Mycobacterium tuberculosis and Tuberculosis (page 2)
(This chapter has 4 pages)
© Kenneth Todar, PhD
The Disease Tuberculosis
TB infection means that MTB is in the body, but the immune system
keeping the bacteria under control. The immune system does this by
macrophages that surround the tubercle bacilli. The cells form a hard
that keeps the bacilli contained and under control. Most people
TB infection have a positive reaction to the tuberculin skin test.
People who have TB infection but not TB disease are NOT infectious,
they cannot spread the infection to other people. These people usually
have a normal chest x-ray. TB infection is not considered a case
of TB disease. Major similarities and differences between TB infection
are given in the table below.
Tuberculosis: Infection vs Disease
||TB disease in lungs
|Tuberculin skin test positive
||Tuberculin skin test positive
|Chest X-ray normal
||Chest X-ray usually reveals lesion
|Sputum smears and cultures negative
||Sputum smears and cultures positive
||Symptoms such as cough, fever, weight loss
||Often infectious before treatment
|Not defined as a case of TB
||Defined as a case of TB
Predisposing factors for TB infection include:
- Close contact with large populations of people, i.e., schools,
homes, dormitories, prisons, etc.
- Poor nutrition
- iv drug use
- HIV infection is the #1 predisposing factor for MTB infection.
10 percent of all HIV-positive individuals harbor MTB. This is
the rate associated with the general public
Only 3-4% of infected individuals will develop active disease upon
infection, 5-10% within one year. These percentages are much higher if
the individual is HIV+.
Stages of the Disease
The following stages that will be explained are for a MTB -
host. It should be realized that, as stated previously, only a small
of MTB infections progress to disease and even a smaller percent
all the way to stage 5. Usually the host will control the infection at
Disease progression depends on:
- Strain of MTB
- Prior exposure
- Infectious dose
- Immune status of the host
Droplet nuclei are inhaled. One droplet nuclei contains no
than 3 bacilli. Droplet nuclei are so small that they can remain
for extended periods of time. The most effective (infective) droplet
tend to have a diameter of 5 micrometers. Droplet nuclei are generated
talking coughing and sneezing. Coughing generates about 3000
nuclei. Talking for 5 minutes generates 3000 droplet nuclei but singing
generates 3000 droplet nuclei in one minute. Sneezing generates
most droplet nuclei by far, which can spread to individuals up to 10
Spread of droplet nuclei from one individual
to another. CDC. After droplet nuclei are inhaled, the bacteria are
taken up by alveolar macrophages. However, the macrophages are not
and are unable to destroy the intracellular organisms.
Tuberculosis begins when droplet nuclei reach
the alveoli. When a person inhales air that contains droplets most of
larger droplets become lodged in the upper respiratory tract (the nose
and throat), where infection is unlikely to develop. However, the
droplet nuclei may reach the small air sacs of the lung (the alveoli),
where infection begins.
Begins 7-21 days after initial infection. MTB multiplies virtually
unrestricted within unactivated macrophages until the macrophages
Other macrophages begin to extravasate from peripheral blood. These
also phagocytose MTB, but they are also unactivated and hence can not
destroy the bacteria.
At this stage lymphocytes begin to infiltrate. The lymphocytes,
T-cells, recognize processed and presented MTB antigen in context of
MHC molecules. This results in T-cell activation and the liberation of
cytokines including gamma interferon (IFN). The liberation of IFN
in the activation of macrophages. These activated macrophages are now
of destroying MTB.
It is at this stage that the individual becomes tuberculin-positive.
This positive tuberculin reaction is the result of the host
a vigorous cell mediated immune (CMI) response. A CMI response must be
mounted to control an MTB infection. An antibody mediated immune
will not aid in the control of a MTB infection because MTB is
and if extracellular, it is resistant to complement killing due to the
high lipid concentration in its cell wall.
Although a CMI response is necessary to control an MTB infection,
it is also responsible for much of the pathology associated with
Activated macrophages may release lytic enzymes and reactive
that facilitate the development of immune pathology. Activated
and T-cells also secrete cytokines that may also play a role in the
of immune pathology, including Interleukin 1 ( IL-l), tumor necrosis
(TNF), and gamma IFN.
It is also at this stage that tubercle
formation begins. The
center of the tubercle is characterized by "caseation necrosis",
it takes on a semi-solid or "cheesy" consistency. MTB cannot multiply
tubercles because of the low pH and anoxic environment. MTB can,
persist within these tubercles for extended periods.
Although many activated macrophages can be found surrounding the
many other macrophages present remain unactivated or poorly activated.
MTB uses these macrophages to replicate, and hence, the tubercle grows.
The growing tubercle may invade a bronchus. If this happens, MTB
can spread to other parts of the lung. Similarly the tubercle may
an artery or other blood supply line. The hematogenous spread of MTB
may result in extrapulmonary tuberculosis otherwise known as milliary
tuberculosis. The name "milliary" is derived from the fact that
tubercles are about the same size as a millet seed, a grain commonly
The secondary lesions caused by milliary TB can occur at
any anatomical location, but usually involve the genitourinary system,
bones, joints, lymph nodes and peritoneum. These lesions are of two
1. Exudative lesions result from the accumulation of PMN's
around MTB. Here the bacteria replicate with virtually no resistance.
gives rise to the formation of a "soft tubercle".
2. Productive or granulomatous lesions occur when the host
hypersensitive to tuberculoproteins. This situation gives rise to the
of a "hard tubercle".
For unknown reasons, the caseous centers of the tubercles liquefy.
liquid is very conducive to MTB growth, and the organism begins
to rapidly multiply extracellularly. After time, the large antigen load
causes the walls of nearby bronchi to become necrotic and rupture. This
results in cavity formation. This also allows MTB to spill into other
airways and rapidly spread to other parts of the lung.
As stated previously, only a very small percent of MTB infections
result in disease, and even a smaller percentage of MTB infections
to an advanced stage. Usually the host will begin to control the
at some point. When the primary lesion heals, it becomes fibrous and
When this happens the lesion is referred to as the Ghon complex.
Depending on the size and severity, the Ghon complex may never subside.
Typically, the Ghon complex is readily visible upon chest X-ray.
Small metastatic foci containing low numbers of MTB may also
However, in many cases these foci will contain viable organisms. These
foci are referred to Simon foci. The Simon foci are also
upon chest X-ray and are often the site of disease reactivation.