Leprosy as a Model of Immunity

Yang Degang; Kazuaki Nakamura; Takeshi Akama; Yuko Ishido; Yuqian Luo; Norihisa Ishii; Koichi Suzuki


Future Microbiol. 2014;9(1):43-54. 

In This Article

Ridley–Jopling Classification as a Model of Immunity: Gradually Weakened Cellular Immune Response With Increasing Bacilli Load?

Clinical manifestations of leprosy are classified in five types: tuberculoid (TT), borderline TT (BT), borderline (BB), borderline lepromatous (BL) and lepromatous (LL). This classification made by Ridley–Jopling was based on clinical, histological and immunological differences in the disease, but they are continuous and compose a disease spectrum.[6] At one end (pole) of the spectrum, LL shows multiple, symmetrically distributed lesions throughout the body (nerves, eyes and internal organs in addition to the skin). LL lesions are largely composed of macrophages showing varying degrees of foamy changes; a few show lymphocytes, predominantly of the CD8+ subset.[9] Although acid-fast M. leprae bacilli are numerous within and outside macrophages in LL lesions, LL is usually characterized as having a complete absence of M. leprae-specific cellular immune responses.[10,11] LL patients lack the delayed type hypersensitivity response to lepromin, a suspension of killed bacilli.[12] However, patients with LL are able to mount a normal cell-mediated immune response against other infectious agents, including other mycobacteria,[10,11] suggesting that the cellular immune deficiency is M. leprae-specific. Antibodies against M. leprae are abundant in LL serum, but are ineffective in controlling the progress of the disease.

At the other pole, TT shows few lesions. The lesions that are present have well-defined margins, but acid-fast bacteria are rarely detected. TT skin lesions primarily consist of foci of well-developed epithelioid macrophages surrounded by lymphocytes. T-lymphocyte subsets are predominantly of the CD4+ type. Immunologically, TT shows a strong cellular immune response to M. leprae with significant delayed type hypersensitivity response to lepromin,[13] as reflected clinically and histopathologically in TT lesions, which are restricted in distribution and may even heal spontaneously.[6] With the strong cellular immune response, M. leprae-specific antibodies are usually absent or present at low levels in these patients.

Between the two polar forms of leprosy are the immunologically unstable borderline forms including BL, BB and BT. Within these groups, there is a gradual decrease in cellular immune responses from BT to BL, which is inversely correlated with increasing bacillary load. These BB states are immunologically unstable and may be complicated by type I lepra reactions, which are thought to be an acute inflammatory response to M. leprae components.[9,14,15] Although the persistence of M. leprae outside the dermis and nerves was not discussed within this classification, it may play an important role in the immunopathology of M. leprae infection, as discussed later.