第十讲+b细胞介导的体液免疫应答.ppt

* * 半抗原实质就是一个B细胞表位可供B细胞识别，但是仅有B细胞表位，B细胞并不能活化，不能产生抗体，若给这个半抗原偶联一个载体分子，即提供一个T细胞表位供T细胞识别，T细胞活化后可以给半抗原反应细胞一个辅助，使其活化、最终产生抗体。这就是载体效应。完全抗原等同于一个TD抗原。绝大多数蛋白质抗原如流感病毒表面的血凝素蛋白属于TD-抗原，既含有B细胞表位又含有T细胞表位。 * 初始T细胞在T细胞区被抗原提呈细胞DC活化，只有那些表达趋化因子CXCR5和BCL6基因的T细胞才能分化发育为Tfh,然后迁移至T-B细胞交界处，与B细胞相互作用，分化为生发中心的Tfh细胞。这一过程受细胞因子及信号转录因子调控 Naive CD4+ T?cells interact with antigen-presenting dendritic cells (DCs) in the interfollicular or T cell zones; DC-primed CD4+ T?cells acquire expression of CXC-chemokine receptor 5 (CXCR5) and B?cell lymphoma 6 (BCL-6) to become early T follicular helper (TFH) cells. These cells then migrate to the T?cell–B?cell border and — following interactions with cognate B?cells — differentiate into germinal centre TFH cells. This differentiation process is governed by signals provided by signal transducer and activator of transcription 3 (STAT3)-activating cytokines, including interleukin-6 (IL-6), IL-12, IL-21 and IL-27. These cytokines are secreted by DCs (which produce IL-6, IL-12 and IL-27), B?cells (which produce IL-6 and possibly IL-27) and CD4+ T?cells (which produce IL?21). Cytokine-mediated activation of STAT1 might also contribute to this process (not shown). These cytokines operate individually or collectively to induce or enhance expression of the transcription factors BCL-6, MAF, basic leucine zipper transcriptional factor ATF-like (BATF) and interferon-regulatory factor 4 (IRF4), which then imprint the TFH cell fate on a T?cell by inducing the transcription of signature genes, including CXCR5, inducible T?cell co-stimulator (ICOS), IL21 and programmed cell death protein 1 (PD1). Cell–cell interactions among activated CD4+ T?cells, antigen-presenting DCs and B?cells also promote TFH cell formation. CD28–CD86, CD40 ligand (CD40L)–CD40 and ICOS–ICOS ligand (ICOSL) interactions are central to this process. Notably, ICOSL expression on B?cells is controlled through the opposing effects of B?cell-activating factor (BAFF) signalling via the distinct receptors BAFF re