Defence mechanism of lung

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

6. Cough: 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 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. Mucociliary escalator: 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 tubulin . 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 1 st 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. Trap & clear particles Dilute noxious influences Lubricate airways Humidify inspired air

16. External factors reducing mucociliary clearance Cigarette smoke Local & general anaesthetic agents Bacterial products & viral infections

17. One more Autosomal Recessive condition in which we see defect in ciliary dyenin . “ Kartegenar ” or Primary Ciliary Dyskinesia .

18. “ Kartegenar syndrome” Repeated sinusitis & respiratory tract infection Progress into lung suppression & bronchiectasis Infertility Situs inversus .

19. Surfactant: 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

20. 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.

21. 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.

22. Surfactant proteins: SP-A Most abundant Closely resemble C1q. Enhances alveolar macrophages phagocytosis . SP-D , 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.

23. Other protective fluids in lungs: Apart from surfactant proteins, many other proteins are important in lung defences. Such proteins are derived from plasma. Immunoglobulins Defensins Complement proteins Anti- proteinases

24. 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.

25. 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.

26. Complement proteins During inflammation, the delivery of complement proteins to lungs is increased by plasma exudation. Alveolar macrophages secrete C3a, C3b, C5a. Patient with C3 deficiency 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.

27. Antiproteinases 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

28. 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.

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

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

31. 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.

32. 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 .

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

34. 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.

35. 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. Important in tissue repair

36. Thank you