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Immunobiology of Leprosy:
Clinical and Immunological Features
British Medical Bulletin, S. L. Walker* and
D. N. J. Lockwood Clinical Research Unit,
Department of Infectious and Tropical
Diseases,
London School of Hygiene and Tropical
Medicine
Reported by: Jeni Bomediano
5 August 2010
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• CMI vs HI
▫ HI: ENL
▫ Lepra Reaction?

• Antigen: M. leprae

• Its characteristics affect disease presentation.

▫ Affinity for cooler areas
▫ CMI Response
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• MDT cures the infection BUT immunological

reactions may occur and neuropathy may lead to
disability and deformity
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Fig. 1 The Ridley–Jopling classification and the relationship with host immunity.
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What does this mean?

• The immunological response mounted by the host
dictates the clinical phenotype that develops.
• SPECTRUM
• Tuberculoid disease: high cell-mediated immunity
with a largely Th1 type immune response.
(Th1: proinflammatory responses; g-IFN)
• Lepromatous leprosy: low cell-mediated immunity
with a humoral Th2 response (IL 4, 5, 13 // IgE,
eosinophilic response in atopy, IL-10: anti-
inflammatory)
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Recognition of mycobacterial
lipoproteins in cell wall by TLRs of
monocytes and macrophages

Monocyte differentiation into

macrophages and dendritic cells

Antigen presentation

IL-12

NF-kB T-Cell activation, Th1 Intense phagocytic

lymphocytes activity

Granuloma formation
(macrophages)

Poor granuloma
formation in
lepromatous type
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• Pure neuritic leprosy (PNL) affects peripheral

nerve trunks in the absence of cutaneous signs.
PNL may be any disease type.
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Reversal? Upgrading? Downgrading?

• If, under treatment, there is a rapid increase in cell
mediated immunity (CMI), with a proliferation of "T-Type"
lymphocytes, we refer to the reaction as "Up-grading" or
"Reversal" reaction.

• The reason for this terminology is because the natural

course of Borderline leprosy is DOWN towards the
lepromatous end of the spectrum. Reversing that, turns the
patient around in the direction of the Tuberculoid pole and
- a cure.. More CMI means "Upgrading" or a "Reversal" of
the normal trend. On the contrary, if there is a reduction of
immune response (CMI), we speak of "Downgrading"
towards the lepromatous pole.
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Type 1 Reactions
• Delayed hypersensitivity reactions that occur in
borderline disease
• Acute inflammation in skin lesions or nerves or
both
• The skin lesions become acutely inflamed and
edematous and may ulcerate
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• Acute neuritis leads to nerve function impairment,

which if not treated rapidly and adequately leads
to permanent loss of nerve function causing
peripheral sensory and motor neuropathy.
• Frequently recurrent and can lead to further nerve
damage
• Type 1 reactions can occur at any time but are
frequently seen after starting MDT or during the
puerperium.
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• Reactions may be a presenting feature of the

disease or occur during MDT or even after it has
been completed.
• The treatment of type 1 reactions is aimed at
controlling the acute inflammation, easing pain
and reversing eye and nerve damage.
• MDT should be continued during a reaction.
Moderately inflamed skin plaques or neuritis are
treated with oral corticosteroids.
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Type 2 (ENL) Reactions

• 50% of lepromatous and 10% of borderline
lepromatous cases
• Occur later in the course
• The greater the infiltration of the skin and the
higher the bacterial index (BI), the greater risk of
developing type 2 reactions
• Systemic; affects many organ systems
• Acute in onset; may pass into a chronic phase
and can be recurrent
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• Fever, painful and tender red papules or nodules

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• The majority of ENL reactions require

immunosuppression. The more severe ones
require high doses of corticosteroids, usually
starting with prednisolone 60 mg daily