sp14_-_micro_immuno_exam_3_20141210195229 Flashcards
1
Q
What is a mucosal surface? What are some examples in the human body?
A
- surface that interacts with air that has associated glands for secreting mucus- oral cavity, respiratory tract, reproductive/urinary tract, gastrointestinal tract
2
Q
What are the 3 types of defense for mucosal surfaces?
A
- innate immunity- adaptive immunity- nonspecific barrier defenses
3
Q
Why should we study gastrointestinal diseases?
A
estimated 76 million cases of intestinal infection in the US each year; approximately 500,000 require prolonged hospitalization and 5,000 will die
4
Q
Why should oral health care practitioners care about gastrointestinal disease?
A
transmission of gram-negative mucosal pathogens from feces to mouth
5
Q
How are gram-negative mucosal pathogens transmitted?
A
feces to mouth via any of the “seven F’s”: feces, food, fluids, fingers, flies, fomites, and fornication
6
Q
What is inoculum size? What is indicated about the bacteria by a small inoculum size? By a large inoculum size?
A
- the number of bacteria needed to cause a disease- small inoculum: bacteria is probably resistant to the body’s natural defenses; usually spread directly- large inoculum: bacteria is usually more susceptible to the body’s defenses; microbe is usually growing in food or in contaminated water
7
Q
What are the natural barrier defenses that protect us from gram-negative pathogens?
A
- secretory substances- anatomical and physiological barriers- indigenous microbiota
8
Q
What are the 4 mechanisms through with anatomical and physiological barriers protect us from gram-negative pathogens?
A
- acidity: ranges from pH 1-9- motility: peristalsis- mucous layer and underlying glycocalyx (carb layer that makes it difficult for the microbe to penetrate)- tight junctions
9
Q
Where in the GI tract are gram-positive flora found? Anaerobes? Coliforms?
A
- gram-positive flora: increasingly as you go through the stomach, duodenum, jejunum, ileum, and colon- coliforms: in the ileum and colon- anaerobes: in the ileum and colon
10
Q
What are the 5 secretory antimicrobial compounds? What does each do?
A
- lysozyme: cleaves linkages between NAG and NAM- lactoferrin: bacteriostatic effects via sequestering iron- cathelicidin: disrupts bacterial membranes of gram negative and gram positive (as well as fungi)- defensins: create pores in microbes; alpha defensins are produced by neutrophils and paneth cells while beta defensins are produced by epithelial cells- secretory immunoglobulins: IgA bind/coat pathogens to make it hard to attach to mucosal surfaces
11
Q
What are the 3 ways pathogenic bacteria overcome innate barrier defenses?
A
- acid resistance (microbes with a low infectious dose tend to be acid resistant)- fimbriae/pili: adhere to tissue to resist being shed- bacterial structures: cationic amino acids in the cell membrane reduce effects of antimicrobial peptides and siderophores sequester iron in low iron environments
12
Q
What type of cell is an important component of mucosal immunity and why?
A
- macrophages- recognize microbes via pattern recognition receptors which activate the macrophages and increases the ability of the host to kill many microbes
13
Q
What TLR is the most important for gram-negative pathogens?
A
TLR-4
14
Q
What is the negative side to initiating the inflammatory response at mucosal surfaces?
A
inflammatory cytokines (like TNF-alpha) can disrupt tight junctions between epithelial cells which will allow in microbes of the GI tract
15
Q
What are 2 ways bacteria can resist phagocytosis?
A
- development of capsule to resist phagocytosis- development of mechanisms capable of neutralizing the phagocytic compartment of macrophages
16
Q
Where are the denses clusters of lymph nodes found? What is generated by the lymph nodes?
A
- near mucosal tissue- adaptive immune system
17
Q
What are the two main ways to cause disease in the gastrointestinal tract?
A
- invasive bacterial pathogens- toxin-producing bacterial pathogens
18
Q
What are the examples of invasive GI tract bacterial pathogens discussed in class?
A
- salmonella- shigella
19
Q
What are the examples of toxin-producing GI tract bacterial pathogens discussed in class?
A
- vibrio (v. cholerae)- entertoxigenic E. coli (ETEC)
20
Q
What are the examples of “hybrid” misfit GI tract bacterial pathogens discussed in class?
A
- enterohemorrhagic E. coli (EHEC)- enteropathogenic E. coli (EPEC)
21
Q
What is the difference between invasive, hybrid, and toxin-producing GI tract bacterial pathogens in large intestine vs. small intestine?
A
- invasive: large intestine- toxin-producing: small intestine- hybrid: small and upper large intestine
22
Q
What is the difference between invasive and toxin-producing GI tract bacterial pathogens in volume of stool?
A
- invasive: small volume of stool- toxin-producing: copious amounts of watery stool
23
Q
What is the difference between invasive, hybrid, and toxin-producing GI tract bacterial pathogens in bloodiness of stool?
A
- invasive: bloody stool- toxin-producing: no blood in stool- hybrid: blood in stool (and possibly in urine with EHEC)
24
Q
What is the difference between invasive and toxin-producing GI tract bacterial pathogens in presence of leukocytes in stool?
A
- invasive: leukocytes in stool- toxin-producing: no leukocytes in stool
25
What is the difference between invasive, hybrid, and toxin-producing GI tract bacterial pathogens in tissue ulcerations?
- invasive: tissue ulcerations- toxin-producing: no tissue damage- hybrid: colonization causes attaching and effacing lesion
26
What is the most severe Shigella species? The most prevalent in the US?
- most severe: S. dysenteriae- most prevalent: S. sonnei
27
For Shigella, is the inoculum size small or large? Is it resistant to acid?
- small inoculum- acid resistance
28
Where will Shigella usually multiply/colonize? How are the virulence genes activated?
- in the colon- the anaerobic environment of the colon activates the virulence genes
29
How does Shigella invade the cells of the colon?
- the M cells in the colon naturally sample what is in the lumen of the large intestine so they take in the Shigella via Shigella's INVASION PLASMID ANTIGENS- while the mucosal surfaces is resistant to infection, the basal surface is not so Shigella invades via the basal surface- in the lamina propria, Shigella is ingested by macrophages which produces the inflammatory response that causes the illness- epithelial cells will ingest the bacteria, facilitated by bacterial factors- bacterial proteins lyse the phagosomal vesicle- intracellular spread facilitated by IcsA (an ATPase that causes actin polymerization)
30
What is the purpose of invasion plasmid antigens? What is the purpose of IcsA? What bacteria possesses these proteins?
- help bacteria to invade M cells- ATPase that causes actin polymerization which allows the bacteria to go from one cell to the next without leaving the cell- Shigella
31
What damage is caused by Shigella?
ulcer (invaded cells die and slough off)
32
What type of Shigella is different? How so?
- Shigella dysenteriae type 1- S. dysenteriae type 1 produces the Shiga toxin which kills intestinal epithelial and endothelial cells and disrupts sodium absorption; produces a larger volume of stool that is more watery and bloody
33
What are the 2 major diseases caused by Salmonella?
- gasteroenteritis: S. typhimurium and S. enteritidis- typhoid fever: S. typhi and S. paratyphi
34
How is Salmonella transmitted? Is a small or large inoculum needed? Acid resistant?
- fecal (human or animal) to oral transmission- relatively large inoculum required- more acid-sensitive than shigella
35
What induces the expression of virulence genes in Salmonella?
low pH induces the expression of at least 40 proteins found on the pathogenicity islands on large virulence plasmids
36
How does Salmonella invade cells?
- when Salmonella approaches the cell's surface, they induce an activity of cell signalling pathways and cause an increase in the cellular calcium concentration- this increase induces surface "ruffles" and uptake of the organism (microbe-directed phagocytosis)- Salmonella remains within the cell vesicles for many hours (unlike Shigella)- Salmonella is released into the lamina propria; somehow this induces NaCl loss from host cells- macrophages engulf most Salmonella but some escape to cause a transient bacteremia (the typhoid serovars will survive and grow within the macrophages)
37
How does Salmonella typhi differ from other Salmonella in terms of where it invades?
- enters the lymphatic system- multiplication in macrophages in the liver, spleen, and bone marrow
38
Where does Salmonella typhi colonize in an asymptomatic carrier?
gall bladder
39
What is similar between Shigella and Salmonella?
- both are invasive so they body cause bloody stool with leukocytes in the stool- both are able to respond to environmental changes
40
What is different between Shigella and Salmonella?
- inoculum size- bacteremia (in Salmonella typhi?)- species that cause severe disease are very dissimilar
41
How are invasive enteric pathogens (Shigella and Salmonella) diagnosed? How are they treated?
- identified based on symptoms and stool cultures- oral rehydration- antibiotic resistance first identified in Shigella so fluroquinolones are used- gall bladder removal (for infection with S. typhi)- vaccine to the capsule of S. typhi
42
What Vibrio species was discussed in class?
Vibrio cholerae
43
What are the two types of cholera? How do they differ?
- El Tor- Classical- El Tor mutated the O1 antigen so that there is a new LPS serotype, it is encapsulated, and it affects all age groups
44
What are the virulence factors of V. cholerae?
- flagella- pili: adhere to mucosal tissue; shift from salt water to reduced ion levels found in the body leads to expression of pili and the toxin- cholera toxin: phage encoded
45
What is the mechanism of the cholera toxin?
toxin constiutively activates adenylate cyclase so that cAMP is being made constantly; cAMP accumulates which makes the cell stop absorbing Na and secrete Cl which leads to the loss of water and diarrhea
46
What E. coli is associated with secretory diarrhea? Dysentery-like? Urinary tract infections?
- secretory diarrhea: ETEC and EPEC- dysentery-like: EHEC- urinary tract infections: UPEC
47
Does ETEC have a large or small inoculum? Acid resistant?
- large inoculum- not resistant to gastric acid
48
How does ETEC adhere to mucosal tissue?
colonization factor antigens (cfa)on fimbrae
49
What toxins are produced by ETEC? What is the mechanism of each?
- heat-labile toxin (LT): similar to cholera toxin in that it also activates adenylate cyclase to increase cAMP to decrease Na absorption, increase Cl secretion, and produce diarrhea- heat-stable toxin (ST): same end effect as the heat-labile toxin but activates guanylate cyclase to increase cGMP
50
How is secretory diarrhea bacteria identified?
- rule out Vibrio cholerae (more severe): eaten shellfish, been in endemic area, agar plating, agglutination test, or serological testing- inoculate plates with diluted stool samples without a rich medium and in aerobic incubation
51
How is secretory diarrhea (Cholera and ETEC) treated?
- oral rehydration: mix of sugar and salt- antibiotics can help shorten the duration or reduce the severity (tetracyclines for Vibrio and flouroquinolones for ETEC)
52
What age is most commonly infected with EPEC? What is the symptom of an EPEC infection?
- prevalent in newborns- noninflammatory secretory diarrhea
53
Where does EPEC infect? Large or small inoculum?
- distal small intestine- large infectious dose
54
What is characteristic about EPEC? Describe it.
- characteristic intimate adherence pattern (AKA attaching and effacing lesion)- bundle-forming pili (bfp) assist in adherence from a relative long distance; syringe-like secretion system (called Type III secretion) injects Tir into host cell; Tir binds to intimin on EPEC resulting in pedestal formation
55
What causes diarrhea in an EPEC infection?
no toxin production; malabsorption due to microvilli disruptions and disruption of epithelial tight junctions
56
What is similar and different between EPEC and EHEC?
- EHEC has a set of EPEC genes so it also produces an attaching effacing lesion- EHEC also produces a toxin that can lead to hemolytic uremic syndrome (which is much more serious)
57
What is the most notorious EHEC?
E. coli O157:H7
58
What are the two resulting diseases from the shiga-like toxin of EHEC?
- hemorrhagic colitis (colon)- hemolytic uremic syndrome (HUS) (kidneys)
59
What does the shiga-toxin affect?
attach small blood vessels in the mucosal surfaces of the large intestine; this can be intensified when inflammatory cytokines are present
60
How is a EHEC infection usually diagnosed?
- bloody stool with edema of the ascending colon- EHEC cannot ferment sorbitol- detection of Shiga-like toxins
61
What is the usual treatment for EHEC?
- CDC says no antibiotics because inflammation makes the toxin more potent- supportive therapy: rehydrate if necessary- dialysis if in kidneys (HUS)
62
What is the most common form of bacterial infection of an organ system (not including the mouth) and the most frequent cause of doctor's visits by adults?
urinary tract infection
63
What is cystitis?
inflammation in the bladder
64
How does the prevalence of UTI's differ between males and females?
- females: have increasing chance from age 10 and on- males: have a very low chance until age 45 when the prostate gland is less active and then have an increasing chance
65
What is the difference between an uncomplicated and complicated UTI?
- uncomplicated UTI: all normal defense mechanisms are intact; no recent hospital admissions; disease limited to lower urinary tract- complicated UTI: some structural abnormality in the urinary tract; recently admitted to the hospital; disease most likely will spread to kidneys; immune system repressed
66
What are some natural defenses found in the urinary tract?
- complete voidance of bladder- peristalsis- ureterovesicle valves- mucous layer- normal microbiota (lactobacillus)- pH (low pH due to lactobacillus)
67
What are the 2 ways in which UPEC adheres to uroepithelial cells through fimbriae?
- acute cystitis associated with fimbrial antigen FimH; colonizes the bladder- pyelonephritis is associated with the expression of P fimbriae; colonizes the kidney
68
What does UPEC produce to aid its virulence?
production of aerobactin and hemolysin (associated with pyelonephritis (kidney infection)); hemolysin has the ability to lyse host cells
69
What types of bacteria cause uncomplicated UTIs? Complicated UTIs?
- uncomplicated UTIs: E. coli, Proteus mirabilis- complicated UTIs: Proteus mirabilis, Klebisella
70
Which bacteria causes a more severe UTI: E. coli or Proteus mirabilis?
Proteus mirabilis
71
What are the 5 virulence factors of Proteus mirabilis?
- flagella: to allow Proteus to swim up ureters- adhesin on fibriae: to allow attachment in the urinary epithelium- hemolysins- IgA protease: to degrade IgA- urease: enzyme that raises the pH of the urine; toxic to renal cells; enhances formation of struvite (urinary stones) which can lead to chronic infection
72
How are UTIs diagnosed?
- difficult to positively ID the causative agent of the UTI- count bacteria in urine- Proteus diagnosed by consistently alkaline urine and production of urease
73
What is the treatment for UTIs?
- variety of antimicrobials- trimethoprim-sulfamethoxazone
74
What is the appearance of Klebsiella?
large, mucoid colonies due to large capsule
75
What are the 4 virulence factors of Klebsiella?
- pili: type 1 for adherence in urinary tract ("I gotta go #1!") and type 3 for adherence in the respiratory tract- enterotoxin similar to ST and LT of ETEC (induces secretory diarrhea)- aerobactin: an iron sequestering protein- antiphagocytic capsule: PRIMARY VIRULENCE FACTOR because the lungs have many alveolar macrophages so they need to resist phagocytosis
76
What is one of the most prevalent gram-negative GI bugs?
Helicobacter pylori
77
How is Helicobacter pylori transmitted? Where is it found in the body?
- transmitted oral-to-oral (unique!) and fecal-to-oral- only found in the mucous overlying the mucous secreting cells of the stomach
78
What does Helicobacter pylori do in the body for virulence?
- producer of urease: makes neutral pH in stomach- inflammatory effector molecules: cause epithelial cells to produce IL-8 (acts as chemokine to recruit neutrophils)- cytotoxin is associated with peptic ulcer disease (induces vacuolation and apoptosis of epithelial cells)- down regulation of somatostatin-producing D-cells
79
How can Helicobacter pylori cause cancer?
down-regulates somatostatin-producing D cells; somatostatin normally inhibits gastrin (gastrin leads to cell proliferation); with gastrin unregulated, cell proliferation increases
80
How is Helicobacter pylori treated?
- first line: proton pump inhibitor; antibiotic cocktail- second line: proton pump inhibitor; many antibiotics
81
Is Neisseria gram-negative or positive? Motile? Aerobic or anaerobic? What is their reservoir?
- gram-negative- non-motile (twitching motility from pili)- aerobic (but can grow anaerobically)- humans are their only reservoir
82
What disease is caused by Neisseria?
gonorrhea
83
How is Neisseria diagnosed?
- cultured on chocolate agar in the presence of CO2- modified Thayer-Martin agar- catalase and oxidase reactions both positive- sugar fermentations
84
What are the 2 major species of Neisseria? What are the major differences between them?
- N. meningitidis: invades throat; large capsule; have blebs on the surface- N. gonorrhoeae: invades male urethra or female cervix; no capsule; phase/antigenic variation; smoother surface
85
What is the encounter and entry process of Neisseria meningococci?
- reservoir is human nasopharynx- attach to nasopharyngeal epithelial cells and invade mucous membranes- invasion of the blood stream only occurs in individuals deficient in complement component- Type IV pili (attach organism to meninges in CNS)- lipooligosaccharide (LOS) damages host tissue by eliciting inflammatory response, resulting in hemorrhaging of blood into the skin and mucous membranes
86
What is the encounter and entry process of Neisseria gonococci?
- human reservoir (asymptomatic carriers greater among women)- upon introduction, attach to columnar epithelia of cervix or urethra via pili and surface proteins- adhesins controlled by phase variation (presence/absence) and antigenic variation (composition)
87
How does phase variation in E. coli work?
promoter inversion: expression of gene product is turned on or off at a high frequency based on the direction in which the promoter is facing
88
How does phase variation in N. gonorrhoeae work?
slipped strand mispairing: controls surface proteins (colony opacity-associated opa genes) as well as LPS for whether or not the genes are expressed
89
How does antigenic variation in N. gonorrhoeae work?
reassortment and recombination of the pilS loci changes the composition or structure of surface molecules
90
How does Neisseria spread and multiply?
- gonococci multiply rapidly and are shed in genital secretions (do not have flagella and are not motile)- they attach to non-ciliated cells that have microvilli- ciliated cell motility slows and ceases- ciliated cells die and slough from epithelial surface- non-ciliated microvili engulf bacteria; they are internalized by "parasite-directed endocytosis"- intracellular replication within vacuoles- intracellular traffic (vacuoles fuse with the basement membrane)- exocytosis in which the vacuoles discharge the bacteria into subepithelial connective tissue**KNOW THIS**
91
What protease does Neisseria possess? What does it do?
- extracellular IgA1 protease- removes the Fc-receptor end of the IgA1 antibody to enable escape from phagocytosis**KNOW THIS**
92
What damage is done by Neisseria?
- does not secrete exotoxins- LPS (LOS - lipooligosaccharides) and other cell wall components cause cell damage; induce tumor necrosis factor alpha (TNF-alpha) which leads to sloughing of ciliated cells and non-ciliated cell lysis which releases factors that cause inflammation
93
What do antibodies target on Neisseria? How does Neisseria evade it?
- LPS (LOS), protein I of the outer membrane, as well as other surface proteins- strains alter LPS with host-derived sialic acid which is a surface component of RBCs so they are able to camoflauge; this also leads to the possibility of self recognition
94
What is the difference between the disease caused by N. gonococci and N. meningococci? Why do these differences exist?
- N. gonococci: localized inflammation; rarely lethal (even when spread to the blood stream)- N. meningococci: colonize nasopharynx with no local symptoms; creates 3 general diseases (uncomplicated bacteremic process, metastatic infection of the meninges, and overwhelming systemic infection)***difference in diseases because meningococci are heavily encapsulated and produce hemolysin***
95
What is Pelvic Inflammatory Disease in females? In males? What bacteria causes this?
- females: gonococcal infection of female upper reproductive tract; inflammation of the uterus and fallopian tubes; scarring of upper tract and adjacent organs- males: epididymitis; ascent of organism into upper reproductive tract of men- Neisseria gonococci
96
What is Disseminated Gonococcal Infection? What bacteria causes this?
- can result from Pelvic Inflammatory Disease due to endotoxin; pustular lesions of the skin; inflammation of tendons and joints; suppurative arthritis; more common in women- Neisseria gonococci
97
What is Purpura Fulminans? What bacteria causes this?
- disseminated intravascular coagulation (DIC) due to the ability to survive in the bloodstream; skin manifestations, meningitis, shock, death; response to LOS mediated by TNF-alpha and IL-1; the higher the response, the greater the damage and risk of death- Neisseria meningococcus
98
How is a Neisseria infection treated?
- high resistance to antibiotics- antimicrobial chemoprophylaxis of close contacts is the primary means of preventing secondary cases of sporadic meningococcal disease
99
How is a Neisseria infection prevented?
- behavioral: condoms, partner notification, early diagnosis and treatment- vaccines to gonococci are difficult to produce (antigenic and phase variation, protective intracellular components)- vaccine to meningococci (quadrivalent derived against capsular polysaccharide, tetravalent is a polysaccharide-protein conjugate)**KNOW THIS**
100
Is a vaccine available against Neisseria gonococci? Against Neisseria meningococci?
- vaccines to gonococci are difficult to produce (antigenic and phase variation, protective intracellular components)- vaccine to meningococci (quadrivalent derived against capsular polysaccharide, tetravalent is a polysaccharide-protein conjugate)**KNOW THIS**
101
Is Haemophilus gram positive or negative? Aerobic or anaerobic?
- gram-negative- aerobic (some anaerobic)
102
Where does Haemophilus colonize?
- colonizes upper respiratory tract of almost everyone- H. influenzae probably only infects 1-2% of healthy children, but does NOT cause influenza (which is actually caused by a virus)
103
What is required for Haemophilus influenzae to grow? For other Haemophilus species?
- H. influenzae requires hemin (X factor) and NAD+ (V factor) for growth; access to these factors require lysed blood (chocolate agar) rather than whole-blood (blood agar)- other Haemophilus species require only NAD+; can grow on blood agar**KNOW THIS**
104
What are the two types of Haemophilus influenzae strains?
- typeable: have 7 antigenically distinct capsular polysaccharides- non-typeable: unencapsulated**KNOW THIS**
105
What is the most virulent type of H. influenzae? What does it cause?
- H. influenzae type b (Hib) is the most virulent- bacteremia (bloodstream) and meningitis in children younger than 2
106
What types of diseases are caused by non-typeable strains of H. influenzae?
respiratory tract diseases
107
What are the 4 virulence factors of H. influenzae?
- polyribosyl ribitol phosphate (PRP) capsule: resistance to phagocytosis (as long as antibody is not present); basis for the Hib vaccine- endotoxin: causes pathogen-directed endocytosis- IgA1 protease: similar to Neisseria!- pili and outer membrane proteins: similar to Neisseria!**KNOW THIS**
108
How is the human host able to defend against H. influenzae?
- antibodies against the capsule- immunization of infants: pure Hib PRP polysaccharide vaccine is NOT immunogenic in infants; PRP-conjugated diptheria toxoid (adjuvant) produces good antibody responses in infants
109
Why are antibodies not effective in a N. gonococci infection?
N. gonococci doesn't have a capsule
110
What is the treatment for a H. influenzae infection?
- many H. influenze are resistant to beta-lactam antibiotics because they produce beta-lactamase- chloramphenicol is the drug of choice- third-generation cephalosporins
111
Is Pseudomonas aeruginosa gram positive or negative? Where is it found?
- gram negative- ubiquitous (found in soil and water)
112
Is Pseudomonas motile? Aerobic or anaerobic?
- motile: one or several polar flagella; polar pili (twitching)- aerobic (this species - some strains are anaerobic when grown on nitrate)
113
What is produced by Pseudomonas aeruginosa? What does it smell like?
- colonies produce water-soluble pigments that function as antibacterials- fruity or grape-like odor to colonies (or near wounds)
114
What is required for growth of Pseudomonas aeruginosa?
- grows rapidly, very robust- minimal nutritional requirement (need only acetate and ammonia for C and N sources)- can survive in hand creams, soaps, and dilute antiseptics
115
What virulence factors does Pseudomonas aeruginosa possess that aids in its persistance?
- mucoid polysaccharide capsule (alginate): shields from the immune system- siderophores- elastase- exotoxin A- phospholipase C
116
What virulence factors does Pseudomonas aeruginosa possess that aids in its dissemination?
- toxin A- spreading factors (collagenase, elastase, and exoenzymes)- flagella- heat-stable hemolysin- tissue damage by proteases and toxins
117
What does Pseudomonas aeruginosa use siderophores for? Phospholipase C?
- siderophores: iron binding compounds that compete with transferrin for iron; iron limitation causes increased production of elastase and exotoxin A which damages tissues or creates conditions that make iron more accessible- phopholipase C: hydrolyzes phospholipids (lecithin) in the eukaryotic membrane, releasing usable phosphate
118
How is Pseudomonas aeruginosa encoutered?
- adheres to vegetables and plant matter- in water taps, drains, and wet surfaces (otitis externa - swimmer's ear)- in hot tubs ("hot tub rash")
119
How does Pseudomonas aeruginosa enter the body?
- opportunistic pathogen; needs a local or systemic breach of the immune system or immunocompromised patients- organism does not adhere well to healthy epithelium; can enter through abrasions, cuts, etc.; usually need a large inoculum in order to cause infection
120
What are the 2 things that Pseudomonas' ability to spread and multiply depend upon?
- avoiding phagocytosis- successful adherence to a surface**KNOW THIS**
121
What mediates Pseudomonas' adherence to epithelia?
flagella and pili (interctions with glycolipid which creates a receptor for Type 4 pili on host cells and TLR-5)**KNOW THIS**
122
What is the function of the polysaccharide capsule of Pseudomonas?
- major adhesin and component of biofilm in cystic fibrosis patients- production is highly regulated
123
What damage is created by the LPS of Pseudomonas?
- adhesin- lipid A: endotoxin; interacts with the host TLR4 to initiate inflammatory response- core oligosaccharide interacts with CFTR (an ATP-binding cassette transporter; cystic fibrosis transmembrane conductance regulator); bacterial internalization and initiation of immune response- long O-antigen side chains: responsible for resistance to human serum, antibiotics and detergents
124
What damage is caused by the exotoxins of Pseudomonas?
- cause local inflammation- some kill host cells (exotoxin A)
125
What damage is caused by multifunctional enzymes (proteases) such as elastase and LasA in Pseudomonas?
- elastase: cleaves elastin and collagen (direct tissue damage), cleave proteinase inhibitors, cleaves immune system components (complement and immunoglobulins)- LasA: serine protease that works with elastase to degrade elastin
126
What damage is caused by the Type III Secretion System of Pseudomonas?
- delivers virulence factors directly into host cells (transfer from bacterial cytosol to host cytoplasm)- similar to flagella- targets specific proteins on host cells- induced by host cell contact or low calcium levels
127
What factors are predisposing to a Pseudomonas infection?
- local breach of the immune system- systemic illnesses (ex. diabetes, premature infants, etc.)- both systemic and local (ex. burns)
128
What disease was discussed in class to be associated with Pseudomonas aeruginosa?
cystic fibrosis
129
Why are people with cystic fibrosis more at risk of a P. aeruginosa infection?
- Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is dysfunctional in cystic fibrosis patients- without CFTR, there is a decreased sialylation of surface glycolipids so P. aeruginosa can bind these epithelial cells better than it would in a healthy individual- there is also dehydration of respiratory secretions so there is a thick mucus that impairs the mucociliary system- mucoid exopolysaccharide also shields the organisms from the immune system**KNOW THIS**
130
What is sepsis? How can sepsis be triggered by Pseudomonas?
- sepsis: severe systemic illness marked by hemodynamic derangements and organ malfunction brought about by the interaction of certain microbial products with host reticuloentothelial cells- LPS endotoxin mediated (specifically the lipid A moiety)- triggers production of Tumor Necrosis Factor (TNF) which stimulates macrophages to produce IL-1
131
What is MODS (Multi-Organ Dysfunction Syndrome)?
- high cardiac output, lowered blood pressure- distributive shock (lack of perfusion of selected vascular beds)
132
What are the 3 requirements of sepsis?
1. large population of infecting/colonizing organisms2. presence of bacterial products that stimulate release of host cytokines3. widespread dissemination of microbial products to host's reticuloendothelial system
133
Upon what does the mortality of sepsis depend?
- nature and severity of infection- host defense state- promptness and efficacy of treatment
134
How is a Pseudomonas infection usually diagnosed? Treated?
- easily cultured and identified- antibiotic treatment depends on the geographic location (in some hospitals, certain antibiotic resistant strains predominate); frequently requires antibiotic synergism to treat**KNOW THIS**
135
Is Lysteria gram positive or negative?
gram positive
136
Where is Listeria monocytogenes found?
- intestinal tract of vertebrates, sewage, soil, and water- food-borne pathogen (aided by its exceptional heat resistance and ability to grow at refrigerator temperatures)
137
What are the 2 types of Listeria monocytogenes motility?
- peritrichous flagella- actin polymerization
138
What is Listeriosis?
- infections of fetus, immunocompromised, elderly, and pregnant people- can result in systemic infections such as bacteremia and meningitis- 5-10% of adults are asymptomatic carriers
139
What are the 3 virulence factors of Listeria?
- internalins: mediate adherence and invasion of cells- listerlysin O: enables escape from vacuoles; responsible for beta-hemolytic pattern- phospholipases: aid in escape from vacuoles; movement through the cell via actin polymerization; can cross the placenta
140
How does Listeria spread from cell to cell?
- bacteria enters the cell via phagocytosis- bacteria escapes the vacuole- bacteria uses actin polymerization to push its way into the neighboring cell while still having the cell membrane of the original cell around it; it never needs to go into the extracellular space again
141
How is Listeria prevented?
control of growth in food supply (avoid unpasteurized milk and juices; pregnant and immunocompromised individuals are advised to avoid deli foods, raw meats, and soft cheeses)
142
How is Listeria treated?
antibiotics are effective if diagnosed in time
143
Is Clostridia aerobic or anaerobic? Gram positive or gram negative?
- strictly anaerobic- gram positive
144
Where is Clostridium found? What does it produce?
- found in the environment (soil, water, and animal wastes)- produce endospores- produce proteinaceous toxins that are responsible for disease symptoms
145
What are the 4 species of Clostridium?
- C. difficile: pseudomembranous colitis- C. perfringens: cellulitis, gas gangrene, food poisoning- C. botulinum: botulism- C. tetani: tetanus
146
What are the major diseases caused by Clostridia?
- botulism (food poisoning, infant botulism, and wound botulism)- tetanus- pseudomembranous colitis- gas gangrene- suppurative wounds and abscesses
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What is a bacterial endospore? What causes a spore to form? What makes it germinate?
- metabolically inactive state in which organisms can remain viable for hundreds of years- resistant to adverse conditions (extreme heat, drying, radiation, most chemical disinfectants)- spore induction caused by unfavorable environmental conditions- spores will readily germinate when conditions become favorable for vegetative growth
