抗体抗体的多样性及其产生机制gaobo.ppt

* 因此1968年和1972年 WHO和国际免疫学会分别决定将具有抗体活性或化学结构与抗体相似的球蛋白统称为免疫球蛋白. ， 抗体和免疫球蛋白是两个不同的概念。抗体是个生物学和功能的概念.能与相应抗原特异结合的具有免疫功能的球蛋白.免疫球蛋白是个结构概念,除抗体外,还存在正常个体中天然的免疫球蛋白和病理情况下（骨髓瘤，巨球蛋白血症和冷球蛋白血症等）存在的免疫球蛋白及亚单位.如骨髓瘤中M蛋白.目前这些蛋白功能不清楚。 * 一 * 二 * 四 * * 克隆选择学说的主体思想是 * Recombination Activating Genes (encode RAG-1 and RAG-2) RAG-1 and RAG-2 mediate recognition of signal sequences and rearrangement of DNA segments. Mice deficient in RAG-1 or RAG-2 are unable to rearrange heavy or light chain genes. These mice have no mature B cells. -- B cells will not mature if they cannot express a BCR. （2）重组活化基因 Recombination Activating Genes RAG-deficient mice also lack mature T cells. -- The T cell receptor is also encoded by loci containing gene segments that must be rearranged before the TCR can be expressed. T cells will not mature if they cannot express a TCR. SCID (severe combined immune deficency) mice also have a defect that affects rearrangement of BCR and TCR loci. They also have no mature T or B cells. Flow cytometry of normal vs. RAG-1 deficient mice: Lymph node cells FITC anti-CD19 (B cell marker) and PE anti-CD3 ( T cell marker) Normal mice RAG-1 - deficient mice How recombination in the V regions of antibody happens? A G C T T A T A Terminal deoxynucleotidyl transferase (Tdt) An enzyme that randomly adds in nucleotides during joining of heavy chain (NOT light chain) segments. Read Kuby pages 113-115: Gene Segments Are Joined by Recombinases Productive and nonproductive rearrangements Joining of segments is not precise and may result in loss of the correct reading frame. This may lead to introduction of stop codons -- nonproductive rearrangements. RSS RSS RSS: recombination signal sequence RAG: recombination activating gene P-核苷酸和N-核苷酸的加入 片段断端形成发夹结构 TC AG D TA AT J 内切酶切开发夹结构产生P-核苷酸 T C G A D A T A T J TdT酶加入N-核苷酸 T C G A C T C D G A G C G A T A T J 通过DNA修复，断端连接，恢复双键结构 T C G A C T C G C T A T A A G C T G A G C G A T A T D J P