Transcript Can be environmental-humans accidental host Eg Mycobacterium

Awalia Febriana
Hardyanto Soebono
Agnes Sri Siswati
Faculty of Medicine Gadjah Mada University
 Most


Mycobacteria non-pathogenic:
soil & water organisms
more named each year (sampling)
 Pathogenic

Can be environmental-humans accidental host


Mycobacteria:
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 don’t gram stain
 Mycolic acid cell wall

acid fast staining
 Wall
protects bacteria from environment,
molecular biology
 Wall immunostimulatory: Freund’s
 Mycobacterium


Avian tuberculosis
In humans:



 M.


avium sp. avium:
disease in AIDS
Chronic pneumonia
Lymph node disease in children
avium sp. paratuberculosis:
Inflammatory bowel disease in ruminants,
primates (Johne’s disease)
In humans: implicated by some in Crohn’s
 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
 Acid
high concentration of lipids
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
Vaccine
of Diagnostic tools
development
Structure of M leprae cell wall
PGL-I
Mycolic acids
Arabinogalactans
Peptidoglycan
P
P
P
Membran sel
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
IL-12
CD8
IFN-γ
CD4
Eradication of
infection
IFN-γ
Neutrophils
Macrophages
Macrophages
0
7
Innate immunity
Adaptive immunity
14
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
infection
M. leprae
Spontaneous
heal
CLINICAL SPECTRUM
CMI
BI
TT
BT
BB
BL
LL
TT
TH1
LL
IL-4
IL-5
IL-6
IL-10
IL-13
TH2
IL-2
IFN-
TNF
IL-12
Skin tests  Cellular imunity
MLSA
Peptide antigens
 Serology  Antibody assay

ELISA
MLPA
 How
do we distinguish protective immunity from
pathological immunity ?
 How
 Can
do we induce one and avoid the other ?
we identify those protective antigens by
immunological methods ?
Rates increasing where TB
gone, BCG stopped
BCG discontinued