Mycobacterium Tuberculosis Flashcards
What causes tuberculosis?
Mycobacterium tuberculosis is the major cause of tuberculosis, but this disease can be caused by a group of closely related species of Mycobacterium tuberculosis complex MTC
What’s the definition of tuberculosis?
Chronic disease characterized by delayed hypersensitivity and granuloma
Which bacteria are included in the MTC?
M. tuberculosis
M. Bovis
M. Canetti
M. Microtti
To what is linked the muramic acid of the PGL wall?
Arabinogalactan layer composed of arabinose and galactose
What do we find above this layer?
Large amount of mycolic acid overlain by free lipids and glycolipids
Where polypeptides are located? What derives from them?
Polypeptides are above the lipid layer
PPD, purified protein derivative, derives from them
What is the function of the PPD?
They activate the cell mediated immunity
What makes them virulent?
They are capable of intracellular growth in unactivated alveolar macrophages
What causes the disease primarily?
Disease is primarily caused by the host response to infection
The disease is immunopathological, resulting from the production of granulomas, not caused by exotoxin or LPS..
Who are the reservoir?
Humans
How it is transmitted?
Person to person spread by aerosols from diseased individuals via coughing, sneezing or vocalizing
What are the basic conditions for transmission?
Extent of the disease Extent of the exposure Absence of UV light and improper ventilation Malnutrition Age Frequency of the coughs
When individuals are highly infectious?
When they expectorate the bacteria
What’s the period of exposure in order to be infected?
To be infected, there has to be a long period of exposure to infected individuals
What destroys the bacteria first?
UV light
In which age groups that is a quicker progression of the disease?
In individuals less than 1 year old and in elderly people
How the cough progresses?
It is mild repetitive at the beginning, not as severe as that caused by a viral or different bacterial ideology. In late stages, there is hemoptysis
What’s the problem of MTC?
The resistance to regular disinfectants and detergents
How the primary infection is acquired?
By droplet nuclei because of the small size of the bacteria
Where do they go? Why?
They go to alveoli since there is O2, they also need 5 to 10% of CO2
By which cell they are phagocytosed?
By macrophages
Where do they go then? How they are transported?
They go via these macrophages into regional lymph nodes, hilar lymph nodes
What is the outcome of the primary infection?
Individuals remain chronic carriers of the bacteria, in a dormant state in the granulomas
How the disease is confined?
The disease is confined by these granulomas covered with calcified tissue, that can be detected with a chest x-ray
Are individuals infectious at this stage?
Do they have symptoms? How do we know that they are infected?
They are not infectious, they can live long lives as long as the activated macrophages are controlling, so the macrophage-mediated immunity is stronger
They have no symptoms and the only way to tell they’re infected is the PPD test
When do we talk of a postprimary tuberculosis?
When DTH, delayed type hypersensitivity, prevails
To what is related the disease?
It is related to a chronic granulomatous state that is a DTH disease
What happens in the stage instead of the confinement?
Tissue distruction instead of confinement of the infection
Which other cells participate in the distraction?
Tc lymphocytes and NK cells
How the distruction happens?
There is liquefaction of the casestion part and bursting of the granuloma
What does the bacteria after tissue destruction?
Bacteria multiply rapidly in the caseation part
They will go out, leaving a cavity —> cavitation stage
What happens during the cavitation stage?
It is a source of more extensive coughs with expectoration of more sputum and bacilli
What are the symptoms of this stage?
High fever
Anorexia and weight loss (—>wasting disease)
Which individuals are the most infectious?
Those with open cavities
Where bacteria can go during coughing?
Bronchi, trachea and then the larynx
What is the most infectious stage of tuberculosis?
Laryngeal tuberculosis and it is one of the end stages
What shows a chest x-ray for a postprimary infection?
- Cavitation of the lungs
- An architectural change of the lungs represented by shrinkage and decrease in volume of the lungs because of fibrosis
What is the survival range if individuals are left untreated?
2.5 to 3 years
What happens if they are treated?
They can have long lives, with on and off state, intervals in which they are good, and intervals in which there is reactivation
Why they can’t be cured of the bacilli?
Since they are chronically infected, they can only be cured of the manifestations and the allergic hypersensitivity reaction
What happens if during the primary infection the individual isn’t able to confine the primary complex?
- Bacteria can go to the surface of the lungs without entering them
- In the case of HIV infection before tuberculosis, there is a quick progression of tuberculosis since macrophages are not properly functional and lymphocytes are destroyed
What do we call liquid droplets where bacteria are found?
Droplet nuclei
Why these nonspore forming bacteria are considered as resistant bacteria?
Since they can stay for 9 months to 1 year in an environment without sunlight and ventilation
What is the infectious dose?
5 to 200 bacteria are enough to cause an infection so it is a very small infectious dose
Where bacteria live and replicate? How?
In unactivated macrophages by inhibiting the phagosome-lysosome fusion
In which part of the lungs bacteria are found?
In alveoli
Where bacteria will spread?
In the hilar lymph nodes
From what is composed the primary complex?
From the Ghon focus and the hilar lymph nodes
What are the symptoms? Are they severe?
They are mild symptoms
Low fever, respiratory manifestations, mild cough that can be accompanied with streaking of blood
How the disease is confined in the primary complex?
By the production of the granuloma
Which T lymphocytes will be recruited? When? What is the function?
After 10 days of the infection, activated T cells especially Th type: Th1 that produce lymphokines to recruit macrophages and even Th2
They will produce lymphokines and interleukins to activate macrophages
What is the structure of the granuloma?
- Its central part is formed by unactivated macrophages (multinucleated giant cells that are dead), and necrotic tissue containing bacteria (pus) that has a cheese like consistency, so it is called caseation
- Its outer part is formed of activated macrophages (epithelioid cells) and T cells
Why there will be acidification of the medium?
Because many bacteria are destroyed
What will cover granulomas?
Fibrous tissue and calcification
Why at this stage bacteria are not affected by antibiotics?
Since they are dormant in the center of the granulomas, so there is confinement and recovery of the symptoms not of the bacteria because of chronic infection
By which way we can know that there is an infection?
With the PPD test and chest x-ray where granulomas look like scares in different areas of the lungs
What is the final outcome of the primary infection?
After calcification, bacteria are dormant and the disease is under control
What do we call the lesions forming after the initial infection? What happens to those lesions?
Ghon focus
Mostly, they heal spontaneously and become small calcified nodules
From what is composed of the Ghon complex?
Ghon focus + Regional lymphadenopathy
In which age groups primary pulmonary TB may progress rapidly to clinical illness?
In young children with immature cellular mediated immunity (CMI) and in persons with impaired immunity e.g. those with malnutrition or HIV infection
What happens if bacilli penetrate into the pleural space?
We have pleural effusion
What happens in the primary infection in infants less than 1 year of age?
There is the progression of the disease, there is a tendency to develop a meningitis and a miliary tuberculosis
What do we have during miliary tuberculosis?
There are many white nodules which are the miliary foci of tuberculosis
Why the PPD test in individuals under 1 year with miliary tuberculosis is negative?
Because before invasion of the lungs, PPD test is negative and in those children there is no invasion yet
What causes postprimary tuberculosis after the primary infection?
Depression in cellular immunity
What balance should be present to confine the primary infection?
Between the activity of activated macrophages and TH1 which confine the focus and TH2 which have a destructive effect