(1).gif)
.gif){kind=small}
CMN
group: Corynebacterium, Mycobacterium, Nocardia are grouped
together on the basis of distinguishing factors that include complex cell wall
components, presence and type of mycolic acids, adjuvant activity, presence
of cord factor, sulfolipids, iron-chelating compounds, polyphosphate, and serological
cross-reactivity.
Very
slow growing
Prototrophic
(ability to build all required components from basic carbon and nitrogen sources)
with glucose (carbon source) and ammonium ion (NH4+)(nitrogen source)
or glycerol and asparagine
Many
specific mycobacteriophages
Acid-fast
bacilli (see WebLinked
image; see WebLinked
image; see WebLinked
image); red on blue background with Ziehl-Nielsen acid-fast stain
Non-spore
former, resistant to drying, sunlight, and chemical disinfectants, particularly
in sputum
Obligate
aerobe, but facultative intracellular pathogen with two clinical forms:
Many
immunoreactive substances. Important antigens include: purified protein derivative
(PPD), cord factor, and old tuberculin (OT).
Correlation
of strain virulence with cord factor, but specific determinants of pathogenicity
have not been identified.
Tuberculosis
is leading cause of reportable infectious diseases; 8-10 million new cases and
3 million deaths every year.
Single
most critical factor in tuberculosis infection is the severity of infectiousness
of the source case
Organisms
transmitted from infectious cases via droplet nuclei suspended in the air. Aerosols
produced by talkin, coughing, sneezing, breathing dry to droplet nuclei (1-10
um diameter) that are inhaled deep into the alveoli
of the lungs.
Factors
that influence risk of contracting tuberculosis disease, i.e., progressing from
infection to disease include: age, sex, race, personal habits, co-existing disease,
and socioeconomic status
Treatment
with Isoniazid (INH) or rifampin and second line drugs or attempted preventive
therapy with INH and BCG prophylaxis
Primary
pulmonary infection with secondary infection of pulmonary or extra-pulmonary
sites
Tissue
destruction and fibrosis (fibrous walling off of lesions, i.e. granulomatous
reaction) caused by host response to infection.
Initially,
a the host mounts a non-specific inflammatory response: organisms are phagocytosed
by alveolar macrophages, inhibition of phagolysosome fusion, intracellular multiplication,
and spread to regional lymph nodes, then the blood stream and seeded throughout
the body. Secondary infection is either in a pulmonary site, from ongoing multiplication
of organisms seeded to apices of the lungs or in any extrapulmonary site.
Two
to four weeks after infection, cell-mediated immunity and tuberculin hypersensitivity
develops.
Cytokines
derived from T-cells activate the macrophages and render them capable of killing
the bacteria. A small antigenic burden (limited number of infecting cells) results
in destruction of the bacilli and minimal tissue necrosis. With a large antigenic
burden (large number of bacilli), this cellular immune response results in tissue
necrosis.
The
hypersensitivity response to tuberculin results in localized collections of
cytokine-activated macrophages (granulomas) prevent further spread of the organisms.
Larger, necrotic or walled-off granulomas become surrounded by fibrin (tubercle
formation) which effectively protects the organisms from macrophage killing.
Bacilli remain dormant (quiescent) in this stage for years or decades. When
immunological response wanes, bacilli can reactivate.
Secondary
or reinfection tuberculosis resulting from reactivation of quiescent foci of
bacilli; occurs in small number of infected persons despite acquired cellular
immunity. Lesions remain localized because of cell-mediated immunity Hypersensitivity
promotes fibrotic walling-off of foci (characteristic tubercle granuloma).
Koch
demonstrated Koch’s postulates with M. tuberculosis, but noone has yet
been able to satisfy his postulates with this pathogen’s sister species M.
leprae. M. leprae has never been cultured in vitro.
Formerly
important cause of bovine tuberculosis transmitted by ingestion of contaminated
milk. Is uncommon in the United States, since the advent of pasteurization and
herd surveillance.
Now
important as species from which attenuated strain (M. bovis, Bacillus
of Calmette and Guerin (BCG)) is used for preparation of tuberculosis BCG vaccine
(see WebLinked
image)
CMN
group: Corynebacterium, Mycobacterium, Nocardia are grouped
together on the basis of distinguishing factors that include cell wall components,
presence and type of mycolic acids, adjuvant activity, presence of cord factor,
sulfolipids, iron-chelating compounds, polyphosphate, and serological cross-reactivity.
Hansen’s
disease, Hansen described bacilli in lepromatous skin lesions
Very
slow growing, acid-fast bacilli (see WebLinked
image; see WebLinked
image)
Chronic,
obligate intracellular pathogen; humans are only natural host
Acquired
by direct contact with persons shedding large numbers of bacilli in lepromatous
ulcer exudates or nasal secretions. Major portal of entry is respiratory tract
Never
cultured in vitro ; only cultured in mouse foot pads and nine-banded
armadillos
12
million infected; Geographic, ethnic, and socioeconomic factors contribute to
spread of leprosy
Spectrum
of disease types from relatively benign tuberculoid form (stable) through a
series of unstable intermediate forms to the most severe lepromatous form (stable)
are reflective of the patient’s immune response to the bacilli
In
tuberculoid leprosy, lymphocytes and mature granulomas in skin, organisms
invade Schwann cells of nerves and few can be cultured; strong delayed hypersensitivity
reaction but a weak humoral antibody response relatively few cells because cell-mediated
immune production of cytokines activates killer macrophages.
In
lepromatous leprosy, strong humoral antibody response, but defective
cellular response to M. leprae antigens; histiocyte involvement with
massive numbers of bacilli within dermal macrophages (109 per gram of skin tissue)
and Schwann cells (nerve involvement less than tuberculoid form); organisms
invade vascular channels with continuous bacteremia; bilateral lesions and folding
of skin, especially of the face into a lion-like appearance
Leprosy
is a disease of low infectivity that is most likely associated with a defective
cell-mediated immune response
For
a minimum of two years to life, treatment is:
Koch
demonstrated Koch’s postulates with M. tuberculosis, but noone has yet
been able to satisfy his postulates with this pathogen’s sister species M.
leprae. M. leprae has never been cultured in vitro
(1).gif)
Return to Pathogen List| Lecture Syllabus | General Course Information | Grade Determination |
| Laboratory Syllabus | Interesting WebSite Links | Lab Safety |
