The spectrum of clinical and histopathological manifestations reflects the immune
response elicited by the microorganism in the host leprosy classified into polar groups:
Lepromatous (LL) and Tuberculoid (TT); and borderline spectrum: Borderline Tuberculoid
(BT), Borderline Borderline (BB) and Borderline Lepromatous (BL). This classification,
proposed by Ridley and Jopling This classification widely used in clinical,
immunological, microbiological, and histopathological aspects. While The World Health
Organization classifies leprosy clinically as multibacillary and paucibacillary,
according to the number of skin lesions and nerve involvement.
In the tuberculoid form of leprosy (paucibacillary), the individual manifests an intense
cell-mediated immune response that prevents proliferation of the bacillus, whereas the
cell-mediated immune response is compromised in the lepromatous form (multibacillary)
contributing to multiplication of the bacillus. In the intermediate forms,the patients
exhibit characteristics that vary between the two types.
Leprosy is measured the first disease to be categorized based on the host's immune
response. The clinical symptoms of leprosy vary from one patient to another based on the
spectrum of disease but more importantly on the type of host's immune response to the
bacteria. Both innate and acquired immune responses have been associated with leprosy,
but the disease is typically described by the side of a Th1/Th2 response.
Patients with TT are decided by a relevant T-cell immune response, including
interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-γ (IFN-γ), tumor necrosis factor
(TNF), and IL-17 and lymphotoxin, marked by some neural or cutaneous lesions with a few
or no bacilli.
Infected macrophages are activated by IFN- γ and clonal expansion of T cells is induced
by IL-2 which, in turn, leads to an increase in IFN- γ production. Tumor necrosis factor
alpha (TNF- α) also plays a role in the Th1 response. This cytokine contributes to the
maintenance of this pattern and acts in synchronism with IFN- γ in the activation of
infected macrphages, developing a significant mechanism for the maintenance of the
cell-mediated immune response.
In contrast, patients with LL show a superior humoral immune response, characterized by
multiple lesions, elevated bacterial load, and reduced lymphocyte production develop a
Th2 immune response characterized by intense production of transforming growth factor
beta (TGF- β), IL-4, IL-5 and IL-10.
These cytokines induce an incompetent immune response characterized by the high
production of antibodies that apply no protective effect against the bacterium.
IL-4 exerts an immunosuppressive effect that leads to an increase in bacterial
proliferation and inhibits the proliferation of T cells and monocytes, the expression of
CD14 on monocytes and the production of TNF- α, in addition to blocking the synthesis of
nitric oxide which is essential for the destruction of intracellular microorganisms. In
the 21st century, studies using modern genetic methods such as candidate gene association
studies (CGASs) and genome wide association studies (GWASs) have gradually confirmed that
the host genetic background play important role in the development of leprosy, and many
leprosyassociated variants or genes have been reported. Most leprosy-associated genes are
immune related, which is consistent with the finding that leprosy is caused by infection
with pathogen.
TGF β1 plays roles in the suppression of T cell responses, inhibiting both IFN γ and IL-2
expression, and has the ability to inhibit the lytic activity of macrophages by
suppressing the production of intermediate oxygen-reactive and nitrogen-reactive factors,
leading to the progression of infection. So, the production of TGF β1 by macrophages in
LL and BL skin lesions, probably as part of the M. leprae evasion mechanism.
Experimental studies on these pathogenic agents have demonstrated a role of TGF- β1 as a
suppressor of macrophages. TGF-β1 production in lepromatous patients, which contributes
to the anti-inflammatory situation and bacillary persistence observed