayofcomplementactivationisinitiatedbythe
interactionwithcertainpolysaccharidemoleculescharacteristicof
bacterialsurfaces.
Thelectin-mediatedpathwayisinitiatedfollowingthebindingofa
mannose-bindingproteintomannose-containingmolecules
commonlypresentonthesurfaceofbacteriaandyeast.
TheactivationofthethreepathwaysproducessimilareffectsonC3
andsubsequentcomplementproteins.

14. Complement activation

15. Immune Cells

16. Nonspecificimmune cells
Phagocytes:
Neutrophyles –bacteria
Eosinophyles –enzymes that kills parasites
Macrophages-"big eaters"
Non phagocytic leukocytes:
Basophiles –role in allergic response
Mastocytes
Natural killer lymphocytes –antiviral and anti-tumor activity

17. Nonspecificimmune cells
Macrophageshaveimportantfunctionsinbothinnateandantigen-
specificimmuneresponses.
Asphagocyticcellswithantigennonspecificactivity,theyhelpto
containinfectiousagentsuntilspecificimmunitycanbemarshaled.
Inaddition,earlyinthehostresponse,themacrophagefunctionsas
anaccessorycelltoensureamplificationoftheinflammatory
responseandinitiationofspecificimmunity.
Macrophagesareactivatedbythepresenceofantigentoengulfand
digestforeignparticles.
Activatedmacrophagesactasantigenpresentingcells(APCs)
thatbreakdowncomplexantigensintopeptidefragmentsthatcan
associatewithclassIorIIMajorHistocompatibilityComplex(MHC)
molecules.Macrophagescanthenpresentthesecomplexestothe
helperTcellsothatnonself-selfrecognitionandactivationofthe
immuneresponsecanoccur.

18. Presentation of antigen to helper T cell by an
antigen-presenting cell (APC)

19. NK cells
TheNKcellisanonspecificeffectorcellthatcankilltumorcellsand
virus-infectedcells.
Theyarecallednaturalkillercellsbecause,unlikeTcytotoxiccells,
theydonotneedtorecognizeaspecificantigenbeforebeing
activated.
NKcellskillaftercontactwithatargetcell.TheNKcellis
programmedautomaticallytokillforeigncells.
ProgrammedkillingisinhibitediftheNKcellmembranemolecules
contactMHCself-moleculesonnormalhostcells.
ThemechanismofNKcytotoxicitydependsonproductionofpore-
formingproteins(i.e.,NKperforins),enzymes,andtoxiccytokines.

20. Specific Immunity
Specificoracquiredimmunitydevelopsduringanindividual’slifetime.
Itdistinguishesselffromnonself,andrespondsspecificallytodifferent
pathogensandforeignmolecules.
Components:
Lymphocytesarekeyplayersinthespecificoracquiredimmune
response:
Lymphocytesrepresent20%to40%ofbloodleukocytes;
Tlymphocytes(alsocalledTcells),whichparticipateincell-mediated
immunity(60-70%);
Blymphocytes(alsocalledBcells),whichparticipateinhumoral
immunity(10-20%);
Cell-mediatedimmunityinvolvestheproductionofcytotoxicTcells,which
havetheabilitytodestroyantigen-bearingcells.
HumoralimmunityischaracterizedbythetransformationofBcellsinto
plasmacells,whichsecreteimmunoglobulins(antibodies)thathavespecific
activityagainsttheincitingantigen.

21. T cells
Tcellsarematuratedinthethymus.
There,theylearnhowtodistinguishselffromnonself.OnlytheT
cellsthatignoreselfantigenmoleculesareallowedtomatureand
leavethethymus.Withoutthistrainingprocess,Tcellscouldattack
thebody'scellsandtissues.
MatureTcellsarestoredinsecondarylymphoidorgans(lymph
nodes,spleen,tonsils,appendix,andPeyer'spatchesinthesmall
intestine).
Thesecellscirculateinthebloodstreamandthelymphaticsystem.
Aftertheyfirstencounteraforeignorabnormalcell,theyare
activatedandsearchforthoseparticularcells.

22. T Cells
Pathway for Tcell differentiation

23. Types of T cells
HelperT(CD4)cellshelpotherimmunecells.SomehelperTcellshelpB
cellsproduceantibodiesagainstforeignantigens.Othershelpactivatekiller
Tcellstokillforeignorabnormalcellsorhelpactivatemacrophages
enablingthemtoingestforeignorabnormalcellsmoreefficiently.
TheTh1responseischaracterizedbytheproductionofinterferon-
gamma,whichactivatesthebactericidalactivitiesofmacrophages,and
inducesB-cellstomakeopsonizing(coating)antibodies,andleadsto
cellmediatedimmunity.
TheTh2responseischaracterizedbythereleaseofinterleukin4,which
resultsintheactivationofB-cellstomakeneutralizing(killing)
antibodies,leadingtohumoralimmunity.
Generally,Th1responsesaremoreeffectiveagainstintracellular
pathogens(virusesandbacteriathatareinsidehostcells),whileTh2
responsesaremoreeffectiveagainstextracellularbacteria,parasites
andtoxins.

24. The central role of T
helper cells (CD4)

25. Types of T cells
Th1 cells:
secrete IL-2, IL-12, IFN gamma, TNF-beta;
activate macrophages, amplifying their cytokine secretion
capacity and potential for presentation of antigens;
activate synthesis of IgG but not IgE;
are involved in delayed hypersensitivity reactions;
are activated by signals from intracellular bacteria and viruses;
Th2 cells:
secrete IL-4, IL-5, IL-6, IL-10;
activate the synthesis of IgE;
stimulate proliferation and activation of eosinophils;
are stimulated by allergens or parasite components.

26. Types of T cells
Killer(cytotoxic)Tcells(CD8)attachtoparticularforeignor
abnormal(forexampleinfected)cellsbecausetheyhave
encounteredthembefore.KillerTcellsmaykillthesecellsby
makingholesintheircellmembraneandinjectingenzymesintothe
cellsorbybindingwithcertainsitesontheirsurfacecalleddeath
receptors.
Suppressor(regulatory)Tcellsproducesubstancesthathelpend
theimmuneresponseorsometimespreventcertainharmful
responsesfromoccurring.
SometimesTcells—forreasonsthatarenotcompletelyunderstood
-donotdistinguishselffromnonself.Thismalfunctioncanresultin
anautoimmunedisorder,inwhichthebodyattacksitsowntissues.

27. Types of T cells
ΓδTcells(gammadeltaTcells)representasmallsubsetofTcells,
whichpossessadifferentreceptoronthesurface(TCR).MostT
cellsreceptorconsistsoftwochainsα-andβ-gp.UnlikeTcells,γδ
cellshaveaTCRcomposedofgammaandadeltachains.This
groupismorepoorlyrepresentedthanbetaalphacells.Theyare
abundantintheintestinalmucosa.
NaturalkillerTcells(NKT)areaheterogeneousgroupofTcells,
whichhavepropertiesofbothNKcellsandTcellsandrepresents
only0.2%ofallcirculatingTlymphocytesintheblood.

28. B cells
Bcellsareformedinthebonemarrow.Bcellshaveparticularsites
(receptors)ontheirsurfacewhereantigenscanattach.
Bcellsarethemajorcellsinvolvedinthecreationofantibodiesthat
circulateinbloodplasmaandlymph,knownashumoralimmunity.
InmammalstherearefivetypesofantibodyIgA,IgD,IgE,IgG,and
IgM,differinginbiologicalproperties.
Eachhasevolvedtohandledifferentkindsofantigens.
Uponactivation,Bcellsproduceantibodies,eachofwhich
recognizesauniqueantigen,andneutralizespecificpathogens.

29. B cells

30. B cells
TheB-cellresponsetoantigenshastwostages:
Primaryimmuneresponse:
WhenBcellsfirstencounteranantigen,theantigenattachestoa
receptor,stimulatingtheBcells.
SomeBcellschangeintomemorycells,whichrememberthat
specificantigen,andotherschangeintoplasmacells.HelperTcells
helpBcellsinthisprocess.
Plasmacellsproduceantibodiesthatarespecifictotheantigenthat
stimulatedtheirproduction.Afterthefirstencounterwithanantigen,
productionofenoughofthespecificantibodytakesseveraldays.
Thus,theprimaryimmuneresponseisslow.
Secondaryimmuneresponse
WheneverBcellsencountertheantigenagain,memoryBcellsvery
rapidlyrecognizetheantigen,multiply,changeintoplasmacells,and
produceantibodies.Thisresponseisquickandveryeffective.

31. Primary and secondary phases of the humoral
immune response to the same antigen.

32. 3 germane processes involved
in specific (adaptive ) humoral
immune response
Recognition of Antigen
Processing of antigen
Production of specific antibodies

33. Recognition
An individual does not generally produce
antibodies to antigens regarded as "self".
The system must have a memory so that the
same antigen can be recognized after re-
exposure.
Lymphocytes are the recognition cells which
initiate the immune response.

34. Processing
Subsequent to recognition as foreign, an
antigen's determinants must be processed in
such a way that a specific antibody can be
produced.
Macrophages are believed to perform this
function because they ingest the antigen.

35. Production
The final phase of the immune response is
the production of antibody.
This manufacturing system must be regulated
in some way so that the immune response
can be discontinued when the antigen
stimulation is withdrawn

36. Antigens
Antigensorimmunogensaresubstancesforeigntothehostthatcan
stimulateanimmuneresponse.
Mostantigensaremacromoleculessuchasproteinsand
polysaccharides,althoughlipidsandnucleicacidsoccasionallycan
serveasantigens.
Antigens include:
bacteria
fungi
viruses
protozoans
parasitic worms
substances such as pollen
venom
transplanted organs

37. Antigens
Antigens,whichingeneralarelargeandcomplex,arebiologically
degradedintosmallerchemicalunitsorpeptides.
Thesediscrete,immunologicallyactivesitesonantigensarecalled
antigenicdeterminantsorepitopes.
Itistheuniquemolecularshapeofanepitopethatisrecognizedby
aspecificreceptorfoundonthesurfaceofthelymphocyteorbythe
antigen-bindingsiteofanantibody.
Asingleantigenmaycontainseveralantigenicdeterminants;each
canstimulateadistinctcloneoflymphocytestorespond.
Smallersubstances(molecularmasses<10,000daltons)usuallyare
unabletostimulateanadequateimmuneresponse.
Low–molecular-weightcompounds,knownashaptens,combine
withlargerproteinmoleculestheyfunctionasantigens.

38. Antigens
Multiple epitopes on a complex antigen being recognizedby their respective (A,
B, C) antibodies

39. Immunoglobulins(Antibodies) -
structure

40. Classes and Characteristics of Immunoglobulins
ClassPercentage of
Total
Characteristics
Ig G 75% •Displays antiviral, antitoxin, and antibacterial properties
•Only IgG crosses the placenta
•Responsible for protection of newborn
•Activates complement and binds to macrophages
Ig A 15% •Predominantinbodysecretions,suchassaliva,nasaland
respiratorysecretions,andbreastmilk
•Protects mucousmembranes
Ig M 10% •Forms the natural antibodies such as those for ABO blood
•Antigens
•Prominent in early immune responses
•Activatescomplement
Ig D 0.2% •Found on B lymphocytes
•Needed for maturation of B cells
Ig E 0.004% •Bindstomastcellsandbasophils
•Involvedinparasiticinfections,allergicandhypersensitivity
reactions

41. What is immunity?
Theabilityofanorganismtoresistaparticular
infectionortoxinbytheactionofspecific
antibodies.
Inbiologyimmunityisthebalancedstateofan
organism(usuallymulticellualr)inwhichithas
adequatebiologicalbodydefensestofight
infection,disease,orotherunwantedbiological
invasion,whilehavingadequatetoleranceto
avoid auto-immune diseases and
hypersensitivity.

42. Active immunity
In active immunity-the individual’s own
immune system is the cause of the immunity.
May be natural (Ags introduced thro infection)
through recovery from illness or artificial
through vaccination (Ags introduce thro
vaccine).

43. Passive immunity
Inpassiveimmunity-immunity(preformed
antibodies)aretransferredfromanother
personoranimal.Maybenaturallyacquired
e.gverticaltransmissionfrommotherto
foetusthroughtheplacenta,orthrough
breastmilk
MaybeartificiallyacquiredwhenAbsfrom
anotherpersonoranimalaregiventoan
individuale.gATS,Anti-Rabies,Anti-Snake

44. Active Versus Passive Immunity
Active or acquired immunity
Canbeachievedthroughexposuretoaspecific
antigen.
Itisacquiredthroughimmunizationoractuallyhaving
adisease.
Activeimmunity,althoughlonglastingonce
established,requiresafewdaystoweeksafterafirst
exposuretobecomesufficientlydevelopedto
contributetothedestructionofthepathogen.

45. Active Versus Passive Immunity
Passiveimmunity
Isimmunitytransferredfromonesourcetoanothersource.(e.g.
Aninfantreceivespassiveimmunitynaturallyfromthetransferof
antibodiesfromitsmotherinuteroandthroughamother’sbreast
milk.)
Passiveimmunityalsocanbeartificiallyprovidedbythetransfer
ofantibodiesproducedbyotherpeopleoranimals.
Someprotectionagainstinfectiousdiseasecanbeprovidedby
theinjectionofhyperimmuneserum,whichcontainshigh
concentrationsofantibodiesforaspecificdisease,orimmune
serumorgammaglobulin,whichcontainsapoolofantibodiesfor
manyinfectiousagents.
Passiveimmunityproducesonlyshort-termprotectionthatlasts
weekstomonths.

46. Thanks for
your rapt
attention

47. Immunoglobulin
Deficiency Diseases

48. Immunoglobulin Deficiency
Diseases
Primary immunodeficiency syndrome
Secondary immunodeficiency syndrome
Acquired Immunodeficiency Syndrome (AIDS)

49. Primary immunodeficiency
syndrome
Duetoaprimaryhereditaryconditionthe
cellular,humoralorbothimmunemechanisms
aredeficient.
Atone extreme theremay be
agammaglobulinemiaordysgammaglobulinemia
inwhichoneorseveralimmunoglobulinsare
absentbecauseofBcelldeficiency.
ThymicdysplasiawillresultinaTcelldeficiency.
Wiskott-Aldrichsyndromeinvolvescombined
deficiencies.

50. Wiskott-Aldrich syndrome
Conditionwithvariableexpression,butcommonly
includesimmunoglobulinM(IgM)deficiency.
Alwayscausespersistentthrombocytopeniaand,in
itscompleteform,alsocausessmallplatelets,
atopy,cellularandhumoralimmunodeficiency,and
anincreasedriskofautoimmunediseaseand
hematologicmalignancy.
WASisanX-linkedrecessivegeneticcondition;
therefore,thisdisorderisfoundalmostexclusivelyin
boys.
WAShasbeenthefocusofintensemolecular
biologyresearch,whichrecentlyledtotheisolation
oftheaffectedgeneproduct.

51. Secondary Immunodeficiency
Syndrome
Results from involvement of the immunogenetic system
in the course of another disease.
Tumors of the lymphoid system.
Hematologic disorders involving phagocytes.
Protein losing conditions like the nephrotic syndrome.
Other mechanisms occur which are not well understood
which affect patients with diabetes mellitus and renal
failure.
Drugs and irradiation for cancer therapy may affect
immunologic functions.
Many drugs used therapeutically as immunosuppressive
particularly after transplant surgery.

52. Acquired Immunodeficiency
Syndrome (AIDS)
A condition in which T cell dysfunction results
from a viral agent.
Loss of T cell activity renders the patient
susceptible to a wide variety of rare or
unusual infections.

53. AIDS and T-cells
AIDS (Acquired Immuno-Deficiency Syndrome is caused by
HIV (Human Immunodeficiency Virus)
AIDS victims suffer because HIV has destroyed their CD4
T lymphocytes
AIDS patients are unable to mount an effective immune response
to pathogens
Death is usually due to an infectious agent

54. PEOPLE LIVING WITH HIV/ AIDS
Patient have opportunistic infections: Infections that are rarely
observed in individuals with normal immune systems
Patients
Test positive for HIV
Have a CD4 T-cell number of less than 200/mm3
(normal is 600/mm3)
acquire infections that are not normally found in healthy
individuals
Pneumocystis carinii—pneumonia
Kaposi’s sarcoma –atypical cancer of the cells
lining
blood vessels (purple patches on skin) caused by
herpesvirus 8
A number of fungal diseases
recurrent Salmonella mediated septicemia

55. References
http://www.thebody.com/nih/immune_system.html
http://pathmicro.med.sc.edu/ghaffar/hyper00.htm
http://home.kku.ac.th/acamed/kanchana/bsi.html

56. Thank you