micro 1 and 2 Flashcards
what are the two main areas of the respiratory tract?
- Upper respiratory tract (URT)•Abundant and diverse microbiota
- Lower respiratory tract (LRT)•Normally sterile
how do URT microbial communities vary?
•By age, season
how many air does a healthy person breath each day?
A healthy adult breathes >7000L of air a day
•Approx. 104-106bacteria cells/m3/day
how does the lung have immunity?
- Complex barrier to protect against inhaled pathogens
- Mechanical
- Particles of different sizes get removed at different levels
- Chemical•Produces mucus, complement
- Some epithelial cells can produce cytokines etc
- Immunecells
- Alveolar macrophages (recruit other immune cells when needed)
how much of inhaled particles transported from bronchioles to trachea by the mucociliary elevator?
about 90%
what is the mucocillary elevator?
Part of the innate immune system
•Non selective
•On a very basic and generalised level; •Consists of different components;
•Epithelial (ciliated) •Secretory cells
•Can be impaired/inhibited in certain chronic conditions;•
Cystic Fibrosis
•Primary Ciliary Dyskinesia
how does the mucocillary elevator work?
Secretory cells produce mucuswhich coat the airways
•Goblet cells in trachea→changes to club and serous cells lower down
Inhaled particles become trapped in the mucus
•Mucus “floating” on the PCL which allows the cilia to beat
•Moves mucus up and out of the respiratory tract
what is a respiratory tract infection and what are the different types of ones?
- Respiratory tract infection is a general term for any infectious disease involving the respiratory tract
- Further classified based on localisation
- Upper Respiratory tract infections
- More often acute infections rather than chronic
- Mainly viral but can be bacterial
- Fungal lot less common •Lower Respiratory tract infections
- Tends to be where the more serious infections are based
what are the possible upper respiratory tract infections?
- Pharyngitis: inflammation at the back of the throat (includes tonsillitis)
- Laryngitis: inflammation of the larynx
- Sinusitis: inflammation of the sinuses
- Common Cold: symptoms caused by inflammatory response
what are the possible lower respiratory tract infections?
- Bronchitis: inflammation of the bronchi
- Bronchiolitis: inflammation of the bronchioles (mainly in kids)
- Pneumonia: inflammation of the alveoli
how would you treat a respiratory tract infection?
antibiotics
how can you acquire a respiratory tract infection?
•Generally transmitted by droplets from coughing and sneezing
•Influenza: May contain >0.5 million virus particles per sneeze/cough
•Droplet Vs Airborne transmission•
Can also be caught from contac
how would you prevent infections?
Good general hygiene measures;•Handwashing•Soap/Alcohol rubs•Cough Etiquette•More Healthcare specific;•Patient isolation•PPE•Surface decontamination
what are the common microbiota in COPD?
Some more common species; H. influenzae, S. pneumoniae, M. catarrhalis
•P. aeruginosa more prevalent the more advanced the disease
what is pneumonia and how can you get it?
- Pneumonia causes inflammation of the lung
- Causes the alveoli to fill with fluid
- Can be defined by different sources of infection;•Community
- Any pneumonia acquired outside a hospital
- Hospital•If infection acquired >48 h after admission •Ventilator
- If infection arises >48 h after intubation/mechanical ventilation
what are the common microbiota assoicated with COPD?
- Typical: S. pneumonia, Group A Streptococcus, H. influenza, M. catarrhalis,
- Atypical: Legionella, Mycoplasma, Chlamydia
- Hospital and Ventilator:•G-bacilli (e.g. E.coli and P. aeruginosa)•G+ cocci (particularly MRSA)
what does group A steptococcus cause?
Strep throat ( GAS pharyngitis), Necrotizing Fasciitis, tonsillitis etc etc
is strep A grame positive or negative?
gram positive
how is strep A characteristed?
- Categorised by M-protein antigen (cell surface and fimbriae)
- Supplanted by PCR/sequencing of EMM gene (>200 genotypes)
how is strep A treated?
antibiotics
how do strep A immunoinvade?
- Attachment/Invasion mediated by;
- M proteins, Pili F proteins and hyaluronic acid capsule
- Once body detects GAS, innate immune system kicks into action
- Triggers a proinflammatoryresponse
- Release of cytokines (IL-6 and TNF)•Recruits macrophages and neutrophils
what are the GAS mechanisms?
- Hyaluronic acid capsule
- M-protein
- Secreted enzymes
what is the main cause of TB?
Main cause is Mycobacterium tuberculosis in humans
•Other Mycobacteriumspecies can also cause TB•M. bovis, M. africanum, M. canetti, M. microti
who discovered Mycobacterium tuberculosis?
Koch
is Mycobacterium tuberculosis gram positive or negative?
- Can appear as either Gram Positive OR Gram negative
- Cell wall is rich in lipids
- Mycolic acid
are Mycobacterium tuberculosis fast or slow dividing?
- Grows very slowly•15-20 hours to divide
* Takes 3-4 weeks to culture in a micro lab
what is the TB disease process?
- Bacterium breathed in
- Bacterium ingested by macrophages•Releases chemokines etc to summon lymphocytes
- New cells surround macrophages in a spherical arrangement
- Environmental factors trigger killing of macrophages•Creates a necrotic zone
- Granuloma disintegrates•Spreads to other parts of lung making more granulomas•Spreads to new host via coughing etc
how do you diagnose TB?
- Used 6 needles to inject tuberculin PPD into the skin of the wrist
- Left for 2-7 days and results defined by a scale
- Negative to grade 4 depending on type of reaction
- UK until 2005 then replaced with the Mantoux test
what is Mantoux tests ?
Uses a single needle to inject PPD tuberculin•Used in latent TB diagnosis•Looks for a red bump
what are other ways to diagnose TB?
- Sputum microscopy and culturing
- Mainly for active TB
- Generally 3 samples
- Deep cough, induced sputum or bronchoscopy and lavage
- Preferably 1 from early morning
- Direct microscopy observation following Ziehl-Neelsenstaining
- Needs approx. 5000 bacteria/mL•Cant tell the difference between different Mycobacteria•Culture
how does one do a speutum sample?
•Involves bringing up phlegm from the lungs into a tube•Difficult for some patients•Subjected to additional testing•Microscopy •Culture•Molecular testing/Antibiotic sensitivity
what are the problems associated with phlegm sampling?
culturing of sputum•It will probably contain different microbes•How do you know which one is causing the infection?•It doesn’t account for viruses•It has a low predictive value•Sensitivity and selectivit
what are you looking for when diagnosing tb by radiography?
•Chest X ray or thorax CT•Looking for abnormalities•Still not overly specific•Difficult to distinguish between active and cured TB (scarring)
what is interferon gamma release assay
Uses blood sample from patients
•Looks for T-lymphocyte release of IFN-γ
what are the two licensed Interferon gamma release assay?
- QuantiFERON®–TB Gold In-Tube test
* T-SPOT®.TB test
how would treat sensitive tb?
- Isoniazid and rifampicin for 6 months
* Pyrazinamide and ethambutol for 1st2 months
how would you treat resistant TB?
- 4.6% MDR globally
* Increases treatment time
what is multi-resistant tb resistant to?
Resistance to isoniazid AND rifampicin
how would you treat extremely drug resistant tb?
•As MDR-TB + any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin)
what is the tb vaccine also known as?
In UK give Bacillus Calmette-Guérinvaccine (BCG vaccine)
what microbacteria is the bcg derived from?
Live attenuated vaccine derived from M. bovis
is the bcg part of routeine vaccination?
no-Only 5 local authorities that offered universal BCG vaccination in the UK
what are influenza?
Influenza viruses are single stranded RNA viruses from the family Orthomyxoviridae
what are the 4 genera that cause influenza?
- A and B generally associated with human infections
- A is responsible for pandemics, broken down subtypes
- B is less common than A and almost exclusively infects humans
- C is less common, primarily infects pigs and dogs
- Donly infects pigs and cattle, has the potential to infect humans
what is the influenza structure?
RNA based genome; split into 8 segments, 15 kbptotal
•Hemagglutinin;binds the flu virus to sialic acid on target cell surface
•Neuraminidase; enzyme which cleave sialic acid from glycoproteins (letting virus escape from cells)
•M1 matrix protein; mediates encapsidationand has regulatory functions
•M2 Ion channel; maintains pH across viral envelope during cell entry and during viral maturation
what is antigenetic shift and drift?
igenic Shift•Only occurs in Influenza A
•Causes sudden majorchanges•Genes recombine to produce a new virus subtype
•Is responsible for many pandemic Flu types
Antigenic Drift •Occurs in Influenza A and B •Gradual accumulation of point mutations •Induces small changes and is responsible for seasonal epidemics •Produces a new strain of virus
what determins how serious the infection willl be?
the make up of the virus
where can Hemagglutinin be cleaved?
can only be cleaved by proteases in throat and lungs (mild)•Can be cleaved by variety of proteases throughout the body (highly virulent)
how long does viral replication take in influenza A?
For influenza A viral replication peaks after about 48 hours
when is a virus shedded?(infectious)
5 days
what can infectious cells produce?
Infected cells can go onto produce proinflammatory cytokines and chemokines
is there a treatment for the flu?
no - self limiting- goes away by itself in healthy individuals
who are eligible to get vaccinated for the flu each year?
•Children aged 2-17•Adults over 65•Individual with underlying chronic conditions•Individuals with reduced immunity•Pregnant women•Morbidly obese individuals
what are the two antivirals used in the uk?
- Zanamivir & Osletamivir
* Both are neuraminidase inhibitors (stop viral liberation from cell surface)
what are the other two licensed antivirals in the UK but not recommended?
- Amantadine hydrochloride also licenced in UK but not recommended
- Blocks the M2 ion channel
- Development of resistance can occur rapidly during treatment
what strains were in the 2019 uk and us vaccine?
•A/Brisbane/02/2018 (H1N1)pdm09-like virus•A/Kansas/14/2017 (H3N2)-like virus•B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage)•B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage)
what are the differnt types of vaccines for different types of people in the UK?
•Eligible children 2-17; live attenuated quadrivalentvaccine (nasal spray)
•Adults 18-64; quadrivalent injected vaccine (egg or cell grown)•Adults 65+ given adjuvantedtr ivalent injected vaccine (grown in eggs) or quadrivalent
injected vaccine (cell grown)
what is Respiratory syncytial virus (RSV)?
Common respiratory virus →causes mild, cold like symptoms
•Can also progress into bronchiolitis or pneumonia
what do envloped viruses belong to?
Enveloped RNA virus belonging to Pneumoviridae family
how do symptoms arise from the common cold?
Symptoms arise from interaction with the immune system•Virus dependent •Binds to ICAM-1 receptors and releases inflammatory mediators (Rhinovirus)
what were the other types of coronavirus identified?
- In 2002 →SARS CoV•Approx. 10% died•No additional cases since 2004
- In 2012 →MERS CoV•30-40% people die
what are the current corona vaccines?
- Moderna•95% effectiveness
* Pfizer/BioNTech•95%effectiveness•Oxford/AZ•62-90%effectiveness
