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

Type I Lepra Reaction (Reversal Reaction): What Is the Trigger for Reactivated Cellular Immunity?

Type I lepra or reversal reaction occurs as a result of increased activity of the immune system, particularly a cell-mediated immune response fighting the leprosy bacillus or remnants of dead bacilli. It is histopathologically characterized by a shift in classification towards the TT end of the spectrum with increased lymphocytic infiltration as well as decreased bacterial load. A sudden increase in M. leprae-specific cellular immune responses accompanied by infiltration of CD4+ T cells into skin lesions is found in type I reactions.[16,17] Positive, delayed-type hypersensitivity reactions by peripheral blood lymphocytes demonstrate a restoration of M. leprae activity,[18] which may lead to a local decrease in bacillary load and augmentation of T-cell reactivity, leading to nerve damage, occasionally causing extreme pain beyond endurance.[16] A type I reaction is more common in patients between the two poles of the leprosy spectrum with immunologically unstable borderline forms. Approximately 30% of individuals with borderline leprosy are at risk of a type I reaction,[9,19] with a significantly higher incidence in BB and BL patients as compared with BT patients. According to the WHO classification of leprosy, which is much simpler than the Ridley–Jopling classification, 88% of reactions in multibacillary (MB) patients and 52% in paucibacillary patients involve neuritis with activated immunopathology.[20]

The triggers that induce reactional episodes are thought to be numerous and very complex. These include poor nutrition, genetic defects in the cell-mediated immune response or cytokine production, various types of stress, initiation of MDT therapy, hormonal imbalance, high bacillary load and high antibody titers to M. leprae antigens. Reactions can occur prior to initiation of MDT, during MDT and many years after completing MDT. Therefore, the direct cause of reactions is not whether the bacilli are mostly alive or dead, but rather the changing status of the immune responses in each individual at a particular time point. The mechanism and causation of leprosy reactions remain unclear to date and it is also true that the highest risk of type I reaction occurs during and soon after MDT. Thus, in up to 70–80% of these cases, reactions occur during or after completion of MDT.[20–24]