RESUMO DE IMUNOL IMUNOLOGIA OGIA ( Abbas Caps 1,2,3,4,5,6,7,8,9,10,11,12,14,18,19)
CAPÍTULO 1 (Propriedades Gerais das Respostas Respostas Imunes) Imunes)
Imunidade Inata !"sp#s$as %&"'%a$as " p!#p#!*%#+a a %+-a '" '"."sa %+%*%a *#+$!a &%*!#/#!a+%s&#s C#+s%s$" "& &"*a+%s&#s '" '"."sa *"a!"s " b%#&%*#s, " "%s$"& a$ &"s&# a+$"s 'a %+."*# " " "s$# p!#+$#s pa!a !"sp#+'"! !ap%'a&"+$" a %+."* %+."* "s "s Os p!%+ p!%+*% *%pa pa%s %s *# *#&p# &p#+" +"+$ +$"s "s 'a %&+ %&+%' %'a' a'" " %+a$ %+a$a, a, s# s# ba!! ba!!"%! "%!as as .s%* .s%*as as " &%*a &%*as, s, *#&# *#&# #s "p%$ "p%$%#s %#s " as sbs$: sbs$:+*% +*%as as &%* &%*as as a+$%&% a+$%&%*!# *!#b%a b%a+a +a p!#' p!#';%' ;%'a a +as sp"!.*%"s "p%$"%a%s< Cas .a#*%$!%as (+"$!=>#s " &a*!=.a#s), *as '"+'!$%*as " *as N?< p!#$"+as '# sa+", %+*%+'# &"&b!#s '# s%s$"&a *#&p"&"+$# " #$!#s &"'%a'#!"s '" %+@a&a# " p!#$"+as '"+#&%+a'as *%$#*%+as, " !"a& " *##!'"+a& &%$as a$%%'a'"s 'a %&+%'a'" %+a$a A !"sp#s$a %&+" %+a$a "s$%&a !"sp#s$as %&+"s a'%!%'as
A !"sp#s$a %&+" %+a$a *#+s%s$" "& '#%s p!%+*%pa%s $%p#s '" !"a"s %+@a&a# " '"." '"."sa sa a+$% a+$%% %!a !a A infamação !"."! !"."!"/s "/s" " a# p!#*"s p!#*"ss# s# '" !"*!$ !"*!$a&"+ a&"+$# $# '" "*=* "*=*%$#s %$#s " p!#$"+as pas&$%*as '# sa+", s" a*B&# +#s $"*%'#s " sa a$%a# pa!a '"s$!%! #s &%*!#!a+%s&#s Ess" p!#*"ss# "+#" *%$#*%+as, " s# p!#';%'as p#! *as '"+'!$%*as, &a*!= &a*!=.a .a# #ss " #$! #$!as as Os p!%+ p!%+*% *%pa pa%s %s "* "*=* =*%$ %$#s #s " " s# s# !"*! !"*!$ $a' a'#s #s s# s# #s +"$ +"$!= !=> >#s #s " &#+=*%$#s (" s# $!a+s.#!&a'#s "& &a*!=.a#s $"*%'a%s) Ess"s .a=*%$#s "p!"ssa& "& sa sp"!.*%" !"*"p$#!"s " s" %a& &%*!#!a+%s&#s " #s %+"!"& " !"*"p$#!"s " !"*#+-"*"& !"*#+-"*"& '%."!"+$"s '%."!"+$"s &#*as &#*as &%*!#b%a+ &%*!#b%a+as as " a$%a& as *as C#& a$%a# a$%a# '"ss"s !"*"p$ !"*"p$#! #!"s, "s, #s .a=*% .a=*%$#s $#s p!#' p!#';"& ;"& !a'%*a% !a'%*a%ss !"a !"a$% $%#s #s '" #% #%+%# +%# " +%$!# +%$!#+ +%# %# " "+;%&a "+;%&ass %s#ss %s#ss&% &%*as *as A de deesa esa anti antiira ira!! *#+s%s$" "& !"a# &"'%a'a p#! *%$#*%+as, "& " as *as a'%!"& !"s%s$+*%a %+."*# %!a, " +a '"s$!%# p"as *as N? 'as *as %+."*$a'as p#! !s A %&+%'a'" %&+%'a'" %+a$a *#+>a +a *#"## *#"## '" pa$="+#s pa$="+#s F#s F#ss% s% $#'#s #s !"*"p$#! !"*"p$#!"s "s *#'%>*a'#s Ea %'"+$%>*a Fa'!"s Fa'!"s &#"*a!"s '" Fa$="+#s (FAMFs) (FAMFs)
Imunidade Adaptatia" !"sp#s$as $a!'%as " s# "s$%&a'as p"a "p#s%# a a"+$"s %+."** %+."**%#s %#s#s, #s, *a *a &a+%$ &a+%$'" '" " *apa*% *apa*%'a' 'a'" " '" '"."sa '"."sa a&"+$ a&"+$a& a& *#& *a'a *a'a "p#s% "p#s%# # s*"ss%a a '"$"!&%+a'# #!a+%s&# C#&# *a!a*$"!s$%*as %&p#!$a+$"s, '"s$a*a&/s" sa +#$" "sp"*%>*%'a'" pa!a &#*as '%s$%+$as " sa *apa*%'a'" '" &"&=!%a *"a!, " p"! p"!&%$" &%$" !"s "sp# p#+' +'"! "! *# *#& & &a &a%s %s %+$ %+$"+s "+s%'a' %'a'" " "& "p#s p#s% % "s !"p"$ "p"$%' %'as as a# &" &"ss&# &%*!#!a+%s&# Os p!%+*%pa%s *#&p#+"+$"s s# #s %+.=*%$#s " s"s p!#'$#s s"*!"$a'#s, $a%s *#&# a+$%*#!p#s a+$%*#!p#s A !"sp#s$a !"sp#s$a %&+" a'ap$a$%a a'ap$a$%a a$a %+$"+s%>*a+'# %+$"+s%>*a+'# #s &"*a+%s&#s &"*a+%s&#s p!#$"$#!"s 'a %&+%'a'" %+a$a
O s%s$"&a %&+" a'ap$a$%# $%%;a $!s "s$!a$%as pa!a *#&ba$"! #s &%*!#!a+%s&#s Os a+$% a+$%*# *#!p !p#s #s s" s"*! *!"$a "$a'# '#ss %a %a&/s &/s" " a &%*! &%*!#! #!a a+%s +%s&#s &#s "$! "$!a* a*" "a! a!"s "s,, b# b#" "%a %a& & sa sa *apa*% *apa*%'a' 'a'" " '" %+."*$ %+."*$a! a! *a *ass '# -#sp"' -#sp"'"%! "%!# # " p!#&# p!#&#"& "& %+"s$ %+"s$# # " '"s$! '"s$!%# %# p"#s p"#s .a=*%$#s As *as H"p a&"+$a& a *apa*%'a'" &%*!#b%*%'a '#s .a=*%$#s, " %+"!"& #s &%*!#!a+%s&#s " #s '"s$!#"& E - $a&b& a "s$!a$%a '#s %+.=*%$#s *%$#$=%*#s, +# a '"s$!#"& as *as %+."*$a'as p#! &%*!#!a+%s&#s " s# %+a*"ss"%s a#s a+$%*#!p#s " '"s$!%# .a#*$%*a A %&+%' %&+%'a'" a'" a'ap$a a'ap$a$%a $%a *#+>a *#+>a +a '%"!s% '%"!s%'a' 'a'" " 'a %&+%' %&+%'a'" a'",, # s" s"a, a, $"& !%#s !%#s s"&"+$#s +%*#s " - &a "+;%&a (RAG) " s#!$"%a # s"&"+$# DJ " %a #s !"a!!a+#s +%*#s a a+s s"&"+$#s +%*#s pa!a .#!&a! s"s !"*"p$#!"s +%*#s, !"sp#+s"%s p"a a"a$#!%"'a'" +%*a
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%p#s '" R"sp#s$a R"sp#s$a I&+" A'ap$a$%a I&+%'a'" H&#!a • → M"'%a'a p#! &#*as +# sa+" " a+$%*#!p#s p!#';%'#s p#! %+.=*%$#s K Os a+$%*#!p#s !"*#+-"*"& a+$"+#s &%*!#b%a+#s, +"$!a%;a& sa *apa*%'a'" '" %+."*$a! " p!#&#"& a sa "%&%+a# p#! &"*a+%s&#s "."$#!"s → F!%+*%pa &"*a+%s&# '" '"."sa *#+$!a &%*!#!a+%s&#s "$!a*"a!"s " sas $#%+as → #% #!%%+a&"+$" '">+%'a *#&# & $%p# '" %&+%'a'" pass" '" s"! $!a+s."!%'a a %+'%'#s +# %&+"s, # %!"+s, a$!as '" p#!"s '# sa+" %s"+$as '" *as *#+$"+'# a+$%*#!p#s, #b$%'as '" %+'%'#s p!"%a&"+$" %&+%;a'#s → Os %+.=*%$#s K a$%a'#s p!#%."!a& " '%."!"+*%a&/s" "& pas&=*%$#s, *as " s"*!"$a& *ass"s '" a+$%*#!p#s, *#& .+"s '%s$%+$as A !"sp#s$a 'as *as K a a+$"+#s p!#$"%*#s "%" s%+a%s a$%a'#!"s 'as *as CD4 Os a+$"+#s p!#$"%*#s ap=s %+';%!"& &a p!#'# %+%*%a '" IM, *asa& a p!#'# '" '%."!"+$"s a+$%*#!p#s (IG, IA # IE) A p!#'# '"ss"s a+$%*#!p#! '%."!"+$"s '"+#&%+a'a &'a+a '" *ass" " "%" a a# 'as *as -"p, "s$%&a+'# a p!#'# '" a+$%*#!p#s *#& a>+%'a'" a&"+$a'a p"# a+$"+#
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I&+%'a'" C"a! → M"'%a'a p"#s %+.=*%$#s → F!#&#" a '"s$!%# '#s &%*!#!a+%s&#s " !"s%'"& +#s &a*!=.a#s # a '"s$!%# 'as *as %+."*$a'as pa!a "%&%+a! #s !"s"!a$=!%#s '" %+."*# → #% '">+%'a *#&# a .#!&a '" %&+%'a'" " p#'" s"! $!a+s."!%'a a a+%&a%s +# %&+"s p#! &"%# '" %+.=*%$#s , &as +# p#! &"%# '# pas&a # '# s#!# → Os %+.=*%$#s CD4 -"p a$%a'#s p!#%."!a& " '%."!"+*%a&/s" *#& *as "."$#!as *as .+"s s# &"'%a'as p#! *%$#*%+as s"*!"$a'as U&a 'as !"sp#s$as &a%s %+%*%a%s 'as *as -"p CD4 a s"*!"# '" IL/2, " & .a$#! '" *!"s*%&"+$# " a$a s#b!" #s %+.=*%$#s a$%a'#s, a& '" "s$%&a! sa "pa+s# *#+a → As *as "."$#!as 'a %+-a"& '" *as -"p CD4 s"*!"$a& *%$#*%+as " "s$%&a& a p!#'# '" %&+##b%+a E (IE), a& '" a$%a! "#s%+=>#s, " s# *apa;"s '" &a$a! pa!as%$as !a+'"s '"&a%s '"& a%s pa!a s"!"& .a#*%$a'#s → Os %+.=*%$#s CD8 a$%a'#s p!#%."!a& " '%."!"+*%a&/s" "& CL " '"s$!#"& as *as %+."*$a'as +# *%$#pas&a A# '"s$!%! as *as %+."*$a'as, #s CL "%&%+a& #s !"s"!a$=!%#s 'a %+."*# F!%+*%pa%s Ca!a*$"!s$%*as 'a R"sp#s$a I&+" A'ap$a$%a
#spe$i%$idade e diersidade" As !"sp#s$as %&+#=%*as s# "sp"*>*as pa!a '%."!"+$"s a+$"+#s As pa!$"s '"ss"s a+$"+#s " s# !"*#+-"*%'as "sp"*%>*a&"+$" p"#s %+.=*%$#s s# '"+#&%+a'as '"$"!&%+a+$"s a+$%+%*#s (# "p$#p#) Essa "sp"*%>*%'a'" #*#!!" p#!" #s %+.=*%$#s "p!"ssa& !"*"p$#!"s '" &"&b!a+a " s# *apa;"s '" '%s$%+%! '%."!"+as s$%s +a "s$!$!a '" '%."!"+$"s "p$#p# O +B&"!# $#$a 2
'" "sp"*%>*%'a'"s a+$%+%*as '#s %+.=*%$#s '" & %+'%'# *-a&a/s" !"p"!$=!%# '#s %+.=*%$#s Essa *apa*%'a'" '# !"p"!$=!%# %+.#*%$!%# '" !"*#+-"*"! & +B&"!# &%$# !a+'" '" a+$"+#s *-a&a/s" '%"!s%'a'", " !"s$a 'a a!%ab%%'a'" '" "s$!$!as '#s s$%#s '" %a# '" a+$"+#s p!"s"+$"s +#s !"*"p$#!"s '#s %+.=*%$#s
&em'ria" A "p#s%# '# s%s$"&a %&+#=%*# a & a+$"+# "s$!a+-# a&"+$a a sa *apa*%'a'" '" !"sp#+'"! +#a&"+$" "" a+$"+# "sp"*>*# Essas !"sp#s$as %&+#=%*as s"*+'!%as "!a&"+$" s# &a%s !p%'as, '" &a%#! %+$"+s%'a'" " .!"+*%a '# " a p!%&"%!a !"sp#s$a a# a+$"+# A "p%*a# pa!a %ss# s" '"" a# .a$# '" " a "p#s%# a & a+$"+# "!a *as '" &"&=!%a '" %'a #+a "sp"*>*as pa!a # a+$"+# F#! ""&p#, #s %+.=*%$#s K '" &"&=!%a p!#';"& a+$%*#!p#s " s" %a& a# a+$"+# *#& &a%#! a>+%'a'" '# " #s a+$%*#!p#s p!#';%'#s +a !"sp#s$a !"sp#s$a %&+" p!%&!%as< " as *as '" &"&=!%a !"a"& &%$# &a%s !ap%'a&"+$" " *#& &a%s %#! "s$%&a# a+$%+%*a '# " *as %!"+s #pansão $!ona!" Os %+.=*%$#s "sp"*>*#s pa!a '"$"!&%+a'# a+$"+# s#.!"& *#+s%'"!" p!#%."!a# ap=s a "p#s%# a "ss" a+$"+# R"."!"/s", R"."!"/s", p#!$a+$#, a & a&"+$# +# +B&"!# '" *as " "p!"ssa& !"*"p$#!"s !"*"p$#!"s %'+$%*#s pa!a # &"s&# &" s&# a+$"+#, p"!$"+*"+'# "+$# a & *#+" Iss# p"!&%$" " a !"sp#s$a %&+#=%*a p#ssa 'a! *#+$a '# !%$&# '" '%%s# '#s pa$="+#s #spe$ia!iação" R"sp#s$a '%s$%+$a " "sp"*%a a '%."!"+$"s pa$="+#s &a%&%;a& a ">*%+*%a '#s &"*a+%s&#s '" '"."sa a+$%&%*!#b%a+#s *ão reatiidade ao pr'prio" Capa*%'a'" '# s%s$"&a %&+#=%*# '" !"*#+-"*"! &%$#s a+$"+#s "s$!a+-#s (+# p!=p!%#s), '" !"sp#+'"! a ""s " "%&%+/#s ", a# &"s&# $"&p#, '" +# !"a%! '" &#'# p!"'%*%a s sbs$:+*%as a+$%+%*as p!=p!%as '# %+'%'# A as+*%a 'a !"sp#s$a %&+#=%*a $a&b& '"+#&%+a'a $#"!:+*%a A $#"!:+*%a a+$"+#s p!=p!%#s (a$#$#"!:+*%a) #*#!!" p#! &"*a+%s&#s *#&# a %+a$%a# '#s %+.=*%$#s " "p!"ssa& !"*"p$#!"s "sp"*>*#s pa!a a+s a+$"+#s p!=p!%#s, "! s"a "%&%+a+'# #s %+.=*%$#s a$#!"a$%#s # sp!%&%+'# "ssas *as a$!as 'as a"s '" *as !"a'#!as O+," -oenças autoimunes" A #*#!!+*%a '" a+#!&a%'a'"s +a %+'# # +a &a+$"+# 'a a$#$#"!:+*%a "a a !"sp#s$a %&+#=%*a '%!%%'as *#+$!a a+$"+#s p!=p!%#s A "sp"*%>*%'a'" " &"&=!%a p"!&%$"& " # s%s$"&a %&+" '"s"+*a'"%" !"sp#s$as a*"+$a'as "p#s%# p"!s%s$"+$" # !"*#!!"+$" a# &"s&# a+$"+# ", ass%&, *#&ba$"! %+."*"s p!##+a'as # " #*#!!"& !"p"$%'a&"+$" A '%"!s%'a'" "ss"+*%a pa!a " # s%s$"&a %&+#=%*# p#ssa '"."+'"! # %+'%'# *#+$!a #s +&"!#s#s pa$="+#s p#$"+*%a%s " "%s$"& +# &"%# a&b%"+$" A "sp"*%a%;a# p"!&%$" " # -#sp"'"%!# '"s"+#a !"sp#s$as s#b &"'%'a pa!a &"-#! *#&ba$"! #s '%."!"+$"s $%p#s '" &%*!#!a+%s&#s A a$#$#"!:+*%a "ss"+*%a pa!a a p!""+# '" !"a"s p!"'%*%a%s *#+$!a *as " $"*%'#s p!=p!%#s, &a+$"+'# # a&p# !"p"!$=!%# '" %+.=*%$#s "sp"*>*#s pa!a a+$"+#s "s$!a+-#s
C#&p#+"+$"s C"a!"s '# S%s$"&a I&+#=%*# A'ap$a$%#
Lin'$itos" S# *as " !"*#+-"*"& " !"sp#+'"& "sp"*%>*a&"+$" a a+$"+#s "s$!a+-#s " " a$a&, p#!$a+$#, *#&# &"'%a'#!"s 'a %&+%'a'" -&#!a " *"a! *"a! S# *as #!%%+!%as '" *as $!#+*# +a &"'a =ss"a 3
Lin'$ito +" S# as B+%*as *as *apa;"s '" p!#';%! a+$%*#!p#s Eas !"*#+-"*"& a+$"+#s "$!a*"a!"s " '%."!"+*%a&/s" "& pas&=*%$#s s"*!"$#!"s '" a+$%*#!p#s, a$a+'#, ass%&, *#&# &"'%a'#!"s 'a %&+%'a'" -&#!a Lin'$ito T" S# *as 'a %&+%'a'" *"a! Eas !"*#+-"*"& #s a+$"+#s '" &%*!#!a+%s&#s %+$!a*"a!"s " a'a& #s .a=*%$#s a '"s$!/#s # &a$a& '%!"$a&"+$" as *as %+."*$a'as As *as +# p!#';"& a+$%*#!p#s S"s !"*"p$#!"s '" a+$"+# s# &#*as '" &"&b!a+a ('%s$%+$as '#s a+$%*#!p#s) Os %+.=*%$#s p#ss"& "sp"*%>*%'a'" !"s$!%$a pa!a #s a+$"+#s< ""s !"*#+-"*"& p"p$'"#s '"!%a'#s '" p!#$"+as "s$!a+-as " "s$"a& %a'as a MHCs, " s# "p!"ssas +a sp"!.*%" '" #$!as *as As *as !"*#+-"*"& " !"sp#+'"& a a+$"+#s ass#*%a'#s sp"!.*%" *"a!, &as +# a+$"+#s s#B"%s E%s$"& '%."!"+$"s $%p#s '" p#pa"s 'as *as C.!u!as T /e!p" E& !"sp#s$a "s$%&a# a+$%+%*a, s"*!"$a& *%$#*%+as " s# !"sp#+s"%s p#! !"sp#s$as *"a!"s 'a %&+%'a'" %+a$a " a'ap$a$%a, a$a+'# *#&# &#*as &"+sa"%!as Essas $ito$inas "s$%&a& a p!#%."!a# " a '%."!"+*%a# 'as p!=p!%as *as " a$%a& #$!as *as, %+*s%" as *as K, #s &a*!=.a#s " #$!#s "*=*%$#s E L%+.=*%$#s CD4 -"p As *as H"p, " "!a&"+$" s# CD4, "p!"ssa& &#*as '" sp"!.*%", *#&# %a+$" '" CD40 Lin'$itos T $itot'i$os (CTL)" D"s$!#"& as *as " "%b"& a+$"+#s "s$!a+-#s, *#&# as *as %+."*$a'as p#! !s " #$!#s &%*!#!a+%s&#s %+$!a*"a!"s E L%+.=*%$#s CD8 *%$#$=%*#s Os CL Lin'$itos T re0u!at'rios A$a& +a %+%b%# '" !"sp#s$as %&+#=%*as Lin'$itos T* Es$ "+#%'a +a %&+%'a'" +a$!a *#+$!a !s " #$!#s &%*!#!a+%s&#s %+$!a*"a!"s S# *apa;"s '" !"a%;a! sa .+# '" &#!$" s"& a +"*"ss%'a'" '" "pa+s# *#+a " '%."!"+*%a# Usa& !"*"p$#!"s *#'%>*a'#s p"# DNA pa!a '%."!"+*%a! *as %+."*$a'as p#! pa$="+#s '" *as sa'"%s S# '"sa$%a'as p#! MHCs '" *ass" I → L%+.=*%$# '" M"&=!%a O+," Os %+.=*%$#s " K %!"+s "+$!a& +#s =!#s %+.#%'"s p#! &a a!$!%a, " *-"a& a# "s$!#&a '# =!# a$!as 'a HE As *%$#*%+as " '"$"!&%+a& "& " #*a as *as K " !"s%'%!# +# =!# %+.#%'" s# '# $%p# %&%#*%+as (*%$#*%+as %&%#a$!a$%as), as a%s s" %a& a#s !"*"p$#!"s '" %&%#*%+as +#s %+.=*%$#s C.!u!as Apresentadoras de Ant20enos (APCs)" Cap$!a& a+$"+#s " #s ap!"s"+$a& a#s %+.=*%$#s "sp"*>*#s As *as '"+'!$%*as $"& &a%#! !a '" "sp"*%a%;a#, " s# "as " *ap$!a& &a%s a%&"+$" #s a+$"+#s &%*!#b%a+#s p!#"+%"+$"s '# a&b%"+$" "$"!+#, $!a+sp#!$a+'#/#s a$ #s =!#s %+.#%'"s " ap!"s"+$a+'#/#s a#s %+.=*%$#s %!"+s, " %+%*%a& as !"sp#s$as %&+#=%*as C.!u!as eetoras" A'a& +a "%&%+a# '# a+$"+# Eas &"'"%a& # "."%$# >+a 'a !"sp#s$a %&+#=%*a, " %!a!/s" '#s &%*!#!a+%s&#s S# ""&p#s #s %+.=*%$#s a$%a'#s, #s .a=*%$#s &#+#+*"a!"s " #$!#s "*=*%$#s Os %+.=*%$#s " as AFCs "s$# *#+*"+$!a'#s "& =!#s %+.#%'"s, #+'" %+$"!a"& "+$!" s% pa!a %+%*%a! as !"sp#s$as %&+#=%*as Os %+.=*%$#s $a&b& "s$# p!"s"+$"s +# sa+"< '# sa+" p#'"& !"*%!*a! a$!as '#s $"*%'#s %+.#%'"s " s"! %a'#s a$ #s #*a%s '" "p#s%# a+$%+%*a +#s $"*%'#s p"!%.!%*#s pa!a "%&%+a! # a+$"+# "sp"*>*#
•
Cap$!a " Ap!"s"+$a# '#s A+$"+#s As *as '"+'!$%*as #*a%;a'as +#s "p%$%#s " +#s $"*%'#s *#++$%#s *ap$!a& #s &%*!#!a+%s&#s, '%"!"& sas p!#$"+as "& p"p$'"#s " "p!"ssa&, "& sa sp"!.*%", 4
#s p"p$'"#s %a'#s a &#*a '" MHC, " a &#*a "sp"*%a%;a'a "& ap!"s"+$a# '" a+$"+# a#s %+.=*%$#s •
R"*#+-"*%&"+$# '#s A+$"+#s p"#s L%+.=*%$#s A a$%a# '#s %+.=*%$#s %!"+s "%" # !"*#+-"*%&"+$# '" *#&p"#s p"p$'"#/MHC ap!"s"+$a'#s p"as *as '"+'!$%*as Ess" *#&p"# a$%a as *as " ass"!a " "ss"s %+.=*%$#s p#ssa& %+$"!a%! ap"+as *#& #$!as &#*as Fa!a !"sp#+'"!, as *as p!"*%sa& !"*#+-"*"! $a&b& *#"s$%&a'#!"s, " s# %+';%'#s p"#s &%*!#!a+%s&#s a s"!"& "p!"ssas +as sp"!.*%"s 'as AFCs O !"*#+-"*%&"+$# '# a+$"+# .#!+"*" "sp"*%>*%'a'" !"sp#s$a %&+#=%*a, " a +"*"ss%'a'" '" *#"s$%&a# ass"!a " as *as !"sp#+'a& a &%*!#!a+%s&#s " +# a sbs$:+*%as %+#."+s%as
CAPÍTULO 3 (C.!u!as e Te$idos do ,istema Imune)
4a0'$itos Cas *a .+# p!%&!%a %'"+$%>*a!, %+"!%! " '%"!%! &%*!#!a+%s&#s As !"sp#s$as .+*%#+a%s '#s .a=*%$#s *#+s%s$"& "& !"*!$a&"+$# 'as *as pa!a #s s$%#s '" %+."*#, !"*#+-"*%&"+$# " a$%a# '#s .a=*%$#s p"#s &%*!#!a+%s&#s, %+"s$# p"# p!#*"ss# '" .a#*%$#s" " '"s$!%# '#s &%*!#!a+%s&#s Os .a=*%$#s $& .+"s "."$#!as +a %&+%'a'" %+a$a •
N"$!=>#s ("*=*%$#s p#%&#!.#+*"a!"s) → M"'"%a& as .as"s %+%*%a%s 'as !"a"s %+@a&a$=!%as → F#ss% *%$#pas&a *#& '#%s $%p#s '" !:+#s, & p!""+*-%'# p#! "+;%&as, $a%s *#&# %s#;%&a, *#a"+as" " "as$as" " #$!#, s# %s#ss#&#s " *#+$& "+;%&as " #$!as sbs$:+*%as &%*!#b%a+as, %+*s%" '"."+s%+as " *a$"%*%'%+as → S# p!#';%'#s +a &"'a =ss"a → M%!a& pa!a #s s$%#s '" %+."*# "& p#*as -#!as → S# a$!a'#s p#! IL/8 " C5a(p!#$"+a '# *#&p"&"$#) → a; "p#s# !"sp%!a$=!%a (ROS) " &%"#p"!#%'as"
OKS D"s%# "s"!'a Ma%#! a+$%'a'" '" bas$#+"$"s "P# *as &a%s #"+s 'a s!%" !a+#*$%*a p#s%*%#+a'#s "s"!'a G%*#*#!$%*=%'"s p#'"& *asa! '"s%#s "s"!'a A& '" %+.""s ba*$"!%a+as (*a!a*$"!%;a'a p"a !a+'" a+$%'a'" '" +"$!=>#s) •
M#+=*%$#s (a=*%$# M#+#+*"a!) F#ss% *%$#pas&a !a+a! *#+$"+'# %s#ss#&#s, a*B##s .a#*$%*#s " >a&"+$#s '" *%$#"s""$# C#+s%s$"& "& p"# &"+#s '#%s sb$%p#s '" p#pa"s %+@a&a$=!%a, p#!" !ap%'a&"+$" !"*!$a'a '# sa+" pa!a #s s$%#s '" %+@a&a# $"*%'a, .#+$" '" &a*!=.a#s !"s%'"+$"s '# $"*%'# " a&as *as '"+'!$%*as U&a "; " "+$!a& +#s $"*%'#s, #s &#+=*%$#s a&a'!"*"& " $#!+a&/s" &a*!=.a#s &a$r'a0os " sas .+"s "& a&bas %&+%'a'"s I+"s$# '# &%*!#!a+%s&# *asa+'# sa &#!$" I+"s$# '" *as &#!$as '# -#sp"'"%!# *#&# pa!$" '# p!#*"ss# '" %&p";a ap=s !"s## 'a "s# $"*%'a Ma*!=.a#s a$%a'#s s"*!"$a& p!#$"+as '"+#&%+a'as *%$#*%+as, " s" %a& a#s !"*"p$#!"s p!"s"+$"s "& #$!as *as %+s$!'as a !"sp#+'"!"& '" &a+"%!a "."$%a pa!a '"."sa '# -#sp"'"%!#, a&p%>*a+'# a !"sp#s$a p!#$"$#!a *#+$!a &%*!#!a+%s&#s A$a& *#&# AFCs " ap!"s"+$a& a+$"+#s " a$%a& %+.=*%$#s F!#&#"& # !"pa!# '" $"*%'#s "s%#+a'#s p"# "s$&# a# *!"s*%&"+$# '" +##s as#s sa++"#s " p"a s+$"s" '" &a$!%; "$!a*"a! !%*a "& *#"+# 5
→
Fa!a #s &a*!=.a#s s"!"& a$%a'#s, p!"*%sa& !"*#+-"*"! '%."!"+$"s &#*as &%*!#b%a+as, +as a%s %a&/s" a#s !"*"p$#!"s "sp"*>*#s #*a%;a'#s +a sp"!.*%" # %+$"!%#! '# &a*!=.a# (E R"*"p$#!"s s"&"-a+$"s a #) A& 'a a$%a# p"a %a# '" !"*"p$#!"s '" &"&b!a+a pas&$%*a " #ps#+%+as (sbs$:+*%as " !""s$"& *as pa!a a .a#*%$#s") +a sp"!.*%" '# #!a+%s&# (E R"*"p$#!"s pa!a *#&p#+"+$"s '# s%s$"&a *#&p"&"+$# " !"*"p$#!"s pa!a C '" a+$%*#!p#s) Na %&+%'a'" a'ap$a$%a, #s &a*!=.a#s s# a$%a'#s p#! *%$#*%+as s"*!"$a'as " p!#$"+as '" &"&b!a+a '" %+.=*%$#s
Mas$=*%$#s, Kas=>#s " E#s%+=>#s → #'#s p#ss"& !:+#s *%$#pas&$%*#s p!""+*-%'#s p#! !%#s &"'%a'#!"s %+@a&a$=!%#s " a+$%&%*!#b%a+# → S# "+#%'#s +a !"sp#s$a %&+" *#+$!a -"&%+$#s " +as " *asa& '#"+as a!%*as Mas$=*%$#sPKas=>#s • F#ss% !:+#s *%$#pas&$%*#s p!""+*-%'#s p#! !%#s &"'%a'#!"s %+@a&a$=!%#s " a+$%&%*!#b%a+# Os *#+$"B'#s %b"!a'#s '#s !:+#s %+*"& *%$#*%+as " -%s$a&%+as Ep!"ssa& !"*"p$#!"s '" &"&b!a+a pa!a a p#!# C '" a+$%*#!p#s IE " IG, " #$!#s !"*"p$#!"s " !"*#+-"*"& p!#$"+as '# *#&p"&"+$# S# %&p#!$a+$"s +a '"."sa *#+$!a -"&%+$#s •
•
E#s%+=>#s → Ep!"ssa& !:+#s *%$#pas&$%*#s *#+$"+'# "+;%&as 'a+#sas s pa!"'"s *"a!"s '" pa!as%$as, p#!&, p#'" "s%#+a! $"*%'#s '# -#sp"'"%!#
C.!u!as Apresentadoras de Ant20enos Cas D"+'!$%*as (%&+%'a'" a'ap$a$%a) • → S# as AFCs &a%s %&p#!$a+$"s pa!a a$%a# '" *as %!"+s → F#ss"& #+as p!#""s &"&b!a+#sas " *apa*%'a'" .a#*$%*a → S# a&pa&"+$" '%s$!%b'as +#s $"*%'#s %+.#%'"s, +# "p%$%# 'as &*#sas " +# pa!+%&a '#s =!#s → E& !"sp#s$a a$%a# %+';%'a p#! &%*!#!a+%s&#s, "as $#!+a&/s" &="%s " &%!a& pa!a #s =!#s %+.#%'"s " ap!"s"+$a& a+$"+#s &%*!#b%a+#s a#s %+.=*%$#s Ma*!=.a#s • → S# &"'%a'as p#! *as -"p CD4 → Ap!"s"+$a& a+$"+#s pa!a #s %+.=*%$#s -"p +#s s$%#s '" %+."*# Lin'$itos + → Ap!"s"+$a& a+$"+#s pa!a as *as -"p +#s =!#s %+.$%*#s " +# ba# → OKS Cas D"+'!$%*as #%*a!"s S# *as *#& p!#""s &"&b!a+#sas "& !"as "+!%"*%'as *#& *as K a$%a'as, *-a&a'as *"+$!# "!&%+a$%#s N# s# '"!%a'as 'a &"'a =ss"a " +# ap!"s"+$a& a+$"+#s a#s %+.=*%$#s *#&# as *as '"+'!$%*as *#&+s Cap$!a& a+$"+#s *#&p"a'#s *#& a+$%*#!p#s # p!#'$#s '# *#&p"&"+$# " ap!"s"+$a& "ss"s a+$"+#s "& sas sp"!.*%"s pa!a !"*#+-"*%&"+$# p"#s %+.=*%$#s K C.!u!as C.!u!as T 5e!p C.!u!as T Citot'i$as C.!u!as + de mem'ria C.!u!as T ir0ens
Prote2nas de ,uper2$ies #pressa C-6 C-7 C-38 C-69 6
O+," M#*as '" sp"!.*%" *"a! b"&/'">+%'as "s$!$!a&"+$" $%%;a/s" &a '"s%+a# CD +&!%*a Fa!a "! &a%s &a!*a'#!"s "! ap+'%*" III +aço F!%+*%pa%s .+"s !"$%!a! 'a *%!*a# *as sa++"as "s%#+a'as, a& '" %+%*%a! as !"sp#s$as %&+#=%*as a'ap$a$%as a#s a+$"+#s *ap$!a'#s '# sa+" O pa!+%&a "sp+%*# '%%'%'# "& p#pa "!&"-a (*%!*+'a'#s p#! &a*!=.a#s " p!""+*-%'#s p#! "!%$!=*%$#s) " p#pa b!a+*a (!%*a "& %+.=*%$#s) A .+# 'a p#pa b!a+*a p!#&#"! as !"sp#s$as %&+"s a'ap$a$%as *#+$!a a+$"+#s p!#"+%"+$"s '# sa+" &e$anismos &i$ro:i$idas de 4a0o$itose (*o ;a$es de Leu$'$itos $om as C.!u!as #ndote!iais e #traasamento dos Leu$'$itos Re$rutamento de Leu$'$itos O !"*!$a&"+$# '" "*=*%$#s, %+*s%" '" "*=*%$#s %!"+s " "+$!a& +#s =!#s %+.#%'"s p#! HE, %+.=*%$#s "."$#!"s, &#+=*%$#s " +"$!=>#s pa!a #s s$%#s '" %+@a&a# !"a'# p#! %&%#*%+as Essas, %a&/s" a# s.a$# '" -"pa!%+a '#s p!#$"#%*a+#s s#b!" as *as "+'#$"%a%s " !""s$"& as +as p=s *ap%a!"s " s# ap!"s"+$a'as, '"ssa &a+"%!a a#s "*=*%$#s *%!*a+$"s " s" %a& s sp"!.*%"s "+'#$"%a%s a$!as '" %+$"!a"s *#& &#*as '" a'"s# A '"p#s%# '" %&%#*%+as p!#p#!*%#+a &a a$a *#+*"+$!a# '"ss"s %&%#a$!a"+$"s +#s "*=*%$#s Os s%+a%s '"@a!a'#s '#s !"*"p$#!"s '" %&%#*%+as "a& a & a&"+$# 'a a>+%'a'" 'as %+$"!%+as, !"s$a+'# "& a'"s# >!&" '# "*=*%$# ("$apa *!*%a pa!a &%!a# '#s "*=*%$#s '#s as#s sa++"#s pa!a '"+$!# '# $"*%'# "$!aas*a!) Ro!amento dos Leu$'$itos E& !"sp#s$a a#s &%*!#!a+%s&#s " s *%$#*%+as p!#';%'as p#! *as " "+$!a& "& *#+$a$# *#& a"+$"s %+."**%#s#s, as *as "+'#$"%a%s a&"+$a& !ap%'a&"+$" a "p!"ss# '" s""*$%+as "& sa sp"!.*%" Os "*=*%$#s *%!*a& p!=%&# '#s #*a%s '" !"sp#s$a %&+" %+a$a, "& *#+s"+*%a 'a as#'%a$a# " "+$%>*a# '# @# sa++"# Os %a+$"s '" s""*$%+a '"ss"s "*=*%$#s %a&/s" s s""*$%+as +a sp"!.*%" 'as *as "+'#$"%a%s C#&# a %+$"!a# "+$!" a s""*$%+a "# %a+$" '" s""*$%+a ba%a, *#& !p%'a $aa '" '"s%a&"+$#, "as s# .a*%&"+$" !#&p%'as E& *#+s"+*%a, #s "*=*%$#s '"sp!"+'"&/s" !"p"$%'a&"+$" " %a&/s" +#a&"+$" ", '"ssa &a+"%!a !#a& a# #+# 'a sp"!.*%" "+'#$"%a Adesão #st?e! dos Leu$'$itos ao #ndot.!io C#& a p!#'# '" %&%#*%+as +# #*a '" %+."*#, "& !"sp#s$a a &a a!%"'a'" '" pa$="+#s # "s$&#s "+'="+#s, "as s"!# s"*!"$a'as " $!a+sp#!$a'as a$ a sp"!.*%" &%+a 'as *as "+'#$"%a%s, #+'" s" %a& a#s s.a$#s '" -"pa!%+a '#s %*#sa&%+#%*a+#s " s# "p!"ss#s "& a$as *#+*"+$!a"s N"ss" #*a, as %&%#*%+as %!# s" %a! a#s !"*"p$#!"s "sp"*>*#s '" %&%#*%+as '#s "*=*%$#s "& !#a&"+$# As %+$"!%+as "*#*%$!%as "+*#+$!a&/s" "& ba%a a>+%'a'" a$ # &#&"+$# 7
"& " +# -a%a a s"*!"# '" %&%#*%+as Ap=s a s%+a%;a# '# !"*"p$#! '" %&%#*%+as, a&"+$a a a>+%'a'" 'as %+$"!%+as "*#*%$!%as *#& s"s %a+$"s E, s%&$a+"a&"+$" -a"! a&"+$# 'a "p!"ss# "+'#$"%a '"ss"s %a+$"s '" %+$"!%+a O$!a *#+s"+*%a '"ssa s%+a%;a# # a!pa&"+$# '"ssas %+$"!%+as +a &"&b!a+a, !"s$a+'# "& &a%#! %+$"!a# +a %a# "+$!" as %+$"!%+as "*#*%$!%as " s"s %a+$"s +a sp"!.*%" "+'#$"%a O !"s$a'# >+a '"ssas a$"!a"s *#+s%s$" +a >a# >!&" '#s "*=*%$#s a# "+'#$%# (E$!aasa&"+$# '#s L"*=*%$#s)
CAPÍTULO 6 (Imunidade Inata)
I&+%'a'" I+a$a (Q D"$a-a'a)
A imunidade Inata desempen5a = importantes unç>es" a p!%&"%!a !"sp#s$a a#s &%*!#!a+%s&#s " p!"%+", *#+$!#a # "%&%+a a %+."*# • '# -#sp"'"%!# p#! &%$#s pa$="+#s Os &"*a+%s&#s 'a %&+%'a'" %+a$a !"*#+-"*"& #s p!#'$#s '" *as 'a+%>*a'as " • &#!$as '# -#sp"'"%!# " s"!"& pa!a "%&%+a! $a%s *as, %+%*%a+'# # p!#*"ss# '" !"pa!# $"*%'a A %&+%'a'" %+a$a "s$%&a a %&+%'a'" a'ap$a$%a, %+$"+s%>*a+'# as !"sp#s$as • "sp"*>*as '"ssa %&+%'a'" " $#!+a+'#/as &a%s ">*a;"s *#+$!a '%."!"+$"s $%p#s '" pa$="+#s Re$on5e$imento de &i$ror0anismos ;ia Padr>es &o!e$u!ares de Pat'0enos (PA&P) e Asso$iados a -anos (-A&P) Os !"*"p$#!"s 'a %&+%'a'" %+a$a !"*#+-"*"& #s FAMFs, " s# sbs$:+*%as • &#"*a!"s "p!"ssas p#! '%."!"+$"s *ass"s '" &%*!#!a+%s&#s " DAMFs, " s# &#*as "+'="+as p!#';%'as p#! *as 'a+%>*a'as # &#!$as *#&# !"s$a'# '" 'a+#s *"a!"s p!##*a'#s p#! %+."*"s S# ""&p#s '" FAMFs *%'#s +*"%*#s, p!#$"+as, %p'"#s " *a!b#%'!a$#s *#&p"#s • (LFS 'as !a&/ " * L%p#$"%*#%*# '" !a&Q) p"!$"+*"+$"s a#s &%*!#!a+%s&#s Os !"*"p$#!"s ass#*%a'#s s *as '# s%s$"&a %&+" %+a$# s# "p!"ss#s, • p!%+*%pa&"+$", p#! .a=*%$#s, *as '"+'!$%*as " *as "p%$"%a%s S# '"+#&%+a'#s '" R"*"p$#!"s '" !"*#+-"*%&"+$# '" pa'!"s " s# "p!"ss#s "& '%"!sas #*a%;a"s (+a sp"!.*%" *"a! # +a &"&b!a+a %+$!a*"a!) p"!&%$%+'# " -aa !"sp#s$a a &/ #s p!"s"+$"s .#!a # '"+$!# 'as *as a+'# - a %a# '"ss"s !"*"p$#!"s *#& #s FAMFs # DAMFs, p!##*a a a$%a# 'a • $!a+s'# '" s%+a p!#&#"+'# a !"sp#s$a 'a %&+%'a'" %+a$a OKS Os !"*"p$#!"s '# s%s$"&a %&+" %+a$# s# *#'%>*a'#s p#! "+"s "& sa s"+*%a "!&%+a$%a, "+a+$# #s !"*"p$#!"s 'a %&+%'a'" a'ap$a$%a s# "!a'#s p#! !"a!!a+# '#s "+"s F#! %ss# # !"p"!$=!%# '" "sp"*%>*%'a'"s 'a %&+%'a'" %+a$a &"+#! '# " 'a a'ap$a$%a
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Re$eptores ,eme!5antes a To!! (TLR) F!#'$#s ba*$"!%a+#s " s" %a& a# !"*"p$#! LR s# #s LFS, # * L%p#$"%*#%*# " as • @a"%+as F!#'$#s %!a%s " s" %a& a "ss" !"*"p$#! s# RNA '" >$a 'pa " RNA '" >$a s%&p"s F!#'$#s *#&# p#%ssa*a!'"#s (.B+%*#s) $a&b& s" %a& a "ss" !"*"p$#!
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Os LRs s# "+*#+$!a'#s +a sp"!.*%" *"a! " "& &"&b!a+as %+$!a*"a!"s, ", ass%&, s# *apa;"s '" !"*#+-"*"! &/#s "& '%."!"+$"s #*a%;a"s *"a!"s → LR 1, 2, 4, 5 " 6 / S# "p!"ss#s +a &"&b!a+a pas&$%*a, #+'" !"*#+-"*"& '%"!s#s FAMFs +# a&b%"+$" "$!a*"a! → LR 2 " 4 / !"*#+-"*"& LFS " * L%p#$"%*#%*#, !"sp"*$%a&"+$" → LR 3, 7, 8 " 9 / s# "p!"ss#s +# %+$"!%#! 'as *as, +# RE " +as &"&b!a+as "+'#ss&%*as, #+'" '"$"*$a& '%"!s#s %a+$"s '" * N*"%*#s
Re$eptores Citos'!i$os de PA&P e -A&P S# ass#*%a'#s a %as '" $!a+s'# '" s%+a " p!#&#"& a %+@a&a# # a p!#'# '" I+$"!."!#& '# $%p# 1 Re$eptores seme!5antes a *O- (*LR) F"!*"b"& FAMFs # DAMFs *%$#pas&$%*#s " !"*!$a& #$!as p!#$"+as " '"@a!a& a %+@a&a# E%s$"& 3 sb.a&%as '" NLR, *#s &"&b!# sa& '%."!"+$"s '#&+%#s "."$#!"s pa!a • %+%*%a! a s%+a%;a# *O- 1 e *O- 3" C#+$& '#&+%#s CARD " !"sp#+'"& a p"p$%'"#%*a+as 'a pa!"'" *"a! ba*$"!%a+a S# %&p#!$a+$"s pa!a !"sp#s$as 'a %&+%'a'" %+a$a a pa$="+#s ba*$"!%a+#s '# $!a$# as$!#%+$"s$%+a *LRP" C#+$& '#&+%# '" p%!%+a " !"sp#+'" a FAMFs " DAMFs *%$#pas&$%*#s a$!as 'a .#!&a# '" *#&p"#s '" s%+a%;a# *-a&a'#s %+@a&#ss#&#s, " "!a& .#!&as a$%as '" *%$#*%+a %+@a&a$=!%a IL/1 O+," Infamossomos •
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a+'# #s NLRFs s# a$%a'#s p"#s FAMFs " DAMFs, ""s s" %a& a #$!as p!#$"+as p#! %+$"!a"s -#&#$p%*as "+$!" '#&+%#s "s$!$!a%s *#&pa!$%-a'#s, .#!&a+'# "ss" *#&p"# '" s%+a%;a# (%+@a&#ss#&#) a+'# - !"*!$a&"+$# '# *#&p"# NLRF T ASC (p!#$"+a a'ap$a'#!a), a "+;%&a *aspas" I, " &a p!#$"as" *#& !"s'#s '" *%s$"+a, $#!+a/s" a$%a " p!#&#" a *%a"& '" IL/1 (!"*!$a +"$!=.%#s) " IL/18, "!a+'# .#!&as a$%as '"s$as *%$#*%+as A a$%a# '# %+@a&#ss#&# s# %+';%'as p#! FAMFs, *!%s$a%s a&b%"+$a%s (a&%a+$# # s%*a) # "+'="+#s ('"!%a'#s '" *as &#!$as *#&# !a$# &#+#ss='%*#VGOA " p%!#.#s.a$# '"s%'!a$a'# '" **%#), !"'# 'as *#+*"+$!a"s *%$#pas&$%*as '" ? Q (%+';%'a p#! a&a $#%+a ba*$"!%a+a .#!&a'#!a '" p#!#s) " "!a# '" "sp*%"s !"a$%as '" #%+%# A& '" *a$"ps%+a K, *!%s$a%s '" *#"s$"!#, *%'# B!%*#, "$* a+'# a a$%%'a'" '# %+@a&#ss#&# a+#!&a&"+$" "s$%&a'a, - a p!#'# ""a'a '" IL/1 " p#'" p!##*a! 'a+#s $"*%'a%s A+a%+ (%+"!$%a) +"$!a%;a IL/1 E%s$" !"*"p$#!"s s#B"%s pa!a "ssa sbs$:+*%a Fa!$%*%pa 'a !"sp#s$a &%*!#!a+%s&#s " a !"sp#s$a a %+@a&a# "s$!"# EW A$"!#s*"!#s", A;a%&"!, D%ab"$", G#$a, S%%*#s", D#"+as '# a&%a+$#, "$*
Re$eptores de Le$tinas de tipo C R"*#+-"*"& *a!b#%'!a$#s '"p"+'"+$"s '" Ca2Q +a sp"!.*%" '#s &/#s, .a*%%$a& a • .a#*%$#s" '"ss"s pa$="+#s " "s$%&a& # '"s"+#%&"+$# '" !"sp#s$as %&+#=%*as a'ap$a$%as sbs""+$"s E%s$"& $a&b& #s !"*"p$#!"s " !"*#+-"*"& &a+#s", %*#s", N/a*"$%%*#sa&%+a " • / *a+as Re$eptores ,$aen0er (C-=@) R"a*%#+a'#s *ap$a# '" %p#p!#$"+as #%'a'as pa!a '"+$!# 'as *as • S# pa'!"s '" "+"-"*%&"+$# • S# "p!"ss#s p#! &a*!=.a#s " &"'"%a& a .a#*%$#s" '" &/#s • 10
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L#*a%;a&/s" +a &"&b!a+a '#s .a=*%$#s
Re$eptores *4&LP a&%a '" !"*"p$#!"s '" %&%#*%+as • +# %&%#$a%a '#s .a=*%$#s pa!a a '%!"# '#s &/#s a#s • S# a*#pa'#s p!#$"+a G • C.!u!as -endr2ti$as Fap" "."$#! +a %&+%'a'" %+a$a S# &a%s ">*%"+$"s s"+s#!"s '" FAMFs " DAMFs p#%s "p!"ssa& &a%s $%p#s '%."!"+$"s '" LR " !"*"p$#!"s *%$#pas&$%*#s '" pa'!"s Cas '"+'!$%*as pas&#*%$#%'"s &a%#! .#+$" '" *%$#*%+as a+$%%!a%s, #s I+$"!."!#+s '# $%p# I, s%+$"$%;a'# "& !"sp#s$a s %+."*"s %!a%s Essas *as "p!"ssa& LR "+'#ss&%*#s " !"*#+-"*"& * N*"%*#s '#s !s " .#!a& %+$"!+a%;a'#s p"a *a A !"sp#s$a %+a$a &"'%a'a p"as *as '"+'!$%*as a#s FAMFs "ss"+*%a pa!a a&"+$a! a s%+a%;a# p#! LR, " %+'; as *as '"+'!$%*as a "p!"ssa! &#*as, %+*%+'# &#*as *#"s$%&a'#!"s " *%$#*%+as &o!.$u!as ,o!<eis de Re$on5e$imento e &o!.$u!as #etoras da Imunidade Inata F#! s" %a!"& a#s &/#s, a$a& *#&# #ps#+%+as " a&"+$a& a *apa*%'a'" '" • .a#*%$#s" p"#s &a*!=.a#s, +"$!=>#s " *as '"+'!$%*as C#&p#+"+$"s A+$%*#!p#s Na$!a%s, S%s$"&a C#&p"&"+$#, F"+$!a%+as, C#"*$%+as " • %*#%+as ,istema Comp!emento A"s Ops#+%;a# '" &/#s, "s$%&a# 'a %+@a&a# (XD"."sa " X!"*!$a&"+$#) " • %s" p#! MAC A a$%a# #*#!!" p#! 'as &a+"%!as '%s$%+$as • → %a Css%*a Usa &a p!#$"+a pas&$%*a '"+#&%+a'a C1 pa!a '"$"*$a! a+$%*#!p#s %a'#s sp"!.*%" '" & &%*!#!a+%s&# Ap=s a %a# C1 p#!# C '#s a+$%*#!p#s, 'as s"!%+as p!#$"as"s ass#*%a'as s# a$%a'as, C1! " C1s, %+%*%a+'# &a *as*a$a p!#$"#$%*a 'as '"&a%s p!#$"+as '# s%s$"&a *#&p"&"+$# IM s# &%$# ">*%"+$"s +a %a# C1 F"+$!a%+as $a&b& p#'"& s" %a! a C1 " %+%*%a! a %a *ss%*a #!&a C3 *#+"!$as" →
%a A$"!+a$%a '"s"+*a'"a'a a+'# &a p!#$"+a '# s%s$"&a *#&p"&"+$# *-a&a'a C3 !"*#+-"*", '%!"$a&"+$", *"!$as "s$!$!as *#&# LFS ba*$"!%a+# C3b s" -%'!#%sa "sp#+$a+"a&"+$" " +$a&"+$" *#& # .a$#! Kb .#!&a a C3 *#+"!$as"
OKS O !"*#+-"*%&"+$# '" &/#s p#! a"! &a 'as %as '# s%s$"&a *#&p"&"+$# !"s$a +# !"*!$a&"+$# s""+*%a " +a &#+$a"& '" #$!as p!#$"+as '"s$" s%s$"&a "& *#&p"#s '" p!#$"as"s •
C#&p"# '" A$a" M"&b!a+a (MAC) → U& *#&p"# '" p!#$"as" *-a&a'# C3 *#+"!$as" *%a C3 p!#';%+'# C3a " C3b O .!a&"+$# &a%#! C3b, " &a #ps#+%+a " p!#&#" a .a#*%$#s" '" &/#s,s" %a a #$!as p!#$"+as '# s%s$"&a *#&p"&"+$#, .#!&a+'# &a p!#$"as" *-a&a'a C5 11
*#+"!$as", " *%a "& C5 "!a+'# C5a " C5b O C5b %+%*%a a .#!&a# '" & *#&p"# p!#$"%*# '# s%s$"&a *#&p"&"+$# .#!&a'# '" C6, C7, C8, ass#*%a'#s !%#s C9, # MAC O MAC p!##*a a %s" 'as *as "& " # *#&p"&"+$# a$%a'#
F"+$!a%+as R"*#+-"*" FAMFs *#&# • M#*as " &#+$a& +as p"+$!a%+as C#"*$%+as, >*#b%%+as " C#&p"&"+$#(%a& a# • .a$#! C1) Ap=s a &#+$a"&, - &a *as*a$a '" s%+a%;a# pa!a #ps%#+%;a! a "%&%+a# '# pa$="+# &a p!#$"+a " s"!" *#&# s"+s#! '" &a .+*%#+a&"+$# $"*%'a C#"*$%+as " %*#%+as Ops%#+%;a& pa!a .a#*%$#s", a$%a& a %a *ss%*a '# *#&p"&"+$# •
CAPÍTULO 9 (Anti$orpos e Ant20enos) •
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Anti$orpos e Ant20enos Ant20eno" U&a &#*a " s" %a a & a+$%*#!p# # a & CR Os a+$"+#s " s" %a& a#s a+$%*#!p#s %+*"& $#'as as *ass"s '" &#*as A &a%#!%a '#s CRs %a/s" s#&"+$" a .!a&"+$#s '" p"p$'"#s '" p!#$"+as *#&p"a'#s *#& &#*as '" MHC< a&b#s %a+$"s '" p"p$'"# " p!#$"+a +a$%a '#s a%s s# '"!%a'#s s# *-a&a'#s '" a+$"+#s '" *a Anti$orpos" S# p!#$"+as *%!*a+$"s p!#';%'as +#s "!$"b!a'#s "& !"sp#s$a "p#s%# a "s$!$!as "s$!a+-as *#+-"*%'as *#&# a+$"+#s Anti$orpos mono$!onais" A+$%*#!p# " "sp"*>*# pa!a & a+$"+# " p!#';%'# p#! & -%b!%'#&a '" *a K (&a %+-a"& *"a! '"!%a'a 'a .s# '" &a *a K B+%*a +#!&a " &a %+-a"& $&#!a '" *a K %&#!$a) Os a+$%*#!p#s &#+#*#+a%s s# a&pa&"+$" sa'#s "& p"s%sa, '%a+=s$%*# *+%*# " $"!ap%a Anti$orpos po!i$!onais" s# a+$%*#!p#s p!#';%'#s p#! &%$#s *#+"s '" %+.=*%$#s K " p#'"&, *a'a &, s" %a! a '%."!"+$"s p#!"s ("p$#p#s) '" & a+$"+# Imunidade /umora!" $%p# '" !"sp#s$a %&+" a'ap$a$%a &"'%a'a p#! a+$%*#!p#s p!#';%'#s p"#s %+.=*%$#s K # p!%+*%pa &"*a+%s&# '" '"."sa *#+$!a &%*!#!a+%s&#s "$!a*"a!"s " sas $#%+as
A+$%*#!p#s, MHCs " !"*"p$#!"s '" a+$"+# '" *a s# as $!s *ass"s '" &#*as sa'as p"# S%s$"&a I&+" A'ap$a$%# pa!a s" %a! a#s a+$"+#s D"ss"s $!s #s a+$%*#!p#s s" %a& a a+$"+#s *#& &a%#! .#!a A %a# A+$%*#!p#/A+$"+# +# *#a"+$" " !""!s", s" ' a$!as 'as .#!as %+$"!&#"*a!"s *#+-"*%'as *#&# %a"s '" -%'!#+%#, %a"s '" a+ D"! Yaas " $a&b& a$!as '" %a"s %+%*as Cara$ter2sti$as da !i0ação do Ant20eno pe!as &o!.$u!as do ,istema Imune Bue Re$on5e$em o Ant20eno I&+##b%+a (I)
L#*a %a# a+$"+#
R"*"p$#! '" *a (CR) '" C#&p#s$# '" a$ $!s C#&p#s$# '" a$ $!s '# CDRs +#s '#&+%#s H CDRs +#s '#&+%#s Z " $!s CDRs +#s " $!s '#&+%#s '#&+%#s L
Na$!";a '# Ma*!#&#*as C#&p"#s a+$"+# " (p!#$"+as, %p'"#s, MHC p#'" s"! p#%ssa*a!'"#s) " %a'# p""+#s !"a"+$"s
M#*as '" MHC
"+'a '" %a# '# p"p$'"# *#&p#s$a p#! '#&+%#s Z1 E Z2 (MHC '" *ass" I) " '#&+%#s Z 1 " 1 (MHC '" *ass" II) p"p$'"#/ F"p$'"#s
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&%*#s Na$!";a '#s D"$"!&%+a+$"s '"$"!&%+a+$"s %+"a!"s " a+$%+%*#s *#+.#!&a*%#+a%s '" !"*#+-"*%'#s !%as &a*!#&#*as " p!#'$#s &%*#s
D"$"!&%+a+$"s %+"a!"s '#s p"p$'"#s< s#&"+$" 3 # 2 !"s'#s '" a&%+#*%'#s '" & p"p$'"# %a'# a &a &#*a '" MHC
D"$"!&%+a+$"s %+"a!"s '#s p"p$'"#s, s#&"+$" a+s !"s'#s '" a&%+#*%'#s '" & p"p$'"#
Os a+$%*#!p#s s# s%+$"$%;a'#s s#&"+$" p"as *as 'a %+-a"& '" %+.=*%$# K " "%s$"& "& 'as .#!&as a+$%*#!p#s %a'#s &"&b!a+a +a sp"!.*%" '#s %+.=*%$#s K .+*%#+a& *#&# !"*"p$#!"s '" a+$"+#s " a+$%*#!p#s s"*!"$a'#s +"$!a%;a& as $#%+as, p!"%+"& a "+$!a'a " "spa-a&"+$# '#s pa$="+#s " "%&%+a& #s &%*!#!a+%s&#s O !"*#+-"*%&"+$# '# a+$"+# p"#s a+$%*#!p#s %a'#s &"&b!a+a +as *as K %&a$!as a$%a "ss"s %+.=*%$#s a %+%*%a!"& &a !"sp#s$a %&+" -&#!a As *as K a$%a'as s" '%."!"+*%a& "& pas&=*%$#s " s"*!"$a& a+$%*#!p#s 'a &"s&a "sp"*%>*%'a'" '# !"*"p$#! '# a+$"+# As .#!&as s"*!"$a'as '# a+$%*#!p# "s$# p!"s"+$"s +# pas&a sa++"#, +as s"*!""s &*#sas " +# @%'# %+$"!s$%*%a '#s $"*%'#s Na .as" "."$#!a 'a %&+%'a'" -&#!a, "ss"s a+$%*#!p#s s"*!"$a'#s s" %a& a#s a+$"+#s " '%spa!a& !%#s &"*a+%s&#s "."$#!"s " "%&%+a& #s a+$"+#s A "%&%+a# '# a+$"+# .!""+$"&"+$" +"*"ss%$a 'a %+$"!a# '# a+$%*#!p# *#& #$!#s *#&p#+"+$"s '# s%s$"&a %&+", %+*%+'# &#*as $a%s *#&# p!#$"+as '# *#&p"&"+$# " &#*as " %+*"& .a=*%$#s " "#s%+=>#s As .+"s "."$#!as &"'%a'as p#! a+$%*#!p# %+*"& • • • •
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N"$!a%;a# '#s &%*!#!a+%s&#s # p!#'$#s &%*!#b%a+#s $=%*#s< A$%a# '# s%s$"&a *#&p"&"+$#< Ops#+%;a# '#s pa$="+#s pa!a .a#*%$#s" a&"+$a'a< C%$#$#%'a'" &"'%a'a p#! *a " '"p"+'"+$" '" a+$%*#!p# (p"a a #s a+$%*#!p#s $& *#&# a# *as %+."*$a'as pa!a a %s" p"as *as '# s%s$"&a %&+" %+a$#) A$%a# '" &as$=*%$# &"'%a'a p#! a+$%*#!p# pa!a "p"%! "!&"s pa!as%$as
Cara$ter2sti$as 0erais da #strutura do Anti$orpo O$!# +#&" *#&& pa!a a+$%*#!p# %&+##b%+a ( a s"+'a %&+##b%+a &a%s ab+'a+$" +# s#!#) #'as as &#*as '" a+$%*#!p# *#&pa!$%-a& as &"s&as *a!a*$"!s$%*as "s$!$!a%s bs%*as, &as ap!"s"+$a& &a!*a+$" a!%ab%%'a'" +as !"%"s #+'" #s a+$"+#s s" %a& Essa a!%ab%%'a'" 'as !"%"s '" %a# '# a+$"+# !"sp#+s" p"a *apa*%'a'" '" '%."!"+$"s a+$%*#!p#s s" %a!"& a & !a+'" +B&"!# '" a+$"+#s "s$!$!a&"+$" '%"!s#s Ca'a *#+" '" *a K p!#'; &#*as '" a+$%*#!p# *#& #s &"s&#s #*a%s '" %a# '# a+$"+# " '%."!"+$"s +"s$"s #*a%s '#s a+$%*#!p#s p!#';%'#s p#! #$!#s *#+"s U&a &#*a '" a+$%*#!p# $"& &a "s$!$!a s%&$!%*a '# +B*"# *#&p#s$a '" 'as *a'"%as ""s %'+$%*as " 'as *a'"%as p"sa'as %'+$%*as A&bas as *a'"%as "" " p"sa'a *#+$& &a s!%" '" +%'a'"s -#&=#as !"p"$%'as, *a'a &a *#& *"!*a '" 110 !"s'#s '" a&%+#*%'#s '" *#&p!%&"+$#, " s" '#b!a& %+'"p"+'"+$"&"+$" '" & &#$%# #ba! " *-a&a'# '" dom2nio I0 U& '#&+%# I *#+$& 'as *a&a'as '" .#-as /p!""a'a, *a'a *a&a'a *#&p#s$a '" $!s a *%+*# >$as '" *a'"%a p#%p"p$'%*a a+$%pa!a"a As 'as *a&a'as s# &a+$%'as +%'as p#! p#+$"s '" '%ss."$# A&bas as *a'"%as "" " p"sa'a *#+s%s$"& "& !"%"s a!%"%s '" a&%+#$"!&%+a () " pa!$%*%pa& +# !"*#+-"*%&"+$# '# a+$"+# " !"%"s *a!b#%$"!&%+a%s *#+s$a+$"s (C)< as !"%"s C 'as *a'"%as p"sa'as &"'"%a& as .+"s "."$#!as As !"%"s a!%"%s s# ass%& *-a&a'as p#! *asa 'as sas s""+*%as '" a&%+#*%'#s a!%a+'# "+$!" #s a+$%*#!p#s p!#';%'#s p"#s '%."!"+$"s *#+"s K (R"%"s " &'a& '" %+.=*%$# K pa!a %+.=*%$# K) A !"%# '" &a *a'"%a p"sa'a ( H) " a !"%# *#+$a '" &a *a'"%a "" ( L) .#!&a& & 13
#*a '" %a# '# a+$"+# F"# .a$# '" a +%'a'" "s$!$!a '# +B*"# '" *a'a &#*a '" a+$%*#!p# *#+$"! 'as *a'"%as p"sa'as " 'as *a'"%as ""s, *a'a &#*a '" a+$%*#!p# $"& p"# &"+#s '#%s #*a%s '" %a# '# a+$"+# As !"%"s C 'a *a'"%a p"sa'a %+$"!a"& *#& #$!as &#*as "."$#!as " *as '# s%s$"&a %&+" ", ass%&, &"'"%a& a &a%#!%a 'as .+"s b%#=%*as '#s a+$%*#!p#s A& '%ss#, as *a'"%as p"sa'as "%s$"& "& 'as .#!&as " '%."!"& +as $"!&%+a"s *a!b#%$"!&%+a%s &a .#!&a 'as *a'"%as p"sa'as a+*#!a #s a+$%*#!p#s %a'#s &"&b!a+a +as &"&b!a+as pas&$%*as '#s %+.=*%$#s K, " a #$!a "+*#+$!a'a s#&"+$" +#s a+$%*#!p#s s"*!"$a'#s As !"%"s C 'as *a'"%as ""s +# pa!$%*%pa& +as .+"s "."$#!as " +# "s$# '%!"$a&"+$" %a'as s &"&b!a+as 'as *as (Os %s#$%p#s 'a !"%# *#+s$a+$" 'a *a'"%a "" s# ? " [ As *a'"%as p"sa'as " ""s "s$# *#a"+$"&"+$" %a'as p#! p#+$"s '%ss."$# .#!&a'as "+$!" #s !"s'#s '" *%s$"+a +# *a!b#%$"!&%+a 'a *a'"%a "" " +# '#&+%# C H1 'a *a'"%a p"sa'a As %+$"!a"s +# *#a"+$"s "+$!" #s '#&+%#s C L " CH1 $a&b& p#'"& *#+$!%b%! pa!a a ass#*%a# 'as *a'"%as p"sa'as " ""s As 'as *a'"%as p"sa'as '" *a'a &#*a '" a+$%*#!p# "s$# *#a"+$"&"+$" %a'as p#! p#+$"s '%ss."$#
4ra0mentos proteo!2ti$os de uma mo!.$u!a de I0G" • 4a: (.!a&"+$#, %a# '# a+$"+#) D#%s .!a&"+$#s %'+$%*#s " *#+s%s$"& "& *a'"%a "" *#&p"$a (L CL) ass#*%a'a a & .!a&"+$# H CH1 'a *a'"%a p"sa'a Ess"s .!a&"+$#s !"$& a -ab%%'a'" '" s" %a! a# a+$"+#, p#!" *a'a & p#ss% '#&+%#s L " C L pa!"a'#s S# sa'#s *#&# a+$a#+%s$as p#%s a& '" +# a$%a! # !"*"p$#!, ""s b#"%a& # s$%# '" %a# *#& # !"*"p$#! • 4$ (.!a&"+$#, *!%s$a%;") s" %a a *as " ap!"s"+$"& !"*"p$#!"s *, *#&# p#! ""&p# #s &a*!=.a#s a&b& s" %a& a ba*$!%as #ps#+%;a'as A& '%ss# p#'"& a$%a! *#&p"&"+$# • 4(a:D)3 ap!"s"+$a& '#b!a'%a " as p#+$"s '" '%ss."$# %+$"!*a'"%as %+$a*$as " '#%s #*a%s '" %a# '# a+$"+# %'+$%*# F#'"& s"! sa'#s pa!a a$%a! *a (a#+%s$a) &as +# p#'"& a$%a! p!#$"+as '# *#&p"&"+$# Cara$ter2sti$as #struturais das Re0i>es ;ari?eis do Anti$orpo A &a%#!%a 'as '%."!"+as '" s"+*%a " a!%ab%%'a'" "+$!" #s '%."!"+$"s a+$%*#!p#s "s$ *#+>+a'a a $!s p""+#s $!"*-#s +a !"%# 'a *a'"%a p"sa'a " a $!s $!"*-#s +a !"%# 'a *a'"%a "" Es$"s s"&"+$#s '" &a%#! '%"!s%'a'" s# *#+-"*%'#s *#&# re0i>es 5iperari?eis Na &#*a '" a+$%*#!p#, as $!s !"%"s -%p"!a!%"%s '# '#&+%# L " as $!s !"%"s -%p"!a!%"%s '# '#&+%# H s# &a+$%'as +$as pa!a *!%a! &a sp"!.*%" '" %a# a# a+$"+# F"# .a$# '" "ssas s""+*%as .#!&a!"& &a sp"!.*%" " *#&p"&"+$a! .#!&a $!%'%&"+s%#+a '# a+$"+# %a'#, as !"%"s -%p"!a!%"%s $a&b& s# *-a&a'as '" !"%"s '" '"$"!&%+a# '" *#&p"&"+$a!%"'a'" (CDRs) F!#*"'"+$"s '" *a'a !"%# a&%+#$"!&%+a L # H, "ssas !"%"s s# *-a&a'as '" CDR1, CDR2 " CDR3 As CDR3 '" a&b#s s"&"+$#s H " L s# as &a%s a!%"%s 'as CDRs A -ab%%'a'" '" &a !"%# "& s" '#b!a! "& & '#&+%# I p!%&#!'%a&"+$" '"$"!&%+a'a p"as s"+*%as *#+s"!a'as '" !"%"s a'a*"+$"s a#s CDRs A %a# '# a+$"+# p"as &#*as '" a+$%*#!p# p!%&a!%a&"+$" &a .+# 'as !"%"s -%p"!a!%"%s '" H " L O *#+$a$# &a%s "$"+s# *#& # a+$"+# #*#!!" *#& a !"%# CDR3 E+$!"$a+$#, a %a# '# a+$"+# +# p!%&a!%a&"+$" &a .+# '#s CDRs " #s !"s'#s '# a!*ab## $a&b& p#'"& .a;"! *#+$a$# *#& # a+$"+# As !"%"s '" a!*ab## 'a p#!# a!%" 'a *a'"%a p"sa'a s# *-a&a'as '" (R)
Cara$ter2sti$as #struturais das Re0i>es Constantes do Anti$orpo As &#*as '" a+$%*#!p# p#'"& s"! '%%'%'as "& *ass"s " sb*ass"s '%s$%+$as *#& bas" +as '%."!"+as +a "s$!$!a 'as !"%"s C 'a *a'"%a p"sa'a As *ass"s '" &#*as '" a+$%*#!p# $a&b& s# *-a&a'as '" %s#$%p#s " s# +#&"a'#s *#&# IA (sb$%p#s IA1, 2 (Z1 # Z2)), ID, IE, IG (IG1/4 (\1, \2, \3 # \4) " IM As !"%"s C 'a *a'"%a p"sa'a '" $#'as 14
as &#*as '" a+$%*#!p# '" & %s#$%p# # sb$%p# $"& "ss"+*%a&"+$" a &"s&a s"+*%a '" a&%+#*%'#s Es$a s"+*%a '%."!"+$" +#s a+$%*#!p#s '" #$!#s %s#$%p#s # sb$%p#s D%."!"+$"s %s#$%p#s " sb$%p#s '" a+$%*#!p#s !"a%;a& '%s$%+$as .+"s "."$#!as A !a;# pa!a %ss# " a &a%#!%a 'as .+"s "."$#!as '#s a+$%*#!p#s &"'%a'a p"a %a# 'as !"%"s C 'a *a'"%a p"sa'a a#s !"*"p$#!"s * (CRs) +as '%."!"+$"s *as, $a%s *#&# .a=*%$#s, *as N? " &as$=*%$#s ! p!#$"+as pas&$%*as, *#&# p!#$"+as '# *#&p"&"+$# Os %s#$%p#s " sb$%p#s '" a+$%*#!p# '%."!"& "& sas !"%"s C ", ass%&, #+'" ""s s" %a& " a%s .+"s "."$#!as !"a%;a!# As &#*as '" a+$%*#!p# s# @""%s (# &a""%s), p"!&%$%+'# " "as s" %"& a '%."!"+$"s a+$"+#s Essa @"%b%%'a'" *#+."!%'a, "& !a+'" pa!$", p#! &a re0ião de do:radiça #*a%;a'a "+$!" CH1 " C H2 '" *"!$#s %s#$%p#s " .a; *#& " s" a*#&#'" b"& as %a"s *#& # a+$"+# A& '%ss#, a&a @"%b%%'a'" 'as &#*as '" a+$%*#!p# '"*#!!"+$" 'a -ab%%'a'" '" *a'a '#&+%# H "& s#.!"! !#$a# *#& !"sp"%$# a# '#&+%# CH1 a'a*"+$" As Is s" ass#*%a& *#& # a+$"+# .#!&a+'# '%."!"+$"s :+#s %ss# s" ' p#!" a &#*a '" a+$%*#!p# $"& !#$a# +# s" p!=p!%# "%# A+$%*#!p#s s"*!"$a'#s " ass#*%a'#s &"&b!a+a '%."!"& +a s"+*%a '" a&%+#*%'#s 'a p#!# *a!b#%$"!&%+a 'a !"%# 'a *a'"%a p"sa'a Na .#!&a s"*!"$a'a, "+*#+$!a'a +# sa+" " "& #$!#s @%'#s "$!a*"a!"s, a p#!# *a!b#%$"!&%+a -%'!#.%*a A .#!&a %a'a +a &"&b!a+a '# a+$%*#!p# *#+$& & p"'a# *a!b#%$"!&%+a " %+*% '#%s s"&"+$#s &a !"%# $!a+s&"&b!a+a -%'!#.=b%*a Z/-"%*#%'a, s"%'a p#! &a p#!# *a!!"a'a p#s%$%a&"+$" +a !"%# %+$!a*"a! s$a&"&b!a+a! Nas &#*as IM " ID 'a &"&b!a+a, a p#!# *%$#pas&$%*a 'a *a'"%a p"sa'a *!$a, s#&"+$" $!s !"s'#s '" a&%+#*%'#s '" *#&p!%&"+$# +as &#*as '" IG " IE 'a &"&b!a+a, "a & p#*# &a%s #+a, a$ 30 !"s'#s '" a&%+#*%'#s '" *#&p!%&"+$# As .#!&as &$%&!%*as '#s a+$%*#!p#s s" %a& a#s a+$"+#s &a%s a%'a&"+$" '# " as .#!&as &#+#&!%*as # .a;"&, &"s&# s" a&b#s #s $%p#s '" a+$%*#!p#s *#+$%"!"& !"%"s ab " s" %a& %+'%%'a " %a&"+$" b"& a# a+$"+# Os a+$%*#!p#s a+$%/CR s# a#+%s$as b%a"+$"s '# !"*"p$#! CR " p#'" a$%/# p#%s s%&a # a+$"+# +a %a# *#& # CR D#"+a '# s#!# Os a+$%*#!p#s '" '%s$%+$as "sp*%"s '%."!"& & '#s #$!#s +as !"%"s C "& pa!$"s 'a !"%# C#& %ss#, a+'# &#*as '" I '" &a "sp*%" s# %+$!#';%'as "& #$!a, # !"*"b"'#! as "+"!a *#&# "s$!a+-as, &#+$a &a !"sp#s$a %&+" " p!#'; #s a+$%*#!p#s *#+$!a as !"%"s C 'a I %+$!#';%'a Iss# %&%$a !a+'"&"+$" a -ab%%'a'" "& $!a$a! %+'%'#s *#& a+$%*#!p#s p!#';%'#s "& #$!as "sp*%"s A=$%p#s a+'# & a!%a+$" p#%&=!>*# "+*#+$!a'# "& a+s %+'%'#s '" &a "sp*%" p#'" s"! !"*#+-"*%'# p#! & a+$%*#!p#, " '"$"!&%+a'# '" a+$%*#!p# a+$%a#$p%*# As '%."!"+as "+$!" as !"%"s '# a+$%*#!p# "s$# *#+*"+$!a'as +#s CDRs " *#+s$%$"& #s idi'tipos '#s a+$%*#!p#s
Li0ação dos anti$orpos a ant20enos E&b#!a $#'#s #s a+$"+#s s"a& !"*#+-"*%'#s p#! %+.=*%$#s "sp"*>*#s # p#! a+$%*#!p#s, s#&"+$" a+s '""s s# *apa;"s '" a$%a! #s %+.=*%$#s M#*as " "s$%&a& as !"sp#s$as %&+"s s# *-a&a'as '" %&+="+#s Ma*!#&#*as s# "."$%as pa!a "s$%&a! #s %+.=*%$#s K a %+%*%a!"& as !"sp#s$as %&+"s -&#!a%s, p#!" a a$%a# 'a *a K +"*"ss%$a " &B$%p#s !"*"p$#!"s '" a+$"+#s s"a& &a+$%'#s +$#s (%a# *!;a'a) a"! a+$%*#!p# s" %a a s#&"+$" &a p#!# '# a+$"+# " *-a&a'a '" '"$"!&%+a+$" # ep2topo
15
A+$"+#s p#%a"+$"s s# %&p#!$a+$"s p"# p#+$# '" %s$a 'a a$%a# 'a *a K, &a "; " &%$as .+"s "."$#!as '#s a+$%*#!p#s s# '%spa!a'#s #$%&a&"+$" a+'# 'as # &a%s &#*as '" a+$%*#!p#s s# &a+$%'as p!=%&as +$as p"a %a# a & a+$"+# p#%a"+$" (%&+#*#&p"#s)
Reação $ruada" A+s a+$%*#!p#s p!#';%'#s *#+$!a & a+$"+# p#'"& s" %a! a & a+$"+# '%."!"+$", &as "s$!$!a&"+$" !"a*%#+a'# Os a+$%*#!p#s " s# p!#';%'#s "& !"sp#s$a a & a+$"+# &%*!#b%a+# a&as ";"s $"& !"a# *!;a'a *#& #s p!=p!%#s a+$"+#s, # " p#'" s"! a bas" '" *"!$as '#"+as %&+#=%*as
CAPÍTULO @ e 8 (&o!.$u!as do &/CE Apresentação do Ant20eno aos Lin'$itos T e Re$eptores Imuno!.0i$os e Transdução de ,ina!) Apresentação do Ant20eno para o Lin'$ito T Fa!a " & %+.=*%$# s"a a$%a'#, # a+$"+# '"" s"! ap!"s"+$a'# a "" p#! *as ap!"s"+$a'#!"s '" a+$"+# (AFCs), " %+*"& as *as '"+'!$%*as, #s &a*!=.a#s " as *as K As *as '"+'!$%*as s# as &a%s "."$%as pa!a a$%a! *as %!"+s, "+a+$# #s &a*!=.a#s " *as K a$a& p!%+*%pa&"+$" +a ap!"s"+$a# a#s %+.=*%$#s - CD4 As !"%"s a!%"%s 'as *a'"%as α " β '# CR *#+$& !"%"s -%p"!a!%"%s (CDR), #+'" s" *#+*"+$!a a &a%#! $aa '" a!%ab%%'a'" !s CDR 'a *a'"%a α " $!s 'a *a'"%a β .#!&a&, "& *#++$#, a pa!$" '# CR " !"*#+-"*" # *#&p"# p"p$'"#/MHC "sp"*%>*a&"+$"
&/C Os %+.=*%$#s !"*#+-"*"& s#&"+$" a+$"+#s %a'#s s &#*as '# *#&p"# p!%+*%pa '" -%s$#*#&pa$%b%%'a'" (MHCs) +a sp"!.*%" 'as *as '# -#sp"'"%!# %a CR, " +# '%!"$a&"+$" a+$"+#s '# &%*!##!a+%s&# # a+$"+#s s#B"%s +a *%!*a#, "s$a *a!a*$"!s$%*a '"+#&%+a'a !"s$!%# '" MHC Os MHCs %a&/s" ap"+as p"p$'"#s, p#! %ss#, a &a%#!%a '#s %+.=*%$#s !"*#+-"*" ap"+as p"p$'"#s %+"a!"s *!$#s As &#*as '" MHC s# p#ss"& "+"s "$!"&a&"+$" p#%&=!>*#s, ap!"s"+$a+'# !a+'" a!%"'a'" "+$!" %+'%'#s, # " !"p!"s"+$a a bas" 'a !""%# a $!a+spa+$"s O MHC +# ."%$# '" !"a!!a+# +%*#, &as s%& '" !%#s s"&"+$#s +%*#s -"!'a'#s p"#s pa%s, *#'%>*a+'# "+"s '%."!"+$"s "+$!" as p"ss#as Ca'a *ass" '" MHC $"& 3 "+"s " # *#'%>*a O MHC '" *ass" I "s$ p!"s"+$" "& $#'as as *as +*"a'as '# *#!p# Ap!"s"+$a *a'"%a Z, a a p#ss% a ."+'a "& " s" a#a #s p"p$'"#s " &a p""+a *a'"%a " p#ss% &a%#! .+# "s$!$!a .#!&a'# p"#s "+"s HLA/A, HLA/K " HLA/C, " *#'%>*a& $!s &#*as *#& # &"s&# +#&" Os %+.=*%$#s CD8 !"*#+-"*"& MHC '" *ass" I a+'# &a *a +# ap!"s"+$a MHC '" *ass" I +a sp"!.*%", "a &#!$a p"as *as +a$!a ]%"!s (N?) O MHC '" *ass" II "s$ p!"s"+$" +as AFCs A ."+'a .#!&a'a p"a *a'"%a Z " p"a *a'"%a Ap!"s"+$a #s "+"s HLA/DF, HLA/D " HLA/DR Os %+.=*%$#s CD4 !"*#+-"*"& MHC '" *ass" II A "p!"ss# '" '"$"!&%+a'#s a"#s '" MHC '" *ass" II "& & %+'%'# " '"$"!&%+a a sa *apa*%'a'" '" "!a! !"sp#s$a pa!a a+$"+#s "sp"*>*#s Os !"s'#s '" a&%+#*%'#s p#%&=!>*#s "s$# #*a%;a'#s +a ."+'a '" %a# a# p"p$'"# " a'a*"+$"s a "a A ."+'a '# MHC .#!&a'a p#! 'as α/-%*"s " &a :&%+a/β p!""a'a As α/-%*" *#+s$%$"& a pa!"'" 'a ."+'a " *#+$a*$a& as !"%"s CDR1 " CDR2 '# CR< a :&%+a/β p!""a'a *#+s$%$% a bas" 'a ."+'a " #+'" - %a# '# a+$"+# D"%'# 16
a!%ab%%'a'" '"ssa !"%#, #s '%."!"+$"s MHCs %a&/s" " ap!"s"+$a& '%."!"+$"s a+$"+#s As !"%"s a!%"%s O %+$"!."!#+s IN/ α, IN/ β " IN/\ a&"+$a& # +" '" "p!"ss# '" MHC '" *ass" I, " s# *%$#*%+as p!#';%'as +a .as" %+%*%a 'a !"sp#s$a %&+" %+a$a O IN/\ a p!%+*%pa *%$#*%+a "s$%&a'#!a 'a "p!"ss# '" MHC '" *ass" II, " p#'" s"! p!#';%'a p"as *as N? '!a+$" a !"sp#s$a %&+" %+a$a " p"#s %+.=*%$#s a$%a'#s p#! a+$"+#s +a !"sp#s$a %&+" a'ap$a$%a
CAPÍTULO 7 (-eseno!imento dos Lin'$itos e RearranFo dos Genes dos Re$eptores de Ant20enos) -eseno!imento de Lin'$itos e RearranFo do Genes dos Re$eptores de Ant20enos Os p!#"+%$#!"s '#s %+.=*%$#s (*as " +# "p!"ssa& !"*"p$#!"s '" a+$"+#s) +# $%&# " +a &"'a =ss"a passa& p#! & p!#*"ss# '" '"s"+#%&"+$# "& " s" '%."!"+*%a& "& %+.=*%$#s &a'!#s Ess"s %+.=*%$#s "p!"ssa& !"*"p$#!"s '" a+$"+# a$a&"+$" '%"!s#s " $"& a *apa*%'a'" '" !"*#+-"*"! &a !a+'" a!%"'a'" '" sbs$a+*%as "s$!a+-as A &a$!a# %+%*%a'a p#! s%+a%s '" !"*"p$#!"s '" sp"!.*%" *"a! " $"& 'as .+"s p!%+*%pa%s ""s p!#&#"& a p!#%."!a# '" p!#"+%$#!"s " %+%*%a& # !"a!!a+# '#s "+"s !"*"p$#!"s '" a+$"+#s
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%s# "!a '# '"s"+#%&"+$# '" %+.=*%$#s E"+$#s '" &a$!a# '" %+.=*%$#s " #*#!!"& +#s =!#s %+.=%'"s O $omprometimento de $.!u!as pro0enitoras $om a !in5a0em !inoide + ou T Cas/$!#+*# -"&a$#p#%$%*as +# .a'# ."$a " +a &"'a =ss"a, '# #!%"& a#s %+.=*%$#s A &a$!a# 'as *as K a pa!$%! '#s p!#"+%$#!"s *#&p!#&"$%'#s *#& "ssa %+-a"& #*#!!" p!%+*%pa&"+$" +a &"'a =ss"a ", a+$"s '# +as*%&"+$#, +# .a'# ."$a Os p!"*!s#!"s '#s %+.=*%$#s '"%a& # .a'# ."$a a+$"s '# +as*%&"+$# " a &"'a =ss"a '!a+$" a %'a " *%!*a& a$ # $%&#, #+'" *#&p"$a& sa &a$!a# O *#&p!#&"$%&"+$# *#& a %+-a"& K # '"p"+'" 'as %+s$!"s !"*"b%'as '" !%#s !"*"p$#!"s '" sp"!.*%" *"a!, " %+';"& !"a'#!"s '" $!a+s*!%# "sp"*>*#s " "a& & p!#"+%$#! %+.#%'" *#&& a ass&%!, '" &#'# "sp"*>*#, # '"s$%+# '" &a *a K # &a *a N# *as# '" *as K "& '"s"+#%&"+$#, # =*s 'a *a'"%a p"sa'a 'a %&+##b%+a (I), %+%*%a&"+$" "& &a *#+>!a# %+a*"ss" *!#&a$%+a, ab"!$#, '" &#'# " $#!+a/s" a*"ss" s p!#$"+as " &"'"%a& # !"a!!a+# " "p!"ss# '#s "+"s 'as I N# '"s"+#%&"+$# '" *as Z, # =*s '# "+" '# !"*"p$#! '" *as (CR) # p!%&"%!# a s" $#!+a! '%sp#+"
A pro!ieração de $.!u!as pro0enitoras e $.!u!as imaturas $omprometidas em est?0ios ini$iais espe$2%$os de deseno!imento D!a+$" # '"s"+#%&"+$# 'as *as K " , as *as p!#"+%$#!as p!#%."!a&/s", p!%&"%!a&"+$", "& !"sp#s$a s *%$#*%+as ", p#s$"!%#!&"+$", "& !"sp#s$a a s%+a%s "!a'#s p#! & p!/!"*"p$#! '" a+$"+#, " s""*%#+a as *as " !"a!!a+a!a& '" &a+"%!a "."$%a # p!%&"%!# *#++$# '" "+"s '#s !"*"p$#!"s '" a+$"+#s
O rearranFo seBuen$ia! e ordenado dos 0enes dos re$eptores de ant20enos e a epressão de prote2nas dos re$eptores de ant20enos → Ca'a *#+" '" %+.=*%$# K # p!#'; & !"*"p$#! '" a+$"+# *#& &a "s$!$!a B+%*a '" %a# a a+$"+#s E& a"! & '#s %+.=*%$#s "& '"s"+#%&"+$#, #s "+"s " *#'%>*a& #s '%"!s#s !"*"p$#!"s '" a+$"+# s# "!a'#s p"# !"a!!a+#'" '%."!"+$"s s"&"+$#s +%*#s 'a !"%# a!%" () *#& s"&"+$#s +%*#s '" '%"!s%'a'" (D) " +# (J) D%"!s#s !"*"p$#!"s '" a+$"+#s s# "!a'#s " "p!"ss#s a+$"s '" "+$!a! "& *#+$a$# *#& #s a+$"+#s 17
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R"*#&b%+a# (D)J O p!#*"ss# '" !"*#&b%+a# (D)J "& a"! =*s '" I # CR "+#" a s""# '" & "+" , & s"&"+$# D (a+'# p!"s"+$") " & s"&"+$# J "& *a'a %+.=*%$# " # !"a!!a+# '" & '"ss"s s"&"+$#s, '" &#'# a .#!&a! & B+%*# #+ (D)J " *#'%>*a! pa!a a !"%# a!%" &a p!#$"+a '# !"*"p$#! '" a+$"+# N#s #*% 'a *a'"%a "" 'as I " 'as *a'"%as Z " \ '# CR, +as a%s .a$a& s"&"+$#s D, & B+%*# !"a!!a+# +$a & "+" s""*%#+a'# a"a$#!%a&"+$" a & s"&"+$# J, $a&b& s""*%#+a'# a"a$#!%a&"+$" Os #*% 'as *a'"%as H 'as I " " ^ '# CR *#+$& s"&"+$#s D, " +"ss"s #*%, '#%s ""+$#s '" !"a!!a+# '%s$%+$#s '""& s"! %+%*%a'#s s"pa!a'a&"+$", +$a+'# & p!%&"%!# D a & J ", "& s"%'a, & s"&"+$# pa!a s"! .+'%'# a & s"&"+$# DJ
#tapas seBuHn$iais no pro$esso de rearranFo 0Hni$o" Ab"!$!a 'a *!#&a$%+a "& !"%"s "sp"*>*as '# *!#&#ss#&# pa!a $#!+a! #s s"&"+$#s +%*#s '" !"*"p$#!"s '" a+$"+#s a*"ss"%s s "+;%&as " &"'"%a& a !"*#&b%+a# D#%s s"%&"+$#s +%*#s s""*%#+a'#s '""& s"! ap!#%&a'#s & '# #$!#, a$!a"ssa+'# &a '%s$:+*%a *!#&#ss&%*a *#+s%'"!" "b!as s# %+$!#';%'as +a 'pa >$a +as "$!"&%'a'"s *#'%>*a'#!as '"s$"s '#%s s"&"+$#s< N*"#$'"#s s# a*!"s*"+$a'#s # !"&#%'#s +as "$!"&%'a'"s "b!a'as< As "$!"&%'a'"s p!#*"ssa'as s# %a'as pa!a p!#';%! "+"s !"*"p$#!"s '" a+$"+#s *#+a%s B+%*#s, p#!& '%"!s#s, " p#'"& s"! $!a+s*!%$#s '" &a+"%!a ">*%"+$"
A $%%;a# '" '%."!"+$"s *#&b%+a"s '#s s"&"+$#s , D, " J " a a'%# " !"&## '" +*"#$'"#s +as +"s *#+$!%b"& pa!a a '%"!s%'a'" $!"&"+'a '#s !"*"p$#!"s '" a+$"+# A &a%#! *#+$!%b%# pa!a a '%"!s%'a'" '" !"*"p$#!"s '" a+$"+# ."%$a p"a !"&## # a'%# '" +*"#$'"#s +as +"s '" s"&"+$#s " D, D " J # " J +# &#&"+$# "& " "ss"s s"&"+$#s s# +%'#s D"%'# '%"!s%'a'" +*%#+a, a+$%*#!p#s " &#*as '# CR &#s$!a& a &a%#! a!%ab%%'a'" +as +"s 'as !"%"s " C, " .#!&a& a $"!*"%!a !"%# -%p"!a!%" # CDR3
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#entos de se!eção Bue preseram as $.!u!as Bue produiram re$eptores un$ionais e e!iminam $.!u!as poten$ia!mente peri0osas Bue re$on5e$em ortemente ant20enos pr'prios O p!#*"ss# '" '"s"+#%&"+$# '" %+.=*%$#s *#+$& +&"!#sas "$apas %+$!+s"*as, '"+#&%+a'as p#+$#s '" *#+$!#", +as a%s as *as "& '"s"+#%&"+$# s# $"s$a'as " s#&"+$" *#+$%+a& a a&a'!"*"! s" a "$apa a+$"!%#! '# p!#*"ss# $%"! s%'# *#+*'a '" &a+"%!a ">*a; ,e!eção positia" p!#*"ss# p"# a *as "& '"s"+#%&"+$# +# $%&# ($%&=*%$#s) *#s CRs s" %a& s p!=p!%as &#*as '" MHC s# saas 'a &#!$" *"a! p!#!a&a'a, a# pass# " #s $%&=*%$#s *#s !"*"p$#!"s +# !"*#+-"*"& as p!=p!%as &#*as '" MHC &#!!"& A s""# p#s%$%a a!a+$" " as *as &a'!as s# !"s$!%$as a# p!=p!%# MHC " as *as CD8 Q s# "sp"*>*as pa!a *#&p"#s '" p"p$'"#s *#& &#*as '" MHC '" *ass" I " *as CD4 Q pa!a *#&p"#s '" p"p$'"#s *#& &#*as '" MHC '" *ass" II As *as &a'!as *#s p!"*!s#!"s $"+-a& s%'# s""*%#+a'#s p#s%$%a&"+$" p#! &#*as '" MHC p!=p!%# +# $%&# s# *apa;"s '" !"*#+-"*"! a+$"+#s '" p"p$'"#s "s$!a+-#s ap!"s"+$a'#s p"as &"s&as &#*as '" MH* p!=p!%# "& *as ap!"s"+$a'#!as '" a+$"+#s "& $"*%'#s p"!%.!%*#s ,e!eção *e0atia" # p!#*"ss# " "%&%+a # a$"!a #s %+.=*%$#s "& '"s"+#%&"+$# *#s !"*"p$#!"s '" a+$"+#s (a$#!!"a$%#s) %a&/s" .#!$"&"+$" a a+$"+#s p!=p!%#s p!"s"+$"s +#s =!#s %+.=%'"s "!a'#!"s Ess" p!#*"ss# *#+$!%b% pa!a a &a+$"+# 'a a$#$#"!:+*%a As *as "& '"s"+#%&"+$# *#& &a a$a a>+%'a'" p#! a+$"+#s p!=p!%#s s# "%&%+a'as p#! ap#p$#s", & ."+&"+# *#+-"*%'# *#&# de!eção $!ona! Cas K %&a$!as a$a&"+$" a$#!"a$%as p#'"& s"! %+';%'as a !"a%;a! &a%s !"a!!a+#s +# "+" 'as I ", ass%&, "%$a! a a$#!"a$%%'a'" "+&"+# *#+-"*%'# *#&# edição do re$eptor S" a "'%# .a-a, as *as K a$# !"a$%as &#!!"& A s""# +"a$%a '" %+.=*%$#s %&a$!#s & &"*a+%s&# %&p#!$a+$" pa!a a &a+$"+# 'a $#"!:+*%a a &%$#s 18
a+$"+#s p!=p!%#s< %ss# $a&b& '"+#&%+a'# to!ern$ia $entra! p#!" s" '"s"+#" +#s =!#s %+.=%'"s *"+$!a%s ("!a'#!"s)
D%."!"+*%a# 'as *as K " "& sbp#pa"s .+*%#+a&"+$" " ."+#$%p%*a&"+$" '%s$%+$as (K *as .#%*a!"s, 'a ;#+a &a!%+a, K/1) ( Z CD4 Q " CD8Q, *as N? " *as \^) •
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R"sp#s$a &"'%a'a p"#s %+.=*%$#s K → E%s$"& '#%s $%p#s '" !"sp#s$as '"p"+'"+$" %+'"p"+'"+$" M"&=!%a Capa*%'a'" '" &a s"+'a !"sp#s$a '" &a%#! &a+%$'" " !ap%'"; .!"+$" a & s"+'# "+*#+$!# *#& & a+$"+# "sp"*>*# A+$%"+#s /%+'"p"+'"+$"s '# $%p# I s# $%'#s p#! a""s " s# !"*#+-"*%'#s p"a %&+%'a'" %+a$a, # s"a, LFS " %+'"p"+'" 'a "sp"*%>*%'a'" " s" %a a # 4, " $a&b& CFG " s# .!a&"+$#s ba*$"!%a+#s %a+$"s '" # 9 J #s a+$%"+#s / %+'"p"+'"+$"s '# $%p# II s# *a!b#%'!a$#s (ap!"s"+$a& *a'"%as !"p"$%$%as) R"sp#s$as -&#!a%s /%+'"p"+'"+$"s a+'# a$%a'as +a as+*%a '" *%$#*%+as %+%*%a& ap"+as a s"*!"# '" IM Na p!"s"+a '" *%$#*%+as p#'"& s#.!"! $!#*a '" *ass" A *a " passa a s"*!"$a! IG +# #$a a s"*!"$a! IM O %+.=*%$# K s" .#!&a a pa!$%! '" p!#"+%$#!"s (*as %+'%."!"+*%a'as) *#& # a%# '" *as "s$!#&a%s +a &"'a =ss"a Sa .+# p!#';%! a+$%*#!p#s O KCR, a+$%*#!p# '" &"&b!a+a, a &#*a " *a!a*$"!%;a # %+.=*%$# K Is#$%p#s '%."!"+$"s '" %&+##b%+a s# "p!"ss#s +a sp"!.*%" 'a &"&b!a+a '# %+.=*%$# K O p!%&"%!# %s#$%p# s"&p!" a s"! "p!"ss# +a &"'a =ss"a # IM A& '"ss", # %+.=*%$# K $a&b& "p!"ssa #$!# %s#$%p# '" &"&b!a+a, # ID, " *#& %ss# $"& *#+'%"s '" sa%! 'a &"'a =ss"a '" .#!&a &a'!a A# sa%! 'a &"'a, # %+.=*%$# K $"& '#%s '"s$%+#s F#'" %!a! &a *a '" &"&=!%a # a$%+%! & "s$%# '" pas&=*%$# O pas&=*%$# a .as" s"*!"$#!a '# %+.=*%$# K #+'" "" "s$ p!#';%+'# a+$%*#!p#s O %+.=*%$# K sa% 'a &"'a "& '%!"# a#s =!#s %+.#%'"s s"*+'!%#s " $"*%'#s as"s 'a !"sp#s$a %&+" -&#!a A a$%a# '" *a K %+%*%a'a p"# !"*#+-"*%&"+$# "sp"*>*# '" a+$"+#s p#! &"%# '" !"*"p$#!"s I '" sp"!.*%" 'as *as O a+$"+#, a& '" #$!#s "s$&#s, %+*%+'# *as a%%a!"s, "s$%&a&a p!#%."!a# " a '%."!"+*%a#'" *#+"s "sp"*>*#s '" *as K A p!#+%" '# *#+"p#'" s" '%."!"+*%a! "& pas&=*%$#s s"*!"$#!"s '" a+$%*#!p#s, p#'" s#.!"! &a$!a# 'a a>+%'a'" # p#'" p"!s%s$%! *#&# *as '" &"&=!%a A %a+$"s*a "pa+s# +"*"ss!%a pa!a &a+$"! # &"s&# !%$&# '#s &%*!#!a+%s&#s " s" '%%'"& !ap%'a&"+$" O %+.=*%$# K a$a *#&# *a ap!"s"+$a'#!a '" a+$"+#, pa!$%*%pa $a&b& 'a sp!"ss# '" !"sp#s$as %&+"s " s"*!"# '" a+$%*#!p#s Os %+.=*%$#s K &a'!#s ap=s a "s$%&a# a+$%+%*a p##a& #s =!#s %+.=%'"s p"!%.!%*#s, " s# #*a%s #+'" #s %+.=*%$#s %+$"!a"& *#& a+$"+#s "s$!a+-#s O a+$"+# s" %a s %&+##b%+as M " %D '" &"&b!a+a +as *as K %!"+s &a'!as " as a$%a A&as *as K a$%a'as *#&"a& a p!#';%! #$!#s $%p#s '" a+$%*#!p#s a& 'a IM " IDp"# p!#*"ss# '"+#&%+a'# tro$a de isotipo ($!asse) de $adeia pesada
&aturação de A%nidade C#+.#!&" &a !"sp#s$a %&+" -&#!a s" '"s"+#", *as K a$%a'as p!#'$#!as '" a+$%*#!p#s " s" %a& a a+$"+#s #& a>+%'a'" *!"s*"+$" passa& a '#&%+a! p!#!"ss%a&"+$" a !"sp#s$a As !"sp#s$as '" a+$%*#!p#s a a+$"+#s p!#$"%*#s !""!"& " # a+$"+# s"a • %+$"!+a%;a'# p#! *as K "sp"*>*as, p!#*"ssa'#s " s"s p"p$'"#s ap!"s"+$a'#s a#s %+.=*%$#s a%%a!"s CD4 Q, " p#! sa "; a$%a& as *as K F#! %ss# as p!#$"+as s# *ass%>*a'as *#&# ant20enos Tdependentes O $"!&# %+.=*%$# a%%a! s" '"" a# .a$# '" as *as "s$%&a& # a%%a& #s %+.=*%$#s a p!#';%! a+$%*#!p#s 19
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A $!#*a '" %s#$%p# " a &a$!a# 'a a>+%'a'" s# *a!a*$"!%s$%*a&"+$" #bs"!a'as "& !"sp#s$as %&+"s -&#!a%s '"p"+'"+$"s a a+$"+#s p!#$"%*#s A *a a%%a! .#%*a!, .a*%%$a a .#!&a# '" *"+$!#s "!&%+a$%#s, #s a%s s# "s$!$!as "!a'as "& =!#s %+.=%'"s, #+'" #*#!!"& !%#s ""+$#s !"a*%#+a'#s s !"sp#s$as %&+%$!%as -&#!a%s /'"p"+'"+$"s E& !"sp#s$as /'"p"+'"+$"s, #s pas&=*%$#s &%!a& '#s *"+$!#s "!&%+a$%#s "& =!#s %+.=%'"s p"!%.!%*#s, #+'" s# p!#';%'#s, pa!a a &"'a =ss"a, p#'" p#'"& %"! p#! &%$#s a+#s Ess"s pas&=*%$#s '" %'a #+a s"*!"$a& *#+$%+a&"+$" a+$%*#!p#s " p!#p#!*%#+a& p!#$"# %&"'%a$a s"&p!" " & &%*!#!a+%s&# " p#'" s"! !"*#+-"*%'# p#! "ss"s a+$%*#!p#s %+."*$a # %+'%'# A&as %+-a"+s '" *a K a$%a'as '" .#!&a '"p"+'"+$" p#'"& s" '%."!"+*%a! "& *as '" &"&=!%a, " s#b!"%"& "& & "s$a'# '" !"p#s#, s"& s"*!"$a! a+$%*#!p#s, &as &#+$a& !"sp#s$as !p%'as "& "+*#+$!#s p#s$"!%#!"s *#& # a+$"+# As *as '"+'!$%*as ap!"s"+$a& &%$#s MHCs " &#*as *#/"s$%&a$=!%as (p#! ""&p# # pa! CD28 T K7 (1" 2)) Ea p"!&%$" " # pH +# %+$"!%#! '# .a#%s#ss#&# s"a bs%*# " *#& %ss# *#+s"" a!&a;"+a! a+$"+#s '" .#!&a ">*%"+$" " ass%& ap!"s"+$a/#s O %+.=*%$# K +a%" +# b#& AFC a+$# as CD p#%s ap!"s"+$a& p#*#s MHCs " &#*as *#/"s$%&a$=!%as O p!#*"ss# '" a$%a# '# %+.=*%$# K .a; *#& " "" "p!"ss" "& sa &"&b!a+a &a%s MHCs " &#*as *#/"s$%&a$=!%as -ab%%$a+'#/# a s"! AFC As !"sp#s$as '" a+$%*#!p#s a a+$"+#s &$%a"+$"s (*a'a &#*a *#& !%#s "p$#p#s %'+$%*#s) +# p!#$"%*#s *#& '"$"!&%+a+$"s !"p"$%$%#s, $a%s *#&# p#%ssa*a!'"#s, a+s %p'"#s " *%'#s +*"%*#s, +# !""!"& a pa!$%*%pa# '" %+.=*%$#s a%%a!"s a+$"+#/"sp"*>*#s S# '"+#&%+a'#s ant20enos T independentes
A estrutura do $omp!eo prot.i$o +CR As IGM " IGD '" &"&b!a+a ap!"s"+$a& *a'as *%$#pas&$%*as *!$as " +# $!a+s';"& s%+a%s "!a'#s ap=s # !"*#+-"*%&"+$# '" a+$"+# Os s%+as &"'%a'#s p#! I s# $!a+s';%'#s p#! 'as #$!as &#*as *-a&a'as IZ " I " "s$# ass#*%a'as s I '" .#!&a +# *#a"+$" Essas p!#$"+as *#+$"& & &#$%# a$%a$=!%# IAM *a'a +as sas *a'as *%$#pas&$%*as " ap!"s"+$a !"s'#s '" $%!#s%+as " s# a#s '" .#s.#!%a"s &"'%a'as p#! %+as"s A .#s.#!%a# '#s !"s'#s '" $%!#s%+a '#s IAMs a*%#+a $#'#s #s ""+$#s '" s%+a%;a# sbs"_"+$"s '# KCR IZ " I s# .!#a&"+$" %a'as a $%!#s%+#%+as"s 'a .a&%a S!* $a%s *#&# L`+, `+ K], " a+'# .#s.#!%a'#s a$%a& &a s"+'a "+;%&a s%+a, S`?, " &%!a pa!a # +B*"# " p!#&#" a $!a+s*!%# '" "+"s !"a*%#+a'#s *#& a a$%a# 'a *a K O %+.=*%$# K ap!"s"+$a & *#!!"*"p$#! " !"*#+-"*" .!a&"+$#s '# *#&p"&"+$# *#a"+$"&"+$" %a'#s a# a+$"+# # .a;"& pa!$" '#s %&+#*#&p"#s *#+$"+'# # a+$"+# Ess" !"*"p$#! a&"+$a a .#!a '" a$%a# '# %+.=*%$# K, p#$"+*%a%;a+'# "& a$ 10 ";"s O *#!!"*"p$#! CD2I !"*#+-"*" # .!a&"+$# '# *#&p"&"+$# C3' " #ps#+%;a # a+$"+#, "a+'# a a$%a# 'a *as*a$a '" FI3? " & a&p%>*a'#! '# KCR H #$!#s '#%s *#!!"*"p$#!"s, # CD19, " sa'# *#&# &a!*a'#! '" %+.=*%$# K " $a&b& # CD81, *a a sa .+# +# b"& "*%'a'a Os !"*"p$#!"s %+%b%$=!%#s '# %+.=*%$# K ap!"s"+$a& &#$%# IIM " !"*!$a .#s.a$as"s " "!a& '".#s.#!%a"s +#s !"s'#s '" $%!#s%+a " s"!"& *#&# s%+a %+%b%$=!%# pa!a a *a U& !"*"p$#! %+%b%$=!%# '# %+.=*%$# K # CRII, " !"*"p$#! %+%b%$=!%# " s" %a a p#!# C '" IG p!#';%'a +# '"*#!!"! 'a !"sp#s$a %&+"
CAPÍTULO J (Atiação dos Lin'$itos T) ATI;AKO -O, LI*4MCITO, T O #b"$%# 'a a$%a# "!a! a pa!$%! '" & p""+ss%&# +B&"!# '" %+.=*%$#s %!"+s *#& # !"*"p$#! "sp"*>*# pa!a # a+$"+# " "s$#, & !a+'" +B&"!# '" *as 20
"."$#!as .+*%#+a%s ass%& *#&# '" &a p#pa# '" *as '" &"&=!%a, " s"a& *apa;"s '" !"a%! !ap%'a&"+$" "& & s"+'# "+*#+$!# *#& "ss" a+$"+#
APC As AFCs ap!"s"+$a& # *#&p"# p"p$'"#/MHC s *as a$!as '# !"*#+-"*%&"+$# '# *#&p"# p"# CR (1 s%+a) " "+%a& *#"s$&#s a'%*%#+a%s (2 s%+a), +"*"ss!%#s pa!a a *#&p"$a a$%a# '# %+.=*%$# Ess"s *#"s$%&a'#!"s s# &#*as p!"s"+$"s +a &"&b!a+a 'as AFCs A& '%ss#, s"*!"$a& *%$#*%+as "ss"+*%a%s pa!a " a *a s" $#!+" "."$#!a A# #*#!!"! a ap!"s"+$a# s *as , as AFCs !"*"b"& s%+a%s '"ss" %+.=*%$# " %+$"+s%>*a& a sa .+# '" ap!"s"+$a# '" a+$"+# Na p!"s"+a '" &%*!##!a+%&#s, as AFCs a&"+$a& a "p!"ss# '" MHC '" *ass" II " '" *#"s$%&a'#!"s, a&"+$a+'# a ">*%+*%a +a ap!"s"+$a# '" a+$"+#s " ""a+'# a s"*!"# '" *%$#*%+as Ess"s ""+$#s a&p%>*a& a *apa*%'a'" 'as AFCs "& a$%a! a !"sp#s$a '" *as
C.!u!as dendr2ti$as a AFC &a%s p!#>ss%#+a p#! s" #*a%;a!"& "s$!a$"%*a&"+$" +as p#!$as '" "+$!a'a '" pa$="+#s< $"! *apa*%'a'" '" &%!a# '#s $"*%'#s pa!a as ;#+as '" *as +#s =!#s %+.#%'"s s"*+'!%#s< ap!"s"+$a! !a+'" '"+s%'a'" '" MHC "& sa sp"!.*%" &a "; '"$"*$a'# # a+$"+#< p#! ap!"s"+$a! *#"s$&#< " $"! *apa*%'a'" '" &a+$"! # pH '# .a#%s#ss#&# &a%s bs%*#, p"!&%$%+'# " a '"!a'a# '# a+$"+# s"a "+$a, # " .a; *#& a " a ap!"s"+$a# p"!'!" &a%s Os a+$"+#s " *!;a& as ba!!"%!as "p%$"%a%s # s# p!#';%'#s +#s $"*%'#s s# *ap$!a'#s p#! *as '"+'!$%*a %&a$!as< #s a+$"+#s *%!*a+$"s s# *ap$!a'#s p#! *as '"+'!$%*as '# ba# A# !"*#+-"*"!"& & a+$"+# %a'# a & FAMF %a !"*"p$#!"s FRRs " "+'#*%$/#, "ss" a+$"+# '"!a'a'# p"as "+;%&as '# %s#ss#&# " a'"+$!a& # MHCIIC, " & *#&pa!$%&"+$# *#+$"+'# #s MHCs '" *ass" II "& .#!&a# E+$# &a "+;%&a !"sp#+s" p#! '"!a'a! $#'a a *a'"%a %+a!%a+$", '"%a+'# ap"+as # p"p$'"# CLIF +a ."+'a O HLA/DM p#ss% a$a a>+%'a'" p#! "ss" p"p$'"#, ##, "" s" %a a# p"p$'"# CLIF %+s$ab%%;a+'# # MHC Fa!a " # MHC s" "s$ab%%;" +#a&"+$", # p"p$'"# '# a+$"+# %a/s" a "" +a ."+'a "& &a *#+.#!&a# "s$"+'%'a D"ssa &a+"%!a, #s MHCs '" *ass" II *#+$"+'# # a+$"+# s# "a'#s sp"!.*%" 'as *as '"+'!$%*as p#! &"%# '" a*B##s A& '" "p#! #s MHCs '" *ass" II +a sp"!.*%", as *as '"+'!$%*as &a'!as passa& a "p!"ssa! # !"*"p$#! '" %&%#*%+as CCR7, " !"*#+-"*" 'as %&%#*%+as, a CCL19 " CCL21, p!#';%'as +as ;#+as '" *a +# %+.#+#'# D"ss" &#'#, a *a '"+'!$%*a &a'!a &%!a '# $"*%'# pa!a # %+.#+#'# a$!as 'a %+.a p"#s as#s %+.$%*#s a."!"+$"s As *as %!"+s $a&b& "p!"ssa& CCR7, p#! %ss#, "as &%!a& pa!a a &"s&a !"%# '# %+.#+#'# a$!as 'a "%a '" "+'#$%# a$# (HE), #+'" "s$# *#+*"+$!a'as as *as '"+'!$%*as *#& # a+$"+# Iss# &a%&%;a a p!#bab%%'a'" '# "+*#+$!# "+$!" a '"+'!$%*a *#& # a+$"+# " a *a %!"& *#& # !"*"p$#! "sp"*>*# pa!a a"" a+$"+# U&a "; #*#!!%'# # !"*#+-"*%&"+$# '# a+$"+# p"# CR, # !"*"p$#! CD28 '# %+.=*%$# !"*#+-"*" as &#*as *#"s$%&a'#!as K7/1 " K7/2 (CD80 " CD86), "p!"ssas "& a$#s +"%s +a *a '"+'!$%*a &a'!a, "!a+'# # 2 s%+a Iss# "a *#&p"$a a$%a# '# %+.=*%$# CD4 As *as - CD4 a$%a'as "p!"ssa& # CD40L, " s" %a a# CD40 "p!"ss# +a *a '"+'!$%*a, "+%a+'# s%+a%s " a&"+$a& a "p!"ss# '" K7 +a sp"!.*%" Essa aa '" !"$!#a%&"+$a# s"!" pa!a a&p%>*a! a !"sp#s$a 'a *a As p!#$"+as !"sp#+s"%s p"a $!a+s'# '# s%+a s# a CD3, " .a;"& pa!$" '# CR (!"*"p$#! p!#p!%a&"+$" '%$# Q CD3)
O+," Ap"+as %+.=*%$#s %!"+s ap!"s"+$a& s""*$%+a (V CD62L) " p"!&%$" # p!#*"ss# '" !#a&"+$# E" +# !"*%!*a pa!a # $"*%'# p"!%.!%*# p#%s +# ap!"s"+$a as &#*as '" a'"s# cNa as+*%a '" *#"s$%&a#, a *a "+$!a "& & "s$a'# '" a+"!%a, s" $#!+a+'# +#/!"sp#+s%a 21
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Apresentação cruzada: #*#!!" a .s# '# .a#ss#&# *#+$"+'# #s a+$"+#s %+"!%'#s *#& #
!"$*# "+'#pas&$%*#, " "+$#, "ss"s p"p$'"#s s# $!a+s#*a'#s '# RE pa!a # *%$#s# a$!as '" %as p#*# *#+-"*%'as, #+'" #*#!!" a '"!a'a# '#s p"p$'"#s &a!*a'#s *#& b%%$%+a +# *%$#pas&a p"# p!#$"#ss#&a Ess"s p"p$'"#s s# b#&b"a'#s pa!a # !"$*# "+'#pas&$%*# a$!as 'a p!#$"+a AF N# RE - # '#b!a&"+$# '" MHC '" *ass" I " +"ss" p!#*"ss# - %+$"!a# *#& #s p"p$'"#s E+$#, "ss"s MHCs '" *ass" I %a'#s a# p"p$'"# s# $!a+sp#!$a'#s pa!a a sp"!.*%" p#! &"%# '" "s*as '# G#% D"ss" &#'#, as *as '"+'!$%*as s# ap$as a a$%a! %+.=*%$#s CD8 %!"+s %a MHC '" *ass" I
&a$r'a0os Na !"sp#s$a %&+" *"a!, #s &a*!=.a#s .a#*%$a& # a+$"+#s " # ap!"s"+$a& *a -1 "."$#!a Essa *as '%."!"+*%a'as "p!"ssa& # CD40L " s"*!"$a& IN/ ɣ " a$%a& # &a*!=.a# %+$"+s%>*a+'# a a# &%*!#b%*%'a '#s &a*!=.a#s, *a!a*$"!%;a+'# a %a *ss%*a '" a$%a# '#s &a*!=.a#s Os &a*!=.a#s a$%a'#s &a$a& #s &%*!##!a+%s&#s .a#*%$a'#s p!%+*%pa&"+$" p"as a"s 'as "sp*%"s !"a$%as '" #%+%#, =%'# +$!%*# " "+;%&as %s#ss&%*as #'#s "ss"s a"+$"s &%*!#b%*%'as s# p!#';%'#s '"+$!# '# %s#ss#&# Ess"s &a*!=.a#s a$%a'#s $a&b& "s$%&a& a %+@a&a# p#! &"%# 'a s"*!"# '" *%$#*%+as " &"'%a'#!"s %p'%*#s '" *!$a '!a# Os &a*!=.a#s a$%a'#s p"a -2 *#+$!%b"& pa!a # !"&#'"a&"+$# $"*%'a " .#!&a# '" $"*%'# >b!#s# Is$# p#%s a IL/4 " IL/13 a$%a& #s &a*!=.a#s pa!a "p!"ssa! "+;%&as " p!#&#"& a s+$"s" '" *#"+# " >b!#s" (%a a$"!+a$%a) As *%$#*%+as 'a -2 sp!%&"& a a$%a# '#s &a*!=.a#s p"a %a *ss%*a
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Cas K
Na !"sp#s$a %&+" -&#!a, #s %+.=*%$#s K %+$"!+a%;a& #s a+$"+#s " ap!"s"+$a& p"p$'"#s '"!%a'#s '"ss" a+$"+# *a -"p"! Essa ap!"s"+$a# "ss"+*%a pa!a a p!#'# '" a+$%*#!p#s '" '"p"+'"+$"s '" *as -
Respostas un$ionais dos !in'$itos T 1) A!teraç>es na epressão de mo!.$u!as de super2$ie D"+$!# '" a&as -#!as ap=s a a$%a#, as *as a&"+$a& a "p!"ss# '" CD69, " &a p!#$"+a '" &"&b!a+a Essa p!#$"+a a !"sp#+s" p#! !"';%! a "p!"ss# '# !"*"p$#! S1FR1, " !"*#+-"*" # !a'%"+$" '" *#+*"+$!a# '# %p'%# S1F A *#+s"+*%a '%ss# " as *as a$%a'as p"!&a+"*"& $"&p# s>*%"+$" +# =!# %+.#%'" pa!a !"*"b"! #s s%+a%s " a$%a& sa p!#%."!a# " '%."!"+*%a# "& *as "."$#!as " '" &"&=!%a D"p#%s 'a p!#%."!a#, # +" '" "p!"ss# '" CD69 '%&%+% " as *as #$a& a "p!"ssa! a$#s +"%s '" S1FR1, p"!&%$%+'# " as *as "."$#!as " '" &"&=!%a sa%a& '#s =!#s %+.#%'"s D"+$!# '" 24 a 48 -#!as ap=s a a$%a#, as *as "p!"ssa& a$#s +"%s '" CD40L " p"!&%$" " "as ""*$"& sa .+# "."$#!a, " a '" a'a! #s &a*!=.a#s " *as K A& '%ss#, "a& !"$!#a%&"+$a# p#s%$%a " a&p%>*a a !"sp#s$a *"a! '# %+.=*%$# Ap=s a a$%a#, as *as !"';"& a "p!"ss# '" &#*as " # *#+';"& a$ #s =!#s %+.#%'"s, *#&# a L/s""*$%+a " # !"*"p$#! CCR7 A "p!"ss# '" CLA/4 $a&b& a&"+$a +# *!s# '" 24 a 48 -#!as ap=s a a$%a# '# %+.=*%$# O CLA/4 # !"*"p$#! %+%b%'#! '# *#"s$%&a'#! K7 O CD28 p#ss% # &"s&# %a+$", p#!&, sa a>+%'a'" p"# K7 '" 20 a 50 ";"s &"+#!, s"+'# ass%&, "" s" a*#pa a# K7 ap"+as a+'# "s$" s" "+*#+$!a "& a$#s +"%s U&a "; " as AFCs +# "s$# &a%s 22
"p#s$as a# a+$"+# " #s +"%s '" K7 s# '%&%+'#s, # CLA/4 %a/s" a# K7 p!"."!"+*%a&"+$", "a+'# a# b#"%# '# *#"s$&#
3) ,e$reção de $ito$inas de IL3 e epressão do re$eptor de IL3 (IL3R) Essa *%$#*%+a & .a$#! '" *!"s*%&"+$#, s#b!"%+*%a " '%."!"+*%a# '#s %+.=*%$#s CD4 As *as " !"*#+-"*"& # a+$"+#, p!#';"& IL/2 Ea a" +as &"s&as *as " a p!#';"& " +as *as a'a*"+$"s, %ss# a!a+$" " as *as "sp"*>*as pa!a # a+$"+# s"a& as " &a%s p!#%."!"&, *a!a*$"!%;a+'# a "pa+s# *#+a
,inapse Imuno!'0i$a a+'# # *#&p"# CR !"*#+-"*" p"p$'"#s %a'#s a# MHC +a AFC, !%as p!#$"+as '" sp"!.*%"s " &#*as '" s%+a%;a# %+$!a*"a! 'as *as s# !ap%'a&"+$" &#b%%;a'as pa!a # p#+$# '" *#+$a$# "+$!" "ssas *as " a AFC, p"!&%$%+'# & *#+$a$# "s$" Essa !"%# '" *#+$a$# .s%*# *#+-"*%'a *#&# s%+aps" %&+#=%*a As %+$"!%+as LA/1 'a sp"!.*%" 'a *a p"!&a+"*"& +a p"!%."!%a 'a s%+aps", #+'" a$a& "s$ab%%;a+'# " p!##+a+'# # *#+$a$# "+$!" as 'as *as a$!as 'a %a# a# ICAM/1 'a AFC Is$# #*#!!" p#%s a *a p!"*%sa sp"!a! #s p!#b"&as '" ba%a a>+%'a'" '# CR p"# a+$"+# " 'a !"';%'a '%sp#+%b%%'a'" '" &#*as '" MHC '%sp#+"%s *#& # a+$"+# "sp"*>*# A s%+aps" *#+s$%$% # #*a "& " # a*#pa&"+$# !"p"$%'# '# CR p#'" s"! ss$"+$a'# p#! "ss" +B&"!# '" p"p$'"#/MHC !"';%'#, %ss# .a*%%$a a s%+a%;a# ">*a; " p!##+a'a 'a *a
-ieren$iação das $.!u!as T C-6 As *%$#*%+as a$a& s#b!" as *as "s$%&a'as p"# a+$"+#, %+';%+'# a $!a+s*!%# '" "+"s '" *%$#*%+as *a!a*$"!s$%*as '" a& sb$%p# A &"'%'a " #*#!!" a a$%a#, #s "+"s " *#'%>*a& as *%$#*%+as '# sb$%p# s" $#!+a& &a%s a*"ss"%s, "+a+$# #s '"&a%s "+"s s" $#!+a& &a%s %+a*"ss"%s D"ss" &#'#, "ssas *as s" $#!+a& *a'a "; &a%s p#a!%;a'a As *%$#*%+as " %+';"& a '%."!"+*%a# 'a *as CD4 "& & '"$"!&%+a'# sb$%p# s# p!#';%'as p"as AFCs O p!#*"ss# '" '%."!"+*%a# 'as *as CD4 *-a&a'# '" p#a!%;a# As *a!a*$"!s$%*as " *a!a*$"!%;a& # sb$%p# 'a *as CD4 "."$#!a s# as *%$#*%+as " p!#';"& -1 p!#'# '" IL/12, IL/18 " IN/ ɣ. ⋅ -2 p!#'# '" IL/4, IL/5 " IL/13 ⋅ -17 p!#'# '" IL/17 " IL/22 ⋅
cAs *as "."$#!as $"+'"& a sa%! '#s =!#s %+.#%'"s " &%!a! pa!a #s s$%#s '" %+."*# #+'" "s$# p!"s"+$"s #s &%*!##!a+%s&#s
C.!u!as de mem'ria A&as *as p#'"& s" '%."!"+*%a! "& *as '" &"&=!%a F#ss"& *apa*%'a'" '" s#b!"%"! p#! #+#s p"!#'#s "& & "s$a'# %"s*"+$" '"p#%s " # a+$"+# "%&%+a'# " &#+$a! !"sp#s$as &a%s ">*%"+$"s " &a%s !p%'as "& & s"+'# "+*#+$!# *#& "ss" a+$"+# a+'# *#&pa!a'# s *as %!"+s, p#%s as *as "sp"*>*as pa!a "ss" a+$"+# s" "+*#+$!a& "& &a%#! a+$%'a'" A& '%ss#, as *as '" &"&=!%a p#ss"& a$#s +"%s '" !"*"p$#! pa!a IL/7, p#%s a *%$#*%+a &a%s %&p#!$a+$" pa!a a sa s#b!"%+*%a
CAPÍTULO 1N (&e$anismos #etores da Imunidade Ce!u!ar) &#CA*I,&O, #4#TOR#, -A I&U*I-A-# C#LULAR 23
Os %+.=*%$#s CD8 s" p!#%."!a& " s" '%."!"+*%a& "& %+.=*%$#s *%$#$=%*#s (CL), " ap!"s"+$a& !:+#s *%$#$=%*#s " p#'"& &a$a! *as " "p!"ssa& p"p$'"#s '"!%a'#s '#s a+$"+#s *%$#s=%*#s (" p"p$'"#s %!a%s) " s# ap!"s"+$a'#s %a'#s a# MHC '" *ass" I Os CL CD8 &a$a& ba*$!%as %+$!a*"a!"s *asa+'# a &#!$" 'a *a %+."*$a'a a+'# "p#s$as *as %+."*$a'as, "as %b"!a& !:+#s *#& *%$#$#%+as *#&# p"!.#!%+as " !a+;%&as A p"!.#!%+a .a*%%$a a "+$!a'a 'a !a+;%&a +a *a/a#, " a !a+;%&a '"@a!a !%as %as '" ap#p$#s" A "sp"*%>*%'a'" *as %+."*$a'as p#ss" '"%'# a s%+aps" %&+#=%*a, %s$# " "ssas &#*as s= s# s"*!"$a'as +# *#+$a$# '# CL " 'a *a/a# As *as -1 #*#!!"& "& !"sp#s$a a#s &%*!##!a+%s&#s " a$%a& &a*!=.a#s, *as '"+'!$%*as " *as N? O IN/ ɣ a p!%+*%pa *%$#*%+a '" a$%a# '#s &a*!=.a#s pa!a &a$a!"& #s &%*!##!a+%s&#s .a#*%$a'#s (%a *ss%*a) p!#';%'# p"as *as -1, N? ("& !"sp#s$a a# IL/12) " CD8 ("& !"sp#s$a a# !"*#+-"*%&"+$# '# a+$"+# " p!#'# '" IL/12 " IL/18) As *as -2 #*#!!"& "& !"sp#s$a a -"&%+$#s " a!"+#s Es$%&a a p!#'# '" IE " a$%a #s "#s%+=>#s " &as$=*%$#s pa!a a "%&%+a# '#s -"&%+$#s A IL/4 s"*!"$a'a p!#&#" # sd%$*- '" %s#$%p#s 'a *a K " p!#'# '" IE< a IL/5 s"*!"$a'a a$%a "#s%+=>#s pa!a %b"!a!"& # *#+$"B'# '#s !:+#s " '"s$!%! #s -"&%+$#s, p#!&, $a&b& p#'" "s%#+a! # $"*%'# '# -#sp"'"%!#< a IL/4 " IL/13 +$as p!#&#"& p!#$"# +as ba!!"%!as "p%$"%a%s " "s$%&a& a a$%a# '" &a*!=.a#s p"a %a a$"!+a$%a As *as -17 #*#!!"& "& !"sp#s$a a ba*$!%as " .+#s "& %&p#!$a+$" pap" +a %+."*# %+$"s$%+a "& .+# s%"+*%a'#!a '" -2 R"*!$a +"$!=>#s, " %+"!"& " &a$a& # &%*!##!a+%s&#
CAPÍTULO 11 (Atiação da C.!u!a + e Produção de Anti$orpos) Atiação do Lin'$ito + no ,istema Imune
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Respostas de anti$orpos dependentes de $.!u!as Taui!iares a ant20enos prot.i$os O a+$"+#, "& sa *#+.#!&a# +a$%a, %+$a*$a, " +# p!#*"ssa'# p#! AFCS ap!"s"+$a'# s *as K A %a# '# a+$"+# a# !"*"p$#! %b"!a s%+a%s b%#&%*#s s *as K, " %+%*%a& # p!#*"ss# '" a$%a# O !"*"p$#! %+$"!+a%;a # a+$"+# %a'# "& "s*as "+'#ss#&a%s ", s" # a+$"+# .#! &a p!#$"+a "" p!#*"ssa'# "& p"p$'"#s " p#'"& s"! ap!"s"+$a'#s %a &#*a MHC *ass" II +a sp"!.*%" 'a *a K pa!a # !"*#+-"*%&"+$# p#! *as a%%a!"s O pa! '" &#*as CD40 (p!"s"+$" +# %+.=*%$# K) " %a+$" CD40L (p!"s"+$" +# %+.=*%$# a%%a!) .#!+"*" s%+a pa!a a a$%a# '# %+.=*%$# K (%+'; a p!#%."!a# " '%."!"+*%a# 'a *a K, %+%*%a&"+$" +#s .#*#s "$!a.#%*a!"s ", '"p#%s +#s *"+$!#s "!&%+$%#s) C%$#*%+as p!#';%'as p"# %+.=*%$# s# %&p#!$a+$"s pa!a a a$%a# '# %+.=*%$# K *#+$!%b%+'# pa!a p!#*"ss#s '" $!#*a '" *ass" A %+$"!a# "+$!" as *as a%%a!"s " #s %+.=*%$#s K %+%*%a'a p"# !"*#+-"*%&"+$# '# &"s&# a+$"+# p!#$%*# p"#s '#%s $%p#s *"a!"s " s"" &a s"+*%a p!"*%sa '" ""+$#s As *as CD4 %&a$!as s# a$%a'as p"# a+$"+# (s#b a .#!&a " p"p$'"#s p!#*"ssa'#s) +as ;#+as 'as *as p#! &"%# 'a ap!"s"+$a# p#! *as '"+'!$%*as ", "+$#, '%."!"+*%a&/s" "& *as a%%a!"s As *as K %&a$!as s# a$%a'as +#s .#*#s p"# &"s&# a+$"+# ("& sa *#+.#!&a# +a$%a) " .#% $!a+sp#!$a'# pa!a As *as a%%a!"s " as *as K a$%a'as &%!a& "& '%!"# &a #$!a " %+$"!a"& +as b#!'as '#s .#*#s pa!a .#!&a! #s *"+$!#s "!&%+a$%#s, +#s a%s &a !"sp#s$a '" a+$%*#!p#s &a%s "sp"*%a%;a'a &#+$a'a As *as a%%a!"s " as *as K a$%a'as p"# a+$"+# &#"&/s" &a "& '%!"# #$!a "& !"sp#s$a a#s s%+a%s '" %&%#*%+as (CWCR5) 24
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A a$%a# /'"p"+'"+$" '" *as K +#s .#*#s "$!a.#*a!"s p!#'; a+$%*#!p#s '" ba%a a>+%'a'" " p#'"& *%!*a! " %&%$a! a p!#paa# '" &a %+."*# A !"sp#s$a "$!a/ .#%*a! $a&b& a%%a +a "!a# '" *as a%%a!"s .#%*a!"s (H) " &%!a& pa!a # .#*# " s# +"*"ss!%as pa!a a .#!&a# '# *"+$!# "!&%+a$%# A&as *as K a$%a'as p"# a+$"+# +# .#*# "$!a.#%*a! $a&b& !"$#!+a& a# .#*#, pa!$%*%pa& +a .#!&a# '# *"+$!# "!&%+a$%# " s#.!"& a$"!a"s " !"s$a& "& &a !"sp#s$a -&#!a &a%s p#$"+$" " '" #+a '!a# Os ""+$#s *a!a*$"!s$%*#s 'as !"sp#s$as -&#!a%s '"p"+'"+$"s '" *as a%%a!"s, %+*%+'# a &a$!a# 'a a>+%'a'", $!#*a '" %s#$%p#, " a "!a# '" pas&=*%$#s " *as K '" &"&=!%a '" %'a #+a, #*#!!"& p!%+*%pa&"+$" "& "s$!$!as #!a+%;a'as '"+#&%+a'as *"+$!#s "!&%+a$%#s, " s# *!%a'#s '"+$!# '#s .#*#s %+.=%'"s '!a+$" as !"sp#s$as %&+"s /'"p"+'"+$"s Ca'a *"+$!# "!&%+a$%# *#&p"$a&"+$" .#!&a'# *#+$& *as '"!%a'as '" & B+%*# *#+", # '" p#*#s, '" *as K "sp"*>*as pa!a # a+$"+# Na !"%# "s*!a '#s *"+$!#s "!&%+a$%#s #*#!!" %+$"+sa p!#%."!a# '" *as K A !"%# *a!a ap!"s"+$a &a%s %+.=*%$#s " $a&b& *as '"+'!$%*as .#%*a!"s " +# s" ass"&"-a& *#& as *#+"+*%#+a%s p#%s +# ap!"s"+$a& a+$"+#s %a MHC Eas s# "sp"*%a%;a'as +a !"$"+# '" a+$"+# p#! ap!"s"+$a! %&+"*#&p"#s ass#*%a'#s A ass#*%a# '" %&+"*#&p"#s "a a a$%a# '# *#&p"&"+$# " s" >a& +a p#!# C '# a+$%*#!p# As *as '"+'!$%*as .#%*a!"s $& &%$#s !"*"p$#!"s pa!a C '" a+$%*#!p# " *#&p"&"+$# " *#& %ss# !"$& *#&p"#s " *#+$& # a+$"+#
Tro$a de Isotipo (C!asse) da Cadeia Pesada A&as ";"s #*#!!"& $!#*as '" %s#$%p# "& *as K " s" "+*#+$!a& +#s .#*#s "$!a*"a!"s '"%'# a a# 'as *as a%%a!"s "$!a.#%*a!"s p!"s"+$"s< +# "+$a+$#, %ss# #*#!!" *#& &a%s .!"_+*%a "& *"+$!#s "!&%+a$%#s, s#b a %+@"+*%a 'as H A -ab%%'a'" 'as *as K '" p!#';%! '%."!"+$"s %s#$%p#s '" a+$%*#!p#s p!#p#!*%#+a &a +#$" pas$%*%'a'" +as !"sp#s$as %&+"s -&#!a%s p#! &"%# 'a "!a# '" a+$%*#!p#s " ""!*"& .+"s "."$#!as '%s$%+$as " "s$# "+#%'#s +a '"."sa *#+$!a '%."!"+$"s $%p#s '" a"+$"s %+."**%#s#s As *as a%%a!"s .#%*a!"s p!#';"& IL/21 " %+'; a a$%a# " $!#*a '" *ass" '# %+.=*%$# K C%$#*%+as p!#';%'as p#! H, ass#*%a'as a IL/21 %+';"& a $!#*a '" *ass" " #*#!!" +a ;#+a *a!a IN/\ %+'; a $!#*a pa!a a *ass" IG " a IL/4 %+'; a $!#*a pa!a IE A &'a+a pa!a IA "s$%&a'a p"# .a$#! $!a+s.#!&a+$" '" *!"s*%&"+$#/ O!'"& '#s Is#$%p#s +as $!#*as '" *ass" IM T IG3 T IG1 TIG2b T IG2a T IE T IA &aturação de A%nidade # p!#*"ss# " *#+'; a & a&"+$# 'a a>+%'a'" '" a+$%*#!p#s a & '"$"!&%+a'# a+$"+#, *#+.#!&" p!#!%'" a !"sp#s$a -&#!a / '"p"+'"+$" " # !"s$a'# 'a &$a# s#&$%*a '#s "+"s I s"%'a p"a s#b!"%+*%a s""$%a 'as *as K p!#'$#!as '" a+$%*#!p#s *#& &a%#! a>+%'a'" As *as a%%a!"s " as %+$"!a"s CD40CD40L s# +"*"ss!%as pa!a " s" %+%*%" a -%p"!&$a# s#&$%*a +as *as K "& p!#%."!a# +#s *"+$!#s "!&%+a$%#s " s" *a!a*$"!%;a *#&# &$a"s p#+$a%s +as !"%"s a!%"%s 'as %&+##b%+as A p!"s"+a '" &$a"s "s$ !"a*%#+a'a a# a&"+$# 'a a>+%'a'" '#s a+$%*#!p#s a# a+$"+# " %+';% a !"sp#s$a As *as " s#.!"& +"+-&a # &$a"s '" ba%a a>+%'a'" &#!!"& A "s$%&a# !"p"$%'a p#! a+$"+#s p!#$%*#s '"p"+'"+$"s '" *as "a a# a&"+$# '# +B&"!# '" &$a"s +#s "+"s I 'as *as K "sp"*>*as a "ss"s a+$"+#s +# *"+$!# "!&%+a$%# A&a '"ssas &$a"s s# &a%s p!#"%s '" s" &#s$!a!"& B$"%s &a "; " p!#';%!# a+$%*#!p#s '" a$a a>+%'a'" N# "+$a+$#, &%$as 'as &$a"s p#'"& "!a! &a '%&%+%# # a$ &"s&# &a p"!'a 'a *apa*%'a'" '" %a# a# a+$"+#
A %a# 'as *as K a# a+$"+# ap!"s"+$a'# p"as *as '"+'!$%*as .#%*a!"s +"*"ss!%a pa!a %&p"'%! a &#!$" p!#!a&a'a 'as *as K As *as K $a&b& ap!"s"+$a& a+$"+# pa!a as *as H '# *"+$!# "!&%+a$%#, " p#! sa "; p!#&#" a s#b!"%+*%a 25
'a *a K As *as K " s" %a& a a+$"+#s *#& a$a a>+%'a'" s# s""*%#+a'as pa!a s#b!"%"! A "+;%&a *-a" +"*"ss!%a pa!a a $!#*a '" %s#$%p# " &a$!a# '" a>+%'a'" a '"a&%+as" %+';%'a p#! a$%a# (AID) *a "p!"ss# a$%a'a p!%+*%pa&"+$" p#! s%+a%s '" CD40 +as *as H A "+;%&a '"sa&%+a *%$#s%+as "& &#'"s '" DNA '" >$a s%&p"s, *#+"!$"+'# !"s'#s '" *%$#s%+a (*) "& !"s'#s '" !a*%a ()
4unç>es das I0s • I0&" # KCR +a sp"!.*%" 'a &"&b!a+a '# %+.=*%$# K a+'# s"*!"$a'a p"+$a&!%*a " p#ss% 10 s$%#s a$%#s '" %a# a a+$"+# (s# b#as pa!a !"a"s '" a$%+a#) Na .#!&a s#B" p#'" "s$a! ab"!$a # +a .#!&a '" !a&p# a+'# s" "+*#+$!a +a sp"!.*%" '" & &%*!#!a+%s&# .a#!"*" a a$%a# '# *#&p"&"+$# • I0-" &a I '" &"&b!a+a " +# "%s$" +a .#!&a s"*!"$a'a I0G ab+'a+$" +# s#!# A$!a"ssa& pa*"+$a " ap!"s"+$a !"*"p$#!"s pa!a a sa • p#!# C a&b& a$%a& *#&p"&"+$# p#!& s# &"+#s ">*%"+$"s " IM +"ssa .+# I0A Ap!"s"+$a& *#+*"+$!a"s ba%as +# s#!# S# "+*#+$!a'as "& !"%"s '" • &*#sa, !%*a "& G/Z " IL/10 %+'$#!as '" IA '%&!%*a %a'a p"a p!#$"+a J +a .#!&a s"*!"$a'a $!a+s#*%$a'a pa!a # B&"+ '# %+$"s$%+# (!"%# '" &*#sa) " a% +"$!a%;a ba*$!%as • I0#" Ap!"s"+$a& *#+*"+$!a"s ba%as " a+'# "& *#+*"+$!a"s &a%s ""a'as s"!"& *#&# %+'*%# '" p!#*"ss#s a!%*#s " %+."*# p#! "!&" R"*"p$#!"s C As *as p!%+*%pa&"+$" 'a %&+%'a'" %+a$a "p!"ssa "ss"s !"*"p$#!"s #+'" #s a+$%*#!p#s s" %a& " %+';"& a"s &%*!#b%*%'as (p#! ""&p# +# &a*!=.a#)
CAPÍTULO 13 (&e$anismos #etores da Imunidade /umora!) -ieren$iação e 4unç>es das C.!u!as T C-7 #etoras Os !s "#!a& pa!a $%%;a! !%as &#*as 'a sp"!.*%" *"a! pa!a #b$"! "+$!a'a +as *as '# -#sp"'"%!# " pa!a sa! a &a%+a!%a "+$%*a " '" s+$"s" p!#$%*a 'as *as '# -#sp"'"%!# pa!a s" !"p%*a! " '%ss"&%+a! '" &a *a pa!a #$!a Os !s +# p#'"& s"! '"s$!'#s s" as *as %+."*$a'as +# p#ss!"& &"*a+%s&#s &%*!#b%*%'as %+$!+s"*#s, # s" #s !s "s$%"!"& +# *%$#s# #+'" s# %+a*"ss"%s a "ss"s &"*a+%s&#s '" &#!$" N"ssas s%$a"s, a B+%*a &a+"%!a '" "!!a'%*a! a %+."*# "s$ab""*%'a &a$a+'# a *a %+."*$a'a, %b"!a+'# # !s pa!a # &"%# "$!a*"a! " pa!a%sa+'# a sa *apa*%'a'" '" s#b!"%"! " s" !"p%*a! Essa .+# '" p!#&## '" &#!$" '" *as *#& !s +"& s" *%$#s# &"'%a'a p#! %+.=*%$#s *%$#$=%*#s CD8 Q As *%$#*%+as p!#';%'as p#! "ssas *as $a&b& *#+$!%b"& pa!a a "%&%+a# '" &a a!%"'a'" '" &%*!#!a+%s&#s %+$!a*"a!"s A s"+'a .+# %&p#!$a+$" 'as *as CLs CD8 Q a "!!a'%*a# '" '%"!s#s $&#!"s Cas CD8Q %&a$!as !"*#+-"*"& a+$"+#s (!s # a+$"+#s '" $&#!"s), &as p!"*%sa& s" p!#%."!a! " s" '%."!"+*%a! pa!a "!a! & *#++$# s>*%"+$"&"+$" !a+'" '" CLs pa!a '"s$!%! a #!%"& '# a+$"+# D"+$!# '# *%$#pas&a '" CLs '%."!"+*%a'#s, "%s$"& +&"!#s#s %s#ss#&#s &#'%>*a'#s (!:+#s) " *#+$& p!#$"+as, %+*%+'# p"!.#!%+as " !a;%&as, *a .+# &a$a! #$!as *as A& '%ss#, #s CLs '%."!"+*%a'#s s# *apa;"s '" s"*!"$a! *%$#*%+as, p!%+*%pa&"+$" IN/\, " $"& a .+# '" a$%a! .a=*%$#s O .a$#! '" $!a+s*!%# $/K"$ *#+$!%b% pa!a # +" ""a'# 'a "p!"ss# '"s$s p!#$"+as %s#ss#&a%s " IN/\ As *as '"+'!$%*as ap!"s"+$a& a+$"+#s %a MHC '" *ass" I a *as CD8 Q Es$a %a '" ap!"s"+$a# !""! " #s a+$"+#s p!#$%*#s "s$"a& p!"s"+$"s +# *%$#s# '" *as %+."*$a'as '" &#'# " "s$as p!#$"+as p#ssa& '"!a'a! "& p!#$"#ss#&as, pa!a, "& s"%'a, "+$!a! +# !"$*# "+'#pas&$%*# p#! &"%# '# $!a+sp#!$a'#! AF As *as '"+'!$%*as "sp"*%a%;a'as %+"!"& as *as %+."*$a'as, *as $&#!a%s # p!#$"+as "p!"ssa'as p#! "ssas *as, $!a+s."!"& #s a+$"+#s p!#$%*#s pa!a # *%$#s# " p!#*"ssa& 26
#s a+$"+#s pa!a a "+$!a'a +a %a '" ap!"s"+$a# '" a+$"+#s p#! MHC '" *ass" I pa!a # !"*#+-"*%&"+$# p#! *as CD8Q A a$%a# *#&p"$a '" *as CD8 Q %&a$!as " sa '%."!"+*%a# "& CLs .+*%#+a%s " *as '" &"&=!%a p#'"& !""!"! a pa!$%*%pa# '" *as CD4 Q a%%a!"s a+'# a$%a'as as *as CD4 Q a%%a!"s "p!"ss# # %a+$" CD40L " s" %a a# CD40 ' *as '"+'!$%*as *a!!"a'as *#& a+$"+#s Essa %+$"!a# a$%a as AFCs pa!a $#!+/as &a%s ">*%"+$"s "& "s$%&a! a '%."!"+*%a# 'as *as CD8 Q, "& pa!$", %+';%+'# a "p!"ss# '" *#"s$%&a'#!"s
CAPÍTULO 16 (To!ern$ia Imuno!'0i$a e Autoimunidade)
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CAPÍTULO 17 (-ist
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CAPÍTULO 1J (Respostas Imunes -ependentes de I0# e -oenças A!.r0i$as)
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31
