Lower Respiratory Tract Infections, LRTI - Pathogenesis, Virulence Factors, Toxins, Host Response Evasion
Pathogenesis, Virulence Factors of Lower Respiratory Tract Infection (LRTI)
Pathogenic microorganisms possess traits or produce products that promote colonization and subsequent Lower Respiratory Tract Infection (LRTI) in the host.
The virulence factor of disease-producing micro-organisms depends upon:
adherence
tissue damage
production of toxins
ability to disseminate
avoiding host immune response
Adherence
The etiologic agents of respiratory tract disease must first adhere to the mucosa of the lower respiratory tract (LRT). A load of indigenous micro-organisms and the state of the host immune system affect the ability of micro-organisms to adhere. Except for those micro-organisms inhaled directly into the lungs, all etiologic agents of disease must first colonize the respiratory tract prevailing possible Lower Respiratory Tract Infection (LRTI).
Streptococcus pyogenes possess specific adherence factors such as fimbriae (lipoteichoic acids + M proteins). These molecules appear as a thin layer of fuzz surrounding the bacteria.
Staphylococcus aureus and certain viridans Streptococci possess lipoteichoic acid.
Many gram-negative bacteria- Enterobacteriaceae, Legionella spp., Pseudomonas spp., Bordetella pertussis, Haemophilus spp. do not contain lipoteichoic acid and hence also adhere by means of proteinaceous finger-like surface- fimbriae.
Viruses possess either a haemagglutinin (influenzae and parainfluenza viruses) or other proteins that mediate their epithelial attachment.
Toxins
Certain micro-organisms if present in the respiratory tract are considered etiologic agents of Lower Respiratory Tract Infection (LRTI).
Corynebacterium diphtheriae produces disease through the action of extracellular toxins. Once the organism colonizes the upper respiratory epithelium, the toxin produced is disseminated systematically, adhering preferentially to the central nervous system (CNS) cells and muscle cells of the heart. The local disease can lead to respiratory distress and systemic disease is characterized by peripheral neuritis myocarditis.
Growth of Corynebacterium diphtheriae causes necrosis and slouching of epithelial mucosa, producing a “diphtheritic (pseudo) membrane” which may extend from the anterior nasal mucosa to the bronchi and may be limited to the area in between- usually between tonsillar and peritonsillar areas. The membrane causes difficulty in breathing and swallowing.
Non-toxic strains of Corynebacterium diphtheriae cause local disease and are much milder than its toxigenic strains.
Some strains of Pseudomonas aeruginosa produce toxins similar to that of diphtheria toxin. But whether this toxin contributes to the pathogenesis of respiratory tract infection has not yet been confirmed.
Bordetella pertussis – an agent of whooping cough also produces toxins but the role of these toxins in the production of the Lower Respiratory Tract Infection (LRTI) is not clear. They may act to inhibit the activity of phagocytic cells or damaged cells of the respiratory tract.
Staphylococcus aureus and β-hemolytic streptococci procedure extracellular enzymes capable of damaging host cells or tissues. Extracellular products of Staphylococcus aureus aid in the production of tissue necrosis, and destruction of phagocytic cells, and contribute to abscess formation. It has not been proven to cause pharyngitis even though isolation has been done from throat specimens.
Micro-organism growth
Pathogens can cause Lower Respiratory Tract infections (LRTI) by merely growing in host tissue. They interfere with normal tissue function, attracting host immune effectors such as neutrophils and macrophages.
Once these cells begin to attack invading pathogens and repair the damaged host tissue, an expanding reaction ensues (to follow in order) with more non-specific and immunologic factors attracted to the area, increasing host tissue damage.
Respiratory viral infections usually progress in this manner, as do many types of pneumonia caused by Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitis, Moraxella catarrhalis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and most gram-negative bacilli.
Host response evasion
S. pneumoniae, N. meningitidis, H. influenzae, Klebsiella pneumoniae, mucoid P. aeruginosa, and Cryptococcus neoformans, among others possess polysaccharide capsules that serve by preventing engulfment by host phagocytic cells and by protecting somatic antigen from being exposed to host immunoglobulins.
Some micro-organisms such as pneumococci produce capsular material in such abundance that soluble polysaccharide antigen particles can bind host antibodies, blocking them from serving as opsonins.
Vaccines containing capsular antigens provide host protection from infection from micro-organisms like H. influenzae, S. pneumoniae, and N. meningitidis indicating the importance of capsular polysaccharide as a virulence mechanism.
Some respiratory pathogens responsible for Lower Respiratory Tract Infection (LRTI) evade the host immune system by multiplying within host cells. Eg: Chlamydia trachomatis, C. psittaci, C. pneumoniae, and all viruses. Once inside host cells, these pathogens are protected from host humoral immune factors and respective phagocytic cells. The protection lasts until host cells become sufficiently damaged to be recognized as foreign and then attacked.
Other groups of organisms causing respiratory disease are Legionella, Pneumocystis jirovecii (Pneumocystis carinii), Histoplasma capsulatum, etc. These organisms are capable of survival within phagocytic cells (usually macrophages) where they multiply.
Mycobacterium tuberculosis is a classic representative of an intracellular pathogen. The tubercle bacilli multiply slowly within macrophages of the lymph nodes (usually in hilar or other mediastinal chains) where they are protected from phagosome-lysosome fusion capable of destroying the bacteria.