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甘肃农业大学:《微生物学》课程教学课件(Microbs)Chapter 24 Microbial Diseases of the Respiratory System

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1/26/2016 Structure and Function of the Microbes Respiratory System Learning Objective Invisible Invaders Describe how microorganisms are Amazing Allies prevented from entering the respiratory system. Chapter 24 Microbial Diseases of the Respiratory System Structure and Function of the Structures of the upper respiratory system Respiratory System Upper respiratory system -Nose,pharynx,middle ear,and eustachian tubes -Saliva and tears protect mucosal surfaces Sirus Lower respiratory system -Larynx,trachea,bronchial tubes,and alveoli Oral cavity Epiglottis -Respiratory mucus protects mucosal surfaces

1/26/2016 1 Invisible Invaders Amazing Allies Chapter 24 Microbial Diseases of the Respiratory System Structure and Function of the Respiratory System Learning Objective Describe how microorganisms are prevented from entering the respiratory system. Structure and Function of the Respiratory System • Upper respiratory system – Nose, pharynx, middle ear, and eustachian tubes – Saliva and tears protect mucosal surfaces • Lower respiratory system – Larynx, trachea, bronchial tubes, and alveoli – Ciliary escalator moves particles to the throat via ciliary action – Alveolar macrophages destroy microorganisms in the lungs – Respiratory mucus protects mucosal surfaces Structures of the upper respiratory system Sinus Nasal cavity Oral cavity Tongue Sinus Middle ear Auditory (eustachian) tube Opening of Tongue auditory tube Epiglottis Larynx (voice box) Trachea (windpipe) auditory tube Tonsils Pharynx (throat) Spine (backbone) Esophagus

1/26/2016 Structures of the lower respiratory system Normal Microbiota of the Bronchiole Branch from (h Respiratory System Learning Objective Left lung Trache Characterize the normal microbiota of the upper and lower respiratory systems. Normal Microbiota of the Microbial Diseases of the Upper Respiratory System Respiratory System A wide variety of microorganisms Learning Objective colonize the upper respiratory tract Differentiate pharyngitis,laryngitis Normal microbiota suppress pathogens tonsillitis,sinusitis,and epiglottitis. by competing for nutrients and producing inhibitory substances Lower respiratory system is nearly sterile due to the ciliary escalator in the bronchial tubes

1/26/2016 2 Structures of the lower respiratory system Pharynx (throat) Larynx ( b) Bronchiole Branch from the pulmonary vein Branch from the pulmonary artery Blood (voice box) Trachea (windpipe) Right lung Bronchus Bronchiole Pleura Left lung H t Blood capillaries Alveoli Pleura Diaphragm (breathing muscle) Heart Normal Microbiota of the Respiratory System Learning Objective Characterize the normal microbiota of the upper and lower respiratory systems. Normal Microbiota of the Respiratory System • A wide variety of microorganisms colonize the upper respiratory tract • Normal microbiota suppress pathogens by competing for nutrients and pg y roducing inhibitory substances • Lower respiratory system is nearly sterile due to the ciliary escalator in the bronchial tubes Microbial Diseases of the Upper Respiratory System Learning Objective Differentiate pharyngitis, laryngitis, tonsillitis, sinusitis, and epiglottitis

1/26/2016 Microbial Diseases of the Upper Bacterial Diseases of the Upper Respiratory System Respiratory System ·Pharyngitis -Sore throat,inflammation of mucus membranes in the throat Learning Objective ·Laryngitis -Larynx is the site of infection ·Tonsillitis List the causative agent,symptoms, -Inflamed torsils prevention,preferred treatment,and ·Sinusitis laboratory identification tests for streptococcal pharyngitis,scarlet fever -Usually self-limiting diphtheria,cutaneous diphtheria,and otitis media. Bacterial Diseases of the Upper Respiratory System Diphtheria Streptococcal pharyngitis(strep throat) Caused by Corynebacterium diphtheriae -Caused by group A streptococci(GAS) -Gram-positive rod:pleomorphic .Streptococcus pyogenes Forms a tough grayish membrane in the throat -Resistant to phagocytosis -Streptokinases-lyse clots -Fibrin and dead tissue -Streptolysins-cytotoxic to cells -Blocks passage of air to the lungs -Local inflammation,fever,tonsillitis Exotoxin produced by lysogenized bacteri enlarged lymph nodes -Diagnosis-enzyme immunoassay tests ci5botdonogeshe Scarlet fever Cutaneous diphtheria-forms skin ulcer -Erythrogenic toxin produced by Prevented by DTaP vaccine lysogenized5.pyogenes -Diphtheria toxoid

1/26/2016 3 Microbial Diseases of the Upper Respiratory System • Pharyngitis – Sore throat, inflammation of mucus membranes in the throat • Laryngitis – Larynx is the site of infection • Tonsillitis – Inflamed tonsils • Sinusitis – Heavy mucus discharge from the sinuses – If opening is blocked, then pressure and pain occur – U ll lf Usually self-li iti m ng • Epiglottitis – A flap-like structure that prevents ingested material from entering the larynx – Most life-threatening disease of the upper respiratory system; develops rapidly with death in a few hours – Haemophilus influenzae type B Bacterial Diseases of the Upper Respiratory System Learning Objective List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for streptococcal pharyngitis, scarlet fever, di hth i t s di hth i d di phtheria, cu taneous di phtheria, and otitis media. Bacterial Diseases of the Upper Respiratory System • Streptococcal pharyngitis (strep throat) – Caused by group A streptococci (GAS) • St t rep ococcus pyogenes – Resistant to phagocytosis – Streptokinases - lyse clots – Streptolysins - cytotoxic to cells – Local inflammation, fever, tonsillitis, enlarged lymph nodes – Diagnosis - enzyme immunoassay tests • Scarlet fever – Erythrogenic toxin produced by lysogenizedS. pyogenes Diphtheria • Caused by Corynebacterium diphtheriae – Gram-positive rod; pleomorphic • F m g g y mm or ms a tou gh gra yish m e mbrane in the throat – Fibrin and dead tissue – Blocks passage of air to the lungs • Exotoxin produced by lysogenized bacteria – Circulates in the blood; damages the heart and kidneys • Cutaneous diphtheria – forms skin ulcer • Prevented by DTaP vaccine – Diphtheria toxoid

1/26/2016 Otitis Media Acute otitis media,with bulging eardrum Infection of the middle ear -Formation of pus puts pressure on the eardrum Causes -Streptococcus pneumoniae (35%) -Nonencapsulated Haemophilus inflenzde(20-30%) -Moraxella(10-15%) -Staphylococcus aureus (1-2%) Common in childhood due to smaller auditory tube 8 million cases each year in the US Viral Disease of the Upper The Common Cold Respiratory System Over 200 different viruses -PCR aids rapid identification Learning Objective -Rhinoviruses(30-50%) ·Thrive in temperatu lower than body temperature List the causative agents and treatments Coronaviruses(10-15%) for the common cold. -20%-30%unknown Sneezing,nasal secretion,congestion -Can lead to laryngitis and otitis medic -Not accompanied by fever First three days,nasal secretions contain high numbers of cold viruses Antibiotics are of no use Relief via cough suppressants and antihistamines

1/26/2016 4 Otitis Media • Infection of the middle ear – Formation of pus puts pressure on the eardrum • Causes – Streptococcus pneumoniae (35%) – Nonencapsulated Haemophilus influenzae (20–30%) – Moraxella catarrhalis (10–15%) – S. pyogenes (8–10%) – Staphylococcus aureus (1–2%) • Common in childhood due to smaller auditory tube • Treated with broad-spectrum penicillins (one-fourth of the antibiotic prescriptions) • 8 million cases each year in the US Acute otitis media, with bulging eardrum Bulg g in eardrum Viral Disease of the Upper Respiratory System Learning Objective List the causative agents and treatments for the common cold. The Common Cold • Over 200 different viruses – PCR aids rapid identification – Rhinoviruses (30–50%) • Th i i l h b d Thrive in temperatures lower than body temperature – Coronaviruses (10–15%) – 20% - 30% unknown • Sneezing, nasal secretion, congestion – Can lead to laryngitis and otitis media – Not accompanied by fever • First three days, nasal secretions contain high numbers of cold viruses • Antibiotics are of no use – Relief via cough suppressants and antihistamines

1/26/2016 Microbial Diseases of the Lower Structures of the lower respiratory system Respiratory System Bronchiole Branch from Caused by many of the same bacteria () Brinch from the and viruses as the upper respiratory (vpice box Left lung system Trache As the bronchi become involved -Bronchitis -Bronchiolitis -Pneumonia Pulmonary alveoli are involved Bacterial Diseases of the Lower Pertussis(Whooping Cough) Respiratory System Caused by Bordetella pertussis Learning Objectives -Gram-negative coccobacillus List the causative agent,symptoms. ·Produces a capsule prevention,preferred treatment,and -Allows attachment to ciliated cells in the laboratory identification tests for trachea pertussis and tuberculosis. Destroys ciliated cells and shuts down the Compare and contrast the seven bacterial ciliary escalator pneumonias discussed in this chapter. Tracheal cytotoxin of cell wall damages List the etiology,method of transmission, ciliated cells;escalator does not work and symptoms of melioidosis. Pertussis toxin enters the bloodstream associated with systemic symptoms 5

1/26/2016 5 Microbial Diseases of the Lower Respiratory System • Caused by many of the same bacteria and i th i t d viruses as th e upper respira tory system • As the bronchi become involved – Bronchitis – Bronchiolitis – Pneumonia • Pulmonary alveoli are involved Structures of the lower respiratory system Pharynx (throat) Larynx ( b) Bronchiole Branch from the pulmonary vein Branch from the pulmonary artery Blood (voice box) Trachea (windpipe) Right lung Bronchus Bronchiole Pleura Left lung H t Blood capillaries Alveoli Pleura Diaphragm (breathing muscle) Heart Bacterial Diseases of the Lower Respiratory System Learning Objectives List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for pertussis and tuberculosis. Compare and contrast the seven bacterial pneumoni di d i hi h ias discussed i n thi s c hapter. List the etiology, method of transmission, and symptoms of melioidosis. Pertussis (Whooping Cough) • Caused by Bordetella pertussis – Gram-negative coccobacillus • Produces a capsule – Allows attachment to ciliated cells in the trachea • Destroys ciliated cells and shuts down the ciliary escalator • Tracheal cytotoxin of cell wall damages ciliated cells; escalator does not work • Pertussis toxin enters the bloodstream associated with systemic symptoms

1/26/2016 Ciliated cells of the respiratory system infected with Bordetella pertussis Pertussis(Whooping Cough) Stage 1:catarrhal stage,like the common cold Stage 2:paroxysmal stage,mucus accumulates, violent coughing.gasping for air Stage 3:convalescence stage,may last for months Infants do not cope with the coughing and brain damage often occurs as a result Prevented by DTaP vaccine Treated with erythromycin or other 网2m macrolides;must occur before coughing starts Pertussis CDC reported Pertussis cases in the US:1922-2013 Before vaccines,6000 people died annually in the United States from Whole c pertussis Today the acellular pertussis vaccine (DTaP)is given 6

1/26/2016 6 B. pertussis Ciliated cells of the respiratory system infected with Bordetella pertussis Cilium Pertussis (Whooping Cough) • Stage 1: catarrhal stage, like the common cold • Stage 2: paroxysmal stage, mucus accumulates, violent coughing, gasping for air • Stage 3: convalescence stage, may last for months • Infants do not cope with the cougg g hin and brain damage often occurs as a result • Prevented by DTaP vaccine • Treated with erythromycin or other macrolides; must occur before coughing starts Pertussis • Before vaccines, 6000 people died annuall i th U it d St t f lly in the United States from pertussis • Today the acellular pertussis vaccine (DTaP) is given CDC reported Pertussis cases in the US: 1922-2013 Pertussis component Whole cell heat Whole cell, heat-killed Pertussis component acellular

1/26/2016 Pertussis Number of Pertussis cases eported in Washington state:2012s2013 Increasing pertussis cases due to: -Breakdown in herd immunity Are new measures working? -Mutation of the organism 260 -Better diagnostic test leading to more reporting 200 Acellular vaccine having lower long-term immunity 180 New strategies for fighting pertussis -New booster for teens,adults,and pregnant 100. women -Additional vaccination requirements for students -More government health campaigns 15101520253036404650 Onset week Tuberculosis fungus-like wth in a smear from lung tissue Caused by Mycobacterium tuberculosis -Acid-fast rod:obligate aerobe -20-hour generation time -Lipids in the cell wall make it resistant to drying and antimicrobials ·Other causes Mycobacterium bovis Bovine tuberculosis:1%of U.S.cases Transmitted to humans via contaminated milk or food -Mycobacterium avium-intracellulare complex .Infects people with HIV 1 2.5 pm infection lurgs of ac >

1/26/2016 7 Pertussis • Increasing pertussis cases due to: – Breakdown in herd immunity – Mutation of the organism – Better diagnostic test leading to more reporting – Acellular vaccine having lower long-term immunity • New strategies for fighting pertussis – New booster for teens, adults, and pregnant women – Additional vaccination requirements for students – More government health campaigns Number of Pertussis cases reported in Washington state: 2012 vs 2013 Are new measures working? Tuberculosis • Caused by Mycobacterium tuberculosis – Acid-fast rod; obligate aerobe – 20-hour generation time – Lipids in the cell wall make it resistant to drying and antimicrobials • Other causes – Mycobacterium bovis • Bovine tuberculosis; <1% of U.S. cases • Transmitted to humans via contaminated milk or food – Mycobacterium avium-intracellulare complex • Infects people with late-stage HIV infection Lesions on the lungs of a cow Mycobacterium tuberculosis fungus-like growth in a smear from lung tissue Corded growth

1/26/2016 Pathogenesis of Tuberculosis Pathogenesis of tuberculosis phagoyied by Mycolic acids in the cell wall stimulate an inflammatory response maero re the lled-off ·I8nea2ae26Pl b5brsea-6ce8,eaera lymphatic systems -Miliary tuberculosis:disseminated infection Pathogenesis of tuberculosis Diagnosis of Tuberculosis In some ind ·Tuberculin skin test le is fo Outer lay -Positive reaction means a sin th current or previous infection d form an Followed by an X-ray or CT avity exam,acid-fast staining of outside the m Tubercle bacillu sputum,and culturing of bacteria New rapid blood test for IFN- y and PCR test alveolar wall -Higher specificity and less cross-reactivity

1/26/2016 8 Pathogenesis of Tuberculosis • Inhaled organisms are phagocytized by alveolar macrophages • Mycolic acids in the cell wall stimulate an inflammatory response • Organisms are isolated in the walled-off tubercle • Tubercles (lump or nodule) heal and become calcified (Ghon's complexes) • Tubercle breaks down, releasing bacteria into the lungs and cardiovascular and lymphatic systems – Miliary tuberculosis: disseminated infection Pathogenesis of tuberculosis Blood capillary Alveolar walls In ested Tubercle bacilli that reach the alveoli of the lung are ingested by macrophages, but often some survive. Infection is present, but no symptoms of disease. Tubercle bacilli multiplying in macrophages h t ti th t b i Interior of alveolus Interior of alveolus Ingested Tubercle bacillus Alveolar macrophage Bronchiole Early tubercle Infiltrating macrophage (not activated) cause a chemotactic response that brings additional macrophages and other defensive cells to the area. These form a surrounding layer and, in turn, an early tubercle. Most of the surrounding macrophages are not successful in destroying bacteria but release enzymes and cytokines that cause a lung-damaging inflammation. Aft f k di t Tubercle bacillus Caseous center Lymphocyte Activated macrophages After a few weeks, disease symptoms appear as many of the macrophages die, releasing tubercle bacilli and forming a caseous center in the tubercle. The aerobic tubercle bacilli do not grow well in this location. However, many remain dormant (latent TB) and serve as a basis for later reactivation of the disease. The disease may be arrested at this stage, and the lesions become calcified. Outer layer In some individuals, disease symptoms appear as a mature tubercle is formed. The disease progresses as the caseous center Pathogenesis of tuberculosis Tubercle bacillus Tuberculous cavity y of mature tubercle progresses as the caseous center enlarges in the process called liquefaction. The caseous center now enlarges and forms an air￾filled tuberculous cavity in which the aerobic bacilli multiply outside the macrophages. Liquefaction continues until the Rupture of alveolar wall tubercle ruptures, allowing bacilli to spill into a bronchiole and thus be disseminated throughout the lung and then to the circulatory and lymphatic systems. Diagnosis of Tuberculosis • Tuberculin skin test – Positive reaction means a current or previous infection • Followed by an X-ray or CT exam, acid-fast staining of sputum, and culturing of bacteria • New rapid blood test for IFN- γ and PCR test – Higher specificity and less cross-reactivity

1/26/2016 Treatment of Tuberculosis Tuberculosis Minimum of 6 months of drug therapy due to slow growth and dormancy 9 million develop TB annually:2 million die First-line drugs:isoniazid,ethambutol, 1/3 of the world's population infected Pyrazinamide,rifampin Leading cause of death for those with HIV Second-line drugs:aminoglycosides fluoroquinolones,para-aminoslicyclic acid (PAS) BCG vaccine:live culture of avirulent M. Multi-drug-resistant (MDR)strains:resistant bovis to first-line drugs -Not widely used in the United States due to Extensively drug-resistant (XDR)strains: questionable effectiveness resistant to second-line drugs Distribution of tuberculosis Distribution of tuberculosis 100.000 among Amerlcan ethnic groups in 2012 White 5 101520 Reported cases per 100,000 population 9

1/26/2016 9 Treatment of Tuberculosis • Minimum of 6 months of drug therapy due to slow growth and dormancy • First-line drugs: isoniazid, ethambutol, pyrazinamide, rifampin • Second-line drugs: aminoglycosides, fluoroquinolones, para-aminoslicyclic acid (PAS) • Multi-drug-resistant (MDR) resistant (MDR) strains strains resistant : resistant to first-line drugs • Extensively drug-resistant (XDR) strains: resistant to second-line drugs Tuberculosis • 9 million develop TB annually; 2 million die • 1/3 of the world's population infected • Leading cause of death for those with HIV • BCG vaccine: live culture of avirulent M. bovis – Not widely used in the United States due to questionable effectiveness Distribution of tuberculosis B. pertussis Distribution of tuberculosis

1/26/2016 Bacterial Pneumonias Pneumococcal Pneumonia ·Typical pneumonia Caused by 5.pneumoniae Two-thirds of pneumonia cases :encapsulated diplococc tmerirgiis,sfit 3 Atypical pneumonia -Caused by other microorganisms s8品2a8n助gen ·Lobar pneumonia uptake -Infects the lobes of the lungs ·Bronchopneumonia ‘8o35a,g2ecaniemar2,ble Infects the lungs des and Pleurisy -Pleural membranes inflamed conjugoted peumococcl Haemophilus influenzae Pneumonia Mycoplasmal Pneumonia Gram-negative coccobacillus Also causes meningitis Caused by Mycoplasma pneumoniae Predisposing factors:alcoholism,poor No cell wall nutrition,cancer,or diabetes -3 weeks to grow Symptoms resemble those of pneumococcal .Mild but persistent respiratory symptoms: pneumonia low fever,cough,headache Diagnosis:isolation on special media for -Common in children and young adults nutritional requirements(X and V factors) "Fried-egg"appearance on media Treated with cephalosporins Diagnosis:PCR and serological testing Treated with tetracyclines 10

1/26/2016 10 Bacterial Pneumonias • Typical pneumonia – Two-thirds of pneumonia cases – Caused by Streptococcus pneumoniae • Atypical pneumonia – Caused by other microorganisms • Lobar pneumonia – Infects the lobes of the lungs • Bh i ronc hopneumonia – Infects the alveoli adjacent to the lungs • Pleurisy – Pleural membranes inflamed Pneumococcal Pneumonia • Caused by S. pneumoniae – Gram-positive; encapsulated diplococci – 90 serotypes – Also causes meningitis, sepsis, otitis media • Infected alveoli of the lung fill with fluids and RBCs; interferes with oxygen uptake • Diagnosis: optochin-inhibition test, bile solubilit y g test, or antigen in urine • Treated with macrolides and fluoroquinolones • Prevented with conjugated pneumococcal vaccine Haemophilus influenzae Pneumonia • Gram-negative coccobacillus • Also causes menin gitis • Predisposing factors: alcoholism, poor nutrition, cancer, or diabetes • Symptoms resemble those of pneumococcal pneumonia • Diagnosis: isolation on special media for nutritional requirements (X and V factors) • Treated with cephalosporins Mycoplasmal Pneumonia • Also called primary atypical pneumonia or walking pneumonia; 20% of pneumonias • C d b Caused b y Ml i ycoplasma pneumoniae – No cell wall – 3 weeks to grow • Mild but persistent respiratory symptoms; low fever, cough, headache – Common in children and young adults • "Fried-egg" appearance on media • Diagnosis: PCR and serological testing • Treated with tetracyclines

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