Today’s immunolosy has made an tremendous advancements in the role of
lymphocytes and macrophages against infectious diseases. According to the new insights
into the role of lymphocytes and cytokines, the classical view of immunology of leprosy
needs to be changed. In the classical view of cell-mediated immunity(CMD in leprosy
was seen as a process in which macrophages phagccytize M. leprae and present
antigens to the CD4 T helper lymphocytes which stimulate infected macrophages to
eliminate the intracellular pathogen. CD8 T suppressor lymphocytes were thought to
suppress functions of T helper lymphocytes on M. leprae antigens, which allow M.
leprae to prolific growth.
Recently one of major cell wall protein of M. leprae, heat shock protein(hsp) 10, was
applied to field trial in Venezuela to find out possibility as a candidate for skin test and
vaccine. Both of dead and live M. leprae can induce CMI in the dermis, but only live
M. lepare cause leprosy. Secretory antigens from live M. leprae appear to be important
targets for T cells. They may be rapidly produced during the initial stage of infection
and appear to induce protective immunity. A major breakthrough in bacteriology has
been the recent development of so-called in vivo expression technologies(IVET) with
which it is becoming possible to identify virulence gene. It is impossible to find out
those genes with traditional in vitro system. Virulence genes may involve many aspects,
in adhesion and invasion to macrophages, in evading antigen presentation and inhibition
of fusion of phagolysosome. This technique will be applied to mycobacteria sooner or
later. The identification of such genes are necessary for the development of new drugs
and further understanding of the certain neurotropism of M. leprae.
Up to date we have found no antigens that are exclusively recognized by either
leprosy patients or healthy exposed individuals. Due to the difference of HLA type
different M. leprae antigens can be presented to lymphocytes. HLA genes do not
determine susceptibility to leprosy per se, but rather, control the type of leprosy that
develops upon infection of susceptible individuals. DR3 induce strong T-cell responses
Instead DQ1 may induce a state of unresponsiveness.
Contrary to the classical view, CD4 cells do not always help macorphages to eliminate
M. leprae. CD4 lymphocytes are also able to kill M. leprae-pulsed macrophages, and
keratinocytes and melanocytes, once they have come in contact with M. leprae. These
cytotoxic CD4 may mediate protective immunity by killing old M. leprae-burdened
macrophages, and bacilli can be taken by newly arrived macrophages. When CD8
negative mice were infected with M. tuberculosis, they rapidly died whereas control
mice survived relatively longer. This means that CD8 cells are an important subset in
protective immunity against virulent mycobaderia.
It is clear that human T helper cells consist of functionally distinct subsets that differ
in the cytokines they can produce. They are called Th-1 for T helper 1, Th-2 for T
helper 2, and Th-0 for T helper cells which can produce both type of cytokines type of
cytokines 3nd may regulate Th-1 or Th-2 helper cells. Th-1 cells produce Th-1 type
cytokines IL2, IFN-γ and TNF which are abudundant intuberculoid lesions Th-2 cells
elaborate Th-2 cytokines IL4, IL5, IL10 which are particularly enriched in lepromatous
lesion. Immunotherapy based on cytosine productions in tuberculoid, lepromatous lesion
reaction state include cytokines and their neutralizing antibodies which can enhance
protective immunity without elicit of pathological immunity in near future.
T cells from lepromatous leprosy show unresponsiveness to M. leprae, if the same T
cells are stimulated with purified, individual antigens such as 36 kD protein, hsp65 and
15K they respond rather well toward those antigens. This means that there is
something in M. leprae that suppress immunity and if we take out something a way
without knowing what it is, immunity starts to reappear. When we find any antigen
that are able to trigger M. leprae specific T cells in lepromatous leprosy without
inducing unresponsiveness, that will be a hopeful candidate for vaccine production using
vehicle of recombinant BCG.
One of characteristics of M. leprae infection is triggering acute neuritis in all most
case. But we do not have any clear explanations about the mechanism of Schwann cell
injury. Lately isolated T cells from nerve lesions do indeed respond to M. leprae and
some antigens, providing a direct link between M. leprae and neuritis.
In spite of multidurg therapy(MDT) for 7 or 8 years in India, there are no significant
impact on the incidence of leprosy. Until we can manage leprosy in hand, we need to
search for a better understaing of leprosy and its immunology to develop new kind of
chemotherapy, immunotherapy and vaccine for prevention and control of the disease
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