TUBERCULOSIS

Cell Wall Lipoarabinomannan (LAM)

◦ Inhibits macrophage activation by interferon-gamma.

Virulent Factors

Pathogenesis

Polymorphism in the NRAMP 1 gene NRAMP1

◦ Transmembrane protein in lysosomes◦ Pumps Ca++ out of lysosome◦ May inihibit growth by Limiting availability of ions

needed by bacteria

Susceptiblity Gene

Stimulate macrophages to kill TB bacteria◦ Stimulates formation of phagolysosome in

infected macrophages◦ Stimulates expression of NO synthase Nitric

oxide ( destroy bacterial cell wall to DNA ) Differantiation of macrophages Epitheloid

histiocytes◦ Halts infection

Mature TH1

TB Granuloma

Clinical Features

• 1. Reinfected with mycobacteria, • 2. Reactivate dormant disease• 3. Progress directly from the

primary mycobacterial lesions into disseminated disease.

Result of:

• A. Virulent • B. Host is particularly susceptible. Cause:

Secondary Disseminated Tuberculosis.

Ghon complex

Slowly progressive infection Low Communicability Affecting the skin & peripheral nerves Disabling deformity Most are contained in the skin Likely transmitted by aerosols from lesions

in the Upper Respiratory Tract Hematogenous grows only in relatively Cool

Tissues of the skin & Extremities

Leprosy

No Toxin produced

Virulence factor

Immunization to bacille Calmette-Guerin alone

• Confers 50% protection against M. leprae infxn

Disease

• Tuberculoid leprosy

• Lepromatous leprosy

Leprosy

IL-12• Produced by antigen presenting

cells• Important to the generation of

TH1 cells

IFN g• Produced by TH1 Lymphocytes• Critical to mobilizing an effective

host macrophage response

Antibody production

• Usually not protective• May form immune complex

• Causing Glomerulonephritis, vasculitis

Leprosy- immune response

Paucibacillary Leprosy Have dry , scaly, skin lesions Lack sensation , Asymmetric peripheral nerve

involvement Have TH1 response

◦ Normal immune response◦ Granuloma containing less microbe

Damage neurons Production of IL-2 & IFN- g Lepromin skin test is strongly (+)

T cell response – Delayed Hypersensitivity rxn to lepromin

Tuberculoid Leprosy

Anergic Leprosy• Have Defective TH1 response• Unresponsiveness of host immune

system. • Lack T cell immune response

Damage to nervous system

• Due to widespread bacterial dissemination

• Advanced cases • (+) BACTERIA sputum & blood

Dominant TH2 response

• IL 4 , IL5, IL10 are produced• Suppress macrophages activation

Lepromatous Leprosy- Multibacillary