This document discusses the defence mechanisms of the lungs. It outlines several lines of defence, including physical barriers like mucus and cilia, surfactant, immunoglobulins, antimicrobial peptides, complement proteins, and cellular defences such as alveolar macrophages. Alveolar macrophages patrol the lungs and destroy pathogens via phagocytosis. They also initiate and control inflammatory responses by secreting chemokines and cytokines and help repair tissue damage. The lungs have robust protective mechanisms to filter pathogens from the air we breathe daily.

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.