immunobiology of leprosy

8/8/2019 Immunobiology of Leprosy

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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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immunobiology of leprosy

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