UNIT 3 Cell-Mediated Immunity
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Transcript of UNIT 3 Cell-Mediated Immunity
8/8/2019 UNIT 3 Cell-Mediated Immunity
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UNIT 3 Cell-mediatedImmunity
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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
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F igure 22.8 The Thymus
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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)
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F igure 10-9
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F igure 8-27
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F igure 8-31
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F igure 6-9
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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
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IMMUNE RECOGNITION ACTIVATION OF T CELL
clonal expansioneffector functions
anergy
apoptosis no effect
T cell T cell T cell
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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
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F igure 6-16
III_6_2_TCR_Signaling.mov
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F igure 4-25
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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
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F igure 8-15
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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
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F igure 8-40
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F igure 8-41
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F igure 8-18
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F igure 5-2
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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
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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
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Immun o to leran c e
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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.
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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.
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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.
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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.
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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).
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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.
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F igure 6-24
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F igure 6-25
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