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DEFENSE MECHANISM OF LUNG| Tutorial B-1 RS

130110110177|Gabriella Chafrina| 29/11/13


Function: to protect itself against potentially toxic inhaled material

Have major categories:
1) Physical/Anatomic factors and Functional factors
Function: deposition and clearance inhaled materials
- Anatomic factors/defenses
o Function: promote deposition of particles in upper airways prevents the majority inhaled particles
from reaching alveoli
o Determinant:
Particle size
>10 um: settle in nose
5 um 10 um: settle in trachea, conducting airways
<5 um: reach distal lung parenchyma many bacteria in this size range so that
deposition along airways not very effective for excluding bacteria from the LRT
Inspiratory flow rate
in velocity of inspiratory flow promotes deposition of particles by impaction in upper
airways
- Functional factors/defenses
o Function: promote clearance of particles through actions, such as:
Cough
Is important protective mechanism, frequently triggered by stimulation if airway irritant
receptors that are activated by inhaled or aspirated foreign material
Receptors found in larynx, trachea, and major bronchi. More common at point of bifurcation
Afferent: vagus, trigeminal, and glossopharyngeal nerves
Efferent: recurrent pharyngeal nerve (a branch of vagus control glottis, phrenic, and spinal
nerves contract diaphgram and expiratory muscles of chest and abdominal walls)
Mucociliary transport/clearance
Is a process of waves of beating cilia moving a blanket of mucus (and any material trapped
within the mucus) progressively upward along the tracheobronchial tree
From trachea down to respiratory bronchioles, has cilia projecting into airway lumen
Cilia: beat in coordinated manner,
frequencies between 600-900 beats/min,
speed 6-20 mm/min when do ciliary
beating (to remove debris deposited on
mucous blanket), have structure identical
to cilia found elsewhere in body
Ciliary beating: move a blanket of mucus in
cephalad direction (i.e: from distal to more
proximal parts of tracheobronchial tree)
Mucous blanket: there are 2 layers
comprise:
Sol layer
Located adjacent to cilia
Origin unknown
Gel layer
Located at the luminal surface
Consists of complex polymer of
mucopolysaccharides, produced by goblet and
mucus-secreting cells
More viscous
Cough and mucociliary transport is happening when particles deposited in
trachea or bronchi, but when it deposit in alveoli, cellular defense will take
control

DEFENSE MECHANISM OF LUNG| Tutorial B-1 RS
130110110177|Gabriella Chafrina| 29/11/13
2) Phagocytic and inflammatory cells
Cellular defense are triggered when particles deposit in alveoli include activation of phagocytic and
inflammatory cells.
- Dendritic cells and Pulmonary Alveolar Macrophages
Function: Scavanged bacteria and particles
o Dendritic cells
Located in the airway epithelium, alveolar walls, and peribronchial connective tissue
Closely related in lineage to monocytes and macrophages
Cells have long and irregular cytoplasmic extension
o Pulmonary Alveolar Macrophages
Large, mobile cells approximately 15-50 um in diameter
Descendants of circulating monocytes derived from bone marrow
Cytoplasm contains granules of digestive enzymes, part of mononuclear phagocyte system
Release chemoattractants cytokines (chemokines) that recruit other inflammatory cells
- Phagocytosis
Process: Alveolar macrophage exposed to inhaled particles/bacteria attachment of foreign material
to surface of macrophage particles/bacteria engulfed within plasma membrane (which invaginates
and pinches off within the cell to form a cytoplasmic phagosome)
All process facilitated by opsonins
Proteins bind to extracellular materials and make them more adherent to phagocytic cells and
more amenable to engulfment or ingestion
Coat the foreign material
- Polymorphonuclear Leukocytes (PMN)
Important component of defense mechanism for established bacterial infection of lower respiratory
tract
Normally, few PMNs in small airway and alveoli when bacteria overwhelmed initial defense
mechanism PMN replicate within alveolar spaces
Prominent component of inflammatory response is an outpouring of PMNs into alveolar space
PMN attracted to the lung by a variety of stimuli, particularly products of complement activation
and chemotactic factors that release by alveolar macrophages
Variety of factors that mediate adhesions of PMNs to vascular endothelium, such as integrins 9on the
surface of PMNs) and adhesion molecule (on the surface of the vascular endothelial cells)
Neutrophil contains several antimicrobial substances, including defensins, lysozyme, lactoferrin.
Neutrophil also capable of generating products of oxidative metabolism that are toxic to microbes

3) Immune responses
- Humoral Immune Mechanism
o Immunoglobulin A
Functions:
May bind to viruses and bacteria prevent
attachment to epithelial cells
Efficient in agglutinating microorganisms
agglutinated microbes are more easily cleared by
mucociliary transport system
Neutralize a variety of respiratory viruses and bacteria
Is a polypeptide-glycoprotein immunoglobulin complex
Found in nasopharynx and upper airways constitute
primary antibody type
Quantities much greater in respiratory tract than in serum
IgA present in areas Secretory IgA
Includes a pair of IgA molecules (joined by polypeptide)
+ extra glycoprotein component (=secretory component)
Synthesized locally
DEFENSE MECHANISM OF LUNG| Tutorial B-1 RS
130110110177|Gabriella Chafrina| 29/11/13

o Immunoglobulin G
Particularly abundant in lower respiratory tract
Synthesized locally to a large extent
Has number of biologic properties: agglutinating
particles, neutralizing viruses and bacteria toxins,
serving as an opsonin for macrophage handling of
bacteria, activating complement, and causing lysis of
gram-negative bacteria in presence of complement





- Cellular Immune Mechanism
o T Lymphocytes
Functions:
Produce a variety of soluble, biologically active mediators called cytokines, some of which (i.e
interferon ) have the ability to attract or activate other protective cell types, particularly
macrophages
Interacting with the humoral immune system and modifying antibody production
2 cell types: CD4
+
and CD8
+.
On exposure to specific antigens, both types produce a variety of
cytokines interact with other components of the immune system, particularly B lymphocytes
and macrophages



T- Lymphocytes: produce lymphokines and regulate immunoglobulin synthesis
B-Lymphocytes: produce antibodies
Lymphokines and Immunoglobulin: sensitize and activate cells of the defense system
Natural Killer (NK) cells: Capable of killing bacteria without prior sensitization
Immunoglobulin A: Bind to viruses and bacteria to prevent attachment and facilitate agglutination of the microorganism
Lysozyme (in leukocytes) and lactoferrin (synthesized by PMN): can destroy/detoxified organism

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-Antitrypsin: inactivates proteolytic enzymes released from bacteria, neutrophils, and necrotic cells
Interferon (by macrophages and lymphocytes): antiviral capacity
Lymphocytes --> lining trachea, carina, and hilum of each lung