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Immunobiology of Leprosy:Clinical and Immunological FeaturesBritish Medical Bulletin, S. L. Walker*
and D. N. J. Lockwood ClinicalResearch Unit, Department ofInfectious
and Tropical Diseases,London School ofHygiene and TropicalMedicine
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 todisability and deformity
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Fig. 1 The RidleyJopling classification and the relationship with host immunity.
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What does this mean?
The immunological response mounted by the hostdictates the clinical phenotype that develops.
SPECTRUM
Tuberculoid disease: high cell-mediated immunitywith a largely Th1 type immune response.
(Th1: proinflammatory responses; g-IFN) Lepromatous leprosy: low cell-mediated immunitywith a humoral Th2 response (IL 4, 5, 13 // IgE,eosinophilic response in atopy, IL-10: anti-inflammatory)
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Recognition of mycobacteriallipoproteins in cell wall by TLRs of
monocytes and macrophages
Monocyte differentiation intomacrophages and dendritic cells
Antigen presentation
T-Cell activation, Th1lymphocytes
IL-12
NF-kB Intense phagocyticactivity
Granuloma formation(macrophages)
Poor granulomaformation 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 thenatural course of Borderline leprosy is DOWNtowards the lepromatous end of the spectrum.
Reversing that, turns the patient around in thedirection of the Tuberculoid pole and - a cure.. MoreCMI means "Upgrading" or a "Reversal" of thenormal trend. On the contrary, if there is a reductionof 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 orboth
The skin lesions become acutely inflamed and
edematous and may ulcerate
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Acute neuritis leads to nerve functionimpairment, which if not treated rapidly andadequately leads to permanent loss of nervefunction causing peripheral sensory and motorneuropathy.
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 thepuerperium.
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Reactionsmay be a presenting feature of the
disease or occur during MDT or even after it hasbeen completed.
The treatment of type 1 reactions is aimed atcontrolling the acute inflammation, easing pain
and reversing eye and nerve damage. MDT should be continued during a reaction.
Moderately inflamed skin plaques or neuritis aretreated 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 thehigher 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 phaseand 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 onesrequire high doses of corticosteroids, usuallystarting with prednisolone 60 mg daily
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