Plasma Flashcards
(145 cards)
1
Q
What is plasma?
A
Fluid left over after blood cells are removed.
can CLOT
2
Q
Can plasma clot?
A
Yes plasma can clot
it is the fluid left over after blood cells are removed
3
Q
What is serum
A
Fluid left after the blood clot and cells are removed
4
Q
Can serum clot?
A
No the blood clot and cells are removed
no clotting
5
Q
Which organ synthesize the majority of the plasma? Its a major source of plasma?
A
Liver
6
Q
Plasma activates what two systems?
A
Activates
1) Factor 12 (hageman factor) activation
2) Complement Activation
7
Q
Which complement is important to MACs?
A
C5b
8
Q
Which complement is important for phagocytosis?
A
C3b and C5a (the latter to actually initiate phagocytosis)
9
Q
Which complements are anaphylatoxins?
A
C3a, C4a, and C5a
10
Q
Plasmin coverts what complement to its active form?
A
C3 to C3a
11
Q
What protein activates plasmin?
A
Kallikrein
12
Q
What are two important functions of plasmin?
A
1) degrades fibrin
2) coverts C3 to C3a
13
Q
TNF-alpha and IL-1B and IL-6 are cytokines that induce the liver to produce what ?
A
Acute phase proteins
14
Q
List 5 groups of acute phase proteins?
A
1) serum amyloid protein (SAP)
2) C-reactive protein (CRP)
3 Fibrinogen
4) MBL
5) SP-A and Sp-D
15
Q
Which acute phase proteins are part of pentraxin family?
A
CRP c-reactive protein
SAP serum amyloid protein
16
Q
What does pentraxin acute phase protein ‘CRP’ do?
A
opsonization, complement activation
17
Q
What does pentraxin acute phase protein’SAP’ do?
A
opsonization, complement activation, binding of mannose/galactose
18
Q
C reactive protein binds to XXX on bacterial surfaces, acting as an opsonin and also activating what?
A
CRP binds to PHOSPHOCHOLINE on bacterial surfaces acting as OPSONIN and also activating COMPLEMENT
19
Q
MBL binds to mannose residuces on bacteria’s surface acting as an what and also activating what?
A
acting as OPSONIN and activating COMPLEMENT
20
Q
When the liver is stimulated by TNF, IL-6, and IL-1 what three important acute phase proteins does it produce?
A
C-reactive Protein opsonization, complement activation
Serum amyloid protein (SAP) opsonization, complement activation, and mannose-galactose binding
Fibrinogen helps with clotting
21
Q
What stimulants does the liver need to produce actue phase proteins CRP, SAP, and fibrinogen?
A
TNF, IL-1, IL-6
22
Q
High CRP levels in serum are used as a dx measure of what?
A
Ongoing inflammation
BOTH actute and Chronic
23
Q
CRP and SAP besides opsonizing pathogens, also bind to WHAT to facilitate the WHAT ?
A
CRP and SAP also bind to CHROMATIN and facilitate the CLEARANCE OF DAMAGED CELLS
24
Q
Your lab test shows high CRP levels in the serum?
A
Ongoing infection can be BOTH ACUTE and CHRONIC inflammation
25
Complement proteins are present as XXX forms in plasma and are numbered C1-C9?
Compelment proteins are present as INACTIVE forms in PLASMA and are numbered C1-C9.
26
What are 3 pathways to activate complement pathway?
Classical Pathway
MB-Lectin Pathway
Alternative Pathway
27
Describe Classical Pathway
Ag:Ab complexes
28
Describe MB-Lectin Pathway
Lectin binding to pathogen surfaces
29
Describe Alternative pathway
Pathogen surfaces
One of 3 pathways that opsonize and kill pathogen
pathway is activated when C3a binds to pathogen
30
What are the outputs of complement activation?
1) Recruit inflammatory cells
| 2) Opsonize and kill pathogens
31
What complements are associated with the Classical Pathway?
(5 complements) C1q, C1r, C1s, C4, C2
32
What complements are associated with the MBL pathway?
(5 things) MBL, MASP-1, MASP-2, C4, C2
33
What compelments are associated with Alternative pathway?
(3 things) C3, factor B, Factor D
34
C3a and C5a are what?
Peptide Mediators of INFLAMMATION, and PHAGOCYTE RECRUITMENT
35
C3b does what?
Binds to COMPLEMENT RECEPTORS on PHAGOCYTES
Opsonize pathogens
REMOVAL OF IMMUNE COMPLEXES (important for immune diseases)
36
Terminal complement components C5b, C6-C9 does what?
MAC membrane attack complex, LYSIS of certain pathogens and cells
37
Can macrophage phagocytosed a MBL complexed bacteria if only the C3b binds to CR1?
No it also needs C5a to activate the macrophage to phagocytose via CR1
38
Peptide mediators of inflammation, phagocyte recruitment?
C3a C5a
> Increase vascular permeability
> Fluid leakage from blood vessels
> Extravasation of IgG and IgM and compement molecules
> Migration of macrophages PMN leukocytes
> Microbicidal activity of PMNs and macrophages are increased
39
Early events: which compelment is common to the classical and MBL pathway that needs to be activated for the proteolysis of which two compement?
MBL and Classical pathway acts on C1 to activate it so it can cleave C4 and C2 into C4b2b that functions as C3 CONVERTASE
40
What is made of C3 Convertase?
C4b2b from MBL and Classical
| C3bBb from Alternative
41
How is C3 Convertase made?
C3 Convertase is made by C1 active form proteolysing C4 and C2 creating C4b2b which is C3 convertase
can be via MBL or CLassical
42
Which pathway does LPS, Complex polysacchrides, cobra venome stabilize the spontaneous cleavage of WHAT and breakdown of WHat?
ALTERNATIVE PATHWAY: LPS, Complex polysacchrides, cobra venome stabilize spontaneous cleavage of C3 (C3b) and FACTOR B (Bb). C3bBb is a C3 convertase
43
What two complexes are considered as C3 convertases?
C4b2b from MBL and CLassical pathway (activated by C1 activated form)
C3bBb from Alternative Pathway
44
What two things activate the C1 to proteolytically cleave C4 and C2 into C4b2b (C3 convertase)?
Classical:
> Ab:Ag:C1
MBL
MBL:Pathogen:C1
45
MBL directly bind to pathogens and directly activates C1 and thus indirectly initiates the WHAT?
indirectly initiates the Classical Pathway
46
T/F C3 Convertase converts C3 to C3a and Cb
True
C3 convertases
MBL/CLassical C4b2b
Alternate 3bBb
47
C5a and C3a are generated from complement pathway but are also generated via WHAT and WHAT proteases?
Plasmin or lysomal proteases
48
T/F all three pathways MBL, Classical, Alternate can generate C3b.
True
49
C3b from all three pathways can bind to C3 Convertase (C4b2b and C3bBb) to produce C5 convertase (C4b2b3b and C3bBb3b) which cleaves C5 to C5a and C5b. C5b remains attached to complex and forms binding substrate for complement components 1-9. Polymerized WHAT forms a channel in lipid membranes called MAC
polymerized C9
MAC allow fluid and ions to enter > LYSIS of pathogens
50
MAC kills pathogen by
allowing FLUID and IONS to enter causing cell LYSIS
51
Deficiencies that decrease MAC formation cause minor/major immune susceptibilities s?
MINOR , suceptibility to Neisseria
52
decrease MAC formation increase susceptibility to what organism?
Neisseria
53
C3a, C5a, C4a simulate what release from what cells (increases vascular permeability, cause vasodilation), they are called what toxins?
HISTAMINE release from Mast Cells and C3a, C4a, C5a are called anaphylatoxins
54
Anaphylatoxins are which compelments?
C3a C4a C5a
55
Which complements stimulate histamine release from mast cells?
C3a C4a C5a
56
C5a is a anaphylaxtoxins that stimulates histmaine release form mast cells, but it also activates what pathway in neutrophils and monocytes?
The LIPOXYGENASE pathway to produce interleukins and lipoxins
57
Which complement other than recruiting other immune cells also induce mast cells' histamine release also activates the LOX pathway of AA in neutrophils and monocytes?
C5a
58
C5a also activates LOX pathway of AA in which two cells?
Neutrophils and Monocytes
59
C5a is also a what for monocytes and MNP leukocytes?
C5a is also CHEMOATTRACTANT for monocytes, neutrophils, eosinophils, basophils
60
List 3 functions of C5a?
- like C3a and C4a, it is ANAPHYLAXTOXINS and induces histamine release from mast cells
- it also activates the LOX pathway neutrophils and monocytes producing interleukins and lipoxins
- chemoattractant for monocytes, and PMN leukocytes
61
C3b (iC3b is inactive form) act as XXX when fixed to bacterial cell walls and promote which process?
C3b act as OPSONINS fixed to bacterial cell wall and PROMOTE PHAGOCYTOSIS in neutrophils and macrophages
62
Neutrophils can phagocytose T/F
True
63
In general what if you fail to activate complement?
Suceptibilities to FATAL infections
64
If you're deficient in MAC formation your suceptibility to what rises?
deficient in MAC increases susceptibilities to NEISSERIA
65
Deficiencies in C2 and C4 are associated with what disorders such as what because of what?
Deficiencies in C2 and C4 lead to AUTOIMMUNE disorders like LUPUS because IMMUNE COMPLEXES CANNOT be efficently CLEARED
66
Deficiency in what leads to increased Suceptibility to Nisseria?
MAC deficiency
67
Deficiency in what leads to disorders like LUPUS because it can't efficently clear away Immune COmplexes?
C2 and C4
68
Deficiency in the classical pathway leads to what?
Deficiency in C1, C2, C4 of the classical pathway leads to immune complex disease
69
Deficiency in the MBL leads to what?
Bacterial infections mainly in childhood
MBL, MASP1, MASP2, C2, C4
70
Deficiency in Alternative Pathway leads to ?
Factor D and Factor P deficient
Infection with pyogenic bacteria and NEIsseria spp. NO immune complex disease
71
What causes increased susceptibility with pyogenic bacteria adn Neisseria but NO immune-complex disease?
Alternative Pathway
| Factor D and Factor P
72
Deficiency leads to immune-complex disease?
C1, C2, C4
73
Deficiency leads to bacterial infection mainly in childhood?
MBL, MASP1. MASP2, C2, C4
74
C3 deficiency leads to what?
infection with pyogenic bacteria and Neisseria sapp and SOMETIMES IMMUNE COMPLEX DIsease
75
C5-C9 deficiency leads to what infection
Neisseria Spp. only
76
What deficiency leads to infection with pyogenic bacteria, nisseria spp, and sometimes immune complex disease?
C3
77
What leads to to infection with pyogenic bacteria, nisseria spp, but no immune complex disease
Factor D and Factor P of alternative pathway
78
What leads to Nisseria spp only?
C5-C9
79
Key inhibitory point of complement pathway?
C3 and C5
80
How to inhibit C3 and C5?
Decay Accelerating Factor (DAF) or by cleaving C3b (Factor 1)
81
What is Factor 1
C3b
82
What does CiiNh inhibit?
1) C1
2) Hageman Factor (Factor 12)
3) Kallikrein
83
CD59 inhibits what?
Mac formation
84
C1 is inhibited by what?
CiiNH
85
MAC formation is inhibited by?
CD59
86
C3 and C5 are inhibited by what?
DAF
| or cleaving C3b (factor 1)
87
Hageman Factor is inhibited by?
CiiNH which also inhibits Kallikrein and C1
88
Kallikrein is inhibited by?
CiiNH which also inhibits Hageman Factor and C1
89
CiiNH deficiencies lead to what?
Excessive production of vasoactive mediators > episodic edema in Skin, extremeties, intestinal and laryngeal mucosa
90
Excessive production of vasoactive mediators with episodic edema in skin, extremities, intestinal laryngeal mucsoa is associated with what deficiency?
CiiNH
91
What is a spefic mediator of edema in CiiNH deficiency?
Bradykinin
92
Bradykinin is a specific mediator of edema in what deficiency?
CiiNH
93
Bradykinin is a specific mediator of what?
Edema in CiiNH deficiency
94
Besides complemnt activation, Plasma also participates in producing?
clotting factors
detection injury
wound repair
95
Activation of Hageman factor (factor 12 of INTRINSIC clotting pathway) is caused by contact with?
NEGATIVELY charged surfaces like COLLAGEN and BASEMENT MEMBRANE
96
Activation of Hageman factor is extrinsic/intrinsic clotting pathway?
INTRINSIC
97
PRekallikrein activator (factor 12a) converts prekallikrein to what ?
activated Prekallikrein activator (factor 12a) activates Kallikrein by transforming Prekallikrein to Kallikrein
98
Bradykinin causes what?
CONTRACTION OF SMOOTH MUSCLE
increases vascular permeability
dilation of blood vessels
pain
99
What causes vascular permeability, smooth muscle contraction, dilation of blood vessels, and pain
Bradykinin
100
What activates prekallikrein to Kallikrein
Prekallikrein activator (12a)
101
HMWK high molecular weigh kinongen is a cofactor to what?
Factor 12 hageman factor along with NEGATIVELY CHARGED surfaces like collagen and basement membrane and activated platelets to turn into Factor 12a
102
HMWK is a cofactor to what?
promoting the activation of factor XII
103
what is the cofactor to promoting the activation of factor XII?
HMWK kinogen
104
What else besides HMWK acts as a potent activator of the Hageman factor?
Kallikrein
105
List 3 functions of Kallikrein
> convert C5 into C5a
> Activator of Hageman Factor
> activates Plasminogen to Plasmin
106
How do you inactivate Bradykinin?
Kininase in the PLASMA or Angiotensis-converting enzyme when it goes thru the LUNG
107
Intrinsic clotting pathway?
> liver produces Hageman factor
| > inactivated form circulates in plasma until activated by TISSUE DAMAGE
108
Liver produce Hageman factor which circulate in inactive form in plasma until it encoutners tissue damage?
Intrinsic clotting pathway
109
Extrinsic clotting pathway
TISSUE FACTOR from damaged endothelial cells, microparticles, innate immune cells, and or platelets
110
Tissue factor from damaged endothelial cells, microparticles, innate immune cells, and or platelets.
Extrinsic clotting pathway
111
Difference between intrinsic and extrinsic clotting pathways?
intrinsice: Hageman factor produce by the liver circulates in plasma in inactive form until its activated by damaged tissue
Extrinsic: TF from damaged EC cells, microparticles, innate immune cells, and or platelets
TISSUE FACTOR
112
Extrinsic/Intrinsic pathway coverages at where?
Factor 10, or Factor X
113
What coverts prothrombin to thrombin?
Activated factor X
114
Factor X activated coverts what
Prothrombin to thrombin
115
Thrombin converts what to what?
Fibrinogen to fibrin
116
Fibrinogen to fibrin is coverted by
Thrombin
117
Fibrin is converted by blood clot by
Factor 13
118
Factor 13 converts
fibrin to blood clot
119
Chemical released from injury site and by contact with underlying collagen, Platelets are activated and become
spiked and stick to each other and the wound site
120
Initial platelets are activated by
Chemical released from injured cells and contact with broken collagen
121
Bound platelets do what?
Release chemicals that activate and attract other platelets
122
In coagulation fibrinogen is converted to fibrin, which form what?
Fibrin forms a mesh that traps more platelets and RBC producing clots
123
Steps of clotting
1) injury
2) vascular spasm, smooth muscle contracts to prevent blood loss
3) Platelet plug formation
4) coagulation fibrin form mesh trap more platelets and rbc
124
Chemokines and PG both use what receptors?
GPCR
125
Besides generating fibrin, thrombin promotes proinflammatory activation of cell by activating their?
Protease activated receptors
126
How does factor 12a counterbalance clotting?
ACleaves Fibrin via kinin cascasde by Plasmin
127
Plasmin coverts what compelments?
C3 to C3a and (C5)
128
Kallikrein activates what ?
Kallikrein activates plasminogen to plasmin
129
Plasmin does what?
Covernts C3 to C3a and cleaves Fibrin
130
Describe the effects of NO?
> reduce leukocyte adhesion
> reduce platelets adhesion
> vascular smooth muscle relaxation
> vasodilation
131
What reduces:
1) leukocyte adhesion
2) Platelets adhesion
3) vasodilation
4) relaxation of vascular smooth muscle
NO Nitric Oxide
132
NO is generated from what a.a via what enzyme?
L-Arginine by enzyme nitric oxide synthase (NOS)
133
NOS generates what from L-Arginine?
Nitric Oxide
134
List 3 types of NOS enzymes?
eNOS= endothelial NOS calcium dependent
nNOS= neuronal NOS, calcium dependent
iNOS = inducible NOS, calcium INDEPENDENT
- regulated by transcription
- induced by TNF and other cytokines
- in MACROPHAGES
135
What NOS enzyme is calcium dependent?
eNOS
nNOS
neuronal and endothelial NOS
136
Which NOS enzyme is calcium INDEPENDENT?
iNOS in macrophages which are regulated by transcription.
iNOS's expression is induced by TNF and other cytokines
137
* List 4 things NO do?
1) potent vasodilator
2) reduces platelet aggregation
3) inhibits MAST cells inflammation
4) is microbial
138
No contributes to both
ACTIVE pathogen defense and RESOLUTION of inflammation
139
What participates in ACTIVE pathogen defense and RESOLUTION of inflammation?
Nitric Oxide
140
What reduces platelet aggregation, potent vasodilator, microbial, and inhibits mast cell inflammation?
Nitric Oxide
141
Oxygen derived free radicals released by leukocyte is dependent upon?
activation of NADPH oxidative system
142
Species of Oxygen Derived free redicals?
Superoxide anion production, Hydrogen Peroxide, hydroxy radical
143
What interacts with superoxide anion, hydroxyl radiacal, hydrogen peroxide to produce reactive nitrogen intermediates?
Nitrogen Oxide
144
What interacts with Nitrogen Oxide to produce reactive nitrogen intermediates?
superoxide anion, hydrogen peroxide, and hydroxyl radical
145
What is dependent on oxidative NADPH system from activation?
Oxygen derived free radicals released by leukocyte after exposure to microbes, chemokines, cytokines, immune complex, phagocytic challeng
