Exam 3 Flashcards
1
Q
how many human cells in body vs microbial cells?
what % of cells in human are microbial?
A
- 10^14 human cells
- 10^13 microbial cells
- 90% of cells in the human body are microbial
2
Q
What determines if an organism is a pathogen?
A
- characteristic of virulence (ability to cause infection)
- non-pathogens = avirulent
- can have different strands of same organism that are virulent or avirulent (ex. TB H37Rv is virulent, TB H37Ra is avirulent)
3
Q
Types of host-bacterial interactions (4)
A
- infestation: distinct from bacterial infections - animal parasites such as worms
- infectious disease: manifestations of the fight due to pathogenic origins
- mutualism: relation between two different organisms in which both benefit
- opportunist: pathogens that attack persons with a compromised immune system
4
Q
Who do opportunistic pathogens usually attack?
A
- those on immunosuppressants or immunocompromised
5
Q
Commensal Microbiota
A
- makeup of microbiota depends on various factors: environment, nutrition, stress, age, etc
- normal microbiota are important
- microbiota varies depending on anatomic sites
- contributes to immune defense
6
Q
Difference between a pathogen and commensal
A
- pathogens can establish in areas devoid of commensal populations
- pathogens possess inherent ability to cross barriers and evade hosts defenses
- pathogenic characteristics are genetically encoded
7
Q
Innate immunity
A
- early response: recognition and pro-inflammatory response
- non-clonal distribution, all cells of a class are identical
- perfect self-nonself discrimination
- recognition in conserved molecular patterns (LPS, glycans, mannans)
- response is co-stimulatory molecs, cytokines (IL-1b, IL-6), chemokines (IL-8)
8
Q
Adaptive Immunity
A
- later response: elimination of pathogens in late phase
- very specific recognition
- clonal distribution, all cells of a class are distinct
- imperfect self-nonself discrimination (selected in individual somatic cells)
- recognition in detailed molecular structure (proteins, peptides, carbohydrates)
- response is clonal expansion, IL-2, effector cytokines (IL-4, IFNgamma)
9
Q
Timeline for Innate, Early induced innate, and adaptive immune responses
A
- innate immunity: immediate, 0-4 hours
- Early induced innate response: early, 4-96 hours
- Adaptive immune response: late, >96 hours
10
Q
Innate Immunity: Physical Barriers
A
- Barriers to infection –> skin (pH 5-6)
- tight junctions between cells
- mucus lining interior epithelial surface (coated with Mucin and other glycoproteins reduces ability of microbes to stick)
- Antimicrobial peptides
11
Q
Antimicrobial peptides also called what and what it do
A
- defensins
- can create holes in membrane of bacteria
12
Q
Places where epithelial surfaces provide first line of defense (4)
A
- Skin
- Gut
- Lungs
- Eyes/Nose/Oral cavity
13
Q
Phagocytic cells (overview)
A
- macrophages long lived and abundant in areas where infection likely to occur (among first cells to encounter invading microbes)
- Neutrophils are most abundant white blood cell (short lived and not present in normal healthy tissue)
- both unleash weapons once they phagocytose the pathogen (NADPH oxidase complex which kills pathogen but is also highly toxic)
- key is pathogens need to be recognized for this to happen
- production of these toxic compounds leads to a respiratory burst (increased O2 consumption)
- macrophages survive this but neutrophils usually die.. major component of pus in wounds
14
Q
Neutrophils sense ____ of pathogenic DNA
A
- CpG tracts
15
Q
Innate immunity: conserved pathogenic features
A
- human cells recognize conserved pathogenic features (Pathogen-associated molecular patterns –>PAMPS)
- recognition of these triggers innate immune response
- inflammatory responses
- apoptosis of autophagy of infected cell
- phagocytosis by cells such as neutrophils and macrophages
- complement action
16
Q
Lipopolysaccharide
A
- conserved pathogenic feature of gram (-) bacteria
- has lipid component, sugar component, and antigen component
17
Q
Innate Immunity: Pattern Recognition Receptors (PRRs)
A
- responsible for detection (binding) of PAMPS
- Toll-like receptors (TLRs) represent major family and most extensively studied class of PRRs
- also cytoplasmic PAMP receptors (RLR, NLR) and DNA sensors
18
Q
Toll-like receptors (TLRs)
A
- major family of PRRs, 10 primary TLRs
- abundant on epithelial cells lining lungs and gut
- abundant on macrophages and neutrophils
- act as an alarm system for both the innate and adaptive immune systems
- membrane bound
- PAMP recognition by leucine-rich repeat on outside of membrane, gives signal to Toll/interleukin-1 receptor (TIR) homology domain
19
Q
Is there communication between the innate and adaptive immune systems?
A
- yes
20
Q
Cytoplasmic PAMP receptors
A
- RIG-1-like receptors (RLR)
- NOD-like receptor (NLR)
- less studied that TLRs
- responsible for detecting PAMPs inside of cells
- inside our cells, have the ability to detect DNA and RNA that is non-self
21
Q
PAMPs and detection by TLRs, RLRs, NLRs, and DNA sensors
A
- TLRs: viruses, gram (+), gram (-), fungi, protozoa
- RLRs: just RNA of viruses (primarily good at detecting intracellular RNA)
- NLRs: DNA, RNA of viruses, DNA and PG of gram (+)s, and DNA, PG, and Flagellin of gram (-)s
- DNA sensors: DNA of viruses, DNA of gram (-) and gram (+)
22
Q
Fungi have b-glycan and mannan that are detected by TLRs.. what category are those molecules?
A
- polysaccharides
23
Q
TLRs and adaptive immunity
A
- pathogens that usually cause harm evade the innate immunity
- pathogen binds to PRR on cell membrane with stimulates release of IL-12 and also stimulates a T-cell to bind
24
Q
Complement pathway
A
- non-adaptive immunity pathway
- 3 distinct pathways (Alternative pathway, lectin pathway, classical pathway) involving 20 interacting proteins
- binding domains that can tag outside of a pathogen
- surveillance proteins that see what is tagged and respond through signaling of neutrophils and others
25
lectins
- proteins that bind sugars
26
membrane-attack complex
- part of the complement pathway
| - make a hole in the pathogen and allows content to escape
27
engulfment of C3 fragments
- part of the complement pathway
| - pathogens are tagged with C3, phagocyte comes and engulfs
28
Human Health and Gut Microbiota
- 500-1000 different species of bacteria in humans
- normal gut microbiota helps with digestion and immunity
- altering microbiota results in disease esp in adults (crohn's, obesity)
29
majority of antibiotic resistance found where?
- in hospitals because of the potent antibiotics used there.. pathogens can develop broad-spectrum resistance
30
What colors do gram (+) vs gram (-) stain?
- Gram (+) : purple, thick wall takes up stain
| - Gram (-) : red, stain washes away with alcohol from outer membrane, then perfused with safarin
31
in general what shapes are gram (+) vs gram (-)s
- gram (+): clusters, grape-like
| - gram (-): rod-like, smaller
32
Which gram-positive bacteria doesn't stain?
- Mycoplasma
33
Antibiotic resistant Threat levels criteria
how much infection they cause in US and world and what are the antibiotic resistance patterns that makes it a problem
- ranges from concerning to serious to urgent
- few gram + in urgent, many in serious
34
Microbial Resistance Evolution
- WT, Multidrug resistant (MDR), extremely drug resistant (XDR, resistant to >3 antibiotic categories)
35
Staphylococci
- Gram positive cocci in CLUSTERS
- coagulase negative except for S. aureus which is coagulase positive
- colonize skin, nose, axilla, groin
- range from benign to pathogenic
36
what does coagulase +/- tell us?
-differentiates whether to treat and what to treat with
37
primary pathogen
- causes infection in patients w/ and w/o risk factors
38
Staphylococcus Aureus
- numerous infections
- #1 cause of bloodstream infections in US
- multi-drug resistance
- high morbidity and mortality
- MRSA (methicillin-resistant staph aureus)
* classified as "serious"
* 11,000 deaths/year, 80k severe infections/yr
39
Pathogenicity of Staphyloccus Aureus
- can cause toxic shock syndrome
| - can attach to many surfaces: joints, valves
40
Pathogenicity of Staphylococci
- toxin production
* TSST-1, Panton Valentine Leukocidin (PVL) Superantigen toxins, alpha-cytotoxins
- accessory gene regulator
- microcapsule (ghost capsule) can live with or without a capsule
- slime-adhesion (biofilm) production
41
S. aureus virulence factors (5 main categories) and notes about resistance
- Attachment, persistence, evading/destroying host defenses, tissue invasion/penetration, toxin-mediated disease and/or sepsis
- very tolerant to antibiotic therapy
- many antibiotics have been tried, the S. aureus becomes resistant
42
MRSA encodes resistance to ____ which is the backbone to antibiotics
- b-lactam
43
Vancomycin-resistant S. aureus
- threat level concerning
- plasmid with resistance: not common, but multiple types
- only 13 cases in 10 years in US
- leaves little to no treatment options
44
Hospital associated S. aureus epidemiology
- MRSA, multi-drug resistant
- variety of infection types
- invades pop at risk
- reduces fitness of the pathogen (not rapidly aggressive)
- less common virulence factors
45
Community associated S. aureus epidemiology
- susceptible to many non b-lactams
- variety of infection types but most commonly in skin infections
- invades normal healthy people
- increased fitness (not harboring as much resistance in genome, can be more fit)
- more common virulence factors
46
S. epidermis
- not really a pathogen, will infect when on things
- collinizer
- often a contaminant when found in culture
- adheres to prostetic surfaces (biofilm formation)
- prosthetic joints, IV catheters, surgical site infections examples of where it harbors
- biofilm leads to antibiotic resistance that's hard to treat
47
Streptococcus species (2 main groups)
- b-hemolytic and a-hemolytic
- b-hemolytic has group A, B, and C
- a-hemolytic has s. pneumoniae and viridans streptococci which has group D
48
Streptococci features
- classification on how they lyse RBCs (A,B,C,D,G,H,K)
- Toxin production (scarlet fever, "flesh eating bacteria")
- often found in normal flora
- infection types: cellulitis, abscess, URI, LRI, bacteremia, endocarditis, septic arthritis, neonatal sepsis
49
S. pneumonia
- a-hemolytic
- virulent and pathogenic diplococci
- major cause of meningitis, CAP, otitis media, other URI
- also colonizer of mouth nasopharynx
- encapsulated (polysaccharide capsule) with over 90 serotypes
* target for vaccine (adults 25 valent vaccine, 9 in children, 13 in children since 2010)
- reduced susceptibility to penicillins, macrolides, fluoroquinolones becoming a concern
- drug resistant s. pneumonia
* threat level serious
* PCN and erythromycin resistant
* 1.2 mil infections/yr, 7k deaths
50
S. pneumoniae reasons why differences in vaccine coverage
- different strands affect different age groups
- younger children: PCV7 more likely
- as age, PPV23 more likely
51
S. Pyogenes
- Group A strep
- virulent and pathogenic
- common cause of strep throat, impetigo, cellulitis, necrotizing faciitis, toxic shock syndrome
- most common in children and elderly
- still highly sensitive to penicillin
- erythromycin-resistant subset
* threat level concerning
* 1300 infections/yr, 160 deaths
52
S. algalactiae
- Group B strep
- normal vaginal flora in up to 40% of women
- if (+) treat continuously during delivery
- infection types:
* Children: #1 neonatal sepsis
* immunocompromised adults: pneumonia, bacteremia, endocarditis, UTI, SSTI
- PCN treatment still most effective
- can be resistant to **Clindamycin**
* threat level concerning
* 7600 cases, 440 deaths
53
Enterococcus species
- Gram-positive cocci in chains
- normal flora of GI, mouth, female genital tract
- not very pathogenic but highly drug resistant
- associated infections: bacteremia, IE, UTI, wounds
- organisms: E faecalis and E faecium
- vancomycin resistant enterococci (VRE) continues to increase
* serious threat level
* 20,000 infections and 1300 deaths/yr
54
Gram Pos Anaerobes
- Normal flora of mouth, URT, GI, skin, and female genitourinary tract
- commonly occur as polymicrobial infections
- infections: aspiration pneumonia, GI, SSTI
- cocci and bacilli
55
E faecalis
- enterococcus species
- common
- more antibiotic susceptible
56
E faecium
- enterococcus species
| - nosocomial, antibiotic resistant (aminoglycosides, b-lactams, glcopeptides)
57
gram pos cocci (anaerobes) (2 and where located)
- mouth
- peptococcus, peptostreptococcus
- mostly PCN and clyndamycin suceptible
58
gram pos bacilli (anaerobes) (4) and where located
- lower gi
- clostridium, propionibacterium, lactobacillus, actinomyces
- suceptibility varies by organism
59
Clostridium species (2)
- c. perfingens
| - c. difficile
60
c. perfringens
- Clostridium species
- gas gangrene
- produces toxins and acidic enzymes that cause tissue necrosis
- rapidly progressive, high mortality rate
- may involve other Clostridium species
61
c. difficile
- cause of antibiotic associated pseudomembranous colitis
- spore form difficult to eradicate
- produces A/B toxin causing GI tissue destruction and necrosis
- threat level urgent
- causes life-threatening diarrhea
- 250,000 infections per year
- 14,000 deaths
- 1 BILLION in excess medical costs / year
62
Corynebacterium species (diptheriae)
- corynebacterium diptheriae
- produces a deadly toxin resulting in organ failure and death
- PCN and erythromycin are generally recommended
- vaccination for this
63
Corynebacterium and actinomyces
- widely distributed in the environment as normal inhabitants of soil and water
- common colonizing organisms
- indicated in multiple infection types
64
Bacillus spp
- bacillus anthracis
- gram-positive rod from soil
- non-anthrax species are normally contaminants of human cultures
65
Anthrax (bacillus anthracis)
- 3 routes of exposure:
* cutaneous: naturally occurring, 95% of all anthrax cases
* GI: associated within 1-5 days after eating undercooked meat
* inhalational: bioterrorism route: universally fatal w/o antibiotics
- many antibiotic options for treatment!
66
Listeria monocytogenesis
- aka listeria
- uncommon cause of illness in the general population
- specific groups are susceptible: neonates, pregnant women, elderly, transplant, and others with impaired cell-mediated immunity
- mostly foodborne transmission
- intracellular and able to move from cell to cell without being exposed to antibodies, complement, or neutrophils
- manifestations: CNS meningitis, endocarditis, bloodstream infection, septic emboli, febrile gastroenteritis
- treatment: beta-lactam plus aminoglycoside
67
Atypical Bacteria: 3 categories
- Mycoplasma
- Ureaplasma
- Mycobacteria
68
Mycobacterium
- Gram (+) "ghosts", acid fast +
- commonly found in water and soil
- infections: lung, skin and soft tissue, lymph nodes, GI tract, other
- M. tuberculosis and nontuberculous mycobacteria
69
Myobacterium Tuberculosis (Mtb)
- Aerobic, non-spore forming, non-motiile bacillus
- high cell wall lipid content
- slow growing 15-20 / hour turnover
- carried in airborne particles
- 10% infection risk with + PPV (vaccine)
- Multi-drug resistance prevlant
- historically significant pathogen
- humans only reservoir for species
- started germ theory
70
M. tuberculosis worldwide
- 1/3 world's population infected with TB
- leading killer of people living with HIV
- much eradication in US
71
Risks for antibiotic resistance in TB
- exposure to a person who has known-antibiotic resistant TB
- exposure to person with active TB who has had prior treatment for TB and whose susceptibility tests unknown
- exposure to person with active TB from areas in which drug-resistant TB is prevalent
- exposure to person who continues to have positive sputum smears after 2 months of combo chemotherapy
- travel in an area of high prevalence drug resistance
72
M. Tuberculosis identification
- culture is gold standard
- may take weeks to grow
- Acid-fast bacilli = mycobacteria
- Mtb can be detected in any biological fluid
- QuanterFERON gold: detection of latent and active TB (blood test)
73
Latent vs active TB: Latent
- infected (alive bacteria, not active)
- skin or blood test positive
- normal chest x-ray or sputum, no symptoms, not contagious
- requires single drug treatment, 3-5% risk active Mtb in year 1, 5% lifetime risk thereafter
- treatment lowers to <1%
74
Latent vs active TB: Active
- infected (alive and active bacteria)
- skin or blood test positive
- abnormal chest x-ray or sputum
- symptoms of disease, coughing, fever
- contagious
- requires multi-year treatment
75
TB vaccine
- Bacillus Calmette- Guerin (BCG) vaccine
- live- attenuated strain of M. bovis
- often used in young children throughout much of the world with high TB prevalence
- 60-80% decrease in disease
- does not prevent infection, but does often prevent progression to clinical disease
- effectively prevents disseminated disease in young children
- increases likelihood of positive PPD
76
Non-tuberculosis mycobacteria (1)
- Mycobacterium Avium-intracellulare (MAI)
* primarily disease of HIV/AIDS
- many others
77
Drug-resistant TB threat level
- threat level serious
78
Antibiotic Targets and resistance in Mtb
- inhibit cell wall synthesis (isonazid, ethambutol)
- inhibit RNA synth (Rifampin)
- disrupt energy metabolism and plasma membrane (pyranzinamide)
- COME BACK TO THIS
79
Nontuberculosis Mycobacteria
- M. avium-intracellulare (MAI)
* environmental organism, relatively avirulent in the normal host
* infection: pulmonary, systemic, and lymphadenitis (children), other sites less common
* Prevention: 1 antibiotic; treatment: multiple
- More than 120 species of Nontuberculous Mycobacteria (NMT)
* environmental organism, common water source
* M. Fortuitum and M. abscessus common in skin/soft tissue, bone, and resp infections
* treatment often complicated and long
80
Mycobacterium Leprae
- armadillos (WATCH SLIDE)
81
MAC/MAI
- Mycobacterium avium and mycobacterium intracellulare (MAI) --> MA complex (MAC)
- found in water, soil, and animals, not spread from person to person
- causes pulmonary disesase, lymphadenitis, and disseminated disease
- lymphadenitis mostly children
- pulmonary disease mostly older patients with COPD
- disseminated disease: patients with AIDS with CD4 cell count < 50/mm
82
Clinical Manifestations and Diagnosis of MAC
- WATCH
83
What other two atypicals make up 25% of community acquired pneumonia (CAP) besides mycoplasma pneumoniae?
- Legionella pneumoniae
| - Chlamydophila pneumoniae
84
Legionella Pneumoniae
- Legionnaires Disease
- widespread in water
- actually a gram (-) rod, not a true atypical
- treatment options: fluorquinolones, macrolides, tetracyclines
85
Chlamydia Pneumoniae
- Often causes mild RTIs
- actually a gram (-) rod, not a true atypical
- obligate intracellular pathogen
- causes epidemics of CAP (military bases, schools, nursing homes)
- often cannot be differentiated from other CAP organisms
- detected in clinic by: Serologic testing to identify anti-C. pneumoniae immunoglobulin G (IgG), IgA, and IgM antibodies... also PCR testing and other rapid testing
- treatment options: fluoroquinolones, macrolides, tetracyclines
86
Mycoplasma spp
- prokaryotes lacking a cell wall = no gram-stain
- smallest known free living organism
- intracellular and extracellular pathogen
- M. pneumoniae, M. penetrans, M. genitalium, M. fermantans, and M. hominis
- outbreaks in perosns with close contact and commonly described for pneumonia
- no cell wall and therefore susceptible to non-cell wall active antibiotics
* fluoroquinolones, macrolides, tetracyclines
87
Ureaplasma
- 7 species identified
- Ureaplasmas and highly prevalent in the genital tracts of healthy sexually active women, with infection rates of 60-70% (10-20% for males)
- U. parvum strains account for 70% of ureaplasms; 30% U. urealyticum
- opportunists of the lower genital tract
88
U. urealyticum clinical implications
- associated with adverse pregnancy outcome including chorioamionitis, intrauterine infection, and premature birth
- supperative arthritis in patients with hypogammaglobulinemia
- neonatal disease: pneumonia, meningitis, sepsis
- low birthweight babies (<1 kg) at increased risk
- non-cell wall active antibiotics required for treatment
89
how many organisms are listed as urgent, serious, or concerning? (how many gram pos vs gram neg)
- 18
| - 50% are gram negative
90
why has antibiotic discovery gone down?
- no incentive for companies to produce antibiotics
91
Gram negative membrane makeup?
- two cell membranes, (balloon within a balloon) thin cell wall between membranes
- surface protein on cell wall: lipopolysaccharide (LPS)
92
2013-2015: how many new FDA approved antibiotics? how many gram negative ones?
- 5 new antibiotics
| - 2 activity against gram negatives
93
newer antibacterial agents incorporate which types of inhibitors?
- beta lactamase
94
Pathogenic features of gram negatives
- infections
- endotoxin- lipopolysaccharide on cell wall
- intrinsic resistance mechanisms exist in some species
- Enterotoxins
- community and nosocomial (hospital) acquisitions
