1. IMMUNE RESPONSE TO MYCOBACTERIAL INFECTION
Awalia Febriana
Hardyanto Soebono
Agnes Sri Siswati Faculty of Medicine Gadjah Mada University

2. Mycobacteria 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

3. Pathogenic Mycobacteria: Properties
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

4. Non-tuberculous Mycobacteria pathogenic to humans
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 (Johne’s disease)
In humans: implicated by some in Crohn’s
M. leprae
The agent of leprosy

5. Mycobacteria are not limited to the tropics
Leprosy in Norway,
Rates low in cities where TB rates high

6. Mycobacteria Slow growing, aerobic, intracellular bacilli
Contain high concentration of lipids
Acid resistant staining

8. Importance of Study Immunology
Immunopathogenesis of the diseases
Development more accurate diagnostic tests
Development effective vaccines

9. Mycobacteria Antigenic components of mycobacteria Host Immune Response
Innate immunity
Adaptive immunity
Development of Diagnostic tools
Vaccine development

10. Structure of M leprae cell wall
PGL-I
Mycolic acids
Arabinogalactans
Peptidoglycan P
Membran sel P P

11. ANTIGENIC COMPONENTS OF M. LEPRAE
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

12. Immunity to mycobacteria
Control of infection NK
CD8
IFN-γ
IL-12
CD4
Eradication of infection
IFN-γ
Neutrophils
Macrophages
Macrophages 7
Innate immunity
Adaptive immunity 14

13. Components of innate immunity
Epithelial barriers
Phagocytes
(neutrophils/monocytes/macrophages)
Natural killer cells
Complement system
Other plasma proteins (mannose binding
lectin, C-reactive protein)

14. After infection with mycobacteria
Macrophages are infected and used as host cells
Clinical disease may develop in 5 % cases
Some clinical damages are caused by immune response

15. Mycobacteria is intracellullar parasites
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

16. Adaptive Immunity
Akira et al, Nature Immunol 2001;2:675-80

18. Subclinical infection M. leprae
Spontaneous heal
CLINICAL SPECTRUM
CMI BI
TT BT BB BL LL

19. TT
TH1
IL-4
IL-5
IL-6
IL-10
IL-13
IL-2
IFN-
TNF
IL-12 LL
TH2

20. DIAGNOSTIC TESTS Skin tests  Cellular imunity MLSA Peptide antigens
Serology  Antibody assay
ELISA
MLPA

21. VACCINES DEVELOPMENT
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 ?

22. thank you

23. Non-tuberculous mycobacterial infections in Swedish children
Rates increasing where TB gone, BCG stopped
BCG discontinued