DEFENSE MECHANISM OF RESPIRATORY TRACT

Winarti Bagian/SMF Patologi Anatomi FK UNUD

Defense mechanism of respiratory tract consists of:

Physical or anatomic factors Antimicrobial peptides Phagocytic and inflammatory cells Adaptive immune response

Physical or Anatomic Factors

Contribute in deposition and clearance of inhaled material
Nasal hair Sneeze reflex Cough reflex Branching bronchial tree Mucocilliary apparatus

Mucocilliary clearance
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 The apparatus
Cilia of the respiratory epithelium Mucus blanket

Cilia
The contractile structure named dynein arm Move coordinately (wave) to cephalad direction (pharynx) to be swallowed or expectorated 6-20 mm/min

Mucus blanket
Sol layer
Bathing the cells and cilia directly Aqueous Produced by serous cells and osmotically driven Contain antimicrobial peptides

Gel layer
Floating on top of sol layer Viscous Produced by goblet cells and submucosal gland epithelial cells Trapping particles

Antimicrobial peptides

Lysozyme
Present along the respiratory tract, most prominent in proximal airways Produced by: respiratory epithelial cells, serous glandular cells, macrophages Inducing lysis of the cells Most active against gram +ve organism

Lactoferrin
Produced by serous cells and neutrophils Acts to:
Agglutinate and kill bacteria (block iron metabolism) Enhance neutrophil adherence Prime neutrophil superoxide production

Defensins
Two most important types in the lung
-defensins, produced by resident neutrophills -defensins, produced by respiratory epithelial cells

Broad antimicrobial activity Act by making microbial cell walls permeable release of microbial content and destruction of membrane potential Highly sensitive to salt concentration inactive in cystic fibrosis

Collectins (SP A and D)

Binding and aggregating microbes Facilitating interaction with other immune cells Contribute in regulating pulmonary alveolar macrophages activity

Respiratory IgA
Produced by respiratory epithelium Does not require prior exposure Acts:
To prevent bacteria and viruses attach to epithelium To agglutinate microorganis easily cleared by mucocilliary apparatus To neutralize viruses, some bacteria

Also involve in humoral immune mechanism

Phagocytic and inflammatory cells

Pulmonary alveolar macrophages Dendritic cells PMN leukocytes NK cells

Pulmonary alveolar macrophage

Phagocytosis process

Dendritic cells

PMN leukocytes

PMNs attract to alveoli by factors release by macrophage Kill the bacteria by phagocytosis process Produced antimicrobial peptides

NK cells

Adaptive Immune Response

Humoral immunity Cellular immunity

Humoral immunity
B cell plasma cell Antibody (IgA and IgG) IgA in upper, IgG in lower respiratory tract IgG acts:
To agglutinate particles To neutralize viral and bacteria toxin To serve as opsonin for macrophage handling To activate complement To lyse gram (-)ve bacteria

CELLULAR IMMUNITY
Cellular immunity plays roles in protecting against:
Mycobacteria Viruses Fungi Bacteria

Failure of Respiratory Defense Mechanism

Impairment of Physical Clearance
Inability to cough effectively Impaired mucocilliary clearance
Dyskinetic cilia syndrome Viral RTI Cigarette smoking High concentrations of O2 for prolonged periods General anesthesia

Impairment of antimicrobial peptides Impairment of phagocytic and inflammatory cells

Causes of problems with macrophage function
Viral RTI Cigarettes smoking Alcoholism Starvation Cold exposure Hypoxia Corticosteroid therapy HIV/AIDS

Causes of decreased number of PMN

Bone marrow replacement by tumor Cancer chemotherapeutic agents

Defect in adaptive immune system

Humoral
Hypogammaglobulinemia Agammaglobulinemia

Cellular
Corticosteroid Cytotoxic drug Hodgkins ds and other lymphoma HIV/AIDS

Summary
Factors responsible for defense mechanism of respiratory tract include anatomic factors, antimicrobial peptides, phagocyte and inflammatory cells and adaptive immune system Any impairment of one/more of those component may contribute to respiratory tract infections or injury