Primary tuberculosis occurs when a non-immune host inhales tuberculosis bacteria, which are then taken up by macrophages and begin proliferating. Within a few weeks, the host develops cell-mediated immunity that helps control the infection in 90% of cases. However, the bacteria can remain dormant and cause disease later if immunity breaks down. Secondary tuberculosis occurs when a partially immune host is reinfected by larger numbers of bacteria or their dormant bacteria reactivate, usually due to a weakened immune system. This triggers an immune response that forms caseous granulomas and can lead to disseminated disease if not contained.

1. The immunopathology
of Tuberculosis
Dr Niranthi Perera

2. The difference between infection and
disease
Infection – seeding of a focus with organisms.
- may or may not cause clinically significant
tissue damage
Disease - when there is clinically significant
tissue damage

3. Primary Tuberculosis
occurs in a non-immune host who inhales the bacillus
entry of virulent impaired phagolysosome
mycobacteria formation and
into macrophage mycobacterial proliferation
pre-allergic lympho-haematogenous
dissemination to other organs
and seeding of multiple sites

5. Primary complex in pulmonary
tuberculosis

6. Primary Tuberculosis - ctd
Within 2-4 weeks, an immune response develops
- cell-mediated immunity
- delayed hypersensitivity to tubercular antigen
EFFECTS
- macrophage activation leading to destruction of
some tubercle bacilli (MAF)
- inhibition of macrophage migration (MIF)
- delayed Type IV hypersensitivity with caseous
necrosis of granuloma in Gohn’s focus and
elsewhere
- tuberculin conversion occurs

7. Primary tuberculosis - ctd
Asymptomatic or mild flu-like illness
In 90% , immunity stops disease progression
and healing occurs by fibrosis / calcify
In the others, complications occur.
1. rapidly progressive pulmonary disease with
caseous pneumonia in immunodeficient children
2. tuberculous bronchopneumonia
3. miliary tuberculosis

8. Effects of Primary tuberculosis
1. Tuberculin positivity – may remain for many yrs
2. Partial immunity to tuberculosis – such a person
requires a higher dose to be re-infected by
tubercle bacilli
3. Presence of dormant tubercle bacilli – in lung,
brain, meninges, bone, kidney, lymph nodes,
intestines.
Not all bacilli are killed by the immune response
and remain dormant within inactive caseous
granuloma – hence need for chemoprophylaxis

9. Secondary tuberculosis
Occurrence of disease in a patient who has had a
primary infection
HOST – partially immune, hypersensitised host
Mechanisms
1. Reinfection – requires large numbers of
organisms as partial immunity is present.
eg from a patient with active TB
2. Reactivation – represents a breakdown of
immunity –eg when tuberculin positive patient
is given corticosteroids.

10. Secondary Tuberculosis - ctd
Multipliation of Tubercle bacilli occurs due to a
rapidly developing secondary immune response
due to specifically activated T lymphocytes
secrete lymphokines
limit dissemination of infected macrophages
localise the tubercle bacilli to the area of infection
enhanced delayed hypersensitivity produces a
heightened local response with extensive caseous
necrosis

11. • Lung lesion is commonest site
• frequently apical
(? better ventilated zone of lung favours
multiplication of aerobic tubercle bacilli)
• small epithelioid granuloma coalesce to
form a solid mass of fibrocaseous material
which forms a cavity
• dissemination via the blood stream can
occur early in immunocompromised patients
or late in other patients, resulting in the
development of secondary granuloma at
other sites.

12. TUBERCLE / GRANULOMA
Caseous necrosis
when present is
minimal

13. TUBERCLE / GRANULOMA
• collection of
epithelioid cells and
multinucleate
Langhan-- type
giant cells
• peripheral cuff of
lymphocytes

15. COMPLICATIONS –
1. haemorrhage from a blood vessel
2. extension to pleura – effusions, adhesions,
fibrosis
3. erosion into a bronchus – infected material
coughed up - infects mucosa of trachea and
larynx.
4. if this material is swallowed, - intestinal TB
5. bacilli enter blood stream or lyphatics.