CELL-MEDIATED IMMUNITY (CMI) The bodys immune systemself non-self Educ tion in the Thymus fo!

T cells "one m !!o#$ fet l li%e! ("u!s of & b!icius) " cells' Immune !es(onse in%ol%es both) Antibody ((!edomin nce of ntibody !es(onses) Cellul ! ((!edomin nce of cellul ! !es(onses) T#o bo%e !e inse( ! ble) Ab !e sec!eted by cells Antibodies medi te cellul ! immunity e* ADCC$ hy(e!sensiti%ity etc "oth nti*en s(ecific nd non-s(ecific cells o(e! te in CMI +(ecific cells) CD, Th- nd Th. (hel(e!) CD/ (cytoto0ic) Non-s(ecific cells) N1 cells$ m c!o(h *es$ neut!o(hils$ eosino(hils CMI di!ected m inly * inst) Mic!obes #ithin (h *ocytes Mic!obes infectin* non-(h *ocytic cells Anti*ens !eco*nised in ssoci tion #ith M2C T-Cell Acti% tion !e3ui!ements) 4!im !y si*n l-TC5 com(le0 #ith CD, o! CD/ co!ece(to! nd (e(tide M2C com(le0 Co-stimul to!y molecule (th!ou*h inte! ction bt#n T cell nd A4C' Memo!y cells need little o! no co-stimul tion' Co!ece(to!s (Di *! m)

Anti*en 4!ocessin* nd 4!esent tion

(Di *! m)

Endo*enous nti*ens) Cytosolic ( th# y 6i!uses Int! cellul ! b cte!i ) Listeria, Shigella, chlamydia,Rickettsia,Mycobac' Int! cellul ! ( ! sites) Toxoplasma 4!ote some Multifunction l (!ote se com(le0 fo! !outine de*! d tion of host cytosolic (!oteins A!e l !*e &unctions in n AT4-de(endent (!ocess Used by I7+ystem to *ene! te (e(tides fo! M2C I (!esent tion E0o*enous nti*ens) Endocytic ( th# y &!ee e0t! cellul ! (!oteins C (tu!ed nd t 8en in cell th!u (h *ocytosis$ (inocytosis$ !ece(to!- medi ted endocytosis Lysosomes Collection of mo!e th n ,9 cid-de(end nt hyd!ol ses includin*) 4!ote ses Nucle ses :lycosid ses Li( ses 4hos(holi( ses 4hos(h t ses (chlo!o3uine ! ises (h of com( !tment the!efo!e inhibit A* (!ocessin*) Effecto! Molecules Acti% tion---------4!olife! tion----------Diffe!enti tion (effecto! cells) (Anti*en si*n l) (IL-.) (IL-.) Cell ty(e Th+oluble effecto!s Memb! ne effecto!s

IL-.$ IL-;$ TN&-$ I&N- (TN&-) :M-C+& (hi*h)

Th.

IL-;$ IL-,$ IL-<$ IL-=$ IL--9 IL--;$ :M-C+& (lo#) cytoto0ins ((e!fo!ins$ *! n>ymes o! f! *mentins) I&N-*$ TN&-b

CD,9 li* nd & s li* nd (& sL)

CTL

-Cytoto0ins ((e!fo!ins$ *! n>ymes)$ & s li* nd (& sL)) medi te t !*etcell dest!uction by CTL -TN&-$ I&N-$ :M-C+&) (!omote m c!o(h *e cti% tion by Th- cell -IL-,$ IL-<$ IL-=$ CD,9 li* nd) (!omote "-cell cti% tion CMI by CD4 Cells CD, cells-A* in inte!n lised %esicles in A4C-Associ tion #ith M2C II CD/ cells-A* in cyto(l sm-Associ tion #ith M2C I Diffe!ent mic!obes stimul te Th- o! Th. cell subsets CD, T cell cti% tion---IL--. o! IL-, (!oduction by M?---stimul tion of diffe!enti tion of CD, cells Th- cell subset-----IL-.$ I&N-*---cellul ! immunity Th. cell subset-----IL-,$ IL-<$ IL--9--- ntibody !es(onse (&unctions of cyto8ines in CMI) (Di *! m) Destruction by CTL: Con@u* te fo!m tion-TC57M2C7A:7CA5ECE4TA57CAM4LEB Memb! ne tt c8-by (e!fo!ins ((o!e fo!min*)C *! n>ymes (DNA f! *ment tion) CTL dissoci tion occu!s -then T cell *oes to tt c8 nothe! cell T !*et cell dest!uction-cells die th!ou*h (o(tosis-DNA f! *ment tion cti% ted by *! n>ymesNK Cells Constitute <--9D of !eci!cul tin* lym(hocyte (o(ul tion N tu! l immune defences * inst %i!uses nd tumou!s

4!oduce I&N-$ thus im(o!t nt in immuno!e*ul tion Acti%ity stimul ted by I&N-$ I&N-$ IL--. nd (e 8s in ; d ys fte! %i! l infection &unction l CTL come u( in bout E d ys (ost-%i! l infection N1 cells h %e no s(ecific nti*en !ece(to!s They distin*uish bt#n he lthy nd dise sed cells th!ou*h Fb l nce of cti% tin* ( N15-4- nd othe!s) nd inhibito!y !ece(to!s (CDG,7N1:.$ 1I5 f milyH Addition l N1-cell cti% tin* si*n ls !e th!ou*h) I&N- nd I&N-$ TN&-$ IL--. nd IL-<' M !8e!s fo! N1 cells) CD -= nd CD <= ADCC (Antibody-dependent cell-mediated cytotoxicity Cytoto0ic cells e0(!ess memb! ne !ece(to!s fo! &c !e*ion of I* Cells include) N1$ m c!o(h *es$ monocytes$ neut!o(hils$ nd eosino(hils A"( ntibody) binds t !*et cell-5ece(to! be !in* cell binds to A" &c !e*ion-+ubst nces sec!eted by cytoto0ic cells medi te lysis of t !*et cells (Lytic en>ymes$ (e!fo!in$TN&$*! n>ymes etc)' No com(lement-medi ted lysis is in%ol%ed The cytoto0ic cells !e non-s(ecific fo! nti*en' "ut s(ecificity is th!ou*h A:7A" bindin* (Di *! m) !ra"t-#ersus-$ost %eaction Is n in %i%o indic tion of CMI E0(e!ienced #hen immunocom(etent cells !e in@ected into immunocom(!omised llo*eneic host-Dono! nd 5ece(ient !e not *enetic lly identic l 5eci(ient cells !e tt c8ed nd 8illed' E'* "one m !!o# t! ns(l nt tion$ DT$ (Delayed-type &ypersensiti'ity( DT$ type I# 5e ction fi!st desc!ibed by 5obe!t 1och in -/G9 Abse!% tion # s th t indi%idu ls #ith T" de%elo(ed loc lised !e ction #hen in@ected i'd #ith cultu!e filt! te of Mtb' &i!st c lled Ftube!culin !e ctionH

C lled del yed bec use it occu!s I ., h!s follo#in* e0(osu!e to nti*en This !e ction is cell medi ted s o((osed to ntibody medi ted !e ction ty(es I$II$II nd 6' M c!o(h *es nd T cells !e in%ol%ed-m c!o(h *es !e m @o! cells Memo!y T cells !eco*ni>e nti*en on M c!o(h *es-- M2C cl ss II conte0t T cells !e cti% ted nd (!olife! te +oluble medi to!s th t hel( to tt! ct nd cti% te M c!o(h *es (fo! Th-) o! eosino(hils (fo! Th.) Cytoto0ic T cells m y lso be tt! cted to 8ill mo!e cells thus c usin* mo!e tissue d m *e' !ranuloma )ormation &ollo#s continued nti*enic stimul tion +een in Tube!culosis$ +chistosomi sis$ Liste!iosis$ Leishm ni sis$ "l stomycosis (fun* l)$ Le(!osy$ + !coidosis (un8no#n etiolo*y)' (Di *! m)

M c!o(h *es t 8e u( the nti*en (!ocess them nd (!esent them in fo!m !eco*nised by the immune cells'4!ocessed nti*en is (!esented in the conte0t of M2C cl ss - o! .' M2C- (!oteins coded by *enes in the M2C !e*ion nd !e of im(o!t nce in immune !eco*nition nd si*n llin* bet#een cells of the immune system' A((!o(!i te T cells !e !ec!uited to !eco*nise the nti*en on A4C' Anti*en (!esented #ith cl ss - molecules !e !eco*nised by Cytoto0ic7+u((!esso! T cells$ CD/J CE=1D *lyco(!otein on su!f ce'' Anti*ens (!esented in ssoci tion #ith cl ss . M2C !e !eco*nised by T hel(e! cellsC CD,J C=.1D *lyco(!otein on su!f ce' CD,J fu!the! subdi%ided into KTh- nd Th. on b sis of cyto8ines they sec!ete' Th----I&N- * C IL-. C IL--. etc' Th.---IL-,C IL-<C IL--9 etc Anti*en !eco*nition by cells le ds to cti% ion nd (!olife! tion nd if !e3ui!ed some cyto8ine !ele se'

M2C cl ss - molecules dist!ibuted on ll nucle ted cell' This is sensible fo! b!o d cti%ity of cytoto0ic cells du!in* s y %i! l infection' M2C cl ss . molecules only on nti*en (!esentin* cells ( m c!o(h *es$ dend!itic cells L n*e!h ns cells) MAC5A42A:E+ L !*e cells$ in most tissues nd linin* se!ous c %ities nd lun* Athe! M?s !eci!cul te th!ou*h .nd lym(hoid o!* ns LN$ s(leen 4h *ocytic nd lon* li%ed fo! ye !s 4!ocess nd (!esent nti*en Imm tu!e M?s !e monocytes' M? lso effecto! cells- 8ill tumou! cells nd !e mic!obiocid l in ddition to imuno!e*ul to!y functions' AT2E5 M? 5ALE+ Infl mm tion nd fe%e! IL-- (!oduction 4:E (!oduction Lym(hocyte cti% tion Anti*en (!ocessin* nd (!esent tion Mic!obiocid l ction 5ele se of hyd!o*en (e!o0ide 5ele se of o0y*en ! dic ls Acid (2 hyd!olysis Lysosyme !ele se Tumo!icid l Action Cytoto0ic ction TN&- !ele se 4!ote se !ele se Tissue !eo!* nis tion 5ele se of coll *en se $ el st se 5ele se of hy lu!onid se +ec!etion of fib!obl st stimul tin* f cto! +ec!etion of n*io*enesis f cto! +ec!etion of othe! !e*ul to!y cyto8ines e'* IL-/C IL--. etc 4!o(e!ties Af M?s E0(!ess CD-, nti*en +tic8 to *l ss su!f ces 4h *ocytose ny ( !ticul te m tte! CELL MEDIATED CYTATABICITY +(eci lised cells(Cytoto0ic KCD/J T cells) bind nd 8ill undesi! ble cells h !bou!in* s y %i!uses'

5eco*nition of t !*ets is th!ou*h M2C cl ss - molecules'&ollo#in* bindin* to t !*ets$ ch n*es occu! in the cell$memb! ne i'e s#ellin* nd dis!u(tion of cell memb! ne Athe! cytoto0ic cells !e )N1 cells$ 1 cells (Ab7&c !ece(to! medi ted) Cytoto0ic T cells su!%i%e follo#in* lysis nd m y 8ill othe! t !*ets' N1 CELL+-(N tu! l 1ille! Cells) &o!m ( !t of inn te immunity 2ete!o*enous nd found in no!m l nim ls' C n 8ill % !iety of m li*n nt$ %i! lly infected cells in the bsence of ntibody' M !8e!s ) CD -= nd CD <= Antibody medi ted Cellul ! Cyto0i0ity (ADCC) Effecto! cells !eco*nise &c !ece(to!s of ntibody bound to the t !*ets' Ab bound on e'* schistosomule su!f ce !e !eco*nised by eosino(hils nd monocytes le din* to 8illin* of t !*ets