Chapter16 Immunological Tolerance (01) b6 m2

7/26/2019 Chapter16 Immunological Tolerance (01) b6 m2

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ImmunologicImmunologicToleranceTolerance


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ContentsContents

PartPart IntroductionIntroduction

Part Development of Immunologic TolerancePart Development of Immunologic Tolerance

PartPart Mechanism ofMechanism of

Immunologic ToleranceImmunologic Tolerance PartPart Immunologic Tolerance and ClinicImmunologic Tolerance and Clinic

MedicineMedicine


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Definition:A type of spe!ifi! unresponsi"enessto an antigen indu!ed by t#e e$posure of

spe!ifi! lymp#o!ytes to t#at antigen% but

response to ot#er antigens normally (& state of unresponsi"eness to parti!ular

antigeni! epitope)

Tolerogens:antigens t#at indu!e toleran!e As a !on!e'uen!e of ina!ti"ation by antigen%

lymp#o!ytesdeleted or anergic

PartPart IntroductionIntroduction


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0*en first obser"ed

immunologi!toleran!e to

allogeni! antigen in

fetal period in 1234

1 ,ndu!tion of immunologi! toleran!e to

antigen in fetal period and neonate period


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Experiment of Medawar on immunologic tolerance


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oleran!e in and . !ellsoleran!e in and . !ells


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a!tors affe!ting toleran!erole of antigen

a!tors affe!ting toleran!erole of antigen

a!tors *#i!#affe!t response

a"or immuneresponse

a"or toleran!e

7#ysi!al form ofantigen

Route of inje!tion

ose of antigen

arge% aggregated%!omple$ mole!ules%properly pro!essed

;ub!utaneous orintramus!ular

0ptimal dose

soluble% aggregate-free%simple small mole!ules%not pro!essed

0ral or% sometimes%intra"enous

8ery large or "ery smalldose


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a!tors affe!ting toleran!e

t#e role of #ost

a!tors affe!ting toleran!e

t#e role of #ost

a!tors t#ataffe!t response

a"or immuneresponse

a"or toleran!e

Age of respondinganimal

ifferentiationstate of !ells

ully differentiated=memory > . !ells

0lder% immuno-logi!ally mature

e*born (mi!e)% immuno-logi!ally immature

Relati"e undifferentiated .!ell *it# only ,gM% !ells

in t#e t#ymi! !orte$


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9ost age and antigen dose affe!t

toleran!e

9ost age and antigen dose affe!t

toleran!e

ne*born adult


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1 entral tolerance:

6entral toleran!e o!!urs in t#e !entrallymp#oid organs as a !onse'uen!e ofimmature self-rea!ti"e lymp#o!ytesre!ogni?ing ubi'uitous self-antigen

5 !erip"eral tolerance:

toleran!e *as indu!ed in perip#eral organs

as a result of mature self-rea!ti"elymp#o!ytes en!ountering tissue-spe!ifi!self antigensunder parti!ular !onditions


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1 6entral toleran!e

6lonal deletion (apoptoti! !ell deat#)

uring maturation of lymp#o!ytes in t#e

t#ymus for !ell or in t#e bone marro* for .maturation% immature lymp#o!ytes t#at

re!ogni?e ubi'uitous self-antigen*it# #ig#

affinity are deleted bynegati"e sele!tion


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6lonal deletion:negati"e sele!tion of !ells in t#e t#ymus

6lonal deletion:negati"e sele!tion of !ells in t#e t#ymus


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5 7erip#eral toleran!e

clonal deletion and clonal ignorance:

large tissue spe!ifi! antigen delete spe!ifi! !ells

self-rea!ti"e lymp#o!ytes remain "iable and

fun!tional but do not rea!t to t#e self antigens in

any dete!table *ay

lonal anergy and inacti#ation:

fun!tional ina!ti"ation *it#out !ell deat#: la!k !o-

stimulatory signal


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6lonal anergy in !ells6lonal anergy in !ells


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6lonal anergy in . !ells6lonal anergy in . !ells


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PartPart Immunologic Tolerance andImmunologic Tolerance and

Clinic MedicineClinic Medicine


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SummarySummary

efinition of immunologi! toleran!e

eatures of immunologi! toleran!e

,ndu!tion of immunologi! toleran!eMe!#anism of immunologi! toleran!e

6lini!al appli!ation of immunologi! toleran!e

Chapter16 Immunological Tolerance (01) b6 m2

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