Mycobacterium leprae

dr Retno Budiarti Microbiology Department

Structure
Slender curved rods, acid fast and resistant to acids, alkalis, and dehydration. The cell wall contains complex waxes and unique phenolic glycolipids. multiplies very slowly in vivo (12-day doubling time). have the largest doubling time of all known bacteria.

characteristic
a gram-positive aerobic surrounded by a waxy coating. Cant to culture this in the laboratory dependent on its host to receive nutrients and metabolites.

characteristic
an obligate intracellular the replication rate in vivo : 10 to 12 days. resist intracellular degradation by macrophageshe peripheral nerve damage appears to be mediated principally by the host immune response to bacillary antigens.

pathogenesis
The invading M. leprae has three main targets 1. peripheral neural tissues (Schwann cells) 2. small vessels (endothelial cells and pericytes) 3. the monocytemacrophage system.
The bacilli may survive and replicate within the Schwanncells and secondarily penetrate the perineural tissues (perineuralgranulomas). They may also growth within endothelialcells and pericytes and be released to induce bacteremia

 During the hematogenous spread of M. leprae on its way to the nerves, it may be captured by macrophages

pathogenesis

M. leprae enters the lymph and blood vessels to reach its targets, the nerves and their Schwann cells, where it can multiply and disseminate, begin new invasive cycles, and form perineural granulomas.

pathogenesis
When Schwann cells engulf the bacilli within phagocytic vacuoles (phagosomes), however, M. leprae may replicate and age. From there or through the cytoplasm of the endothelial cells, these normal bacilli may migrate to the perivascular connective tissue and be ingested by macrophages rich in lysosomal enzymes capable of killing the organisms

pathogenesis
In Mitsuda-positive patients, the macrophages may destroy all bacilli and obtain normal antigenic information to act as APCs, stimulate cellmediated immunity, and eventually form epithelioid granulomas. In Mitsuda-negative patients, only partial lysis may occur and the bacterial phospholipids may persist. Lepra cells or virchowcytes may appear, but the antigenic information is incomplete and the cells cannot act as APCs.

Tuberculoid leprosy
M leprae phagocytosed by Mitsuda-positive macrophages may be completely destroyed; normal antigenic information may be obtained and expressed on the cell surface. In association with MHC class II, these APCs may secrete IL-12 and stimulate CD4 lymphocytes (Th1), which, in turn, may produce IL-2 and IFN-. New macrophages may then be activated and transformed into epitheloid cells. When MHC class I is involved, however, stimulated CD8 lymphocytes may act on other macrophages to kill the organisms by apoptosis.

Lepromatous leprosy
In Mitsuda-negative patients, only partial lysis may occur and the bacterial phospholipids may persist. Lepra cells or virchowcytes may appear and be phagocytosed by other macrophages; in this way, new antigen presenting cells with modified antigenic information may emerge, and stimulate humoral immunity. This mechanism may explain secondary type 2(ENL) and type 3 (Lucio phenomenon) reactions of lepromatous leprosy.

Lepromatous leprosy
In a later stage of LL, other macrophages may phagocytose the aged lepra cells induce epitheloid cell complete neoantigenic information expressed on their surface withMHCclass II, evolve into newAPC release IL-4, stimulate humoral immunity (CD4 Th-2 and CD8 T lymphocytes, B lymphocytes, and IL-1 and TNF- synthesis) with anti-M. leprae antibody production, and facilitate type 2 (ENL) and type 3 (Lucio phenomenon) leprosy reactions.

The immune bipolarity of leprosy may be the result of two antigens, one derived from normal bacilli and the arising from enzymatically digested bacilli present in Virchow cells. Both antigens, acting independently, may induce the development of normal and new antigen presenting cells, respectively, with the stimulation of CMI in tuberculoid leprosy and humoral immunity in lepromatous leprosy

transmission
Human-to-human transmission requires prolonged contact and is thought to occur via intact skin, penetrating wounds or insect bites, or by inhalation of M leprae and deposition on respiratory mucosa

Diagnosis
clinical signs histologic examination of biopsy specimens taken from lepromas or other skin lesions. the presence of acid-fast bacilli The lepromin skin test, in which a heat-killed suspension of armadillo-derived M leprae is injected into the skin of the patient, has little diagnostic value but will provide information of prognostic importance about the immune status of the individual. PCR

Clinical spectrum
Effective cellular immunity : - tuberculoid leprosy - less lession - there is no or less microbe in tissues - not infectious - Delayed type hypersensitivity

Clinical spectrum
Lack of Cellular immunity Lepromatous leprosy No protection Any microba in lession Much lession with M. leprae in nasal, earlobe Infectious B cell function is not disturbed, but antibody response is not effective

Ridley Jopling clasiffication

TT : tubekuloid BT : borderline tuberkuloid BB : borderline BL : borderline lepromatous LL : lepromatous