Most Mycobacteria non-pathogenic:

soil & water organisms

more named each year (sampling)

Pathogenic Mycobacteria:
Can be environmental-humans accidental host
E.g. Mycobacterium avium
Can be obligate pathogens with no known
environmental reservoir
E.g. Mycobacterium leprae
 Most slow growing, doubling on order of day (c.f. E
coli 30 min.)
Gram-positive, but dont gram stain
Mycolic acid cell wall
acid fast staining
Wall protects bacteria from environment, molecular
biology
Wall immunostimulatory: Freunds
 Mycobacterium avium sp. avium:
Avian tuberculosis
In humans:
disease in AIDS
Chronic pneumonia
Lymph node disease in children
M. avium sp. paratuberculosis:
Inflammatory bowel disease in ruminants, primates
(Johnes disease)
In humans: implicated by some in Crohns

M. leprae
The agent of leprosy
Leprosy in Norway, 1851-1920
Rates low in cities where TB
rates high
 Slow growing, aerobic, intracellular bacilli

Contain high concentration of lipids

Acid resistant staining

Immunopathogenesis of the diseases
Development more accurate diagnostic
tests
Development effective vaccines
Antigenic components of mycobacteria

Host Immune Response

Innate immunity
Adaptive immunity
Development of Diagnostic tools

Vaccine development
 Structure of M leprae cell wall

PGL-I

Mycolic acids

Arabinogalactans

Peptidoglycan
P

P Membran sel
P
Cell wall :
PGL (phenolic glycolipid)
LAM (lipoarabinnomannan)
Cell membrane :
30 32 kDa
35 kDa
45 kDa
Hsp (heat shock proteins) :
18, 28, 36, 65, 70 kDa
 Immunity to mycobacteria

Control of infection

NK CD8

IL-12 IFN-
CD4

Eradication of
IFN- infection

Neutrophils Macrophages Macrophages

0 7 14
Innate immunity Adaptive immunity
 Components of innate immunity

Epithelial barriers
Phagocytes
(neutrophils/monocytes/macrophages)
Natural killer cells
Complement system
Other plasma proteins (mannose binding
lectin, C-reactive protein)
 Macrophages are infected and used as host cells
Clinical disease may develop in 5 % cases
Some clinical damages are caused by immune response
 Antibody response is of little use
The most effective immune response is
immunocompetent cells able to kill infected cells
The most important cells to protect against
mycobacterial infection :
CD4+ T cells
Macrophages
Adaptive Immunity

Akira et al, Nature Immunol 2001;2:675-80

 Subclinical
M. leprae infection

Spontaneous
heal

CLINICAL SPECTRUM
CMI BI

TT BT BB BL LL
 TT
TH1
IL-4 IL-2
IL-5 IFN-
IL-6 TNF
LL IL-10 IL-12
IL-13
TH2
 Skin tests Cellular imunity
MLSA
Peptide antigens
Serology Antibody assay
ELISA
MLPA
 How do we distinguish protective immunity from
pathological immunity ?

How do we induce one and avoid the other ?

Can
we identify those protective antigens by
immunological methods ?
 Rates increasing where TB
gone, BCG stopped

BCG discontinued