MIrocm 442 Ch 5-7 Flashcards
(120 cards)
1
Q
Includes external defenses and internal defenses
A
innate immunity (1st line of defense)
2
Q
-primary response takes time
-targeted to specific microbes
-clonally rearranged receptors
-immunologic memory
A
adaptive immunity (takes days initially)
3
Q
-physical and chemical barriers
-mucous membranes
A
external defenses
4
Q
-complement
-phagocytic cells
-pattern recognition receptors
-inflammatory response
A
internal defenses
5
Q
-antibodies via plasma cells
-cell-mediated response (t-cells)
A
humoral response
6
Q
thick layer of dead cells in the epidermidis
A
skin
7
Q
contain lysozyme, which digests peptidoglycan
A
tears
8
Q
antibacterial enzymes
A
saliva
9
Q
mucus and cilia trap and remove organisms
A
respiratory
10
Q
-mucus=viscous, contains antimicrobial properties
-inner mucus=essentially sterile
-cell surface mucins prevent pathogen binding
A
GI tract mucosa
11
Q
thick due to secretions
A
mucus
12
Q
most bacteria in GI tract is in
A
outer layer
13
Q
secrete gel-forming mucins
A
goblet cells
14
Q
secrete antimicrobial defensins and other proteins
A
paneth cells
15
Q
transport antigens from gut lumen to cells of immune system
A
M-cells
16
Q
the 3 pathways of complement activation
A
classical, lectin, and alternative
17
Q
links innate and adaptive arms of the immune system -> antigen-antibody complexes
A
classical
18
Q
mannose-binding lectin, lectin=protein that binds to sugar, recognizes bacterial sugars
A
lectin
19
Q
pathogen surfaces -> biophysical characteristics of pathogen surface allows inactivation of complement
A
alternative
20
Q
outcomes of complement activation
A
- inflammation and chemotaxis
- osponization (removal of pathogens)
- pathogen lysis (membrane attack complex)
21
Q
genetic deficiencies in terminal complement components predispose to…
A
Nisseria infections
22
Q
osponization targets
A
particles for uptake or phagocytosis but osponization-independent mechanisms can also trigger uptake
23
Q
neutrophils have both
A
complement and antibody receptor to perform phagocytosis
24
Q
ROS helps
A
the phagolysosome by binding to it and helping degrade bacteria
25
NADPH oxidase (which produces ROS) deficiency causes
chronic granulomatous disease
26
PRR are present
-on the cell surface
-in intracellular compartments
-in the cytoplasm
27
PRR bind to
PAMPs
28
Lipoproteins on GP bacteria
TLR1 and TLR2
29
LPS and GN
TLR4
30
flagellin and GN
TLR5
31
DNA on both GP and GN
TLR9
32
TLR signaling cascade leads to
1. cellular activation
2. cytokine production
33
Bacteria avoid TLR by
-modulating structures to prevent recognition
-interfering with signaling pathways
34
Inflammoses are in the
cytoplasm
35
-multi-protein innate immune sensing complexes
-have sensor proteins that detect conserved PAMPs and danger signals
Inflammoses
36
pro-inflammatory programmed cell death
pyroptosis
37
activate the protease caspase-1 and related proteases to activate cytokines and initiate pyroptosis
Inflammoses
38
cytokines cause
1. vasodilation
2. increase vascular permeability
39
inflammatory cells migrate into
tissue
40
B cell receptors/antibodies have
4 components
-light chain + heavy chain = variable region
-constant region = part of heavy chain
41
3 functions of antibodies
1. neutralization
2. osponization
3. complement activation
42
T-cell receptor DNA is
rearranged and creates a dimer
43
cytosolic pathogen peptides bind to
MHC class I and presented to CD8 T-cells
44
extraceullular pathogen peptides bind to
MHC class II and presented to CD4 T-cells
45
CD4 helper t-cells
activate B cells & macrophages, produce cytokines
46
CD8 cytotoxic t-cells
kill infected cells and produce cytokines
47
agent characteristics
-virulence, dose, toxicity
-ability to survive in different environments
-antibiotic susceptibility
48
agent interventions
control/eliminate the infection at its source
49
Host characteristics
-behavior (age, sex, sexual practices, hygiene)
50
host susceptibility
-genetics
-immunological status
-anatomic structure
-disease or medications
51
host interventions
-treat infection
-immunize
-behavior modification
52
environment characteristics
-place, geology, climate
-biologic factors -> insects transmit the agent
-socioeconomic factors -> crowding, sanitation, access to healthcare
53
environment interventions
-sanitation, water
-preventive services
-spray to reduce mosquitoes
-bed nets
54
resevoir
environment in which the infectious agent normally lives, grows and multiplies
55
environmental reservoirs
-plants
-soil
-water
56
skin to skin, kissing, sex, contact with soil/vegetation, droplet spread (sneezing/coughing)
direct transmission
57
airborne (measles can live in air for hours), vehicle borne, vector borne
indirect transmission
58
food, water, fomites
vehicle-borne transmission
59
mosquitoes, fleas, ticks
vector-borne transmission
60
reproduction number (how many people can 1 person infect)
R-naught (R0)
61
1. infectious period
2. mode of transmission
3. contact rate (location, public health measures, not specific to a disease)
factors for R-naught calculation
62
observed>expected at a particular time and place
outbreak
63
used to generate a DNA fingerprint for a bacterial isolate, bacteria from same strain will be indistinguishable -> gold standard
PFGE
64
individual gene or whole genome
sequencing
65
to establish link need not only DNA relatedness but
epidemiological connection
66
natural or innate properties
intrinsic resistance
67
-mutation
-horizontal gene transfer
-often under selection pressure
acquired resistance
68
-efflux pumps
-permeability barriers
-target bypass
intrinsic resistance examples
69
-efflux pumps
-inactivate the antibiotic
-modify the antibiotic target
acquired resistance examples
70
-transformation
-conjugation
-transduction
types of horizontal gene transfer
71
taking up free dna from environment
transformation
72
transfer from one bacterium to another (plasmids/mobile elements)
conjugation
73
bacteriophage infection -> phage picks up dna during infection and inserts it into another cell
transduction
74
biofilms make it hard for antibiotics to
reach the target bacteria
75
-metabolic byproducts
-reduced oxygen
-differences in pH
-some antibiotics sensitive to these changes
altered microenvironment in communities
76
-subpop. go metabolically dormant
-antibiotics=less effective
-revert back to normal later
bacterial persister cells
77
-exoplysaccharides, proteins, dna
-hard for antiobiotics to penetrate
sticky and slimy matrix of communities
78
beta-lactams
cell wall inhibitors
79
glycopeptides
cell wall inhibitors
80
fluoroquinolones
dna targeting
81
macrolides, lincosamides
ribosomal inhibitors
82
tetracyclines
ribosomal inhibitors
83
aminoglycosides
ribosomal inhibitors
84
2 main enzymatic steps in cell wall synthesis
1. crosslinked via stem peptides
2. polymerized into glycan strands
85
-nitromidazoles
-rifampin
-sulfonamides
-polymyxins
other processes of antibiotic classes
86
transpeptidase
PBP that crosslinks
87
glycosyltransferase
PBP that polymerizes
88
different bacteria can have...
both or one of the PBPs
89
what inhibits the transpeptidase activity of the PBPs
beta-lactams -> form a complex and PBPs can no longer crosslink -> cell wall integrity compromised
90
-penicillins
-cephalosporins (start with ceph)
-carbapenems (end in penem)
-monobactems
-beta-lactam/beta-lactamse inhibitors
-cefiderocol
classes/subclasses of beta-lactams
91
cefiderocol + carbapenems
broad-spectrum
92
1-5 generations
cephalosporins
93
1. producing beta-lactamases to hydrolyze/inactivate the antibiotic
beta-lactams resistance mechanisms
94
-amoxicillin/clavulanate
-ampicillin/sulbactam
-piperacillin/tazobactam
combination drugs with beta-lactamases
95
beta-lactamases common in
GN -> chromosomal or plasmid-encoded beta-lactamases e.g. e.coli and klebsiella
96
2. mutating PBPs to lower the affinity for the antibiotic e.g. MRSA
beta-lactams resistance mechanisms
97
-acquired mecA gene from mobile genetic element integrates into chromosome
-mecA encodes an alternative PBP2 protein called PBP2s
-reduced affinity for methicillin and other similar beta-lactams
MRSA
98
3. efflux pumps move the antibiotic out of the cell (see ya!)
beta-lactams resistance mechanisms
99
4. prohibiting entry by decreasing membrane permeability
beta-lactams resistance mechanisms
100
vancomycin -> bind peptidoglycan D-ala D-ala dipeptide to block Tpase crosslinking
glycopeptide
101
-used as a broad spectrum drug against GP
-too large to pass outer membrane (intrinsic resistance)
vancomycin
102
-horizontal gene transfer that encodes for D-ala D-lactate ligase
-vancomycin doesn't recognize anymore
VRE (vancomycin-resistant enterococcus)
103
end floaxin
fluoroquinolones
104
relax/unwind over-twisting positively supercoiled DNA by cleaving and reuniting the strands
type II topoisomerases, dna gyrase and topoisomerases IV in fluoroquinolones
105
-target site mutations in gyrase/topoisomerase
-efflux pumps and permeability barriers
fluoroquinolones
106
peptide chain transfer blocked
oxazolidinoes -> ribosomal inhibitor
107
block trnas from A site on 30S subunit
tetracyclines -> ribosomal inhibitor
108
induce codon misreading at site A
aminoglycosides -> ribosomal inhibitor
109
peptide exit tunnel/translocation blocked
macrolides + lincosamides -> ribosomal inhibitor
110
resistance:
-aminoglycoside-modifying enzymes
-mutations in ribosomal rRNA
-mod of ribosome by methyltransferases (its a hat!)
-decrease membrane permeability
ribosomal inhibitor
111
helpful for stopping toxin production e.g. staphylocoocal toxic shock syndrome + necrotizing soft tissue
ribosomal inhibitor
112
-prodrug enters cell + anaerobic environment promotes reduction to nitroso intermediate products
-these products cause DNA to break
mitroimizadoles/metroindazole
113
-intra-abdominal infections
-bacterial vaginosis
-brain abscess
mitroimizadoles/metroindazole
114
-inhibits rna polymerase
-combo therapy
-penetrates osteoblasts
-DIFFUSES WELL INTO BIOFILMS
rifampin
115
-folate (B9 synthesis)
-important pathway for dna synthesis
-trimethoprim/sulfamethoxazole (SXT) blocks 2 steps in this pathway
sulfonamides
116
intrinsic resistance example:
enterococcus can take up folate from the environment as an alt. source= target bypass
sulfonamides
117
-disrupt OM of GN
-hydrophillic cationic ring + hydrophobic tail = inserts into membranes
-toxic to kidneys + brain
polymyxins
118
not sure what patient is infected with
empiric coverage
119
-effectively targets all PBPs
-amp. targets 4 & 5
-ceftriaxone targets 2 & #
dual beta-lactam therapy (enterococcus)
120
aminoglycoside + cell wall inhibitor
dual therapy (enterococcus)
