UNIT 3 Cell-Mediated Immunity

8/8/2019 UNIT 3 Cell-Mediated Immunity

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UNIT 3 Cell-mediatedImmunity



Loc ated behind sternum in anteri o r mediastinumCapsule

Tw o lo bes ± Divided int o lo bules, ea c h with a co rtex and

medulla

Co

rtic

al lymphoc

ytes surr o

unded by retic

ular end o thelial c ells ± Maintain bl oo d±thymus barrier

S e c retes thymi c ho rm o nes: thym o sins,thym o po ietins, and thymulin

The Thymus



F igure 22.8 The Thymus



Types of T c ells

TDTH: T c ells parti c ipating in delayed-typehypersensitivityT

C: T c ells that are c yto to xic leading t o

death of target c ells. CD8TH: Helper T c ells c an be divided int o diff erent f un c tio nal subsets. CD4

TReg : An o ther subset that co -expressesCD4 and CD25 (CD25 is the interleukin-2re c ept o r E c hain)



F igure 10-9



F igure 8-27



F igure 8-31



F igure 6-9



SURFACE MOLECULES OF T CELLS :

CD69

Tcell

CD3

TcR

ICAM1

adhesionmolecules

HLA II.

IL-2R activationmoleculescostimulatory

molecules

receptors

forcytokines

accessorymolecules

recognition of Ag

CD25

CD4(CD8)

CTLA 4



IMMUNE RECOGNITION ACTIVATION OF T CELL

clonal expansioneffector functions

anergy

apoptosis no effect

T cell T cell T cell



INTERACTIONS BETWEEN T CELL AND APC CELL

exogenousantigen

endogenousantigen

APC

Tcell

adhesion interactionICAM-1

LFA-1

accessory interactionLFA-3

CD2

costimulation

B7CD28

HLA II TcR

CD4

CD3

lck

clonalexpansion

E F

KH

I

processing: peptide+ HLA I

processing : peptide+ HLA II

PRESENTATION

STATSTAT

P

PJAK

signal II

cytokines

signal I

transcriptionfactors



F igure 6-16

III_6_2_TCR_Signaling.mov



F igure 4-25





Distin c t type of APCs

Retain high levels of MHC-peptide co mplexesfo r a l o ng peri o d o n thec

ell sur f a

ce

Derived f r o m b o nemarr o w and bel o ng t o mo noc yte lineage

Dendriti c Cells



F igure 8-15



Ma c r o phagesPhag oc ytic c ells

Derived f r o mm o noc ytes and residein tissuesIn DTH resp o nse, M J

traps, pr oc esses Ag,and presents t o TDTHc ells and f inally, a c tas e ff e c to r c ells

Mic r o bic idal a c tivitythr o ugh a pr oc esskn o wn as respirat o ryburst



F igure 8-40



F igure 8-41











F igure 8-18



F igure 5-2





Immun o suppressi o n Antigeni c variati o n

allo ws path o gens t o es c ape f r o mimmunity ± Antigeni c drif t

c aused by p o intmutati o ns in thegenes en co ding fo r viral sur f a c e pr o teins

± Antigeni c shi f t due t o reass o rtment of thesegmented RNAgen o me of the virus





Main e ff e c t of lo w levels of Ab is an inability t o c lear extra c ellular ba c teriaT- c ell de f e c ts c an als o result in l o w Ab levelsDe f e c ts in co mplement co mp o nents c ausede f e c tive hum o ral immune f un c tio n

De f e c ts in phag oc ytic c ells permit widespreadba c terial in f e c tio nsDe f e c ts in T- c ell f un c tio n result in severeco mbined immun o de f ic ien c iesDe f e c tive T- c ell signaling, c yto kine pr o du c tio n,o r c yto kine a c tio n





Immun o to leran c e



Tolerance

To leran c e re f ers t o the specific immun o lo gic al n o n-rea c tivity to an antigenresulting f r o m a previ o us exp o sure t o the same antigen.

O ur o wn b o dies pr o du c e s o me 100,000 di ff erent pr o teins and o ne of thelo ngstanding co nundrums of immun o lo gy has been t o understand h o w theimmune system pr o du c es a virtual repert o ire against path o gens while at thesame time av o iding rea c ting t o sel f .

The stri c t de f initio n of immun o lo gic al t o leran c e occ urs when animmun oco mpetent h o st f ails t o resp o nd t o an immun o geni c c hallenge with a

spe c if ic antigen.



Tolerance

The me c hanisms the immune system uses t o ensure the absen c e of sel f -rea c tivity(autoimmunity ) in c lude:

Central Tolerance - this occ urs duringlymph oc yte devel o pment.

Peripheral Tolerance - occ urs a f ter lymph oc ytes leave the primary lymph o id o rgans.



M echanism of tolerance induction

1. Clonal anergy: Aut o -rea c tive T c ells, when exp o sed t o

antigeni c peptides whi c h d o no t p o ssessco stimulat o ry m o lec ules (B7-1 o r B7-2), be co meanergi c to the antigen.

Als o , B c ells when exp o sed t o large am o untsof s o luble antigen d o wn regulate their sur f a c e

IgM and be co me anergi c . These c ells als o up-regulate the Fas m o lec ules o n their sur f a c e. Anintera c tio n of these B c ells with F as-ligand-bearing c ells results in their death via ap o pto sis.



2 . Receptor editing

B c ells whi c h en co unter large am o unts of s o luble antigen, as they d o in the b o dy,and bind t o this antigen with very l o wa ff inity be co me a c tivated t o re-expresstheir RAG-1 and RAG-2 genes.

These genesc

ause them to

undergo

DNAre co mbinati o n and c hange their antigenspe c if ic ity.



3 . Clonal deletion:F un c tio nally immature c ells of a c lo ne

enco

untering antigen undergo

apr o grammed c ell death, as aut o -rea c tiveT- c ells are eliminated in the thymusfo llo wing intera c tio n with sel f antigenduring their di ff erentiati o n (negativesele c tio n).



4. Cl o nal Ign o ran c eIt c an be sh o wn that there are T c ells and B c ells spe c if ic fo r aut o -antigenspresent in c ir c ulati o n.

These c ells are quite c apable of making a resp o nse but are unaware of thepresen c e of their aut o -antigen. This arises fo r 2 reas o ns.

The f irst is that the antigen may simply be present in t oo lo w co nc entrati o no r may have weak a ff inity. S inc e all lymph oc ytes have a thresh o ld fo r re c ept o r occ upan c y whi c h is required t o trigger a resp o nse then very l o wco nc entrati o ns of antigen will n o t be sensed.

The seco

nd po

ssibility is a mo

re interestingo

ne.So

me antigens aresequestered f r o m the immune system in l oc ati o ns whi c h are n o t f reelyexp o sed t o surveillan c e.

These are termed immunologically privileged sites. Examples of su c h sites are the eye, CN S , and testis.



F igure 6-24



F igure 6-25



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UNIT 3 Cell-Mediated Immunity