Respiratory system Flashcards
Mycobacteria and TB: mycobacterium TB facts
- 2-4 μ by 0.2-0.5 μ
- Obligate aerobe: well-aerated upper lobes
- Facultative intracellular parasite: usually macrophages - because it’s made up of a lot of lipids so can grow inside the macrophages without being killed
- Slow generation time
15-20 h
M.bovis from cattle
Mycobacteria and TB: Where does TB most commonly affect?
Lungs - pulmonary TB but can also affect the lymph nodes, bones, joints and kidneys and it can cause meningitis
Mycobacteria and TB: How does TB spread and who is more likely to affect?
TB is most commonly spread in droplets being coughed or sneezed into the air
Frequent or close prolonged contact with an infected person is necessary
People with already weakened immune system
Mycobacteria and TB: Who are the at risk groups of TB?
HIV infection
Steroids, chemotherapy, transplants, elderly
Unhealthy, over-crowded conditions
Stay in high-rate country- S.E. Asia, sub-Saharan Africa, parts E.Europe
Those exposed to TB in youth
Children of parents from high-rate countries
Prisoners, drug addicts, alcoholics
Malnourished
Mycobacteria and TB: Where and how does primary TB start?
Droplet nuclei inhaled
Taken up by alveolar
macrophages – not
activated (lipids)
Droplet nuclei (c.5 μ) reach the alveoli where the infection begins
Granuloma in lung = Ghon focus
Enlarged lymph nodes + GF = Primary Complex
—> mild flu like symptoms
Mycobacteria and TB: how does secondary TB occur?
Reactivation of dormant mycobacteria when something happens to the T cells: impaired immune function
Reinfection in a person previously sensitised to mycobacterial antigens
- occurs months, years or decades after primary infection
- reactivation most commonly occurs at apex of lungs - highly oxygenated
Mycobacteria and TB: What is the mechanism of secondary TB?
- Caseous centres of tubercles liquefy
- Organisms grow very rapidly in this
- Large Ag load
- bronchi walls become necrotic and rupture
- cavity formation
- organisms spill into airways and spread to other areas of lung: highly infectious
- Primary lesions heal
- Ghon complex, Simon foci
Mycobacteria and TB: What is milliary TB?
rapid dissemination of th organism
Mycobacteria and TB: How do you classify a TB infection (not lung disease) LEARN
Organism present Tuberculin skin test positive Chest X-ray normal Sputum smears negative Sputum culture negative No symptoms Not infectious Not defined as a case of TB
Only 3-4% of those infected develop active disease upon initial infection, 5-10% within one year
Mycobacteria and TB: How do you classify a TB lung disease? LEARN
Organism present Tuberculin skin test positive Lesion on chest X-ray Sputum smear positive Sputum culture positive Symptoms Infectious Defined as a case of TB
Mycobacteria and TB: What are the most common symptoms?
Cytokines (TNF, IL-3, GM-CSF) Persistent cough, +/- sputum Anorexia Weight loss Swollen glands (usually in the neck) Fever Night sweats Sense of tiredness and being unwell Coughing up blood
can’t really diagnose from symptoms
Mycobacteria and TB: What is the standard recommended regimen?
Isoniazid, rifampicin, pyrazinamide and ethambutol
for two months followed by isoniazid and rifampicin for four months
Trying to treat without the organism becoming resistant to the antibiotic, that’s why there is a standard regime
Mycobacteria and TB: Why is there a standard recommended regimen?
Prevent spread of MDR-TB standardized drug regimens directly observed treatment (DOT) good supply of high quality drugs isolation of infectious patients - negative pressure isolation room
Mycobacteria and TB: What role does vitamin D play in TB?
Vitamin D has role in activating macrophages to destroy mycobacteria
Often a vitamin D deficiency in ethnic populations in UK
Mycobacteria and TB: What is the timeline of treatment of TB?
Non-infectious after c. 2 weeks
Begin to feel better after 2-4 weeks
Treatment must continue for 6 months + - must prevent resistance developing
Longer treatment for TB meningitis or if TB is resistant
Mycobacteria and TB: What are the fatality rates?
Untreated TB - 40 to 60%
Treated TB
- 5 to 50%
- depending on nutrition; quality and availability of medical care; HIV status
Mycobacteria and TB: What is the BCG vaccine and how does it affect the skin test?
Protection restricted to childhood tuberculosis which is rarely infectious
No impact on HIV-related TB
Does not prevent infection – only disease
Invalidates tuberculin skin test
Therefore – targeted vaccination; effective for about 15 y
Mycobacteria and TB: what is the link between TB and HIV?
HIV / AIDS and TB are overlapping epidemics – “the unholy alliance”
- Worldwide 30-80% of AIDS patients get TB
HIV increases risk of acquiring TB
Destroys immune system
TB makes HIV worse
Increases replication rate of HIV
TB treatment slows down HIV and keeps patients alive to get HIV drugs
Mycobacteria and TB: What are the obstacles to TB control?
Lack of financial resources- half of all cases in China, Indonesia, India, Pakistan and Bangladesh
Social instability - e.g. Russia
HIV epidemic
- HIV/AIDS doubles the TB death rate
- 30 to 70% of TB cases in Africa are HIV positive
- reinfection in South Africa
Drug resistance
Stigma
Mycobacteria and TB: What do skin tests do?
Heaf, Tine, Mantoux
- ascertains infection rather than disease
- may be negative in severe TB or concomitant HIV, malnutrition, steroids
- may be positive with BCG or after exposure to environmental mycobacteria
Mycobacteria and TB: What are T- SPOT TB & QuantiFeron gold?
Blood tests to replace tuberculin tests
Detect reactive T cells - specific for mycobacterium TB, not for BCG
Specific for Mtb
Not BCG
Mycobacteria and TB: How is microscopy used to look at TB sputum?
Ziehl-Neelsen stain: Needs > 10,000 organism/ml at 100X lens
or flourescent
Rhodamine-Auramine is more sensitive
One-third of pulmonary TB (two-thirds extra-pulmonary) undiagnosed by microscopy
Mycobacteria and TB: How do you culture TB sputum?
Homogenise (Sputasol - breaks it down)
Decontaminate (4% NaOH Petroff) - kills all bacteria but the mycobacterium
Concentrate (centrifugation)
(Middlebrook’s medium)
Löwenstein-Jensen medium
4-6 weeks for visible colonies
(Liquid media; Kirchner’s)
Mycobacteria and TB: how does automatic culturing work?
MGIT 960
- Fluorescent reaction quenched by O2
- Growth of mycobacteria lifts quenching and tubes fluoresce
- 10 days
another test - MPT64 - antigen ONLY given off by TB so this test is done afterwards
Mycobacteria and TB: Look at nucleic acid detection tests again -
MTB complex - rifampicin resistance genes
Mycobacteria and TB: how is typing carried out?
Spoligotyping
- Variable Number of Tandem Repeats
- Mycobacterial Interspersed Repetitive Units
- VNTR-MIRU
- e.g. VNTR 84455 MIRU 244428223533
17 digit profile given - fingerprint of that organism so can track the infection
Respiratory viruses and atypical pathogens: Why are some viruses restricted to infecting certain areas?
expression of different types of cell expressed receptors.
Respiratory viruses and atypical pathogens: What are the types of infection? and the two types of invaders?
Surface: - local spread
- short incubation e. g. common cold, Candida
Systemic: - spreads from mucosal site of entry to other site in the body
- returns to surface for final shedding stage
- longer incubation: weeks
- e.g. measles, mumps, rubella
Professional invaders:- infect healthy respiratory tract
Secondary invaders: - infect compromised tract
Respiratory viruses and atypical pathogens: What is Rhinitis and sinusitis?
The common cold
Caused by various viruses
Transmission by aerosol
Self-limiting (surface infections) and not systemic in healthy people
Identification usually not necessary unless clinical symptoms worsen- Involvement of LRT.
Molecular methods most common for ID, epidemiololgical info only
no vaccines - viruses change regularly and many of them cause the same symptoms
Respiratory viruses and atypical pathogens: How do viruses cause the classic cold symptoms?
Virus adheres to ciliated epithelium and avoids flushing out
Then enters cells and replicates inside cells, this cell damage leads to release of the clear runny nose fluid.
And leads to activation of host defenses release of cell debris and transient damage to ciliated epithelium.
Then there is an immune response that might be accompanied by overgrowth of normal flora and finally recovery and regeneration of ciliated epithelium.
Respiratory viruses and atypical pathogens: Describe the structure of an adenovirus
Icosohedral symmetry, non-enveloped-resistant to desiccation
Attach via the adhesins on end of penton fibres
dsDNA
Respiratory viruses and atypical pathogens: What is pharyngitis and tonsillitis mostly caused by?
70% caused by virus
A common complication of common colds due to surrounding infections
Also site of entry of EBV (Herpes lecture) and Mumps virus (before dispersal around body)
Respiratory viruses and atypical pathogens: What is mumps?
Paramyxovirus
Air-borne spread (saliva etc.)
Commonly spread and contracted in school age children
Most children now vaccinated- M(easles)M(umps)R(ubella)
MMR fear increased occurrence in UK for a number of years
Complications include Orchitis- Inflammation of the Testicles- PAINFUL especially in adult men
Respiratory viruses and atypical pathogens: What is laryngitis and tracheitis often caused by?
Often caused by parainfluenza viruses, adenovirus and influenza
Burning pain in the larynx and trachea
Can become obstructed easily in children- croup. Specific type of cough with Stridor inhalation
Respiratory viruses and atypical pathogens: What is bronchitis and bronchiolitis caused by?
Several viral causes: Rhinoviruses, coronaviruses (SARs), adenoviruses and influenza
Atypical pathogens: Mycoplasma pneumoniae
Many secondary infections- especially in children- narrow airways- leading to bronchiolitis- and pneumonia
75% of bronchiolitis caused by Respiratory Syncytial Virus
Respiratory viruses and atypical pathogens: What is RSV respiratory syncytial virus? (type of bronchiolitis)
Aerosol and hand-hand/ surfaces transmission
Pathology creates large fused cells (Syncytia)
Outbreaks in winter months
Nearly all children have been infected by age 2- but often nothing more serious than common cold
Severe in young infants- peak mortality 3 months of age (why?)
Infants: Cough, cyanosis, rapid respiratory rate: pneumonia and bronchiolitis
Older children and adults is more like a common cold.
Treatment supportive- hydration- bronchiodilators
Severe cases require ribavirin antiviral or Palivizumab-prophylactic in at risk groups (e.g. prem babies at risk (heart defect, lung disease, immunodef., in season)
VACCINE IMMINENT IN NEXT FEW YEARS
Respiratory viruses and atypical pathogens: What is Orthomyxoviridae? (influenza virus)
Transmitted by aerosol droplet
Occurs worldwide- restricted to coldest months of year
Initial infection: virus attaches to sialic acid receptors on epithelial cells via viral HA protein (quite non specific, on almost every cell in the respiratory tract so can affect the whole tract)
1-3 days: liberated cytokines result in systemic chills, malaise, fever and muscle aches, runny nose and cough
Usually recover after 1 week, but some develop pneumonia and bronchitis and have lingering symptoms.
Secondary invaders can cause lethal infections: pneumococci, staphylococci
Respiratory viruses and atypical pathogens: What is the structure of influence virus?
Two surface glycoproteins:
HA- Haemagglutinin
NA- Neuraminadase
Host-derived viral envelope
ssRNA genome: 8 segments
Nucleoprotein and polymerases
Respiratory viruses and atypical pathogens: What do HA and NA glycoproteins do? (look over viral uptake of HA slide 16)
major antigens
HA: major antigenic determinant
- HA binds sialic acid receptors on epithelial cell surface
- Major source of antigenic variation
NA : second antigen determinant
- Involved in release of the virus from host cells during budding
Respiratory viruses and atypical pathogens: What are the 3 types of influenza?
A: Yearly epidemics and occasional serious worldwide epidemics- important animal reservoirs in birds and pigs
B: yearly epidemics- no animal reservoir
C: minor respiratory illness- no epidemics
Respiratory viruses and atypical pathogens: How is influenza classified?
H- antigen (HA):
- 16 Avian and mammalian types
- Only 3 are human adapted (H1-3) - transmitted within humans
N-antigen (NA):
9 known serotypes
2 human adapted (N1-2)
Respiratory viruses and atypical pathogens: What is antigenic drift?
Small point mutations in HA and NA that accumulate in population over time (mutations usually occur in the antigenic parts of them molecule which prevents antibody binding)
Result in new variant viruses that can re-infect individuals
Source of yearly flu epidemics worldwide
Respiratory viruses and atypical pathogens: How are the yearly flu vaccines produced?
Vaccine strains chosen in
February for northern hemisphere
Strains grown in embryonated hen eggs: not applicable to individuals with Egg allergy
Formalin killed, detergent treated viral ‘split’ vaccines
Southern hemisphere strains used to predict next years northern strains- yearly vaccines of at-risk (current dominant strains are H3N2-types)
Vaccine contains one H3N2 strain, one H1N1 and one B strain
Administered in October each year
Respiratory viruses and atypical pathogens:How does influenza A go through antigenic shift?
Less common
Results in major shift in viral composition
Major gene reassortment resulting in new HA and NA types
Little immunity in population
CAUSE OF MAJOR WORLD PANDEMICS
Only influenza A
Respiratory viruses and atypical pathogens: What are the features of pneumonia?
Many organisms cause identical symptoms
Only organisms less than 5mm can enter the alveoli
Often secondary to preceding damage- Cystic Fibrosis or influenza
Influenced by Immunocompromisation
- e.g. HIV and pneumocystis infections
Children:
- mainly viral causes – RSV, parainfluenza
- secondary bacterial infections
Neonates may acquire Chlamydia from mother in birth
Adults:
Bacterial causes more common-: e.g. Strep. Pneumoniae formerly most common (Prof Douglas lecture)
Respiratory viruses and atypical pathogens: What is atypical pneumonia?
Term originally coined as pneumonia caused by Penicillin resistant organisms
‘Walking pneumonia’- not hospitalised
Typically report chest pain, cough, shortness of breath
- less serious symptoms compared to normal pneumonia
Mainly caused by :
Mycoplasma pneumoniae
Chlamydophila (formerly Chlamydia)
Legionella pneumophila
Respiratory viruses and atypical pathogens: What is mycoplasma pneumoniae?
Very small bacterium with minimalist genome (0.5Mbp)- possibly smallest of any free-living organism in nature (Ventner)- made artificially- SYNTHIA (related spp.)
No peptidoglycan- cholesterol- penicillin resistant…
‘walking’ pneumonia- sick but not hospitalised
Major cause of pnuemonia in young adults and students
Efficient binding to cilial epithelial cells (sialic acid) via a special cytadherence organelle rich in a cytadhesin (P1) for sialic acid rich glycolipids.
