Section d Short Answer: AnswWer-6 out of @ questions (2 points each = 12 points) 1, List and briefly explain 3 ways of generating B or T cell receptor divers (basepairs) during gene seument rearrangement 7 CY Mattie gene Segments V hy that do not directly include adding nucleotides CD Exsmuctease trimming v Deonbinataval divenity ‘ 2. Briefly explain the function of AIRE and its importance in immunology. ‘PERE AIRE gene regulates the autsiterane reg \ Relea) thet can expres tisswe ‘Self antigens by m avtertadve FV celi Shet may cthack He H's silf ti Rrewents aacte immune diseases regulary proteln Crash TEC se Hey ony peergnive Nha fs. \\ at ave the mar goals of lymphocyte development (Le, what constitutes successful development)? Produce Q— Q cells » BCR s a = ts gelvtde Alb De sea COE Hyco remyize MHC ; Sp Ba Ty can recogni PARE : @ Wacrogiges ST rey > Agus > prenect/inl 4 What toes it mean thatthe D segment can be read in all reading franies and hy is tistmee tant? of (BeR or TeR) is it possible for multiple D segments to be incorporated into and how is that possible? RB Ih her te ; aD differs from switching to other subclasses of antibody in B eels. 5 F Trappers. im the Bene meri? and Hf onl pds Aghrly) anh mctan CG cathe agers in te prehry . ‘1? lly try to avoid, occur during T and B cellSection 3 Short Answer Answer-6.outof8 questions (2 points each «12 polnts) 1. List and briefly explain $ ways of generating 8 arT cell receptor diversity that donot directly includ (basepairs) during gone segment rearrangement ot directly include adding nucleotides DH Martie gene Segments We HA Cleage trimming NY ermbnatienal divenity > ‘Peep AIRE ‘ R wok can expres tissme ‘Self antigens) by m Fe ee rae a, Rreveants auchedmnune diseases 2, Briefly explain the regalates the auctshimane rgulalery Protea Crest ‘ TEC so dey om Reaagnire w enptoeyte development (Le, what constitutes succesful development)? Preduce 2 — Q cally ——-» BCR = . calls —p> A Besa ; @-~T att CY Haycen reeeyrze MHCEE dhe: Wh ECOMNIME BARC A Grecia eco 8 ons reareuchs finden 4. What docs it mean that the Dsegine 5 > prevents Tres > nt cabe retinal’ reading fide andy sis oan 4 P 'S. Which receptor (BcR or TcR) is it, Possible for multiple D segments to be incorporated into and how is that possible? ye BBR Hes at OD segrnrts in Qa Be RSs membrane Yow also A+ Miami en Ree ‘ so IgD iis rm steht ote subse of dynes ng happens in the Bene meme? and it Conlee . me Condo. VgHlenls) and muctare Comdae Inf SB cette Mappers in the prephry . "1? cells typically try to avoid, occur during T and cell rearrangementtion 4: Mandatory answers- You must answer the following question (10 points) Given the following V and D gene segments: : “Draw (make a new diagram) the resulting joined contiguous double stranded DNA sequence (4 points) the hat a cleaved at the arrows and the 5 nucleotides (CGAGT) were added by the. i B. Circle the P nucleotides (2 points) i ae C. Draw a square around the N-nucleotides (2 points) 'D. What possible receptor(s)/chain(s)is(are) being generated below and how can you tll?(2 points) \ Vv ars <<) crs Te] Nit A-G-G-c-G-e-c-} i oa s = Hemiy. enain~ becmide H Ht has: Dapipect and me. adel Parc RELA (40 points) A Contain oe eae GMaPAOes wth ecg MHC cas (1) cl (2) o both) = binds 10 eee. lf fi amino acd peptides ws @. Trims long peptides Te eip tsa ae pepe ate sae for MacShort Essay: Answer 1 of 3 questions (8 points) Question 1 1. Ac Briefly explain the B Briefly expla! €, Does this sa and contrast how Mi 3, Compare and contrast the instructive and kinetic signaling m a spLincactve vosel. | oes r. ates t | fe See nique _siss col ak TCRenges Com Siptamaed This sights gerade» pmb oy mew _pemeees ——— tra T cat eapydsHh MHC se it ts D3 DE the Teeth ed with My Me Teall ies engey Won 5. HY egal Bitch \icaage ts \@ ~e> coe cOgt > } ane Nee Canter’ sigmlty-> CD 44 <@ intermpted dpnel sg oyge simy mabe! = Vinelic, is the mest ane Thad makes Sense aah rg peers a oeExperimental Conclusions: answer 2 out of 3 (5 points each = 10 points) Question 1 Control: An A x B mouse (with a m T cells are removed from the spleen (strain A) or the fathe below and then Tc ial chromosome (A] and a paternal chromosome [B]) is infected with a virus} nd incubated with a monolayer of virus infected epithelial cells derived from strain B). Experimental: The same mouse as above (A x B) is treated with the procedures, s from the spleen are incubated with a monolayer of virus infected ae epithelial cells derived from the mother PEN ke (rain A) or the father (eran B) <1 lace aaron A. List what will occur in #s 1-4 i For #3 and #4 briefly explain why this is “ax, Spleen cats crt) LeMvintected » > Ltitv-intetied Lara poe J #2 Killing Se Meet be dertnyed Teels evethat you can draw from the figure to the right? 4 ib cm recegter can’ recent remem meres we self. The ater ¥ 4 no Tat act vac 14 ifthe mice were not previously infected with LCMV? ass wyStudentName wet BMS522 Exam 2 Prof, Mital ‘Multiple Choice and True False: Answer 50 out of 54 questions (one point apiece = 50 points) Please write the one best answer on the line. __1 The cell receptor binds A) soluble peptide antigen ©) free lipid antigen © antigen complexed with MHC D) ll ofthe above 2. The T cell receptor binds its target j @® with less affinity than the BcR C) with greater affinity that the B cell receptor 8) with about equal affinity as the BcR D) the affinity with which a TeR binds cannot be determined — 3. The majority of T cell receptors are comprised of: A) alpha and gamma chains @alpha and beta chains ) gamma and delta chains D) heavy and light chains A __+-To create variability the T cell receptor utilizes: ‘ ‘A) combinatorial diversity only V5 recombination ) somatic hypermutation ) heavy and light chain gene segment rearrangement __5.APCs must be __ before activating CD8+ Te cells ‘A) MHC restricted () activated by 1L10 binding (B) licensed ‘ D) activated by IL-2 binding E —_6 central Tolerance: (A)always occurs in the thymus D) always occurs inthe spleer 'B) always occurs in the bone marrow aay ‘ ©) primarily occurs in the lymph nodes ‘Type I hypersensitivity reactions ‘Type IV hypersensitivity reactions ¥ ells (Tasca) is false? D) Allofthe above are false E) None of the above are false IgG, Igo, Ig6 IeD, CD3Student Name BMSS522 Exam 2 Prof. gpte Choice-and True False: Answer 50 out of $4 questions (one point apiece = 0 points) tease write the one best answer on the line. or'binds Its target pnity than the BR jalaffinity as Bs ocrente variabitty the T cll receptor utlzes: ‘oomibinstorial diversity i Bysomatichypermunation D) heavy and SPs marrbe, ‘before activating CDS+ Tecells A) MHC restricted © activated by IL10 binding D) activated by IL-2 binding D) always occurs in the spleen E) none of the above Qype I hypersensitivity reactions °D) Type IV hypersensitivity reactions ‘cells (Trsc.) is false? D) Allof the above are false E) None of the above are false Goss”-t cells die in the thymus? 75% D)95% germ a functional B receptor but has not been exposed to its complementary ©) mature and naive D) activated but naive 1) it can bind foreign antigen antigen ‘expressed on the surface of each cell AandC Cand D (©) Vand the constant region join last D) Vand D join last Jetional or inversional joining is determined by: ‘segment C) The presence of enhancer sequence 1D) The order in which the segments are joined ‘Whether the ig gene segments join via del 4) The sequence of the RSS adjacent tothe gene Dpto Sanseiptional onertation of the segments ws tree see ount of axcboty gene rearrangement in 2B cell does not produce a productive/fun Spe mamaria Goremosome, what can happen nex: - "raxvagementon dhe homologous paternal chromosome C) attempt somatic hypermutation SB Sanrcerranpemeonadifirent maternal chromosome _D) attempt to rearrange the T cell receptor loc \ctional Ab gene (gees eons, Goesese cached to heavy chain regions C) switches the constant region of the light cha Foo pene segment rearrangement ) changes the antigen binding specificity ofthe rissa LB somes nindng ce eres 22 and $2 AOyforma abiding deh berween at in oland ‘= = not membrane bound on the cell surface 1D) None of the; ie ae ee eeeecerreer wast disrupt: MSC presentation C) all of the above D) none of the above in VIDY) coding regions? D) XRCCA with DNA ligase IV £) Ku 70 and Ku 80 manner after cleavage of the inter-strand hai D)XRCC4 with DNA ligaselV on ) ku 70 and Ku 0 IgM to pa gM ina B cell? tal modification of nuclear DNA via RAG-1 abovetage of T cells die inthe thymus? se 75% proximately what perce! __14.API A) 25% aoe B) 45% € ‘A B-cell has rearranged its DNA to forma functional B receptor but has not been exposed to its complementary __15.AB-cell has rearranges antigen, Itis termed: i ) mature and naive immature and nalve ; satire D) activated but naive 'B) mature and activated 16, Which is true of class | MHC: ~ re each MCI D) it can bind foreign antigen ‘A) Each MHC Lis specific for a given antigen ofeach cell AandC 8) Only one type of MHC I molecule is expressed on the surface ) Itcan bind selfantigen Cand D __17,mB cell light chain rearrangements: (Vand the constant region join last A)Vand D join first Vand J join first D) Vand Djoin last 46, whether the Ig gone segments join via deletional or inversiona joining is determined by: 'A) The sequence ofthe RSS adjacentto the gene segment C) The presence of enhancer sequence (The transcriptional orientation of the segments ) The order in which the segments are joined 19, fthe first round of antibody gene rearrangement in a B cell does not produce a productive/functional Ab gene zoe the maternal chromosome, what can happen next: « Gayattempt rearrangement on the homologous paternal chromosome C) attempt somatic hypermutation wy atemptrearrangement ona different maternal chromosome _D) attempt to rearrange the T cell receptor locu 20. 1g class switching; ‘switches the constant regions attached to heavy chain regions _C) switches the constant region of the li in regions = sonst ight chain B) occurs before V(D)] gene segment rearrangement ) changes the antigen binding specificity of the 21 SC claset: forma binding left between 2 and 62 Gora a din forma abiding cleft between al and a2 3) is not membrane bound on the cell surface 'D) None of the ae ao orl proteasome inhibitor would srt: MHC presentation C)allofthe above Pte 'D) none of the above hairpins in V(D)} coding resins? a D) XRCC4 with DNA ligase IV E) Ku 70 and Ku 80 endent manner after cleava 5 cleavage of the inter , D)XRCCS with DNAligae ty 5) Ku 70 and Ku 80 ‘modification of nuclear DNA Ay Pee via RAG-1/e thymus? __ 14 Approximate sym dase 95% 15.A Bell has rearranged its DNA to form a functional B receptor but has not been exposed to its complementary antigen, Itis termed: Jy what percentage of T cells dle in th @ immature and naive ©) mature and naive 'B) mature and activated D) activated but naive __16 Which is true of class I MHC: A) Each MHC Lis specific for a given antigen D) it can bind foreign antigen 8) Only one type of MHC I molecule is expressed on the surface of each cell AandC €) Itcan bind self antigen Cand D 17. In B cell light chain rearrangements: A) Vand D join first ©) Vand the constant region join last BV and } join first D) Vand D join last — 18, Whether the Ig gene segments join via deletional or inversional joining is determined by: A) The sequence of the RSS adjacent to the gene segment C) The presence of enhancer sequence ‘The transcriptional orientation of the segments D) The order in which the segments are joined 19. Ifthe first round of antibody gene rearrangement in a B cell does not produce a productive /functional Ab gene ‘the maternal chromosome, what can happen next: /attempt rearrangement on the homologous paternal chromosome C) attempt somatic hypermutation ++ B)attemptrearrangement on adifferent maternal chromosome _D) attempt to rearrange the T cell receptor locus ns attached to heavy chain regions _C) switches the constant region of the light chain 'segment rearrangement D) changes the antigen binding specificity of the forma a biding cleft between ai and a2 None of the above C)all of the above D) none of the above D) XRCC4 with DNA ligase IV E) Ku 70 and Ku 80 ‘manner after cleavage ofthe inter-strand hairpin? D) XRCC4 with DNA ligase iV cn E) Ku 70 and ku 80Pon neenewing Raure, depicting regions in dsDwA, for Questions 27.30 ‘The thdcated ftoms are fo ~ roms are found in an tg gene. Which ofthe gheted elements serves as a spacer? 2) 7p ) 9 bp Cie dp None ofthe above ®8. Thwhich cells are the Ig loc rearranged by RAL i y RAG-1/22 A) Developing T cells D) Develo, e eveloping monocytes B)devetoping B celts. E) None of the above €) Developing neutrophils KX yrs Must the RSS spacerbe to link the above V element to its appropriate D element? D)12 bp BB E) None of the above 9p Xe: erg must the RSS spacer be to link the above V element to its appropriate J element? é — D)12 bp icomponents that are essential for rearrangement of the Ig loci are not utilized in Noel? D) RSS sequences All of the above are essential for rearrangement of the ithe same MHC haplotype as your sibling is approximately: D)18. E) 116. of the most polymorphic regions of the genome, What does this mean? © There are many introns in this region. D) This region is regulated by many different meck D) number of antigen presenting cells, 5) transmembrane domain, n of T cells? a foreign peptideThe primary cell that can conduct cross presentation is ~~ @PPenairitic cells cpBeells 8) T cells 1D) Macrophages __38. Which of the following represents the earliest tage i T-cell development? A)DP 1p) $P-CD8 By dN E) Mature T cell )sP-cD4 scape the thymus? D> __-39.What happens to autoreactive T cells at z A)They can attack self tissues. ) All of the above 'B) They can be rendered anergic: E) None of the above ) They can negatively regulate other autoreactive cells ceptors leads to cell death? ____40. Binding of which ofthe following cell-surface ay TCR 1D) Caspase-8 B)TLR E)Bcl2 @rs development EXCEPT: 1) T1 B cells transition into T2 Allof the above are true F) None of the above are tue __a1.atlofthe following are true regarding B 2! ‘A Bealls complete maturation inthe spleen ‘culls are mostly developed when they leave che bone ) Bealls are not MHC class restricted C_ #2 marr. cts showers inthe Von ‘Aj high (extensive) @bigh or low depending on active i 5) moderate F high or low depending on CD21 exP' ow (estrcted) {43,8 cel developmental stages are primarily defined by: Qin srtace makers Whether i has interacted with an Antigen presenting cell OF NOK 12 age of the B cell D. Whether it was produced in the bone marrow or thymus. rue/alse: For each statement write whether itis true [T] or false [F] (one point each) 44, B cell receptors and MHC generate their diversity in essentially same way. 45, There are hundreds of MHC alleles in each individual's DNA, or is unable to bind to MHC. tive B cells. can usually rearrange the delta gene segments ing antigen and changes the effector function.ich = 12 points) ersity that do not direct include adding nucleotides q ent gent Seymenty @ Exemuacleate trimmin Qemmbinateial divusity the fu, on oF AIRE an ts inporancincmesotng 5 BES AIRE gene regulates the artitmane mgalatery proieln Chrasbeigie Feberd) thee can expres tissue Self antigens’ iy mTEC So they om Peeignine Sha aubreactive Teel Yet onny wtheck He its self HuOUll — Rrevents arte immune diseases S-Whatare the maior goals ofiymphocyre development hc on - Produce QQ ceils Se Al. NS OT att FSG kyon aay Thee, 5 oP thes Can recoynie MAC 4 eo | proneds/inhitelt ‘4. What does it mean that the D segme1 2° conten ant cafrbe readin all 3 read sFeceptor (BcR or TeR) ist possi nts to be incorporated into and how is Me curze 86 er (eR, seymarts vin ya FAS RSS — for multiple D segme ew’ dhow A Lunt, Setcay mee how clas witching from Ig og Re on: ee be 5 PAS, le a BTSs aspens in the Cane. mri and, Ht Condy Tminanture Condi 1gHenly) and matare Conde gb) Seheleses FAL i Bex happens in the preplry 7 Two potentially damaging genetic events, that human cells typically try to avoid, occur during What are these 2 events. Why do these cells take this risk? Sony) possible clinical uses of Tasccells © Aut immune @ Transplant regection om switching to other sub£8 quest 2 points each = 12 point Mottide gene Seymarts ® D> ®D Exermaciease trimy Bambrnatenl divas < Hep AIRE AN Feld) thet expres tisswe ‘Self ant Peegnize Ha atvendve Toul thet may — Revert ne OY ens, autte immune disexses ‘S.What are the maior goa Produce Q— Q ceils yon mga Ahad can recognise AC © > Krages > penuds int me . tema s Tite or (BER or TR) is tiple D segments tobe incorporated into and how is that po DRO RRS ih ear tM Di segrarts in Qu Fos RSS a T ven ake. behwern membre “2g [ae Ae ay Brakes Ab Sy ) ow class swiching rom 1 mischingt er bcasetentboten beats DP se key AP anf r — Becanxe class switching happens in the Bene mar and if Cone Ss 4 1 Frnaachere CPmdote Igflenly) and matare Conia \y0) ey sy, SEAL mB cells happens in the prephry 17. Two potentially damaging genetic events, that human cells typically try to avoid, occur during T and 8 ce | Whatare these 2 events. Why do these cell take this risk? 5a possible clinical uses of Tax cells. © Aute immune @® Transplant resection eSection 4 Mandatory answers. You must answer the following question (10 points) A. Given the following V and D Rene segments AL DbQW (ih \gram) the resulting joined contiguous double stranded DNA sequence (4 points) if the hairpin was at the atrows and the 5 nucleotides (CGAGT) were added by the ‘enzyme TdT. P hucleotides (2 points) ‘auare around the N-nucleotides (2 points) st possible reeeptor(s)/chain(s) is(are) being generated below and how can you tell? (2 points) ake ew aay eleaved B. Citele the G. Draw as D.Whs 1 eS. a aii oa Tce Cee T-6-¢ as es with hydrophobic amino ack Piasaic intracellular proteins ng MHC | peptides