10-21-09 Humoral Immune Responses I 1. Describe the structures and characteristics of IgM, IgG, IgA, and IgE.

Note: IgM, IgD, IgG, IgA, and IgE are isot pes t!at di""er #ased on t!eir heavy chains, $!i%! are en%oded as mu, delta, gamma, alp!a, and epsilon, respe%ti&el ' IgG (o%ation: E&er $!ere )doesn*t %ross +++, -roperties: Most a#undant and long li&ed Ig Has .%/ re%eptors t!at %an #ind to p!ago% tes Has "our su#%lasses $it! minor "un%tional di""eren%es 0rosses t!e pla%enta to prote%t "etuses .%Rn re%eptors transport maternal IgG to t!e "etus in a pH dependent manner Has a &er long !al" li"e .%Rn re%eptors re% %le IgG #a%1 into %ir%ulation to e2tend !al" li"e .un%tions: Neutrali3es #a%terial to2ins and &iruses )%onse4uentl , IgG is 1no$n as a neutralizing anti#od , 5psini3es pat!ogens to en!an%e p!ago% tosis )using .%/ re%eptors, 6ensiti3es "or 1illing # N7 %ells A%ti&ates %lassi%al %omplement pat!$a

IgM (o%ation: #lood -roperties: Has "our %onstant domains in t!e !ea& %!ains 5%%urs as pentamers $it! J chains Due to its massi&e si3e, IgM %annot enter tissues and is onl "ound in #lood Has !ig! a&idit #ut lo$ a""init No re%eptors on p!ago% tes .un%tions: .irst anti#od to #e produ%ed in a !umoral immune response Most e""e%ti&e in a%ti&ating %omplement Important in rapid %ontrol o" #a%terial in"e%tions

IgA (o%ation: Mu%osal se%retions )epit!elia o" GI and respirator , -roperties: 5%%urs in #lood and e2tra&as%ular spa%es as a monomer

.orms dimers $it! J chains in order to #ind to pol -Ig re%eptors on epit!elial %ells 8ndergoes trans% tosis a%ross t!e % toplasm and is secreted into e2ternal #od "luids #ound to t!e se%retor %omponent %alled S Has t$o su#t pes IgA1 and IgA2 .un%tions: Neutrali3ing anti#od on epithelial surfaces IgD -roperties: 0oe2pressed $it! IgM on t!e sur"a%e o" a mature + %ell .un%tions: A%ts as a %ell sur"a%e re%eptor in&ol&ed in l mp!o% te a%ti&ation and suppression

IgE (o%ation: s1in -roperties: Al$a s a monomer 5%%urs in &er lo$ %on%entration in serum +inds to .%9 re%eptors on mast %ells and eosinop!ils .un%tions: +inds $it! !ig! a""init to mast cells "ound #eneat! t!e s1in, $it!in mu%osa, and along #lood &essels in 0:' Antigen #inding triggers degranulation and release o" in"lammator mediators 0onse4uentl , pla s a role in allerg as $ell as resistan%e to parasite in"e%tions 6ensiti3es "or 1illing # eosinophils

2. How are antibodies transported across epithelial barriers !pg 1"#$ IgA is t!e anti#od t!at gets transported a%ross epit!elia, or spe%i"i%all a%ross GI and respirator epit!elia' IgA is produ%ed # plasma %ells in t!e lamina propria IgA is t!en a%ti&el transported t!roug! epit!elia %ells # an IgA-spe%i"i% .% re%eptor 1no$n as pol%&Ig receptor )$!i%! also re%ogni3es IgM, !en%e t!e ;pol < pre"i2, 5n t!e luminal sur"a%e, IgA is released $it! a portion o" t!e #ound re%eptor' In t!e lumen, IgA re%ogni3es ingested )GI epit!', or in!aled )respirator epit!', mi%ro#es and #lo%1s t!eir entr '. (hat is the )echanis) of isot%pe switching +asi% idea: hea*% chain isot%pe !class$ switching is a #iologi%al me%!anism t!at %!anges a + %ell*s anti#od produ%tion "rom one %lass to anot!er' :!e pro%ess in&ol&es t!e same VH exon being expressed on different CH genes' 6u%! s$it%!ing o%%urs after exposure to the antigen, a"ter $!i%! t!e same &aria#le region is e2pressed alongside di""erent %onstant regions on t!e !ea& %!ain' :!e mole%ular #asis "or %lass s$it%!ing is DNA re%om#ination'

0 to1ines produ%ed # !elper : %ells determine $!i%! !ea& %!ain isot pe is produ%ed # in"luen%ing $!i%! !ea& %!ain %onstant regtion gene pre%ipitates in s$it%! re%om#ination: E2posure o" t!e + %ell to I+&,: produ%es IgE' E2posure o" t!e + %ell to -G.&/: produ%es IgA' Ho$ does isot pe s$it%!ing di""er "rom =)D,> re%om#ination? A"ter all, #ot! in&ol&e DNA rearrangement' Isot pe s$it%!ing is always productive Isot pe s$it%!ing uses di""erent en3 mes Isto pe s$it%!ing !appens after antigen stimulation Isot pe s$it%!ing is N5: random and is regulated # e2ternal signals )i'e' % to1ines "rom !elper :*s, ,. How can antibodies be secreted or act as )e)brane&bound receptors 7e point: Ig*s o" all !ea& -%!ain isot pes %an #e produ%ed eit!er in secreted or membrane bound "orms' A transition "rom mem#rane-#ound to se%reted !ea& %!ain o%%urs at t!e le&el o" 01A pro%essing )a1a alternate RNA spli%ing,'