Graft-versus-host disease (GVHD) has been the primary limitation to the wider application of allogeneic bone marrow transplantation (BMT). The immunobiology of acute GVHD is complex and can be conceptualized to be a three-step process. In step 1, the conditioning regimen (irradiation and/or chemotherapy) leads to the damage and activation of host tissues and induces the secretion of inflammatory cytokines TNF-alpha and IL-1. As a consequence expression of MHC antigens and adhesion molecules is increased, thus enhancing the recognition of host alloantigens by donor T cells. Donor T-cell activation in step 2 is characterized by donor T-cell interaction with host APCs and subsequent proliferation, differentiation, and secretion of cytokines. Cytokines such as IL-2 and IFN-gamma enhance T-cell expansion, induce cytotoxic T cells (CTL) and natural killer (NK) cell responses, and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. These inflammatory cytokines in turn stimulate production of inflammatory chemokines, thus recruiting effector cells into target organs. In step 3, effector functions of mononuclear phagocytes are triggered via a secondary signal provided by lipopolysaccharide (LPS) that leaks through the intestinal mucosa damaged during step 1. This mechanism may result in the amplification of local tissue injury and further promotion of an inflammatory response, which, together with the CTL and NK components, leads to target tissue destruction in the transplant host.

中文翻译：

---

急性移植物抗宿主病的免疫生物学。

移植物抗宿主病（GVHD）是异体骨髓移植（BMT）广泛应用的主要限制。急性GVHD的免疫生物学很复杂，可以被概念化为一个三步过程。在步骤1中，调理方案（辐射和/或化学疗法）导致宿主组织的损伤和活化，并诱导炎性细胞因子TNF-α和IL-1的分泌。结果，MHC抗原和粘附分子的表达增加，从而增强了供体T细胞对宿主同种异体抗原的识别。步骤2中的供体T细胞活化的特征是供体T细胞与宿主APC相互作用以及随后的细胞因子增殖，分化和分泌。IL-2和IFN-γ等细胞因子可增强T细胞扩增，诱导细胞毒性T细胞（CTL）和自然杀伤（NK）细胞反应，并引发其他单核吞噬细胞产生TNF-α和IL-1。这些炎性细胞因子继而刺激炎性趋化因子的产生，从而将效应细胞募集到靶器官中。在步骤3中，单核吞噬细胞的效应子功能是通过脂多糖（LPS）提供的次级信号触发的，该信号通过步骤1中受损的肠粘膜泄漏。该机制可能导致局部组织损伤的扩大并进一步促进炎症反应，其与CTL和NK组件一起，导致移植宿主中靶组织的破坏。这些炎性细胞因子继而刺激炎性趋化因子的产生，从而将效应细胞募集到靶器官中。在步骤3中，单核吞噬细胞的效应子功能是通过脂多糖（LPS）提供的次级信号触发的，该信号通过步骤1中受损的肠粘膜泄漏。该机制可能导致局部组织损伤的扩大并进一步促进炎症反应，其与CTL和NK组件一起，导致移植宿主中靶组织的破坏。这些炎性细胞因子继而刺激炎性趋化因子的产生，从而将效应细胞募集到靶器官中。在步骤3中，单核吞噬细胞的效应子功能是通过脂多糖（LPS）提供的次级信号触发的，该信号通过步骤1中受损的肠粘膜泄漏。该机制可能导致局部组织损伤的扩大并进一步促进炎症反应，其与CTL和NK组件一起，导致移植宿主中靶组织的破坏。