its just an introduction to mycobacterium tuberculosis!

1. Doctor: I have some bad news and
some very bad news.
Patient: Well, might as well give me the
bad news first.
Doctor: The lab called with your test
results. They said you have 24 hours to
live.
Patient: 24 HOURS! That's terrible!!
WHAT could be WORSE? What's the very
bad news?
Doctor: I've been trying to reach you since
yesterday.

2. WEDNESDAY DECEMBER 2012

4. NELSON MANDELA

5. JOHN KEATS

6. PB SHELLY

7. DR.PSIMS&RF

11. What is the
most important
risk factor for
TB?

13. Risk factors for disease given
that infection has occurred ?
RISK FACTOR RELATIVE
RISK
AIDS 200
HIV Infection 30-40
Silicosis 30
Recent Infection 20
Under-nutrition 2-5
Diabetes mellitus 2-5
Relative Risk of
remotely acquired
infection = 1] (0.2%
per year

14. Prevalence of infecton by zone and stratum (1-9 years)
9.1
4.5
7.8
6.5
14.1
9.8
12.6
9.0
10.3
6.1
9.3
6.9
0
2
4
6
8
10
12
14
16
North South West East
%
Rural Urban Zone

16. R
I
S
K
F
A
C
T
O
R
S

17. WHAT IS THE
CAUSATIVE
ORGANISM….?

18.  Mycobacterium tuberculosis is the
etiologic agent of tuberculosis in humans.
Humans are the only reservoir for the
bacterium.
 Mycobacterium bovis is the etiologic agent
of TB in cows and rarely in humans.
 Both cows and humans can serve as
reservoirs.
 Humans can also be infected by the
consumption of unpasteurized milk.
 This route of transmission can lead to the
development of extrapulmonary TB.

19. ROBERT KOCH
 Robert koch isolated Mycobacterium
tuberculosis and proved its role in the
causation of TB

20. GENERAL CHARACTERISTICS
 Mycobacterium tuberculosis is a fairly
large nonmotile rod-shaped bacterium.
 Many non pathogenic mycobacteria are
components of the normal flora of
humans, found most often in dry and oily
locales.
 The rods are 2-4 micrometers in length
and 0.2-0.5 um in width.

21. QUESTION-1
 What is the Mycobacteria component that is
found in the secretions(smegma) of the genitalia
of both males and females?
 CLUE:it is not harmful and it’s a commensal…
 ANS. Mycobacterium smegmatis
 SIGNIFICANT POINT: This may,by its presence in
urine specimens,cause confusion with tubercle
bacilli

22.  Mycobacterium tuberculosis is an obligate
aerobe.
 For this reason, in the classic case of
tuberculosis, MTB complexes are always
found in the well-aerated upper lobes of
the lungs.
 The bacterium is a facultative
intracellular parasite, usually of
macrophages, and has a slow generation
time, 15-20 hours, a physiological
characteristic that may contribute to its
virulence.

23. QUESTION-2
 IS Mycobacterium
tuberculosis A GRAM-
POSITIVE OR GRAM-
NEGATIVE BACTERIUM..?

24.  Mycobacteriun tuberculosis(MTB) is not
classified as either Gram-positive or
Gram-negative because it does not have
the chemical characteristics of
either, although the bacteria do contain
peptidoglycan (murein) in their cell wall.
 If a Gram stain is performed on MTB, it
stains very weakly Gram-positive or not at
all (cells referred to as "ghosts").

25.  Mycobacterium species, along with
members of a related
genus Nocardia, are classified
as acid-fast bacteria due to their
impermeability by certain dyes and
stains.
 Once the Mycobacteria have been
stained,they are not easily
discolourised even with acid
alcohol.
 This resistance to discolourisation is
called “ACID FASTNESS”
 One acid-fast staining method
for Mycobacterium tuberculosis is
the Ziehl-Neelsen stain.

26.  When this method is used,the acid fast
bacilli appear pink in contrasting
background.

27.  Slow generation time. Because of MTB's
slow generation time, the immune system
may not readily recognize the bacteria or
may not be triggered sufficiently to
eliminate them.
 Many other chronic disease are caused by
bacteria with slow generation times, for
example, slow-growing M. leprae causes
leprosy,Treponema pallidum causes
syphilis

28. CELL WALL STRUCTURE…
 The cell wall structure of Mycobacterium
tuberculosis deserves special attention because it
is unique among procaryotes, and it is a major
determinant of virulence for the bacterium.
 The cell wall complex
contains peptidoglycan, but otherwise it is
composed of complex lipids.
 Over 60% of the mycobacterial cell wall is lipid.

29.  Lipid fraction of MTB's cell wall consists of
three major components, mycolic
acids, cord factor, and wax-D.
 Mycolic acids are unique alpha-branched
lipids found in cell walls
ofMycobacterium and Corynebacterium.
Continues……………….

30.  They make up 50% of the dry weight of
the mycobacterial cell envelope.
 Mycolic acids are strong hydrophobic
molecules that form a lipid shell
around the organism and affect
permeability properties at the cell
surface.
 Mycolic Acids are thought to be a
significant determinant of virulence in
MTB. Probably, they prevent attack of
the mycobacteria by cationic
proteins, lysozyme, and oxygen radicals in
the phagocytic granule.
 They also protect extracellular
mycobacteria from complement
deposition in serum.

31.  The high concentration of lipids in the cell
wall of Mycobacterium tuberculosishave
been associated with these properties of
the bacterium:
 Impermeability to stains and dyes
 Resistance to many antibiotics
 Resistance to killing by acidic and alkaline
compounds
 Resistance to osmotic lysis via complement
deposition
 Resistance to lethal oxidations and survival
inside of macrophages

32.  Cord factor. Cord factor (trehalose 6, 6'
dimycolate) is a glycolipid found in the cell walls
of mycobacteria, which causes the cells to grow
in serpentine cords.
 it blocks the macrophage activation by IFN-γ
,induces secretion of TNF-ALPHA and causes MTB
to form cords in vitro.
 Of approximately 4,000 genes in
the Mycobacterium tuberculosis genome,
 525 are involved in cell wall and "cell processes",
 188 genes encode regulatory proteins,
 91 genes are involved in "virulence, detoxification
and adaptation".
 Over 200 genes are identified as encoding enzymes
for the metabolism of fatty acids.

33.  This large number of M. tuberculosis enzymes that
putatively use fatty acids may be related to the ability of
the pathogen to grow in the tissues of the infected
host, where fatty acids may be the major carbon source.
 This is thought to be an important aspect of M.
tuberculosis physiology during infection.
 Some of these genes and their products or activities are
described below.
19-kDa protein. The 19-kDa protein is a secreted
antigenic protein that is immunologically recognized by T
cells and sera from TB patients.
. When M. tuberculosis enters macrophages and other
phagocytic cells, this surface-exposed glyco-lipoprotein
is thought to cause host signaling events as it interacts
with its receptor, TLR2.

34.  LAM-LIPO ARABINO MANNAN:
 . LAM is a complex glycolipid that contains repeating
arabinose-mannose disaccharide subunits.
 It is a major component of the M. tuberculosis cell
wall.
 It is known to be an immunomodulator analogous to
the 19-kDa protein.
 Addition of LAM to murine macrophages depresses IFN-
gamma production.
 . LAM can also scavenge oxygen radicals, in vitro, and
inhibits the host protein kinase C.
 It has been suggested that LAM functions to
downregulate host immune responses to M.
tuberculosis infection, to protect the bacterium from
potentially lethal mechanisms like the respiratory
burst.

35.  TB infection means that MTB is in the
body, but the immune system is keeping
the bacteria under control.
 The immune system does this by producing
macrophages that surround the tubercle
bacilli. The cells form a hard shell that
keeps the bacilli contained and under
control.
 Most people with TB infection have a
positive reaction to the tuberculin skin
test.
 People who have TB infection but not TB
disease are NOT infectious, i.e., they
cannot spread the infection to other
people. These people usually have a
normal chest x-ray.

36.  TB infection is not considered a case of TB disease.
 Major similarities and differences between TB
infection and TB disease are given in the table
below.
TB INFECTION TB DISEASE IN LUNGS
MTB present MTB present
Tuberculin skin test
positive
Tuberculin skin test
positive
Chest X-ray is normal Chest X-ray reveals lesion
Sputum smears and culture
are negative
Sputum smears and culture
are positive
No symptoms Symptoms such as
cough,fever,weight loss
Not infectious Often infectious before
treatment
Not defined as a case of TB Usually defined as a case of
TB