Week 7: Key Terms Flashcards
1
Q
Diarrhea
A
3 or more loose watery stools per day OR a change from normal bowel habits
acute: less than two weeks
chronic: greater than two weeks
2
Q
dysentery
A
diarrhea with blood
3
Q
gastroenteritis
A
infection of the GI tract by viruses, bacteria or parasites
4
Q
<5% dehydration
A
well, alert
drinks normally, not thirsty
skin recoils quickly
5
Q
5-10% dehydration
A
restless, irritable
sunken eyes
thirsty, drinks eagerly
skin recoil slow
6
Q
> 10% dehydration (severe)
A
lethargic, unconscious
sunken eyes
drinks poorly, unable to drink
very slow skin recoil
7
Q
norovirus
A
most common cause of acute gastroenteritis in US
short incubation period, self limited, mild mucosal abnormalities
8
Q
rotavirus
A
common cause of diarrheal mortality in children worldwide
vaccine available
short incubation, destruction of mature enterocytes with loss of absorptive surface
9
Q
salmonella
A
gram-negative bacilli
nontyphoid salmonella causes salmonellosis
s. thyphi, s. parathyphi causes thyphoid fever
virulence factors: T3SS, flagellin, LPS
10
Q
camplobacter
A
common cause of traveler’s diarrhea
virulence factors: cytotoxins
11
Q
shigella
A
gram negative bacilli
resistant to gastric acid
virulence factors: T3SS, Shiga toxin (HUS)
12
Q
vibrio cholerae
A
“rice water stools”
caused by contaminated water often following natural disasters
virulence factor: cholera toxin
13
Q
ETEC
A
traveler’s diarrhea (secretory)
minimal mucosal damage
virulence factors: heat labile and heat stable
14
Q
EPEC
A
diarrhea, particularly infants
superficial mucosal damage with enterocyte effacement
virulence factors: T3SS
15
Q
EHEC
A
spread through uncooked beef, contaminated milk, vegetables
invade mucosal cells, proliferate, damage mucosa
virulence factors: shiga-like toxin can cause HUS
NO antibiotics, increases risk of HUS
16
Q
pseudomembranous colitis
A
antibiotic-associated, c. diff
nosocomial spread
treat: vancomycin, fidaxomicin, fecal transplant
17
Q
giardia
A
non-invasive diarrheaa
treat with oral rehydration and anti protozoan agents
parasite
18
Q
cryptosporidium
A
water-bourne
resistant to chlorine
parasite
19
Q
entamoeba
A
parasite causing infectious diarrhea
20
Q
intussusception
A
telescoping bowel
21
Q
malabsorption
A
chronic diarrhea
carbohydrate of fat malabsorption, cholestatic disorders, exocrine pancreatic insufficiency, decreased bile circulation
steatorrhea
22
Q
inflammatory diarrhea
A
chronic diarrhea
IBS, celiac disease, colitis
fecal leukocytes, persists during fasting
23
Q
hemolytic uremic syndrome
A
microangiopathic hemolytic anemia, thrombocytopenia, renal injury
24
Q
clinical features HUS
A
diarrhea, bloody stools
weakness, lethargy
pallor, petechiae
25
laboratory findings HUS
anemia with shistocytes
thrombocytopenia
Shiga toxin +
26
Management HUS
supportive
avoid antibiotics and anti diarrheals
27
prokaryote
primitive nucleus
bacteria
small
rigid peptidoglycan cell wall
28
eukaryote
true nucleus
protozoa, fungi, plants, animals
large
evolved from fusion of prokaryotic cells
29
species definition: eukaryotes
members can mate and produce fertile offspring
30
species definition: bacteria
arbitrary, isolates that share many characteristics
97% similarity in 16s rRNA
31
Linnean binomial system
genus and species
Escherichia coli
32
subspecies classification of bacteria
determined by serology
33
Gram stain
Gram-positive: thick PG layer, purple
Gram-negative: thin PG layer, pink
34
Gram stain technique
Crystal violet (stain)
Iodine (fixant for CV)
Wash excess with alcohol
Saffrin (counterstain)
35
Molecular Koch's Postulates
1. Gene associated with the pathogenic organism
2. Isolated by cloning
3. Specific inactivation= loss in pathogenicity
4. Complementation= restoration of pathogenicity
36
Koch's Postulates
1. Regularly found in lesions of disease
2. isolated in pure culture
3. similar disease in experimental animals
4. recovered from lesions on those animals
37
prions
infectious proteins
38
virus
acellular infectious agents
39
bacterium
prokaryotic infectious agent
40
fungus
eukaryotic infectious agent
41
parasites
eukaryotic infectious agent
42
protozoan
unicellular parasite
43
helmith
multicellular parasite
44
commensal
microorganism in symbiotic relationship with host
45
colonization
ability of a microorganism to persist and multiply
46
normal flora
colonization with commensal microorganisms
47
pathogen
microorganisms that cause disease
48
virulence
degree of pathogenicity
49
infection
colonization by a pathogen
50
disease
result of infectious process leading to host damage
51
etiology
cause of disease
52
epidemiology
factors and mechanism of disease spread
53
sporadic
limited to a small number of isolated cases
54
endemic
continually prevailing in a region
55
epidemic
outbreak
56
pandemic
worldwide outbreak
57
Stages of infectious disease:
1. incubation
2. prodrome
3. specific illness
4. convalescence
58
quantitative measures of virulence
ID50 and LD50
59
ID50
number of microorganisms needed to infect 50% of host population
60
LD50
number of microorganisms needed to kill 50% of host population
61
virulence is _________ to ID/LD
inversely proportional
62
lower respiratory tract and upper genitourinary tract are
generally sterile
63
Transmission
oral/aerosal
fecal-oral
venereal
vector bourne
zoonotic
64
portals of entry
skin, soft tissue (trauma)
skin, bloodstream (arthropod bite)
respiratory (inhalation)
gastrointestinal (ingestion)
genital (sexual transmission)
transplacental
65
standard precautions
hand hygiene, PPE
66
contact precautions
gloves, gowns, private rooms
norovirus, c.diff
67
droplet precautions
masks, respirators, closed rooms
influenza
68
airborne precautions
N95, isolation room
measles, TB
69
full barrier precautions
airborne + contact + eye protection
SARS, pandemic
70
adhesins
surface virulence factors that confer ability to adhere to host surfaces
pili, fimbriae, protein adhesins, biofilms
71
Exotoxins
bacteria-mediated pathogenesis
enzymes, AB toxins, membrane damaging toxins, superantigens
72
endotoxin
host-mediated pathogenesis
LPS and Gram - only
73
AB toxin
B portion: Binds the surface cell receptor
A portion: is enzymatically Active and is transported to cell interior to be Activated
74
T3SS
syringe secretion system
effector proteins are injected by a needle complex from bacterial cytosol to host cytosol
75
Lipopolysaccharide
endotoxin
released by cell lysis, causes septic shock
76
pathogenicity island
region of DNA encoding for a set of virulence genes
77
secretory gastroenteritis
ETEC
watery diarrhea
proximal small intestine
78
inflammatory gastroenteritis
shigella
EHEC
salmonellosis
campylobacter
dysentery
colon
79
invasive gastroenteritis
salmonella thyphi/parathyphi
enteric fever
distal small intestine
80
Gram-negative, lactose positive bacteria
escherichia
klebsiella
enterobacter
81
gram-negative, lactose negative, glucose positive bacteria
salmonella
shigella
proteus
serratia
yersinia
82
gram-negative bacteria
cocci
83
Escherichia coli
causes diarrhea
ETEC: traveler's diarrhea, non-invasive
EHEC: hemorrhagic; invasive, shiga-toxin
84
K:O:H serotyping
useful for epidemiology; differentiates virulence factors
K: capsular antigens
O: somatic antigen (LPS)
H: Flagellar antigen
85
EHEC
O157:H7
undercooked Hamburger
adheres to large intestinal cells
HUS
86
HUS
hemolytic uremic syndrome
87
Shigatoxin
causes destruction of endothelial cells
toxemia affecting kidneys
88
EHEC virulence factors
T3SS
LEE pathogenicity island
A subunit binds to rRNA, shutting down protein synthesis in the host cell
89
ETEC
Traveler's diarrhea
adhere to small intestinal mucosa
fimbirae, LT and ST toxins
90
Heat labile toxin (LT-1)
AB toxin
B subunit binds to GM1
A subunit locks adenylate cyclase in "on" state, increases cAMP, causes ion imbalance
91
Heat stable toxin (STa)
small peptide toxins
affects ion transport
92
EPEC
no known toxins
93
EAEC
persistent diarrhea in children
stacked bricks
biofilm
94
treatment HUS
dialysis and blood transfusions
95
Treatment E Coli
fluid/electrolyte maintenance
no antibiotics
96
Is salmonella a lactose fermentor?
lactose negative
97
is E Coli a lactose fermentor?
Lactose postitive
98
Salmonella enterica
S. typhi or S. paratyphi
humans are only host, asymptomatic carriers
protected against stomach acid, SOD, and catalase
99
Salmonella enterica treatment
DOCs: ciprofloxacin, levofloxacin
if critically ill, carbapenem then deescalate
100
Shigella dysenteriae
most severe
frequent small bloody, mucous stool and tenesmus
HUS
101
Shigella flexneri
shigellosis in developing world
102
S.sonnei
shigellosis in industrial world
slow lactose fermentor, may get light pink on MacConkey
103
Shigella
humans are only reservoir
low ID
fecal-oral route
lactose negative
non-motile
104
Shigella virulence factors
T3SS mediated invasion
hemolysin
intracellular spread
shiga toxin
105
Shigella treatment
rehydration, antibiotics
DOCs: ciprofloxacin, levofloxacin, ceftriaxone
azithromycin (peds)
106
Campylobacter
gram negative
curved rod
single flagellum
oxidase +, catalase +, urease -
107
C. jejuni
antecedent to Guillain-Barre
lesions resemble ulcerative colitis or Crohns
animal reservoirs: cows, birds, chickens
108
C. fetus
produces a protein capsule (S protein) that is antiphagocytic
109
C. jejuni causes Guillain-Barre
cross-reactivity of LOS and GM1 on neural tissue
110
Campylobacter treatment
usually self limiting, may require antibiotics
azithromycin
c.fetus: carbapenem, aminoglycoside
111
Humoral immune system
liquids and soluble molecules
112
cellular immune system
cell
113
innate immune system
immediate response, targets large groups of pathogens, no memory
114
acquired immune system
gradual response generated over 3-4 days, targets specific pathogens, memory
115
CD (cluster differentiation)
surface molecules of immune cells
116
cytokines
communicate between cells
adjacent: paracrine
themselves: autocrine
systemically: endocrine
117
Antibody
produced by B cells
precise specificity and bind to antigens
composed of two heavy chains and two light chains
118
Fab domain
antigen binding
highly variable, highly specific
119
Fc domain
binds to cells via FcR and gives antibody its specialized properties
non variable
120
FcR
protein found on the surface of certain cells that bind to antibodies attached to infected cells or invading pathogens
important to opsonization, allergies, and antibody-dependent cell-mediated cytotoxicity ADCC
121
lymphocytes
t cells
b cells
NK cells
from lymphoid stem cell
122
NK cells
important defense against tumors and viruses
kill cells using ADCC
type II hypersensitivity
123
macrophages
reside in tissues and are first to encounter pathogen
124
neutrophils
reside in blood and need to be recruited to infection site
125
dendritic cells
stimulate adaptive immunity
126
mast cells/basophils
allergic responses
127
PRR (pattern recognition receptor)
TLR found on cell surface and organelles of body cells
dendritic cells and macrophages use these to recognize pathogens
128
TLR-4 interacts with
LPS on gram - bacteria
129
PAMPs
LPS, peptidoglycan, dsRNA
130
DAMPS
uric acid, extracellular DNA, RNA, and ATP
131
IL1 and TNF alpha
fever
132
IL8
recruits neutrophils
133
IL6
pyrexia via PGE2
134
CD19, CD20, CD21
b cells
135
CD4+, CD8+
t cells
136
BCR
two identical heavy chains and two identical light chains linked by several disulfide bridges
"surface bound antibody"
can bind 2 identical antigens
IgA and IgB do signal transduction
137
TCR
one alpha chain and one beta chain linked by one disulfide bridge
binds one antigen, never shed
CD3 responsible for signal transduction
138
MHC Class I
CD8+ (Tc)
stimulated to kill the presenting cell
expressed on all nucleated cells
HLA-A, HLA-B, HLA-C
activate NKs if missing or altered
139
MCH Class II
CD4+ (Th)
expressed on APC
stimulated to control other cells
HLA-DP, HLA-DQ, HLA-DR
derived from foreign materials
140
Hypersensitivity Type I
IgE mediated
allergies
immunity to helmiths
141
Hypersensitivity Type 2
IgG/IgM cytotoxic
opsonization
142
Hypersensitivity Type 3
immunity to bacterial toxins
143
Hypersensitivity Type 3
immunity to bacterial toxins
144
Hypersensitivity Type 4
immunity to intracellular bacteria, viruses, protozoa
delayed
diabetes, dermatitis
145
Th1
Type 4 hypersensitivity
promote CD8+ responses
secrete IFNy, TNF, IL-2
146
Th2
Type 1 hypersensitivity
promote antibody responses
147
Treg
suppress immune response
148
Th17
secrete IL 17
important to immunity to bacteria and fungi
149
Tfh
follicular B helper cells
150
IL-12
induce Th1
151
IL-4, IL-5, IL-13
allergy
Th2 response
152
IL-4, IL-13 lead to IgE production
Th 2 response
Type 1 hypersensitivity
153
IL-5
stimulates eosinophils
154
anti-sense oligonucleotide (AON)
short, synthetic nucleotide chains that can be used as a therapy to "exon skip"
AON masking splice site is inserted slightly upstream of the exon with a premature stop codon to "skip" it
therapy for Duchenne
155
branch point
step 1 of lariat structure: 2'-OH of Adenine at the branch point attacks the 5' G of intron forming the intermediate structure
156
cryptic splice site
splice site not normally used in WT but are selected for due to mutation elsewhere
example used in class Beta zero thalassemia: mutation in WT splice site resulted in the use of cryptic splice site in intron 2. Part of intron 2 is then retained in protein causing misfolding and ubiquitination.
No beta chain synthesis.
157
exon
part retained for mRNA
158
intron
non coding regions spliced out of mRNA
159
lariat
splicing intermediate formed by 2 consecutive Sn2 reactions
Step 1: 2'-OH at branch point A attacks 5' G of intron
Step 2: OH-G at 3' end of exon 1 attacks 5'-G of exon 2
160
mRNA cap
7-methyl guanosine cap
increases stability
identifies rRNA as cellular (vs. viral)
required for translation
export to cytoplasm
161
poly-A signal
poly(A) polymerase complex recognizes poly-A signal and cleaves about 25 nucleotides down stream
AAUAA
162
poly-adenylation
poly(A) polymerase complex adds 150-200 A residues
no DNA template
marks mRNA as "special"
-translation efficiency
-export to the cytoplasm
-stabilize mRNA
163
pre-mRNA
primary transcript of a protein-coding gene before splicing and modifications
164
RNA binding/splicing regulatory factor
Bind splicing enhancers/silencers
Specify intron/exon boundaries
Regulate utilization of splice sites/binding of snRNPs
Execute development programs of specific splicing
Recognize defects in binding sites or disease factors
165
small nuclear ribonucleoproteins (snRNPs)
set up proper geometry for splicing
hold together exons prior to joining
catalyze cleavage and formation of bonds
antibodies to snRNPs found in systemic lupus (SLE)
only in eukaryotes
166
snRNA
associate with snRNP for lariate structure
U1, U2, U4, U5, U6
167
snRNP U1
recognizes donor exon/intron boundary
168
snRNP U2
recognizes adenosine branch point
169
snRNP U4, U5, U6
form spliceosome
170
Base pairing between U1/U2 and pre-mRNA is an important determinant of
splice site strength
171
splicing signals
conserved nucleotide sequence that are critically important
mutation of splice site=loss of signaling
mutated splice signals often responsible for disease
172
mammalian splice signal
(donor site) AG/G (acceptor site)
173
splicing enhancer
promote splice site
174
splicing silencer
repress splice site
175
splice variant
alter activity or regulation of proteins produced
alter stability or translation of mRNA
176
fibrosis
excessive extracellular matrix accumulation
177
cirrhosis
normal-moderate AST/ALT
increased bilirubin
decreased albumin
decreased clotting factors
increased PTT
abnormal elastography
execessive ECM
regenerating nodules
178
parenchyma
hepatocytes
179
non parenchymal cells
Kupffer cells, hepatic stellate cells, portal fibroblasts, liver sinusoidal endothelial cells, cholangiocytes
180
bile composition
97% water
.7% bile salts
.2% bilirubin
.51% fats
trace inorganic salts
181
bile salts/acids
derived from cholesterol
amphipathic: solubilize fats and cholesterol
hormonal activity
182
bilirubin
derived from heme breakdown
excreted in the stool
183
stellate cells
produce ECM to prevent further scarring to liver
184
Kupffer cells
liver macrophages, primarily breakdown RBCs
185
liver sinusoidal endothelial cells
provide barrier between sinusoids and parenchyma
186
matrix metalloproteinase (MMP)
remodeling proteins
breakdown liver damage, then return after TIMPs to break down collagen
187
Tissue inhibitor of matrix metalloproteinases (TIMP)
inhibit MMPs so stellate cells can lay down collagen
188
Prothrombin time (PTT)
time it takes to clot
189
liver function tests
albumin, bilirubin, PTT
190
liver injury tests
ALT, AST, LDH
non specific
191
A site
amino acid site on 80s ribosome
incoming aa-tRNA binds here
192
P site
peptidyl site on 80s ribosome
holds tRNA bound to nascent position
193
eIF4F (cap binding complex)
three subunit complex that binds 7 methyl guanosine cap on mRNAs
ensures only mRNAs are translated
eIF4E is limiting subunit of cap-binding complex
components: eIF4A, G, E
194
eIF2
escorts initiator methionyl-tRNA to small ribosomal subunit engaged on mRNA
195
eIF1 and eIF3
bind to small ribosome subunit, facilitates binding to eIF4F on mRNA cap
196
Poly A binding protein
interacts with poly A tail and eIF4F bound to CAP
circularizes actively translated mRNA, increases efficiency
197
E site
exit site on 80s subunit, "nake" tRNA binds here after its aa has been added to the protein
198
EF1
elongation factor 1, escorts aa-tRNAs to ribosome
199
EF2
elongation factor 2, hydrolyses GTP and causes translocation of the ribosome
modified and inhibited by bacterial toxins
200
RF
release factor, catalyzes the release of ribosome and new protein from mRNA at stop codon
201
polysome
mRNA covered with multiple, active ribosomes
202
diphtheria toxin (corynebacterium diptheriae) and exotoxin A (psuedomonas aeruginosa)
blocks GTP hydrolysis of EF2
shuts down all translation
203
N-glycosylase
toxins that inhibit ribosome function and cause loss of protein synthesis
shiga toxin (shigella, e. coli), ricin toxin (castor beans)
204
internal ribosome entry site (IRES)
initiation of translation at a site other than mRNA cap
utilized during activation of ER stress response and by RNA viruses to allow some protein translation
205
phosphorylation of eIF2a
inhibits translation
most protein translation stops
transcription of specific mRNA into protein increases
206
4 kinases that can phosphorylate eIF2alpha
PKR-activated by viral dsRNA
GCN5 activated by low amino acids/glucose
HRI- activated by low heme ONLY in immature RBCs
PERK- activated by ER stress or UPR
207
eIF2alpha is an
initiation factor
208
eIF2alpha increases transcription of ATF4 which
increases prorecovery transcription to reduce stress: proteases, chaperones, antioxidants
or
CHOP, causing apoptosis
209
eIF4E is the
limiting subunit for translation
controlling availability will broadly effect
more=pro growth
210
miRNAs
small RNAs that repress translation and cause mRNA degradation
211
post transcriptional gene silencing (PTGS)
therapeutic gene silencing = RNAi
repress translation or destabalize target RNAs
have "hairpin structure" for intramolecular base pairing
212
RNA induced silencing complex (RISC)
uses miRNA to target mRNAs for silencing in PTGS
213
siRNA
short interfering RNA
delivered as drug, processed in cytoplasm, loaded onto RISC, induces mRNA degradation
214
start codon
AUG
215
stop codons
UAA, UGA, UAG
216
how many antibiotics inhibit translation?
1/2
217
aminoglycosides (-mycins)
bind to 30s unit of ribosome and elicit premature termination via incorporation of incorrect amino acid
218
untranslated region (UTR)
sequence in mRNA that are not translated
often contain conserved sequences that affect translation efficiency, mRNA stability
