for pulmonary medicines doctors

1. Defence Mechanisms Of
Lung
Presented by:
Dr. Rohit Mahavarkar
Dept. Of Pulmonary
Medicine

2. • Everyday our lungs is exposed to 7000 litres of
air.
• It is exposed to dust, pollen, bacteria etc.
• Despite these exposures, pathology does not
occur always. This is due to local primary
protective mechanism.
• If infections penetrate primary defences, then
secondary responses including inflammatory and
classical immune responses come to action.

3. • Respiratory tract is protected by different
mechanisms.
Upper airways Cough
Lower airways Mucocilliary clearance
Gas exchange units
( bronchioles &
alveolii)
Surfactants and cellular defenders
including alveolar macrophages

4. • Mucus in upper airways & surfactant in gas
exchange, contains variety of proteins with
defence properties against the infection.
• Cells also have important cytoprotective
antioxidant & anti-proteinase mechanisms.

5. Physical defences.
1. Nose
– Aerodynamic fibres of respiratory epithelium
covering turbinate bones
– Removes large particals
Hairs in anterior nares  mucocilliary action 
filtering

6. • Most important protective mechanism.
• Also, one of the symptoms of resp. diseases.

7. •The efferent pathway of the reflex involves nerve supply
to the larynx, rib cage & diaphragm.
•CNS component of the cough reflex is located in the MEDULLA
OBLONGATA & receptor is involved is 5- hydroxytryptamine
Myelinated irritant fibres &
intravascular non-myelinated J-
receptors
Via C-fibres & myelinated fibres
Transmit cough
•Neuronal
mechanism

8. • 4 phases of cough:
– Inspiration
– Compression of intrathoracic gas against a closed glottis.
– Explosive expulsion as the glottis opens
– Relaxation of the airways
• Results in expectoration of foreign debris & mucus as a
result of high local turbulant airflow.
• Cough contributes little to tracheobronchial clearance 
more in case of COPD where mucociliary clearance
impaired.
• Opiates have a direct, rather sedative effect on CNS
component on cough reflex.

9. – Responsible for tracheobronchial clearance.
– Cough is not enough effective in removing small
inhaled particles.
– Mechanism : it is a complex interaction between
cilia on bronchial epithelial cells & mucus.

10. • Each pseudostratified columnar epithelial cells
lining bronchii possess approx 200 cilia.
• Cilia
– can carry a weight of 10 g.
– Can beat 10-14 times/ sec
• The contractility of cilia is controlled by
• Dynein: ATPase protein, derives it’s energy
from ATP determines the force of the cilia

11. • Ciliary motility: ( how to
determine?)
– can be assessed directly by cytological specimens
from nasal and bronchial brushings, to enumerate
ciliary beat frequency.
– Imaging techniques.

12. • Mucus is secreted by the goblet cells &
submucosal glands of 1st several bronchial
generations.
Chemical mediators which increase mucus secretion
Neuropeptides ( substance P) Vasoactive intestinal peptie &
bombesin
Vagal stimulation Acetylcholine

13. • Mucus is composed of:
–95% water
–Glycoproteins
–Mucins
–Variety of other proteins

14. What is the main
function of
mucus?

15. 1. Trap & clear particles
2. Dilute noxious influences
3. Lubricate airways
4. Humidify inspired air

16. Abnormality in concentration of mucus causes impairement
of mucociliary transport.
• One such condition is “CYSTIC FIBROSIS”
• VERY VICIOUS MUCUS

17. • One more Autosomal Recessive condition in
which we see defect in ciliary dyenin.

19. • Active material lining alveolar surface that
reduces surface tension.
• What is surface tension?
–It is a collapsing force!!!!
–So the surfactant prevents
the alveolii from collapsing

21. • Surfactant is secreted by Type 2 pneumocytes.
• It also helps in alveolar clearance
– At the end of expiration, surface film moves from
alveolus to bronchioles. Thus, carrying small particles
& delivering it to mucociliary transport system.

22. • The composition of surfactant also contains
surfactant proteins
– SP-A
– SP-B
– SP-C
– SP-D
• Surfactant also enhances local non-specific
pulmonary immune defence mechanisms.
• It exerts influence on neutrophils function which
include neutrophil adhesion.

23. Surfactant proteins:
– Most abundant
– Closely resemble C1q.
– Enhances alveolar macrophages phagocytosis.
, may also share same effects of SP-A on
inflammatory cells & macrophages.
• Surfactant can be damaged by a number of noxious
stimuli. Alteration in surfactant is important in
pathogenesis of ARDS.

24. • Apart from surfactant proteins, many other
proteins are important in lung defences. Such
proteins are derived from plasma.

25. Immunoglobulins
• Normally all secretions contain immunoglobulins but in
different proportions.
• IgA, is in excess as compared to IgG & IgM.
• Immunoglobulins produced by a local lung tissue – from
plasma cells & B-lymphocytes
• IgA is secreted maximum in the upper airways.
• Deficiency oF IgA is associated with bacterial infections.

26. Defensins & other proteins
• Defensins is a family of cytotoxic cationic peptides secreted
mainly by the leukocytes.
• The anti-bacterial effect can be correlated with the charge,
which is determined by the argenine content of the
molecule.
• They kill
– gram +ve organism
– Fungi
– Viruses
• Lactoferrin is an iron binding protein which competes with
the bacteria, iron is an essential growth factor in certain
bacteria.

27. Complement proteins
• During inflammation, the delivery of complement
proteins to lungs is increased by plasma exudation.
• Alveolar macrophages secrete C3a, C3b, C5a.
• Patient with have recurrent URTI &
LRTI, with Strep. pneumoniae & H. Influenzae.
• C3 has important role in bacterial defence as it has
action of opsonin (C3b) its is phagocytosed by
macrophages.

29. • Many of these agents may be derived from
alveolar macrophages & airway epithelial
cells.
• During inflammatory & injurious processes
the rate of secretion of these important
protective agents is likely to be greatly
enhanced

31. Secretory leukoproteinase
inhibitor
• SLP inhibitor is produced
by submucosal gland in
bronchi.
• Present in significant
quantity in bronchial
secretion.
• Extremely potent and rapid
inhibitor of neutrophil
elastase, but can also
inhibit cathepsin G,
trypsin& chymotrypsin.
Elafin
• Extremely effective
against neutrophil
elastase.
• But does not inhibit
trypsin, chymotrypsin or
cathepsin G.

32. • Neutrophil Elastase is also known as
one of the most destructive enzymes in the
body.
• Once unregulated, this enzyme disturbs
the function of the lung permeability barrier
and induces the release of pro-inflammatory
cytokines.

33. • Derived from monocytes.
• Patrol the alveolar lining.
• Possess phagocytic activity
• Able to ingest & destroy pathogenic bacteria.
• Can amplify inflammatory response.

34. • Role in repairing inflammatory tissue.
• Have a wide range of degradative enzymes.
• Have capacity to digest proteins, lipids,
carbohydrates.

35. • Activated macrophages form nitrite & nitrate,
which contribute to antifungal, antiparasitic, &
tumorocidal activities.
• Macrophages also call in a number of other
phagocytic cells e.g neutrophil, eosinophil, by
specific generation of chemokines.
• Despite such powerful mechanism, not all
phagocytosed particles are destroyed.
– Minerals such as Quartz & Abestos.
– Number of microorganisms including MTB.

36. Initiation & control of inflammatory response.
• Macrophages secrete a number of chemotactic
proteins including members of 5-LOX & COX
pathway which exert important proinflammatory
effects.
• Leukotriene B4 which is a specific neutrophil
chemotoxin.

37. • Chemokines for neutrophils :
– IL-8, NAP-1, NAP-2
• Chemokines for monocytes & eosinophils:
– MCP-1, MIP-1α, RANTES

38. Other macrophage derived cytokines
• Secondary proinflammatory response.
TNF-α , IL-2
Act on local fibroblast,
epithelial cells & endometrial
cells to produce IL-8 & more
chemokines.
Amplify inflammatory
response
Act on endothelium.
Stimulate expression &
activation of surface adhesion
molecules & emigration.

39. Tissue modelling & repair.
• Alveolar macrophages secrete proteins
– Vitronectin
– Fibronectin
– Lamimin
• Also secrete number of growth factors
cytokines including PDGF, IL-7
• Influence behavioue of fibroblast & secretion
of collagen & other matrix protein.