Exam 4 Flashcards
1
Q
encephalitis
A
inflammation of the brain parenchyma
2
Q
myelitis
A
infection of the spinal cord
3
Q
Most bacterial meningitis is ____
A
nosocomial, not usually community acquired
4
Q
defenses of CNS
A
low complement in the CSF - not lysed efficiently
micro
microglia - similar to phagocytes
5
Q
Damage to the CNS by meningitis
A
inflammation PMNs
vasogenic edema impaired blood flow ischemia
cell death
6
Q
Acute bacterial meningitis in newborns is usually caused by which organisms?
A
Group B strep
E. coli K1
Listeria monocytogenes
7
Q
Acute bacterial meningitis in infants-2 year olds is usually caused by which organisms?
A
Strep pneumo
Neisseria meningitidis
Haemophilus influenzae type B
8
Q
Acute bacterial meningitis in adults is usually caused by which organisms?
A
Strep pneumo
Neisseria meningitidis
9
Q
Listeria monocytogenes features
A
gram pos rod
non-spore
sero-grouped by teichoic acid
motile
soil, food, genital tract of mother
10
Q
Listeria monocytogenes Encounter
A
Environmental - soil
Foodborne outbreaks
Meat, dairy
Genital tract of mother
11
Q
Listeria monocytogenes Entry
A
oral
transplacental
12
Q
Listeria monocytogenes Spread
A
invade non-phagocytes (InlA-E Cadherin)
lyse the phagosome (Listeriolysin O)
escape to cytoplasm
use host actin to spread from cell to cell (ActA)
invade through mucosal surface into bloodstream
cross blood-brain barrier
inflammation can lead to leakiness
13
Q
Listeria monocytogenes evade defenses
A
intracellular
infects macrophages
escapes vacuole
peptidoglycan deacetylation (decreases host response - peptidoglycan is normally recognized by TLR2)
14
Q
Listeria monocytogenes damage
A
inflammation triggered by peptidoglycan
fluid accumulation
increased intracranial pressure, hydrocephalus, and brain damage
15
Q
Listeria monocytogenes outcome
A
highly lethal if not treated
other than mother to baby, not transmitted
16
Q
Haemophilus influenzae type B features
A
gram neg rod
encapsulated (by b antigen)
other types cause less disease
Hib was the primary cause of meningitis in children 6 mo-2 years
vaccine all but eliminated Hib cases and invasive disease
17
Q
Haemophilus influenzae encounter
A
human ONLY
respiratory droplets or saliva
can be endogenous
18
Q
Haemophilus influenzae entry
A
upper respiratory tract (nasopharynx)
adherence factors pili (fimbriae)
Hap (haemophilus adhesion and penetration) - autotransporter
19
Q
Haemophilus influenzae spread
A
goes from upper resp tract into blood, crosses blood-brain barrier to CNS
20
Q
Haemophilus influenzae multiplication
A
fastidious, requires chocolate agar
21
Q
Haemophilus influenzae evade defenses
A
extracellular
capsule
phosphocholine decoration of LOS = anti-LOS IgG
sialylation of LOS
binds complement factor H
IgA protease
22
Q
Haemophilus influenzae damage
A
inflammation
LPS
Protein D - kills ciliated epithelium by cleaving glycerol phosphate (glycerophosphodiesterase)
23
Q
Hib vaccine
A
humoral IgG to capsule prevents systemic infection by opsonization
composed of type B carbohydrate coupled to protein
drastically reduced meningitis by Hib
single serologic type of capsule associated with systemic disease makes single vaccine sufficient
part of the standard infant/child regimen
24
Q
Neisseria meningitidis features
A
gram neg diplococcus
sero-grouped by carbohydrate capsule
25
Neisseria meningitidis encounter
humans only (5-10%colonization - normal flora)
respiratory droplets
can cause epidemic
26
Neisseria meningitidis entry
upper resp tract
adherence - type IV pili
opacity proteins (opa, opc)
27
Neisseria meningitidis spread
through the epithelium into the blood
ciliary stasis and death
crosses blood-brain barrier
infects CNS
28
Neisseria meningitidis evasion of defenses
carbohydrate capsule - numerous serogroups; group B = polysialic acid (antigenic mimicry)
LOS siacylation
factor H protein binding (fhbp)
complement-deficient patients susceptible
29
Neisseria meningitidis - group B capsule
polysialic acid - antigenic mimicry, which means that we can't put this capsule into a vaccine because we don't make antibodies to sialic acid
30
Neisseria meningitidis vaccine
mixture of most prevalent capsular antigens EXCEPT group B
linked to protein
induce IgG to protect blood
mixture of 4 capsule types
good efficacy
shortcoming: should induce IgA
31
Neisseria meningitidis multiplication
it can reach really high levels in the blood
32
Upper vs lower respiratory tract
Upper - ciliated epithelium (everything down to the bronchi)
Lower - non-ciliated epithelium (broncho-alveoli and alveoli)
Upper can be cleared by the mucociliary escalator but lower cannot
33
Upper respiratory tract defenses
physical - ciliary escalator, mucus
particle exclusion - nasal hairs, coughing and sneezing, epiglottis, larynx
chemical - lysozyme (degrades peptidoglycan) and lactoferrin (binds Fe)
Alveolar macrophages (PMNs with inflammation)
34
What size organisms can make it to the lower respiratory tract?
<3 micrometers
35
Cell mediated immunity
cytotoxic lymphocytes throughout the respiratory tract
TH1-macrophages in lower respiratory tract for intracellular pathogens
36
alpha hemolytic and non typable grouping (stept)
partial hemolysis, green
S. pneumoniae
Commensal oral streptococci (viridans streptococci)
usually non-invasive
37
beta hemolytic group (strept)
complete hemolysis, clear
Group A : S. pyogenes (GAS)- >90% pharyngitis
Group B: S. agalactiae (GBS)- neonatal sepsis
Group C: Animal pathogens,
S. dysgalactiae ~5% pharyngitis
38
gamma hemolytic group (strept)
no hemolysis
Group D: Many species of Enterococcus, e. g.
E. faecalis
39
Strep pyogenes features
gram pos cocci in chains
beta hemolysis
Group A carbohydrate
M protein (fibrillar later)
>100 serotypes of M protein - cause different diseases (antigenic variety)
hyaluronic capsule
lipoteichoic acid
40
bacitracin sensitivity test
differentiate
sensitive beta-hemolytic Group A streptococci
(S. pyogenes)
from beta-hemolytic non-Group A streptococci
group A cause more acute pharyngitis
41
CAMP test
Identify presumptive for Group B strep or Streptococcus agalactiae
CAMP factor made by S. agalactiae enhances beta-hemolysis of S. aureus (synergistic effect) by binding to already damaged RBCs
As a result, an arrow of beta-hemolysis is produced between the two streaks.
42
Spe toxin (Strep pyogenes)
causes scarlet fever
43
diseases caused by strep pyogenes
pneumonia
skin infections (superficial - impetigo; deep - necrotizing fasciitis)
streptococcal toxic shock syndrome - systemic from superantigen
44
Nonsuppurative secondary complications of strep pyogenes
Scarlet fever (Strains expressing pyrogenic exotoxin)
rheumatic fever - damage to the heart by the immune system; certain strains
Necrotizing fasciitis
glomerulonephritis - kidneys
Erysipelas, cellulitis (deeper)
Impetigo contagiosum
45
Scarlet fever symptoms
caused by strep pyogenes
pharyngitis + rash (systemic toxin that strep pyogenes makes)
red diffuse rash
"strawberry tongue"
red cracked lips
circumoral pallor
red cheeks
46
Strep pyogenes entry (adherence)
M protein binds fibrinogen
Lipoteichoic acid
fibronectin binding protein
47
Strep pyogenes spread
YES
hyaluronidase - breaks down intracellular matrix
DNase B - DNA from lysed PMNs impedes movement of bacteria because it's gooey so DNase B breaks down that DNA from PMNs so that bacteria can spread more easily
response used in diagnosis
48
Strep pyogenes evade defenses
M protein - binds factor H to inhibit complement
hyaluronic acid capsule - antigenic mimicry, antiphagocytic
C5a peptidase - cleaves C5a to inhibit innate defenses
49
Strep pyogenes damage
primarily through inflammatory response
hemolysins - lyse defense cells - streptolysin O and streptolysin S
pyrogenic exotoxins
50
Streptolysin O
antibody response used in diagnosis
causes beta hemolysis on blood agar
lyses defense cells
51
Streptokinase
prevent walling off of infection by fibrin
52
Streptolysin S
lyses defense cells
53
Spe
Pyrogenic exotoxin
causes scarlet fever rash
phage encoded
causes T cells to secrete cytokines
54
Strep pyogenes outcome
transmission, highly contagious
clinical - highly variable depending on strain/patient/treatment
self-limiting except for rheumatic fever and glomerulonephritis
possible pneumonia/death
simple skin infections can be self-limiting but can lead to glomerulonephritis
serious skin infections (necrotizing fasciitis) can be fatal or require surgery
55
erysipelas
superficial butterfly skin infection, on face
elderly and children
56
cellulitis
deeper skin infection in elderly and newborns, can spread deeper and become fatal
fever and leukocytosis
57
Corynebacterium diphtheriae
Gram positive rods
diphtheria "leather" pseudomembrane in the back of the throat
asymptomatic carriers
58
Corynebacterium diphtheriae clinical manifestations
85-90% sore throat
50-85% low grade fever
26-40% dysphagia
50% pseudomembrane
59
Corynebacterium diphtheriae toxin-mediated manifestations
2/3 carditis
neurotoxicity in severe disease
larynx: croup, asphyxia
renal tubular necrosis
60
Corynebacterium diphtheriae epidemiology
Leading cause of death in infants in early 1900s
Since 2000 - 0-2 cases per year in the US (immunization became available in 1945)
still endemic in many areas in the world where vaccination is low
61
Corynebacterium diphtheriae encounter
humans only
inhalation
62
Corynebacterium diphtheriae entry
restricted to upper resp tract
63
Corynebacterium diphtheriae spread
NONE
64
Corynebacterium diphtheriae multiplication
fastidious
65
Corynebacterium diphtheriae evade defenses
not much to deal with in upper resp tract; adhesion and stuff hasn't been studied much because it's been wiped out so well
66
Corynebacterium diphtheriae damage
diphtheria toxin
67
Corynebacterium diphtheriae outcome
transmission to humans
can be fatal if untreated (5-10%)
68
Corynebacterium diphtheriae treatment
antibiotics + antitoxins
69
Corynebacterium diphtheriae prevention
toxoid vaccine
70
diphtheria toxin
encoded on bacteriophage (lysogenic conversion)
A-B type toxin - ADP ribosylates EF-2, inhibits protein synthesis, cytptpxic, damages heart, nerve, kidneys
heparin binding epidermal growth factor receptor
death from heart/nervous system damage
this is the target for the vaccine - chemical or genetic toxoid
71
Diphtheria toxin mechanism
inactivates EF-2
NAD + EF2 -> EF2-ADP ribose +nicotinamide
acts at diphthamide - modified amino acid residue on EF2
72
Bordatella pertussis features
gram neg rod (or coccobaccillus)
whooping cough
pertussis - severe cough
primarily in infants and children
"cough of 100 days"
73
Bordatella pertussis stages
1. catarrhal (cough, rhinorrhea)
2. paroxysmal (cough spasms, whoop, cyanosis, vomiting, episodes, OK in between)
3. convalescent (decreasing but continuing symptoms)
74
Bordatella pertussis clinical course
5-10 day incubation
catarrhal stage (1-2 weeks) - communicable
paroxysmal stage (1-6 weeks)
convalescent stage (weeks to months)
75
What amount of pertussis infections lead to pneumonia or death?
pneumonia - about 5%
death - 0.2%
76
Bordatella pertussis encounter
human only
inhalation
highly transmissible among unvaccinated (90%)
infected adolescents/adults are the source for infants and children
77
Bordatella pertussis entry
restricted to upper resp tract
adherence to ciliated epis - filamentous hemagglutinin, pili/fimbriae, pertactin
78
Bordatella pertussis spread
NONE
79
Bordatella pertussis multiplication
fastidious; Bordet-Gengou plates
80
Bordatella pertussis evade defenses
not much in upper resp tract in non-immune
ciliated epis - mucociliary escalator - pertussis attacks with trachial cytotoxin
81
Bordatella pertussis damage
pertussis toxin
A-B toxin
ADP-ribosylates G protein increasing cAMP
localized tissue damage
systemic toxicity - hypoglycemia, leukocytosis, neurological damage
82
Tracheal Cytotoxin (TCT)
from B. pertussis
peptidoglycan building block derivative
loss of ciliated cells
stops mucus flow
83
Bordatella pertussis outcome
transmissible
human to human
self-limiting but can be fatal
treatment - antibiotics
84
Bordatella pertussis prevention
vaccine - originally killed the whole cell - neurological problems
current acellular vaccine - pertussis toxoid + FHA; safe but not optimal because it causes stimulation of IgG, which isn't as useful in the upper resp tract, want stimulation of IgA
85
Community acquired pneumonia can be caused by...
S. pneumoniae
Legionella pneumophilia (rarer - immunocomp patients)
86
S. pneumoniae causes __% of community acquired pneumonia
40%
87
Streptococcus pneumoniae features
gram pos diplococcus
carb capsule - >90 serotypes, important for vaccines
alpha hemolytic
88
Pneumococcal pneumonia
S. pneumoniae
>1,000,000 deaths worldwide
predisposed populations - young, elderly, asplenic, complement deficient, sickle cell
89
S. pneumoniae encounter
humans only, spread by respiratory droplet
normal flora
90
S. pneumoniae entry
colonization of oropharynx, aspiration into lung
91
S. pneumoniae spread
pneumonia - not necessary, but frequent - can invade into the blood
meningitis - blood to CNS
otitis media and sinusitis - not necessary
92
S. pneumoniae multiplication
grows will in serous fluid and alveoli space
93
S. pneumoniae evade defenses
extracellular
capsule - antiphagocytic
sIgA protease
94
S. pneumoniae damage
inflammation - peptidoglycan (binds TLR2)
95
Pneumolysin
S. pneumoniae
toxin binds cholesterol in the host membrane
96
LytA
encodes autolysin
97
choline binding surface proteins
PspA and PspC
non covalently bind phosophocholine in teichoic and lipteichoic acid
induce proinflamm molecules
reduce effectiveness of complement
98
Stages of pneumonia
serous - fluid into alveoli
early consolidation (high bact, few WBC)
late consolidation (many WBC)
resolution (effective antibody response, macrophages clear debris)
no permanent damage in pneumococcal pneumonia
99
S. pneumoniae outcome
transmission - droplet/saliva
could be self-resolving or fatal
100
S. pneumoniae prevention
vaccines
-IgG to opsonize
-23-valent polysaccharides
-7-valent polysaccharide conjugated vaccine
-13-valent conjugated
101
Mycobacterium tuberculosis features
acid fast - cell wall waxes/lipids
slow growth - 15-20 hour doubling time
obligate aerobe
antibiotics: Ethambutol + isoniazid + rifampin + pyrazinamide
big problem with resistance (due to point mutations)
102
Mycobacterium tuberculosis encounter
humans only
1/3 of world population is infected - US, mostly immigrants
aerosol-droplet nuclei from actively infected people
resistant to drying (small desiccated respiratory droplets)
103
Without intervention, about ___% of people that have TB in them will develop TB disease (active infection) at some point in life
10%
104
Mycobacterium tuberculosis entry
inhaled directly into alveoli
no URT colonization
105
Mycobacterium tuberculosis spread
YES
phagocytosed by alveolar macrophages
transported to lymph nodes
Ghon complex - inflammation of hilar lymph nodes
can cause bacteremia (hematogenous dissemination)
seed about any tissue in the body
lung single most important site of infection
106
Ghon complex
TB granulomas
inflammation of hilar lymph nodes
107
Mycobacterium tuberculosis multiplication
slow
intracellularly in macrophages - facultative intracellular (don't need to be in cells but can be grown in or out o cells)
lipid metabolism
in areas with high oxygen
cultured on special agar
has unusual colony morphology
108
Mycobacterium tuberculosis evade defenses
intracellular pathogen of macrophages
cell wall inhibits phagolysosome acidification
usually limited by initial cell mediated immune response, but organisms persist for life
immunity measured by PPD skin test or interferon gamma release assay
cell-mediated immunity is required for intracellular pathogens of macrophages
109
interferon gamma release assay
test for TB
blood test of the patient's lymphocytes that stimulates them with microbial antigens and see if they make interferon gamma, which is a cell-mediated immune response
110
IFNgamma stimulates
MO
111
TB vaccine
MYcobacterium bovis strain (BCG)
mycobacterium bovis
live-attenuated
not in US
elicit Th1 cell-mediated immunity to activate macrophages to kill intracellular pathogen
ok efficacy in children, not very good in adults
shortcoming: should not be given to immunocompromised, need more effective vaccine for adults
112
Mycobacterium tuberculosis damage
host cell mediated immune response
delayed type hypersensitivity
granulomas (tubercles)
caseous necrosis
initial symptoms mild or non-existent
113
Mycobacterium tuberculosis outcome
reactivation in only 10% of initially infected people
reactivation in first 5 years = 5%, other 5% is remainder of life based on decreased immunity
114
Who is at higher risk of developing TB?
HIV infected
Persons taking anti-TNF agents (such as anti-psoriasis drugs)
Recently infected
Persons with certain medical conditions
115
Mycobacterium tuberculosis spread and multiplication
primary - alveoli
multiplication in MO, can multiply intra and extracellular
latency and endogenous reactivation
cell mediated immunity prevents active disease after infection
116
Prevention of TB
strictly spread person-to-person
need to identify exposed individuals and prevent them from developing active disease
screening through PPD or IGRA
Vaccine NOT used in the US
117
Legionella pneumophila features
gram neg rod - stains irregularly, use silver stain
Causes legionnaire's disease (pneumonia of predisposed) and Pontiac fever (flu-like in anyone)
118
Legionella pneumophila encounter
environment only
amoeba in water
natural as well as air conditioning
119
Legionella pneumophila entry
inhalation directly into alveoli
no initial URT
120
Legionella pneumophila spread
not usually
121
Legionnaires' disease (Legionellosis)
Legionella pneumophila
flu-like > Outcome depends on host imm resp, specifically cell-mediated; lymphocytes produce IFNgamma, suppressing growth within MO, in part by inducing the MO to sequester Fe
122
Pontiac fever
Legionella pneumophila
milder resp illness w/o pneumonia, resembles acute influenza
123
Legionella pneumophila treatment
antibiotics that can achieve high intracellular concentrations in macrophages (e. g. doxycycline, azithromycin, ciprofloxacin)
124
Legionella pneumophila prevention
surveillance and monitoring of plumbing and water systems
125
Defenses of the skin
shedding, dry, acidic, temperature, lysozyme and toxic lipids, resident microflora (mainly GPC)
126
normal microbiota
gram pos cocci Diphtheroids, Micrococci, Yeasts
127
Diptheriods
Club-shaped, Gram positive, and not usually virulent. e.g., Propionibacterium acnes
128
Micrococci
Staphylococcus, Streptococci, and Micrococcus
129
Yeasts
Low numbers, can cause opportunistic disease. e.g., Candida albicans, Malassezia furfur
130
Methicillin-Resistant S.
aureus MRSA)
resistant to the beta lactam
antibiotic methicillin
131
Staphylococcus aureus features
GPCL
many strains - causes several different diseases
Toxic Shock Syndrome
Scalded skin syndrome (infants)
abscesses
septic arthritis, osteomyelitis
sepsis
pneumonia
endocarditis
food intoxication (food poisoning, not infection)
132
Staphylococcus aureus encounter
humans only (some animals too)
normal flora of skin and nose
direct contact or fomite
nosocomial
133
Staphylococcus aureus entry
skin
catheters, devices
wounds
fibronectin binding proteins
134
Staphylococcus aureus spread
YES, through tissues
135
Staphylococcus aureus multiplication
grows quickly, especially in food
salt resistant
136
Staphylococcus aureus evade defenses
coagulase - stimulates clotting by activating fibrinogen to make fibrin
superantigens disrupt immune response
Panton-Valentine leukocidin
capsule
catalase
Chronic Granulomatous Disease patients at risk
Protein A (binds IgG backkwards)
137
Staphylococcus aureus damage
pyogenic inflammation
peptidoglycan, lipoteichoic acid
Toxic Shock syndrome
Staphylococcal scalded skin syndrome
hemolysins
exoenzymes
138
Staphylococcal scalded skin syndrome
local infection - systemic effects
exfoliative skin toxin (protease - breaks down desmosomes that link the skin cells together)
dermanecrotic toxin (exfoliative toxin)
bullous exfoliative dermatitis
139
Staphylococcus aureus outcome
usually self-limiting, but can be fatal
transmission to humans - both direct and fomite
140
Staphylococcus aureus treatment
antibiotic resistance is problematic
MRSA - resistant penicillin-binding protein
141
Pseudomonas aeruginosa features
gram neg rod
aerobic
green pigment
biofilms
antibiotic resistance
142
Pseudomonas aeruginosa diseases
hot tub dermatitis
opportunistic infections of any body site, particularly skin, burns, lung, UTI, osteomyelitis, endocarditis (IDU)
143
Otitis externa
ear infection
swimmers ear (Pseudomonas aeruginosa)
144
Pseudomonas aeruginosa encounter
environmental - WATER, soil, food, air
catheters
endotracheal tubes
145
Pseudomonas aeruginosa entry
lung, intestine, wound
biofilms
pili
146
Pseudomonas aeruginosa spread
YES - immunocompromised patients or with burns/wounds
147
Pseudomonas aeruginosa multiplication
simple
can grow on diverse substrates, even in disinfectants and cleaning materials
easy to contaminate stuff, especially in hospitals
148
Pseudomonas aeruginosa evade defenses
usually held in check by PMNs, so serious infections are normally in neutropenic patients
no defenses at surface so it's easy to "set up shop"
toxins can kill phagocytes
in cystic fibrosis patients - strains mutate to produce alginate polysaccharide - mucoid
149
Pseudomonas aeruginosa damage
inflammation
exotoxins - exotoxin A, type 3 secreted toxins, extracellular enzymes
150
Pseudomonas aeruginosa outcome
self-limiting in healthy people
can be lethal in immunocompromised and burn patients
not normally transmitted between people
151
Pseudomonas aeruginosa prevention
no vaccine
in hospital - vigilant infection control
clean wounds
for otitis externa keep ears dry
152
Pseudomonas aeruginosa treatment
antibiotics
highly resistant to numerous antibiotics
153
Clostridium tetani
gram positive obligate anaerobe, spore former
154
Clostridium tetani encounter
strictly environmental; spores in soil
155
Clostridium tetani entry
wound contamination with spores
156
Clostridium tetani spread
YES via soil
157
Clostridium tetani multiplication
wound becomes anaerobic
other bacteria consume oxygen
158
Clostridium tetani evade defenses
not really known, but does not need to for long because damage is caused by toxin
159
Clostridium tetani damage
tetanospasmin - very toxic - lethal dose = 1ng/kg
produced during sporulation
A-B toxin
binds to nerves
retrograde transmission to CNS
also through blood
160
Tetanospasmin
inhibits neurotransmitter release (so you say flexed)
vesicles cannot fuse in inhibitory synapses - *no inhibitory signal*
opposing muscles locked on
spastic paralysis
161
Clostridium tetani outcome
death by respiratory failure
transmission = none
162
Clostridium tetani treatment
antitoxin (does not work against toxins that are already bound to nerve cells)
antibiotics
debridement
163
Clostridium tetani prevention
vaccine - tetanus toxoid
IgG to neutralize toxin
immune globulin it it's too late
disease is slow, so time to boost after exposure
164
what bacteria can make endospores
bacillus, clostridium, and sporosarcina
