Which organism causes the majority of the cases of bacterial pneumonia, leading to hospitalization?
Is strep pneumoniae gram positive or negative?
Gram + (Blurple)
What is alpha hemolysis?
-when grown on agar that contains RBC's, a molecule called alpha-hemolysin breaks hemoglobin down to a greenish pigment
What is the outermost layer of pneumococcus?
-a polysaccharide capsule -contains peptidoglycan
What does PMN stand for?
Why is pneumococcus not readily ingested by PMNs?
-The capsule is not recognized by receptors on PMN -in the absence of antibodies to specific capsular polysaccharide, they won't be eaten by PMN -IgG to cell wall can't be "seen" by PMN
Why are antibodies for the cell wall of pneumococcus not immune response inducing?
-The capsular polysaccharides are too long, and shield the Fc region of abs from PMNs **Ig and complement diffuse through capsule, but capsule prevents PMN receptors from interacting with Fc of IgG.
What are the constituents of pneumococcus from the outside going in?
-Polysaccharide capsule -Teichoic acid attached to lipid (lipoteichoic acid) -Choline-Binding Proteins -Peptidoglycan: Principal constiduent of cell wall -Pneumolysin -Autolysin
What factors cause decreased neutrophil function (chemotaxis, ingestion, killing)?
-Diabetes Mellitus -Glucocorticosteroids -Renal insuficiency -Cirrhosis -Alcohol Ingestion -Genetic defects in PMN function
What factors can lead to defective IgG production?
-Congenital -Acquired: myeloma, lymphoma, common variable immunodeficiency -HIV infection
How are splenectomies related to pneumococcal pneumonia?
-doesn't predispose to infection ***but does predispose to overwhelming sepsis and shock in pneumococcal pneumonia
What is pneumolysin?
-a major virulence factor produced by pneumococci -activates complement (inflammation) -Damages ciliated cells and PMN -reproduces changes of pneumonia in animals
What is the difference between epidemiology & pathogenesis?
Epidemiology = where the organism likes to hang out Pathogenesis = how disease comes about
How is pneumococcal pathogenesis related to viral illness?
-viral infection characterizes the major form of pneumococcal disease -virus messes up our normal anatomy (cilia), and pneumococcus gets stuck where its not supposed to be
Describe the microbiology of pneumococcus.
-pairs or chains of elongated cocci -gram positive -colonies on blood agar surrounded by greenish zone (alpha-hemolysis) -colonies collapse in center (autolysin) -optochin susceptibility (ring of death around white thing) -dissolve in bile salts (definitive identification)
Which TLR does Teichoic acid of pneumococcus interact with ?
TLR 2 >>4
What is important about Choline-binding proteins on pneumococcus?
-they contribute to virulence -highly conserved between pneumococci strains
What are bacterial cell wall peptidoglycans made of?
-alternating glucosamine and muramic acid in long chains
Which TLR recognizes cell wall peptidoglycans?
TLR 2 >> 4
What is the epidemiology of pneumococcus?
-Confined to humans -lives in nasopharynx of healthy children/adults -contact or aerosol spread (facilitated by viral resp infection)
What must first happen for bacteria to cause disease?
-adhere to epithelial cells -bacterial surface constituents interact with surface molecules on mammalian cells, causing adherence
What molecule on pneumococcus is responsible for adherence?
What is colonization?
-when bacteria are present in sufficient number that we can find them by culture, AND, they cause no symptoms or signs of infection **some organisms never colonize, mere presence indicates infection (TB)
What is the pathogenesis of pneumococcus?
-carried by secretions to space from which clearance is poor (damage/obstruction) -aspiration & inhalation = pneumonia **organisms get where they do not belong, clearance is damaged, induce inflammation & disease results.
What is the difference between inhalation and aspiration of an organism?
-inhalation = breathing in aerosolized organisms -aspiration = mouth contents bypass glottis
What factors decrease action of cilia and cough in the respiratory tract?
-Smoking -inflammation -viral infection -Alcohol, codeine, morphine (suppress cough) -pollution
How does pneumonia result from pneumococcus infection?
-cocci reach alveoli, activating inflammatory response -WBCs attracted & capillary permeability increased -this means WPCs, plasma constituents, and RBC's collect in alveoli = pneumonia infiltrate
What factors predispose people to infection by pneumococcus?
-Multifactorial: extremes of life, prior hospitalization, malnutrition, alcoholism -Decreased pulmonary clearance -diminished neutrophil function -defective IgG production -absence of spleen
What are the common clinical manifestations of pneumonia?
(often preceded by viral infection) -Cough (90%) -Fever (90+%) -sputum production (variable) -chest pain (50-75%) -general appearance = look sick -can percuss and listen for rales, but xray is best
What are the lab findings for pneumonia?
-High WBC, possible left shift **reduction in EBC = overwhelming infection -opacity in chest xray -decreased O2 sat
How is the diagnosis for pneumonia made?
-gram stained sputum (90%) -Blood culture (bacteremia) (20%) -Urine antigen test (50%) = highly specific
What other diseases are commonly caused by pneumococcus?
-Acute otitis media -acute sinusitis -primary bacteremia -meningitis -acute cardiac events (23%)
What are the vaccine options for pneumococcus?
-Pneumovax (adult) -Protein-conjugated vaccine (children)
How does the pneumovax vaccine work?
-contains capsular polysaccharide of 23 pneumococci serotypes **not protective before age of 2 years, due to immature immune response to polysaccharides
how does the protein-conjugated vaccine for pneumococcus work?
-chemical conjugation of polysaccharide to a protein that alters the mode of presentation, so it works in babies -stimulates antibody in nasopharynx, thus preventing colonization
What are the three main bacterial causes of acute otitis media?
1. Strep pneumo (30%) 2. H. influenzae (25%) 3. Moraxella catarrhalis (15-20%