Lung infection and immunology Flashcards
What constitutes the upper respiratory tract?
Everything above and including the larynx – so, the pharynx, nasal cavity, sinuses, mouth.
What are the three categories of defence for the respiratory system? Examples. (x4, x4, x3)
MECHANICAL DEFENCES: upper respiratory tract acts as a filter e.g. nasal hairs, muco-ciliary clearance, coughing, epithelium acts as a physical barrier. LOCAL DEFENCES: antimicrobial secretions, ANTIPROTEASES (prevents damage from proteases which come from an immune response) and alveolar macrophages. BALT (look at next flashcard). SYSTEMIC DEFENCES: polymorphonuclear granulocytes, complement and antibodies.
What is the lymphoid tissue of the lungs and what does it do?
BALT (Bronchus Associated Lymphoid Tissue): part of the mucosa associated lymphoid tissue (MALT) loosely organised clusters of lymphoid tissue beneath the epithelium of the bronchi in the lungs that samples antigens inhaled through the nose and is the site of priming of adaptive immune responses to airborne pathogens.
What is muco-ciliary clearance?
See respiratory cell biology. Cilia in the airways beat metachronally to waft mucous containing microbes towards the throat.
What is the motion that cilia beat?
If it went forwards then backwards along the same path, then it would catch mucus on the ay back and push mucus the wrong way. So, each cilium has a very coordinated beat. There is a downward stroke and when it gets to vertical, it engages with the mucus and pushes it forward; when it gets to the bottom of the forward stroke, the cilium is withdrawn in a curved fashion (image on the right). Cilia also have little claws on their ends – more in respiratory anatomy – that engage with the mucus. They beat metachronally.
How may muco-ciliary clearance be compromised – two causes (two examples for one category; three for the other)?
ACQUIRED: pathogenic damage: viral infections can lead to destruction of the cilia and tight between epithelial cells, before opportunistic bacteria invade. Cilia must regrow, taking weeks, and can regrow as useless COMPOUND CILIA – compound cilia are shown in the image. Can also be caused by cigarette smoke.
CONGENITAL: MICROTUBULE ABNORMALITIES (abnormal microtubules can lead to non-functional cilia and dextrocardia because microtubules guide cells during embryogenesis (so if dextrocardia, check cilia function)); DYNEIN ARM DEFECTS (lack of outer dynein arm, and there’s only inner arms instead (look at photo) prevents the cilia from mucociliary clearance (look at photo)); PRIMARY CILIARY DYSKINESIA (lack of nasal NO is a cause/biomarker associated with malfunctioning cilia – disorder when mutant cilia do not have dynein arms so cilia are static).
What can ciliary defects lead to?
Ineffective muco-ciliary clearance and BRONCHIECTASIS.
What does congenital mean?
A disease or abnormality present from birth.
What is the pathophysiology of pneumococcal pneumonia and how does it lead to symptoms?
An ACUTE lung infection. It is a type of pneumonia commonly caused by the bacteria STREPTOCOCCUS PNEUMONIAE, which leads to coughing, sputum, fever and dyspnoea because the alveoli become filled with pus, meaning the lung becomes SOLID. There is also PERIPHERAL INFLAMMATION which leads to STABBING PLEURITIC CHEST PAIN – airways are not scarred and some effort can be made to clear infections.
What is pus?
Debris of the host trying to fight the infection. This is what fills the alveoli in pneumonia.
What is the pathophysiology of bronchiectasis? What are the symptoms of bronchiectasis? (x4) Significance of the mucus accumulation?
A CHRONIC lung infection where AIRWAYS BECOME SCARRED, widened and INFLAMED with thick mucous that the patient will struggle to clear. Pockets of mucous form and harbour bacteria that can multiply, but are not cleared leading to chronic infection and inflammation mediated by neutrophils – inability to clear mucous because of damage means airways cannot easily clear infections.
Sputum production, recurrent respiratory infections, breathlessness, fatigue.
Physiotherapy is important. If the lungs are emptied of the mucous that potentially contains pathogens, you remove the stimulus for neutrophils to move in and hence REDUCE INFLAMMATION.
What is the difference between an acute and chronic respiratory infection?
ACUTE: neutrophils secrete proteases to destroy microbes during inflammation and infection, and normally this is balanced by anti-proteases in the airways.
CHRONIC: the number of neutrophils is VERY LARGE, so the anti-proteases are overwhelmed leading to increased free proteases causing damage to the airway epithelia (which in turn impairs the lung defences, making it easier to be infected, and leading to further inflammation, further damage and MORE infection - creating a vicious cycle – LOOK AT PHOTO).
***Where do the proteases come from? Relate this to chronic infection!
When a phagocyte (neutrophil) gets into the airway, it phagocytoses the bacterium and produces PROTEASES that kill the pathogen – some of these proteases are spilled into the surrounding secretions. Antiproteases are sat in the airways to neutralise proteases and stop it from DAMAGING THE BODY. In chronic infection and inflammation, there are too many neutrophils, so the antiproteases are overwhelmed, so you get FREE PROTEASES which sit in sputum and cause damage!
What happens histologically in chronic inflammation and the constant traffic of neutrophils?
Protease chews away at epithelial surface, causing damage and allowing infections to colonise the damaged areas. A CHOCOLATE BROWN SUBSTANCE is produced which is the ELASTIN of the bronchial walls.
What is the general cause of pneumonia, in the context of the microbes naturally found in the lungs?
Lung is not a sterile organ – it contains many of the microorganisms that cause pneumonia, naturally. The advent of a bacterial pneumonia is likely to be in the background of a common viral infection.
What are the two types of pneumonia? What pathogens are associated with each type?
COMMUNITY ACQUIRED PNEUMONIA: Not just Streptococcus pneumoniae (for pneumococcal pneumonia), but viruses like rhinovirus, influenza A/B are associated with the disease. SO, there’s a cooperative process between the virus AND the bacterium, that leads to the disease.
HOSPITAL ACQUIRED PNEUMONIA: Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella species.
What is the epidemiology of pneumonia?
Increases exponentially with age. Death increases with an even greater increase with age too i.e. older people are more susceptible to death with pneumonia.
What are the risk factors of pneumonia? (x8)
- Less than 2 and more than 65 years old.
- Smoking.
- Alcohol consumption.
- Poverty.
- Contact with small children.
- Overcrowding.
- Medications e.g. corticosteroids, immunosuppressants and proton pump inhibitor usage.
- Medical history: COPD, Asthma…
What are the symptoms of pneumonia? (x4)
- Acute lower respiratory symptoms: coughing, sputum, dyspnoea, hypoxia…
- Pleuritic chest pain.
- New X-ray changes i.e. X-ray changes regularly with infection.
- At least one systemic feature: fevers, headache, shivers, aches and pains, increased temperature.
What causes the stabbing pleuritic chest pain in pneumonia?
The pain is actually called ‘stabbing pleuritic chest pain’, so remember it! There are pain fibres on the surface of the lungs, so when the lungs become solid and the inflammation gets out to the periphery, they become stimulated and there’s pain.
What does the lower respiratory tract refer to?
Refers to respiratory tree – describes the branching structure of the airways supplying air to the lungs.
What is hypersensitivity?
Exaggerated response to a foreign substance irrespective of the mechanism – can be immunological or non-immunological.
What is an allergy?
An exaggerated IMMUNOLOGICAL response to a foreign substance (allergen) which is inhaled, swallowed, injected or placed on the skin or eyes. It is a TYPE OF HYPERSENSITIVITY.
What is the mechanism of allergic rhinitis?
KNOWN AS SEASONAL ALLERGIES.
HAY FEVER.
It is an UPPER AIRWAYS allergic disease – refers to NASAL AIRWAYS!
- Allergens pass over epithelium in the airways and are captured by dendritic cells.
- Dendritic cells migrate to lymph nodes and stimulate T helper cells to differentiate into T follicular helper cells (using interleukin-4) and TH2 cells (using interleukin-9) that activate B cells and mast cells respectively.
- T follicular helper cells stimulate B cells to become plasma cells that secrete allergen specific IgE antibodies that bind to FcE receptors on mast cells – specialised cells found in CONNECTIVE TISSUE and AIRWAYS. (NOTE how this is an atopic response.)
- When the allergen CROSS-LINKS WITH IgE ANTIBODIES (basically means ‘to bind’) on mast cells, degranulation occurs leading to histamine release = inflammation and more.
What is the mechanism of extrinsic allergic alveolitis?
- Extrinsic allergic alveolitis concerns very SMALL allergenic particles which penetrate distal airways (bronchioles) and enter alveoli, then interstitium.
- Particles are captured by antibodies in the interstitium to form antigen-antibody complexes.
- Complement and immunological cascades are triggered, and lymphocytes are recruited.
- Immunological response is triggered = INFLAMMATION of the alveoli.
