University:
York University
Course:
SC/BIOL 3120 | Immunobiology
Academic year:

2023
Views:

46

Pages:

2
Author:

Niklas

Mechanism #2: Combinatorial Diversity combinatorial diversity: the rondemness of heavy and light chain pairing REMEMBER heavy and light chains are on different chromesomes and are assembled past translationally, THEREFORE the sequence the heavy chain CDR and the sequence of the light chain COR are seperats and distinct, AND peiring them will cause more randomness combinatorial diversity anly gets us so far: a Finite number of te arrangements out of 10"-18" options where does the rest of the diversity come from? Junctional Diversity! Mechanism #3: Junctional Diversity what happens to 155? they're non-coding 50 they get cut out -RAG 1/2 nicks the DNA ما cuts one strand of the double stranded DNA Step 3. The hydroxyl group that was liberated by the nick at the 3' and of the coding strand attacks the corresponding phosphate group on the noncoding strands of both the Vand the 3 segments to yield a covalently sealed hairpin coding end and a blunt signal end. OH causes second break, forming a coding end and signal end codes RSS Coding end Signal end shen the 855 is temoved, how do we make sure the two segments jom -Artemis cuts the coding end at one of 3 places →fill in gaps with randam segments adds ALOT of diversity Step 5. Opening of the hairpin can result in a 5' overliang, a 3' over hang, or a blunt end. The most common result generated by Artemis is a 3' overhang. Artomis Opening at 1 yields 5' overhang 3 Opening at 2 yields blunt end Opening at 3 yields 3' overheng 3 Steps 8-10 only accur in lg heavy chains. ATAT -strands are filled in with ICGATATA AGCERTAT Pnodantiden random nucleolides -segments are ligated to one another Metemis greek god of Children named because of the mendeficzny that was killing children Step & Exonuease cleavage can result in the loss of nudeutides on alther or both sides of the ending juint Step 9. Nontemplated nucleotides finred) am added to the coding joint by idi oroccasionally by pola. Step 10. Ligation of heavy shain by NHEI mediated by TdT Nucleotidia Pnucleotides Uthen Heavy Chain (Igh) Locus 1. D always joins with first 2. V then rearranges to join with the DJ segment Light Chain (Igl) Locus 1. First kappa, the lamba D Once pearrangement accurs, gene expression con then occur as normal! The Constant Region dictates isotype isotype/class switching B-cell secreles the same antibody with the same specificity BUT the isotype changes vp region remains the same bet constant region changes the B-cell stops making one isotype and begins making another Heavy chain DNA LVT LV D1 16 65 kb 45 b 35 34 21 kb 15 kb 14 12 kb Igh and IgD are the isatges of BLR. 15 isotype made during infection: 2nd isotype made during infection Potential Dengers: auternactiziby some ig's and TCR can react with self-antigen (becoms the methaniam, eccurs at randon) anergy elimination or silencing of autoreactive Band T-cells to prevent autoimmune diseases chrumosomal translocations arising during VDJ recombination or isotype switching may lead to lymphoid malignancies (cancer)