Defense Mechanism (upper respiratory tract)

y y y y y y y y y y

OBJECTIVES 1 Describe the anatomical barriers 2 Describe the mechanical defences and removal of particles 3 Describe the biochemical/humoral, cellular and microbiological defences 4 Describe the specific defences 5 List the hazards and factors which impair defence mechanisms in relation to the respiratory tract

RESPIRATORY TRACT

Hazards to Respiratory Tract* Inhalation of foreign particles y * Inhalation of toxic materials / chemicals y * Inhalation of pathogenic microorganisms y * Physical damage to mucosal surfacey

HOWMaintain temperature y Maintain moisture y Maintain Sterility y Filter particle/foreign bodiesy

* Non-Specific Defence Mechanisms/Innate Defence y * Specific Defence / Immunological Mechanismsy

NONNON-SPECIFIC DEFENCE MECHANISMS* Anatomical / Physical barriers * Mechanical barriers * Biochemical / Humoral defence mechanisms * Cellular defence mechanisms * Microbiological defence mechanisms

NONNON-SPECIFIC DEFENCE MECHANISMSAnatomical / Physical Barriers Nose : Narrow nares : Nasal hairs : Mucosa - vascular, moist : Stratified squamous epithelium : Pseudostratified ciliated columnar epitheliumy

Nasopharynx : Turbulent air flow : Impaction : Mucus : Pseudostratified ciliated columnar epithelium Larynx y : Ciliated columnar epithelium y : Mucus secretions

Pseudostratified ciliated columnar epithelium

Trachea : same y Bronchi : Same : sometimes simple columnar y Bronchioles : simple cuboidal / columnar : ciliated : non-ciliated (Clara cell lineage)y

AlveoliType I alveolar cells / Type I pneumocytes : Squamous epithelial cells : Blood - Gas Barrier y Type II aveolar cells /Type II pneumocytes : Cuboidal : secretes detergent - like phospholipidy

Removal of ParticlesParticle Size 10-15 um Mechanism of Removal Filtered by nasal hairs Deposited in nasopharynx or oropharynx Impacted in nasopharynx, oropharynx or trachea Sedimentation in bronchi & bronchioles Trapped by random movement or diffusion

5-10 um 5 um < 0.5 um

Mechanical Defencesy y y y y

Turbulence in air flow Sneezing Cough reflex Swallowing reflex Mucociliary escalator / elevator

Mucociliary escalator / elevatorterminal bronchioles to larynx y presence of ciliated epithelium & mucus y particles adhere to mucus layer/trapped y continuous, coordinated ciliary action upwards (1000 1500 beats/min) y mucus & particles moved up the bronchial tree y expelled : swallowed / expectoratedy

Biochemical Defence Mechanisms1 Mucus secretion y Buffering /neutralising effect y Mucopolysaccharides block viruses 2 Lysozyme y Bactericidal effect 3 Lactoferrin y bacteriostatic / prevent infection y strengthen non-specific defence 4 Glandulin y bacteriocidal /antimicrobial activities

5 Interferon y induces antiviral response y increases resistance to viruses/ y limits spread 6 Complement y lysis of bacteria y opsonisation y chemotaxis 7 Cytokines y Interleukins, chemotactic factors, y TNF

8 Anti-oxidants y Catalase y Superoxide Dismutase y Glutathione redox system Protect against free radicals 9 P450 MFO system y Clara cells y Type 2 cells Detoxify pollutants

10 Anti-proteases y Alpha 1 anti-trypsin y Leukoprotease inhibitor y TIMP y Alpha 2 macroglobulin Protect against PMN and macrophage enzymes

CELLULAR DEFENCE MECHANISMS1 Alveolar macrophages / Dust cells y Present in lung alveoli & interstitium y Phagocytosis y Remove particulate materials 2 Lymphocytes - natural killer (NK) cells y Present in interstitium & bronchial mucosa associated lymphoid tissue y Active without prior exposure to antigen y No need for antibody y No immunological memory

Local Inflammatory ResponseFollows damage in mucosa Clears organisms by phagocytosis Neutrophils y acute inflammation Macrophages y chronic inflammation Regeneration of mucosa y overall resistance

Microbiological Defence Mechanisms- Normal flora of upper respiratory tract Nose y Streptococci y Staphylococci y Diphtheroids Pharynx y Non-haemolytic/alpha haemolytic streptococci y Aerobic & anaerobic staphylococci y Gram negative diplococci y Diphtheroids

y y y y

Trachea Same normal flora as pharynx Lesser in numbers Bronchi Few bacteria Bronchioles and alveoli Sterile

Colonization ResistanceNormal flora interferes with the colonization of pathogens y How ? Occupy receptor sites Compete for nutrients Secrete metabolic or toxic productsy

bacteriosinsStimulate

cross reacting antibodies

SPECIFIC DEFENCE/IMMUNE RESPONSESComponents of immunity/immune system 1 Antibody-mediated immunity (Humoral immunity) 2 Cell-mediated immunityy

AntibodyAntibody-mediated (humoral) (humoral) immunity IgA

Secretory y Acts locally y Reacts specifically with microorganism s y Neutralize / lyse / inhibit IgE y Low concentration IgG y Low concentrationy

Cellular Components of Immune SystemB y T y y y

Lymphocytes Plasma Cells Lymphocyte subsets CD4+ CD8+

Antibody production

Regulatory function/interleukins Effector function / cytotoxicity

K Cells Cytotoxicity

Macrophages

Antigen presentation (APC ) y Phagocytosis y Cytokine production Eosinophils y Parasitic immunity y Histaminase productiony

Factors Which Impair Defence MechanismsAir pollutants y smoke - cigarette, others Chemical toxins / fumes Alcohol y impairs ciliary action and phagocytosis Malnutrition y decreases resistance

Hazardous Air Pollutants (HAPs)acetaldehyd y toluene y styrene y formaldehyde y mercury y chromium y arsenicy

dioxins polychlorinated biphenyls benzene xylene poly-aromatic hydrocarbons lead

Infections y : viral / bacterial Immunosuppression y congenital or acquired Diseases of respiratory tract y asthma y emphysema y cystic fibrosis

REFERENCES1 .Brooks, Butel & Morse : Jawetz, Melnick & Adelbergs Medical Microbiology. Appleton & Lange 2 .Greenwood D, Slack R & Peutherer J. Medical Microbiology. Churchill Livingstone 3 .Hart T & Shears P, Color Atlas of Medical Microbiology. Mosby-Wolfe 4 .Mims et al, Medical Microbiology. Mosby 5 .http://www.bact.wisc.edu/Bact330/lecturenf NB. All latest editions