Презентация на тему Tuberculosis, morphology and physiology

tuberculosis

Usually involves the lungs but may affect any

organ or tissue in the body

Typically results in caseating granulomas

Tuberculosis

to person
transmission of airborne droplets with organisms
from

an active case to a susceptible host

Intestinal tract

Skin by inoculation

Congenital by transplacental spread

Routes of infection

or sneezed into the air from patients with active

“open” Pulmonary TB
“airborne” or by exposure to contaminated secretions

M. bovis
Transmitted by milk from diseased cows causing intestinal & oropharyngeal TB
Rare disease for human

M. avium-intracellulare
Very low virulence
Rarely cause disease in normal hosts
Cause disseminated infection in 10-30% of AIDS patients

Microorganism

TB

Access of organism: close contact with open cases

of disease, e.g. increased in crowded & unhygienic working and living conditions

Susceptibility of individual: the old, very young, black & Asian populations have and increased susceptibility

Predisposing Factors

privileged “poor”

Occupation: increased incidence of TB in some types

of pneumoconiosis (silicosis & in health workers)

Other Diseases:
pre-existing chronic lung disease,
chronic renal failure,
Hodgkin diseases,
diabetes mellitus,
alcoholism,
corticosteroid,
immunosuppressive cytotoxic drug therapy
Immunodeficiencies including (HIV/AIDS)

Predisposing Factors

Has no known exotoxins, endotoxins

Has waxy coat “high

contents of complex lipids” that causes them to retain the red dye when treated with acid in acid-fast stain & resist de-colorization

tuberculosis.

Early in infection, tuberculosis bacilli replicate essentially unchecked,

while

Later in infection, the T-helper response stimulates macrophages to contain the proliferation of the bacteria.

Pathogenesis

several macrophage receptors:

Macrophages mannose receptors

Complement receptors

Once inside

the macrophage, M. tuberculosis replicates within the phagosome by blocking fusion of the phagosome & lysosome

Pathogenesis

in the nonsensitized individual is characterized by unchecked proliferation

of bacteria in the pulmonary alveolar macrophages & airspaces, with resulting bacteremia & seeding of multiple sites

Despite the bacteremia, most patients at this stage are asymptomatic or have a mild flulike illness

Pathogenesis

the course of the disease

In some people with

polymorphisms in the NRAMP1 gene, the disease may progress from this point without development of an effective immune response “decreased microbicidal function”

NRAMP1 protein is a transmembrane protein found in endosomes and lysosomes & may have role in generation of anti-microbial oxygen radicals

About 3 weeks after infection, a TH1 response against M. tuberculosis is mounted that activates macrophages to become bactericidal

Pathogenesis

to the lymph node, which are presented with class

II major histocompatibility proteins by antigen presenting cells “macrophages”

Differentiation of TH1 cells depends on the presence of IL-12, which is produced by antigen presenting cells that have encountered the mycobacteria

Mature TH1 cells, both in lymph nodes and in the lung, produce IFN-γ

Pathogenesis

to become competent to contain the M. tuberculosis infection

IFN-γ

stimulates formation of the phagolysosomes in infected macrophages, exposing the bacteria to an inhospitable acidic environment

IFN-γ also stimulates inducible nitric oxide synthase (iNOS), which produces nitric oxide (NO)

NO generates reactive nitrogen intermediates and other free radicals capable of oxidative destruction of several mycobacterial constituents, from cell wall to DNA.

Pathogenesis

the TH1 response orchestrates the formation of granulomas &

caseous necrosis

Activated macrophages, stimulated by IFN-γ, produce TNF, which recruits monocytes

These monocytes differentiate into the "epithelioid histiocytes" that characterize the granulomatous response

CD4+ TH1 cells also facilitates development of CD8+ T cells, which can kill the TB-infected macrophages

Defects in any of steps of TH1 response result in poorly formed granulomas, absence of resistance, & disease progression

Pathogenesis

and doesn't cause significant tissue destruction or illness

In some

people, the infection progresses and the ongoing immune response results in tissue destruction due to caseation and cavitation

Pathogenesis

TH1 cells, which stimulate macrophages to kill the bacteria

This immune response, while largely effective, comes at the cost of hypersensitivity and the accompanying tissue destruction

Reactivation of the infection or re-exposure to the bacilli in a previously sensitized host results in rapid mobilization of a defensive reaction but also increased tissue necrosis

Pathogenesis Summary

after infection, intracutaneous injection of 0.1 mL of PPD

induces a visible & palpable induration “at least 5 mm in diameter” that peaks in 48-72 hrs

Positive test indicates cell-mediated hypersensitivity & doesn’t differentiate between infection & disease

False-negative test may be produced by certain viral infections, sarcoidosis, malnutrition, Hodgkin disease, immunosuppression & overwhelming active TB

False-positive test may result from infection by atypical mycobacteria

Type IV Hypersensitivity Reaction in TB