1. MYCOBACTERIA :
slender, aerobic rods that grow in straight or branching
cell wall composed of mycolic acid , which makes them
acid fast (retain stains even on treatment with a mixture
of acid and alcohol).
Mycobacteria stain weakly positive with Gram stain.
M. tuberculosis responsible for most cases of
Reservoir of infection is humans with active tuberculosis.
Most infections are acquired by person-to-person
transmission of airborne droplets of organisms.
M. tuberculosis enters macrophages by endocytosis
mediated by several macrophage receptors.
Once inside macrophage, M. tuberculosis replicates
within phagosome by blocking fusion of phagosome
Thus the earliest stage of primary tuberculosis
(<3 weeks) in nonsensitized individual is
characterized by proliferation of bacteria in
pulmonary alveolar macrophages and
airspaces, with resulting bacteremia .
Despite bacteremia, most patients at this stage are
asymptomatic or have a mild flulike illness.
3. About 3 weeks after infection, Mature TH1 cells produce
IFN-γ ( Interferon-γ ) which drives macrophages to
IFN-γ stimulates formation of phagolysosome in
IFN-γ also stimulates expression of inducible nitric oxide
synthase (iNOS), which produces nitric oxide (NO) and
other free radicals capable of oxidative destruction of
several mycobacterial constituents, from cell wall to
Activated macrophages also produce TNF, which recruits
monocytes which differentiated into "epithelioid
histiocytes" that characterize the granulomatous
4. Morphology :
inhaled bacilli implant in lower part of upper lobe or
upper part of lower lobe.
As sensitization develops, a 1- to 1.5-cm area of
gray-white inflammatory consolidation known as
In most cases, center of this focus undergoes caseous
Tubercle bacilli drain to regional nodes, which also
This combination of parenchymal lung lesion and
regional nodal involvement is referred to as Ghon
5. In 95% of cases, cell-mediated immunity controls
the infection. Hence, Ghon complex undergoes
progressive fibrosis, often followed by
radiologically detectable calcification (Ranke
Histologically: characteristic granulomatous
inflammatory reaction forms both caseating and
non-caseating tubercles( granuloma).
Individual tubercles are microscopic; when
multiple granulomas coalesce they become
6. • The granulomas are usually enclosed within
a fibroblastic rim punctuated by lymphocytes.
• Multinucleate giant cells ( langhans giant cells)
are present in granulomas.
• Immunocompromised people do not form
• No cavity formation in primary T.B.
8. Secondary Tuberculosis:
The initial lesion is usually a small apical focus of
consolidation, less than 2 cm in diameter.
Such foci are sharply circumscribed, firm, gray-white to
yellow areas that have a variable amount of central
caseation and peripheral fibrosis .
In favorable cases, the initial parenchymal focus
undergoes progressive fibrous encapsulation, leaving
only fibrocalcific scars.
Histologically, the active lesions show characteristic
coalescent tubercles with central caseation.
9. The apical lesion enlarges with expansion of area
Erosion into a bronchus evacuates the caseous
center, creating a ragged irregular cavity lined by
caseous material that is poorly walled off by fibrous
With adequate treatment, the process may be
arrested. Irregular cavities, now free of caseous
necrosis, may remain or collapse in surrounding
If treatment is inadequate or if host defenses are
impaired, the infection may spread by direct
expansion via dissemination through
airways, lymphatic channels, or vascular system.
History and physical and radiographic
findings of consolidation or cavitation in
apices of lungs.
Acid-fast smears and cultures of sputum.
PCR amplification of M. tuberculosis DNA.
11. Miliary pulmonary disease :
• occurs when organisms drain through lymphatics
into lymphatic ducts, which empty into venous
return to right side of heart and hence into
• Individual lesions are either microscopic ,or
small visible (2 mm) foci of yellow-white
consolidation scattered throughout lung
• With progressive pulmonary tuberculosis,
the pleural cavity is invariably involved, and
tuberculous empyema may develop.
12. Systemic miliary tuberculosis :
ensues when infective foci in lungs seed pulmonary
venous return to heart.
the organisms subsequently disseminate through
systemic arterial system.
Almost every organ in body can be seeded.
Organs that are typically involved include meninges
(tuberculous meningitis), kidneys (renal
tuberculosis), adrenals (Addison disease), bones
(osteomyelitis), and fallopian tubes
(salpingitis), vertebrae (Pott's disease),and Paraspinal
Lymphadenitis is most frequent form of
extra-pulmonary tuberculosis, usually occurring
in cervical region ("scrofula ).
Oropharyngeal and intestinal tuberculosis by
drinking milk contaminated with M. bovis
is rare in developed nations, but it is still seen
in countries that have unpasteurized milk.
In developed countries today, intestinal
tuberculosis is more often a complication of
advanced secondary tuberculosis secondary
to swallowing of coughed-up infective material.
14. Mycobacterium Avium-Intracellulare
• is common in soil, water, dust, and domestic
• infection is uncommon, except among people
with AIDS and low levels of CD4+ lymphocytes
• MAC causes widely disseminated infections in
many organs, commonly lungs and
• Morphology: abundant acid-fast bacilli within
Granulomas, lymphocytes, and tissue destruction
Leprosy, or Hansen disease, is a slowly progressive
infection caused by Mycobacterium leprae, affecting
skin and peripheral nerves and resulting in disabling
M. leprae transmitted from person to person through
aerosols from lesions in upper respiratory tract.
Inhaled M. leprae, like M. tuberculosis, is taken up by
alveolar macrophages and disseminates through blood,
but grows only in relatively cool tissues of skin and
M. leprae is acid-fast obligate intracellular organism
that grows very poorly in culture.
Like M. tuberculosis, M. leprae secretes no toxins, and
its virulence is based on properties of its cell wall.
Leprosy has two patterns of disease:
The less severe form, tuberculoid leprosy ,have
asymmetric skin lesions.
The more severe form, lepromatous leprosy, have
symmetric skin lesions.
17. Patients with tuberculoid leprosy have a TH1
response, with production of IFN-γ.
As with M. tuberculosis, IFN-γ is critical to cause
an effective host macrophage response.
Patients with lepromatous leprosy have a defective TH1
response; but a dominant TH2 response, which suppress
macrophage activation in response to M. leprae.
Begins as localized skin lesions that are at first flat and
red; then enlarge with irregular shapes and
indurated, elevated, hyperpigmented margins and
depressed pale centers (central healing).
Neuronal involvement dominates tuberculoid leprosy.
19. On microscopic examination:
• granulomatous lesions closely resembling those
found in tuberculosis, and bacilli are almost never
• The presence of granulomas and absence of bacteria
reflect strong T-cell immunity.
involves skin, peripheral nerves, anterior chamber
of eye, upper airways (down to
larynx), testes, hands, and feet.
lesions contain large aggregates of lipid-laden
macrophages (lepra cells) often filled with masses
of acid-fast bacilli seen by modified ziehl neelsen
21. SPIROCHETES :
Spirochetes are Gram-negative, slender , corkscrew-shaped
bacteria with axial flagella .
chronic venereal disease caused by Treponema pallidum
( microaerophilic spirochete).
T. pallidum is visualized by silver stains, dark-field
examination, and immunofluorescence techniques.
Sexual intercourse is usual mode of spread.
Transplacental transmission occurs readily, and active
disease during pregnancy results in congenital syphilis.
Syphilis is divided into three stages:
22. Primary Syphilis:
• occurring 3 weeks after contact with an infected
• as single ,firm, non tender, raised, red lesion (chancre)
located at site of treponemal invasion on
penis, cervix, vaginal wall, or anus.
• The chancre heals in 3 to 6 weeks with or without
• Spirochetes are plentiful within the chancre.
• occurs 2 to 10 weeks after primary chancre in 75%
of untreated patients.
• The skin lesions occur on palms or soles , may be
maculopapular, scaly, or pustular.
23. • Moist areas of skin, such as anogenital region, inner
thighs, and axillae may have condylomata lata which are
broad-based elevated plaques.
• Silvery-gray superficial erosions of mucous membranes
in mouth, pharynx, and external genitalia.
• All these painless superficial lesions contain spirochetes
and so are infectious.
• Lymphadenopathy, mild fever, malaise, and weight loss
are also common in secondary syphilis.
• The symptoms of secondary syphilis last several
weeks, after which the patient enters the latent phase of
24. Tertiary Syphilis:
• occurs in one-third of untreated patients, usually after
a latent period of 5 years or more.
• Tertiary syphilis has three main manifestations:
cardiovascular syphilis, neurosyphilis and so-called
benign tertiary syphilis.
• These may occur alone or in combination.
• benign tertiary syphilis is characterized by formation
of Gummas in various sites.
• Gummas are nodular lesions probably related to
development of delayed hypersensitivity to bacteria.
• Gummas occur most commonly in bone, skin, and
mucous membranes of upper airway and mouth.
25. Serologic Tests for Syphilis: Include:
Non treponemal tests:
• measure antibody to cardiolipin (a phospholipid present
in both host tissues and T. pallidum ).
• These antibodies are detected in Rapid Plasma Reagin
(RPR) , and Venereal Disease Research Laboratory (VDRL)
Treponemal antibody tests :
• measure antibodies reactive with T. pallidum.
• include Fluorescent Treponemal Antibody Absorption
test (FTA-Abs) , and MicroHemaggluination Assay for
T. Pallidum antibodies (MHATP).
The chancre contains an intense infiltrate of plasma
cells, scattered macrophages and lymphocytes , and a proliferative
The endarteritis is seen in all stages of syphilis.
The regional lymph nodes may show nonspecific acute or chronic
lymphadenitis, plasma cell-rich infiltrates, or focal epithelioid
mucocutaneous lesions show the same plasma cell infiltrate and
obliterative endarteritis ,although the inflammation is less intense.
Tertiary syphilis :
The aortitis is caused by endarteritis of vasa vasorum of proximal
27. Higher magnification view of the syphilitic chancre shows an infiltrate composed of
plasma cells, histiocytes, and lymphocytes. The findings are non-specific;
however, a combination of endarteritis and plasma cell infiltrate should point to
28. Syphilitic gummas are white-gray and
rubbery, occur singly or multiply.
On histologic examination, gummas contain
a center of coagulated necrotic material and
margins composed of plump or palisaded
macrophages and fibroblasts surrounded by
large numbers of mononuclear
leukocytes, chiefly plasma cells.
Treponemes are scant in gummas and are
difficult to demonstrate.
The immune response to T. pallidum reduces
the burden of bacteria, but it may also have
a central role in pathogenesis of disease.
The T-helper cells that infiltrate the chancre
are TH1 cells which activate the macrophages
to kill bacteria , and cause resolution of local
Although there are many plasma cells in syphilitic
lesions and treponeme-specific antibodies are
readily detectable, the antibody response does
not eliminate the infection.