ImmunoSero Lec (Midterms - Soluble Mediators) Flashcards
1
Q
Part of the innate system that helps phagocytic cells to clear pathogens, lyse foreign cells, opsonize and tag invaders for clearance, direct the adaptive immune system to the site of infection.
A
Complement system
2
Q
Amplify inflammatory response having 30 soluble and cell bound proteins
A
Complement system
3
Q
Heat labile substance present in normal nonimmune serum
A
Complement system
4
Q
Complement activation is also considered pro-inflammatory in its ability to (3)
A
- Increase vascular permeability
- Recruit monocytes and neutrophils
- Trigger secretion of regulatory molecules that amplify the immune response
5
Q
In the pro-inflammatory role, this serves as an important link between innate and adaptive immunity
A
complement protein
6
Q
A complex series composed of 30 soluble and cell bound proteins that interact in a very specific way to enhance host defense mechanisms against foregin cells including serum proteins, serosal proteins, and cell membrane receptors
A
Complement protein
7
Q
This is where most plasma proteins are synthesized except C1
A
Liver
8
Q
C1 are components which are mainly produced by these cells.
A
Intestinal epithelial cells
9
Q
Tissue composition of Factor D of Alternative Pathway
A
Adipose tissue
10
Q
Nobel prize laureate which elucidated their nature
A
Jules Bordet
11
Q
Coined the term “complement” because it complements the action of antibody in destroying microorganisms.
A
Paul Erlich
12
Q
3 Complement pathways
A
- Classical
- Alternative
- Mannose Binding Lectin
13
Q
Originally called the properdin system, because the protein properdin was thought to initiate this pathway. However, it is know that properdin’s major function is to stabilize a key enzyme complex formed along the pathway.
A
Alternative Pathway
14
Q
Oldest pathway which is another antibody-independent means of activating complement proteins.
A
Mannos Binding Lectin Pathway
15
Q
The major constituent of the MBL Pathway that adheres to mannose found mainly in the cell walls or outer coating of bacteria, viruses, yeast, and protozoa.
A
Mannos- (mannan-) binding lectin
16
Q
Naming system
- Designated as “b”
- Designated as “a”
A
b: larger fragment
a: smaller fragment
17
Q
In this complement protein, “a” is designated as the larger fragment while “b” is the smaller fragment.
A
C2
18
Q
Number of proteins triggered by antigen-antibody combination in the Classical Pathway
A
9 (C1-C9)
19
Q
Immunoglobulins involved in the Classical Pathway
A
IgM, IgG1, IgG2, and IgG3
20
Q
Initiation of Classical Pathway
A
- Antibody binding to the pathogen
- C1 protein binding to the FC receptor of antibody
21
Q
Most efficient because it has multiple binding sites thus it takes only one molecule attached to two adjacent antigenic determinants to initiate the cascade.
A
IgM
22
Q
Number of IgG molecules that must attach to antigen within 30 to 40 nm of each other before complement can bind.
At least how many IgG molecules would it tkae to ensure that it is close enough to initiate such binding?
A
2 IgG molecules;
At least 1000
23
Q
Within the IgG group, IgG3 is the most effective, followed by these two:
A
IgG 1 then IgG2
24
Q
Stablizes C1q, C1r, and C1s.
A
Calcium
25
First complement component of the classical pathway to bind.
C1
26
The ________________ unit is the part that binds to antibody molecules, whereas the ____________________ subunits generate enzyme activity to begin the cascade.
C1q;
C1r and C1s
27
Composed of **6 strands** that forms the **6 globular heads** with collagen tailed portion. This structure has been likened to a **bouquet with six blossoms** extending outward
C1q
28
As long as this is present in the serum, C1r and C1s remain associated with C1q
calcium
29
**Recognizes the fragment crystallizable region** of two adjacent antibody molecules.
C1q
30
At least how many globular heads of C1q must be bound to initiate the classical pathway?
two
31
Binding for IgG and IgM respectively
IgG - CH2 region
IgM - CH3 region
32
Once this complement is activated, the recognition stage ends
C1s
33
This complement is **extremely specific** because its only known **subtrate is C1s**
C1r
34
A complement that has a **limited specificity** with it only **subtrates being C4 and C2**
C1s
35
Formed by C4a + C2b
C4b2a (C3 convertase)
36
Second-most-abundant complement protein with a serum concentration of approximately 600 ug/mL.
C4
37
C1s cleaves C4 to split off how many amino acid fragment called C4a?
77-amino-acid fragment
38
C4b binds mainly to antigen in cluster that are within this radius of C1
40 nm radius
39
First amplification step in the cascade (The Activation Unit)
C4b binds to antigen in cluster that are within 40 nm radius of C1
40
For every one C1 attached, approximately how many molecules of C4 are split and attached?
30
41
Closely associated with the gene for factor B (alternative pathway) on Chromosome 6
C2
42
True or False.
C2 has a short half-life that serves to keep the reaction localized.
True
43
Written as C4b2a to indicate that complex is an active enzyme by which its half-life is estimated to be between 15 seconds - 3 minutes.
C3 convertase
44
Major and central constituent of the complement system
C3
45
a powerful opsonin
C3b
46
Most significant step in the entire process of complement activation
Cleavage of C3 to C3b
47
Half-life estimation of C3b if not bound to antigen.
60 microseconds
48
Written as C4b2a3b
C5 convertase
49
When this attaches to the cell membrane, **formation of the (MAC)** Membrane Attack Complex begins.
C5b
50
Most **significant biological consequences** of the complement system.
Splitting of C5 and the cleavage of C3
51
Forms the Membrane Attack Complex
C6-C9
52
The MAC is the complex of
C5b-C6-C7-C8-C9
53
In MAC, if the complex is soluble in circulation, it is called ...
sC5b-9
54
Functional pore size of completed MAC unit which would allow ions to pass in and out of the membrane.
70 to 100A
55
This form of IgM is found in plasma
Planar form
56
Form of IgM that will bind to the cell
Staple form
57
Recognition unit
C1
58
activation unit
C2, C4, and C3
59
Forms the membrane attack complex
C5b, C6-C9
60
Activated by **recognition of surface moieties** that are found on pathogens and are **independent of antibodies**
Lectin pathway
61
Proteins that bind carbohydrates (manose)
Lectin
62
One key lectin binds to mannose or related surgars in this manner.
Calcium-dependent manner
63
Plays an important role as a defense mechanism in infancy, during the intercal between the loss of maternal antibody and the acquisition of a full-fledged antibody response to pathogens.
Lectin Pathway
64
Acute phase protein produced in the liver that binds to mannose or related sugars
MBL
65
Bacteria that has mannose in their cell wall
Neisseria
Candida
Salmonella
66
Its deficiency is associated with neonatal pneumonia and sepsis.
MBL
67
MBL-associated serine proteases
MASPs
68
The most common MASP because it will be the one to cleave C4 and C2 to form the C3 convertase
MASP-2
69
**Non-antibody** initiated pathway that is **slower** than the classical pathway and **stabilizes the C3 convertase**.
Alternative pathway
70
First step in Alternative Pathway
Conversion of C3
71
In plasma, this is not stable.
Native C3
72
> A serine protease
> Its only substrate is bound Factor B
> Lowest (2 ug/ml)
> It cleaves Factor B into two pieces: Ba and Bb
Factor D
73
> Alternative pathway convertase
> Capable of cleaving additonal C3 into C3a and
C3b
C3bBb
74
Has a high affinity for C5 and exhibits C5 convertase activity
C3bBb3bp
75
True or False.
C3bBb cannot cleave C5, and is only efficient at cleaving C3.
False. C3bBb **can also cleave C5**, but it is much more efficient at cleaving C3.
76
Where all the pathways meet.
C3
77
> Inactivates C1 by binding to the active sites of C1r and C1s
> Inactivates MASP-2 binding to the MBL-MASP
complex
C1 inhibitor (C1-INH)
78
A serine protease that **inactivates C3b and C4bs** only when bound to these regulators:
C4 binding protein (C4BP)
Complement receptor type 1 (CR1)
Membrane cofactor protein (MCP)
Decay-accelerating factor
Factor 1
79
Causing the cessation of the classical pathway
When **C4BP attaches to cell-bound C4b** (it can dissociate it from C4b2a complexes)
80
Also known as **CD35**, which is a **large polymorphic glycoprotein** found mainly on **peripheral blood cells**, including neutrophils, monocytes, macrophages, erythrocytes, eosinophils, B lymphocytes, some T lymphocytes, and follicular dendritic cells.
Complement receptor type 1 (CR1)
81
82
Ability of cells to **bind complement coated particles**
Immune adherance
83
Also known as **CD46**; found on virtually all **epithelial and endothelial cells** except erythrocytes
Membrane cofactor protein (MCP)
84
> **third main receptor**, and it has a **wide tissue distribution**
> found on peripheral blood cells, on endothelial cells and fibroblasts, and on numerous types of epithelial cells
> capable of **dissociating both classical and alternative pathway** C3 convertases
Decay-accelerating factor
85
Its presence on host cells protects them from bystander lysis and is one of the main mechanisms used in discrimination of self from nonself, because foreign cells do not possess this substance.
DAF
86
Acts by **binding to C3b**, preventing the binding of Factor B and as a cofactor that **allows Factor I to break down C3b**
Factor H
87
Accelerates the dissociation of the C3bBb complex because when this binds to C3bBb, Bb becomes displaced.
Factor H
88
Vitronectin
S protein
89
**CD59**, also acts to **block formation of the MAC** and is widely distrubuted in all cells.
Membrane Inhibitor of Release Lysis (MIRL)
90
Biological functions of Complement Proteins
1. Amplifying the inflammatory response
2. Antigen presentation
3. B cell activation
4. Immunologic memory
91
Effector molecules that causes increased vascular permeability, contraction of smooth muscle, and release of histamine and mast cells.
Anaphylatoxin
92
Most potent anaphylatoxin
C3a and C5a
93
**Direct cells** to the source of antigen concentration
Chemotaxin
94
Most common chemotaxin
C5a
95
Most common complement deficiency
C2
96
Most serious complement deficiency
C3
97
These individuals may be more prone to **recurrent** streptococcal and staphylococcal infections.
C2-deficient individuals
98
Individuals with this deficiency are prone to developing severe, recurrent life-threatening infections with encapsulates bacteria and may also be subject to immune complex diseases which can be lodged in the kidney and result in **glomerulonephritis**
C3 deficiency
99
Its deficiency is associated with lupuslike syndrome
C4 deficiency
100
Its deficiency has no known disease association
C9 deficiency
101
Its deficiency is associated wtih neisseria infections
C5-C8
Properdin
102
Its deficiency is associated with paroxysmal nocturnal hemoglobinuria
DAF and MIRL
103
Its deficiency is associated with recurrent pyogenic infections
Factor H or Factor I
104
Its deficiency is associated with pneumococcal diseases
MASP-2
105
Its deficiency is associated with hereditary angioedema
C1INH (C1 inhibitor)
106
Cells are subject to lysis by means of the bystander effect once the complement system has been triggered
DAF Deficiency
107
Acquired autoantibody
C3NeF (C3 Nephrotic Factor)
108
Medium used for radial immunodiffusion into which specific antibody is incorporated.
Agarose gel
109
This serves as the antigen in radial immunodiffusion.
Serum
110
Radial immunodiffusion is commonly performed for this complement
C3
111
Routinely measured in most clinical labs
C3 and C4
112
Measures concentration according to the **amount of light scattered** by a solution containing a reagent antibody and a measured patient sample
Nephelometry
113
Test with high degree of accuracy
Nephelometry
114
Measurement of C1 inhibitor (C1-INH)
ELISA
115
Measures the amount of patient serum required to lyse 50% of a standardized concentration of antibody-sensitized sheep erythrocytes
CH50
116
Tested by doing a serial dilution adding it to sensitized sheep red blood cells.
CH50
117
Tubes in CH50 are then incubated at what temperature?
37C
118
Best screen for complement abnormalities
ELISA
119
alternative pathway assay
AH50
120
Added to the buffer for AH50
Magnesium Chloride & Ethlylene Glycol Tetraacetic Acid (EGTA)
121
Can detect C3bBbP or C3bP
ELISA
122
In one test system, what coats the strip for classical, alternative, and mannose-binding lectin pathway?
Classical -IgM
Alternative - lipopolysaccharide
Mannose-binding Lectin - mannose
123
124
If not tested within 1 to 2 hours, serum should be
frozen or placed on dry ice
125
Both the CH50 and AH50 are low
Terminal pathway
126
CH50 low, AH50 normal
Classical Pathway
127
CH50 normal, AH50 low
Alternative
128
secrete specific antibodies
B lymphocytes
129
secrete soluble mediators, such as interleukin-2 (IL-2) and other ILs, granulocytemonocyte, colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factor-β (TNF-β)
T lymphocytes
130
lymphocytes that secrete IFN-α 4
NK lymphocytes
131
secrete IFN-α, IL-1, and other ILs, TNF-α, and GM-CSF and monocyte colony-stimulating factor (M-CSF)
Monocytes an macrophages
132
Induces fever, proinflammatory
IL-1
133
Induces production of CRP
IL-6
134
Potent stimulator of neutrophils in chemotaxis
IL-8
135
Enhances NK cell function
IL-12
136
Mediate actopms between leukocytes
Interleukins
137
Interferes with viral replication
Interferon
138
Principal mediator of the acute inflammatory response to gram-negative bacteria & other infectious microbes
Tumor necrosis Factor
139
TNF produced by macrophages, lmphocytes and NK cells when encountering bacteria, viruses, tumor cells, toxins and complement protein C5a
TNF-a
140
TNF produced by CD4 and CD8 positive cells after
exposure to specific antigen
TNF-Beta
141
a cytokine that **interacts with a tyrosine kinase membrane receptor**, the protein product of the cellular oncogene c-kit
Stem cell factor
142
may also play a role in** sustaining the viability and proliferative capacity of immature T cells** in the thymus and mast cells in mucosal tissues
Stem cell factor
143
provide a link between the lymphoid and hematopoietic systems
Colony stimulating factor
144
identified as products of virally transformed cells
Transforming Growth Factor
145
It inhibits the proliferation and differentiation of T
cells and the activation of macrophages
Transforming growth factor
146
These factors were found to **induce phenotypic** transformation in nonneoplastic cells
Transforming Gtowth Factor
