Acute Phase Proteins - Hunter Flashcards
1
Q
PAMPs are recognized by the pattern recognition receptors (PRRs) on what cell types?
A
macrophages
2
Q
microbes can cause damage that elicits (blank)
A
DAMPs
3
Q
f-Met-Leu-Phe receptor recognizes what type of pathogen?
A
bacteria
4
Q
mannose receptor recognizes what type of pathogen?
A
bacteria, fungi, viruses
5
Q
scavenger receptor recognizes what type of pathogen?
A
acetylated lipoproteins on bacteria
6
Q
dectin-1 glucan receptor recognizes what type of pathogen?
A
fungi
7
Q
LPS binding protein and CD14 receptor recognizes what type of pathogen?
A
bacteria
8
Q
production of bradykinin produces what symptom?
A
pain
9
Q
pathogens cause macrophages to release cytokines that do what to the blood vessels?
A
dilation and increased vascular permeability
10
Q
What are the systemic effects of IL6?
A
fever
induces acute phase potein production by hepatocytes
11
Q
What are the local effects of TNF-a?
A
- activates vascular endothelium
- increases vascular permeability
- increased entry of complement and cells to tissues
- increased fluid drainage to lymph nodes
12
Q
What are the systemic effects of TNF-a?
A
- fever
- mobilization of metabolites
- shock
13
Q
What are the local effects of IL-1b?
A
- activates vascular endo
- activates lymphocytes
- local tissue destruction
- increases access of effector cells
14
Q
WHat are the systemic effects of IL-1b?
A
- fever
2. production of IL-6
15
Q
What are the local effects of CXCL8?
A
- chemotactic factor recruits neutrophils and basophils to site of infx
16
Q
What are the local effects of IL-2?
A
activates NK cells
17
Q
Which three cytokines are involved in starting the acute phase response?
A
IL6
TNF a
IL1
18
Q
Which cytokine induces acute phase protein production in the liver?
A
IL6
19
Q
Which two cytokines cause fever?
A
IL1
TNFa
20
Q
Production of CRP and mannose binding lecting will activate (blank)
A
complement opsonization
21
Q
Neutrophil mobilization from the bone marrow during the actue phase will lead to what?
A
phagocytosis of the bug
22
Q
Increased body temp via the hypothal and increased energy metabolism to induce fever have what desired effect?
A
decrease viral and bacterial rep
23
Q
T/F: the acute phase includes up and down regulation of protein expression
A
true
24
Q
T/F: acute phase rxn induces behavioral changes
A
true
25
What four proteins are produced by the liver in response to the acute phase rxn?
1. fibrinogen
2. haptoglobin
3. serum amyloid protein
4. CRP
26
What is the function of CRP?
opsonin on microbes
27
What is the function of serum amyloid A?
recruitment of immune cells to inflammatory sites, induction of enzymes, that degrade the eCM
28
What is the function of serum amyloid P component?
opsonin of microbes
29
What is the function of mannan binding lectin?
mannan-binding lectin pathway of complement activation
30
Fibrinogen, prothrombin, FVIII, vWF all trap microbes in (blank)
blood clots
31
what degrades blood clots?
plasminogen
32
What is the inhibits thrombin and thereby inhibits coag?
Alpha 2 macroglobulin
33
What is the inhibitor of fibrinolysis by inhibiting plasmin?
A-2 macroglobin
34
What binds iron and inhibits microbe iron uptake?
ferritin
35
What prevents the release of iron bound by ferritin or ferroportin?
hepcidin
36
What oxidizes iron, facilitates ferritin, and inhibits microbe Fe uptake?
ceruloplasmin
37
What is the function of haptoglobin?
binds Hgb and inhibits microbe Fe uptake
38
What is the function of orosomucoid alpha-1-acid glycoprotein?
steroid carrier
39
What two things are serpins that dwonregulate inflammation?
A-1-antitrypsin
| A-1 anthichymotrypsin
40
What are the five general functions of the positive acute phase proteins?
1. opsonization and trapping of microorganisms
2. activate complement
3. coagulation and fibrinolysis
4. scavenging Hgb and iron
5. neutralizing enzymes
41
Negative APPs reduce (blank)
inflammation
42
What are some examples of negative APPs?
albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin
43
CRP is in the (blank) familiy of proteins
pentraxin
44
CRP binds (blank) in the cell membrane of microorganisms, including LPS of bacteria
phosphocholine
45
CRP promotes osponization via binding (blank) complement
C1q
46
CRP triggers which complement pathway?
classic
47
How many fold can CRP increase in the APR?
50,000x
48
What do you use CRP for?
marker of systemic inflammation
49
What receptor type agonists in the APR help in inflammation associated coagulation>?
TLR agonists
50
APR induces the expression of (blank) from the surfaces of monocytes and vascular endo cells that leads to coag
tissue factor
51
What is the effect of increases levels of plasminogen activator inhibitor?
prevents the formation of plasmin which decreases fibrinolysis
52
Hepatic synth of protein C and AT-III (inc/dec) during the APR
decrease
53
What are the big picture end results of the APR?
increased thrombin activity
decreased fibrinolysis
fibrin formation
thrombosis
54
circulating cytokines can talk with brain centers via what three things?
1. cerebral endothelium
2. vagal nerve
3. circumventricular organs
55
What is the effect of systemic cytokines on brain centers?
effect local cytokine and prostaglandin synth, produce sickness behavior, and fever
56
(TNFa/PGE2) produces sickness behavior
PGE2
57
T/F: APR causes an increase in expression of anti-inflammatory molecules
true
58
How are the actions of IL1 combatted in the APR?
IL1 receptor agonists
59
How are the actions of TNF-a combatted in the APR?
soluble TNF-a receptors that neutralize it
60
T/F: cortisol, ACTH, epi, and a-MSH downregulated immune responses
true; neuroendocrine hormones
61
The nervous system interacts with the immune system via the (blank)
inflammatory reflex
62
Inflammatory mediators produced by infection or injury activate sensory neurons traveling to the brainstem in the (blank)
vagus nerve
63
The inflammatory reflex sends signals to what organ?
spleen
64
Synapses with (T/B) lymphocytes in the inflammatory reflex activate these cells to release the neurotransmitter acetylcholine
T cells
65
Acetylcholine binds to receptors on (blank) cells and stimulates an intracellular signaling pathway that blocks secretion of inflammatory mediators like TNF-a
macrophages
66
What brain center controls body temp?
hypothal
67
What two nuclei in the hypthal receive temperature signals?
preoptic anterior hypothal and posterior hypothal
68
What are the two types of temp signals the hypothal gets?
1. warmth/cold receptors from peripheral nerves in the skin
| 2. temp of blood in that region
69
When is temp the lowest during the day?
6am
70
When is temp the highest during the day?
4-6pm
71
what is the average temp?
36.8C or 98.2F
72
What are the cutoffs for fever in the morning and afternoon?
morning: >37.2 / 98.9
afternoon: >37.7/99.9
73
T/F: fever is the resetting of the hypothal set point
true
74
Once the hypothalamic set point is raised, neurons in the (blank) are activated and vasoconstriction commences
vasomotor center
75
A febrile individual first notices (blank) in the hands and feet; shunting of blood away from the periphery to the internal organs essentially decreases heat loss from the skin, and the person feels cold
vasoconstriction
76
For most fevers caused by infection, how much does the body temp raise?
1-2 C
77
T/F: a whole microorganism is an exogenous pyrogen
true
78
T/F: ALL gram neg bacteria produce endotoxin pyrogen
true
79
T/F: some cytokines cause fever
true
80
What are endogenous pyrogens?
cytokines that cause fever
81
WHich cytokines cause fever?
```
IL1
IL6
TNFa
CNTF: ciliary neurotropic factor
IFN a/b
```
82
T/F: fever can be present in the absence of an infection
true
83
what is the precursor to PGE2?
arachidonic acid
84
WHat two enzymes are upregulated by pyrogenic cytokines?
COX-2 and mPGES-1 (microsomal PGE synthase 1)
85
pyrogenic cytokines upregulate enzyme activity WHERE in the body (be super specific)
endothelium of the blood vessels in the preoptic hypothalamus
86
PGE2 on the brain side of the endothelium binds to the EP-3 receptors on (blank) cells
Glial cells
87
binding of EP 3 on glial cuases the release of (blank)
cAMP
88
cAMP released by glial cells in the hypothal mediates the change in the (blank)
hypothal set point
89
T/F: hypothal endothelium have distinct PAMPs and DAMPs receptors
true
90
T/F: binding of hypothal PAMP and DAMP receptors mimmics the effect of pyrogenic cytokines
true
91
What three cells are activated by endotoxin, inflammation, or pyrogenic stimuli?
monocytes
macrophages
kupffer cells
92
Reducing the levels of (blank) lowers the elevated hypothal set point
PGE2
93
Antipyretic drugs inhibit what enzyme?
COX2
94
T/F: chronic use of antipyretics and NSAIDs inhibits your ability to produce a fever
false
95
T/F: PGE2 plays no role in normal thermoregulation
true
96
By what mechanism do glucocorticoids reduce fever?
lower PGE2 levesl by inhibiting phospholipase A2; blocks mRNA transcription from cytokines
97
What bugs are especially sensitive to fever?
anthrax, pneumococcal pneumonia, leprosy, and various fungal, rickettsial, and viral diseases
98
How does fever alter antibody production?
increased
99
What temp is considered hyperpyrexia? When do you see it?
rectal temp >106.7, seen with CNS hemorrhages and severe infx
100
At what temp does stroke and death happen?
>43 C
