Hastings R C, Gillis T P, Krahenbuhl J L, Franzblau S G
Gillis W. Long Hansen's Disease Center, U.S. Public Health Service, Carville, Louisiana 70721.
Clin Microbiol Rev. 1988 Jul;1(3):330-48. doi: 10.1128/CMR.1.3.330.
Leprosy affects over 10 million people in the world. The disease is a model of graded cell-mediated immunity, in this case to the causative organism, Mycobacterium leprae. The clinical manifestations are due to (i) bacterial progression, (ii) immunologic responses of the host, (iii) peripheral nerve damage due to either or both bacterial progression and immunologic responses of the host, and (iv) preventable secondary deformities following nerve damage, which account for most of the stigma of the disease. Treatment modalities are now available to control or minimize the effects of bacterial progression, harmful immunologic responses of the host, peripheral nerve damage, and secondary deformities. Unique biochemical characteristics of M. leprae reside in the cell wall and associated macromolecules. Some of these molecules are potent immunogens in humans, while others constitute the structural integrity of the bacillus. Proteins of M. leprae are currently under intensive investigation as a result of deoxyribonucleic acid cloning of M. leprae genes. Structure-function and antigenic relationships of M. leprae proteins should become available by using recombinant deoxyribonucleic acid procedures coupled with T- and B-cell cloning to advance our understanding of the immunologic reactions encountered in Hansen's disease. Until recently, the study of the immunology of leprosy has been stymied by the lack of immunologically specific M. leprae antigens. The definition of specific antigens and production of recombinant and synthetic immunologic reagents have fostered state-of-the-art research efforts into new immunodiagnostic procedures and development of a leprosy vaccine. Also discussed is progress in understanding of the mechanism(s) underlying the M. leprae-specific immunodeficiency associated with lepromatous leprosy, including the role of suppressor T cells and defective macrophage function. Metabolic studies of M. leprae suggest intact catabolic pathways and energy generation with purine bases and catalase as possible growth factors. Special attention may also need to be given to biophysical parameters for eventual in vitro cultivation. Rapid in vitro systems, using quantitation of bacillary metabolic activity, may soon replace the lengthy mouse footpad test for determining the viability and drug susceptibility of the leprosy bacillus.
全世界有超过1000万人受麻风病影响。该疾病是分级细胞介导免疫的一个范例,在这种情况下是针对致病微生物麻风分枝杆菌的免疫。其临床表现归因于:(i)细菌的进展;(ii)宿主的免疫反应;(iii)由于细菌进展或宿主免疫反应或两者兼而有之导致的周围神经损伤;以及(iv)神经损伤后可预防的继发性畸形,这构成了该疾病的大部分耻辱感。现在有治疗方法可用于控制或最小化细菌进展、宿主有害免疫反应、周围神经损伤和继发性畸形的影响。麻风分枝杆菌独特的生化特性存在于细胞壁及相关大分子中。其中一些分子在人类中是强效免疫原,而其他一些则构成了杆菌的结构完整性。由于麻风分枝杆菌基因的脱氧核糖核酸克隆,目前正在对麻风分枝杆菌的蛋白质进行深入研究。通过使用重组脱氧核糖核酸程序以及T细胞和B细胞克隆来推进我们对麻风病中遇到的免疫反应的理解,麻风分枝杆菌蛋白质的结构 - 功能和抗原关系应该会变得清晰。直到最近,由于缺乏免疫特异性的麻风分枝杆菌抗原,麻风病免疫学研究一直受到阻碍。特异性抗原的定义以及重组和合成免疫试剂的生产促进了对新免疫诊断程序和麻风病疫苗开发的前沿研究努力。还讨论了在理解与瘤型麻风相关的麻风分枝杆菌特异性免疫缺陷的潜在机制方面取得的进展,包括抑制性T细胞的作用和巨噬细胞功能缺陷。麻风分枝杆菌的代谢研究表明存在完整的分解代谢途径和能量生成,嘌呤碱基和过氧化氢酶可能是生长因子。最终的体外培养可能还需要特别关注生物物理参数。利用细菌代谢活性定量的快速体外系统可能很快会取代耗时的小鼠足垫试验来确定麻风杆菌的活力和药物敏感性。