Emerging Concepts of Adaptive Immunity in Leprosy

Abstract

Leprosy is a chronic intracellular infection caused by the acid-fast bacillus, Mycobacterium leprae. The disease chiefly affects the skin, peripheral nerves, mucosa of the upper respiratory tract, and the eyes. The damage to peripheral nerves results in sensory and motor impairment with characteristic deformities and disability. Presently, the disease remains concentrated in resource-poor countries in tropical and warm temperate regions with the largest number of cases reported from India. Even though innate immunity influences the clinical manifestation of the disease, it is the components of adaptive immune system which seem to tightly correlate with the characteristic spectrum of leprosy. M. leprae-specific T cell anergy with bacillary dissemination is the defining feature of lepromatous leprosy (LL) patients in contrast to tuberculoid leprosy (TT) patients, which is characterized by strong Th1-type cell response with localized lesions. Generation of Th1/Th2-like effector cells, however, cannot wholly explain the polarized state of immunity in leprosy. A comprehensive understanding of the role of various regulatory T cells, such as Treg and natural killer T cells, in deciding the polarized state of T cell immunity is crucial. Interaction of these T cell subsets with effector T cells like Th1 (IFN-γ dominant), Th2 (interluekin-4 dominant), and Th17 (IL-17+) cells through various regulatory cytokines and molecules (programmed death-1/programmed death ligand-1) may constitute key events in dictating the state of immune polarization, thus controlling the clinical manifestation. Studying these important components of the adaptive immune system in leprosy patients is essential for better understanding of immune function, correlate(s) the immunity and mechanism(s) of its containment.

Correlation Analysis between Household Hygiene and Sanitation and Nutritional Status and Female Leprosy in Gresik Regency

“…Women's health, especially those in childbearing age, can affect the immunity dysregulation of her children, if a woman during her pregnancy experienced infection, malnutrition, obesity, and exposure to cigarette smoke [ 7 ]. Failure to resolve the causes of immune system in communities that live in leprosy endemic environments makes transmission of M. leprae bacteria easier since the host becomes more susceptible to leprosy [ 8 ]. The dominant role of women in taking care of their family increases the chance of female with leprosy to transmit the disease to other house members, especially their children.…”

Vitamin D Receptor Gene Polymorphisms Are Associated With Leprosy in Southern Brazil

“…The TT form (also classified as paucibacillary) is characterized by a small number of hypopigmented, well-bordered, anesthetic skin lesions with a low bacillary load, early peripheral nerve impairment, and a T-helper 1 (Th1)-mediated immune response. On the other hand, in form LL (therefore referred to as multibacillary), there is a prevalence of the Th2-mediated immune response, which leads to numerous infiltrated skin lesions displaying high bacillary loads, impaired peripheral nerves, and possible involvement of internal organs (7, 8). However, the predominance of one type of immune response does not mean that cytokines from the other response profiles are not being produced (9).…”

The impact of KIR/HLA genes on the risk of developing multibacillary leprosy

“…All of the known KIRs can be expressed by natural killer T cells (NKT), subsets of γδ+ T cells, and αβ+ T cells; however, in most individuals, they are expressed by CD8+ cells, but are infrequent in CD4+ cells [54]. Thus, KIR receptors could play a role in physiopathology of leprosy through the action of these cells, other than NK cells, but the exact role of all those cells have not been defined till date [30,55].…”