Lecture 16 (Exam 2) Flashcards
(138 cards)
1
Q
Many microbes establish _______ or persistent infections in which the immune response controls but does not eliminate the microbe and the microbe survives without propagating the infection.
A
Latent
2
Q
In many infections, tissue injury and disease may be caused by the host response to the microbe (______ ______) rather than by the microbe itself.
A
Collateral damage
3
Q
T/F. Inherited and acquired defects in innate and adaptive immunity are important causes of susceptibility to infections.
A
True
4
Q
The lack of _______ immune mechanisms leads to very quick expansion of the pathogen.
A
Innate
5
Q
The lack of _______ immunity means the infection is initially controlled by innate immunity, however, the pathogen can not be eliminated completely.
A
Adaptive
6
Q
All Abs are produced by _______ cells in primary (bone marrow) and secondary (LNs) lymphoid organs.
A
Plasma
7
Q
Abs that mediate protective immunity may be derived from _______ or _______ Ab-producing plasma cells.
A
Short-lived
Long-lived
8
Q
Abs perform _______ functions in various tissues distant from their production.
A
Effector
9
Q
The effector functions of Abs are triggered ONLY after Ag binding. The effector functions of Abs are mediated by the heavy chain _______ region (Fc) of Ig molecules.
A
Constant
10
Q
Different Ab _______ serve distinct effector functions.
A
Isotypes
11
Q
The effector functions of Abs against microbes and their toxins are –
1) _______ microbial toxins
2) _______ them for phagocytosis
3) _______ them for Ab-dependent cellular cytotoxicity (ADCC)
4) _______ the complement system
A
Neutralize
Opsonize
Sensitize
Activate
12
Q
Isotype switching results in the production of Abs with distinct _____ regions capable of different effector functions.
A
Fc
13
Q
Affinity maturation increases the ability of Abs to bind to and ________ or eliminate microbes.
A
Neutralize
14
Q
The progressive increase in Ab affinity with repeated stimulation of B cells is one of the reasons for the recommended practice of giving multiple rounds of __________ with the same Ag for generating protective immunity.
A
Immunizations
15
Q
T/F. Abs against microbes and microbial toxins block the binding of these microbes and toxins to cellular receptors.
A
True
16
Q
Influenze viruses use their envelope protein hemagglutinin to infect respiratory epithelial cells. Gram-negative bacteria use pili to attach to and infect a variety of host cells. Abs bind to these microbial structures and interfere with the ability of the microbes to interact with ________ by means of steric hindrance and thereby may prevent an infection.
A
Receptors
17
Q
________ inhibit the spread of microbes from an infected cell to an adjacent uninfected cell.
A
Antibodies
18
Q
________ factors refer to the properties of bacterial gene products that enable a microorganism to cause disease.
A
Virulence
19
Q
_______ block the binding of toxins to cells and thus inhabit the pathologic effects of the toxins.
A
Antibodies
20
Q
Antibodies of the _____ isotype coat (opsonize) microbes and promote their phagocytosis by binding to Fc receptors on phagocytes.
A
IgG
21
Q
Binding of _____ receptors on phagocytes to multivalent Ab-coated particles leads to phagocytosis and the activation in phagocytes.
A
Fc
22
Q
Isotypes _____ and _____ are the most efficient opsonins for promoting phagocytosis via high-affinity FcyRI (CD64).
A
IgG3
IgG1
23
Q
Signals from the _____ receptors activate the phagocytes to destroy these microbes.
A
Fc
24
Q
Signals from the _____ receptors activate the phagocytes to destroy these microbes.
A
Fc
25
The Fc receptor, FcyRI (CD64) has (HIGH/LOW) affinity for Fc.
High
26
The Fc receptor, FcyRII (CD32) has (HIGH/LOW) affinity for Fc.
Low
27
The Fc receptor, FcyRIII (CD16) has (HIGH/LOW) affinity for Fc.
Low
28
The Fc receptor, FceRI, has (HIGH/LOW) affinity for Fc.
High (binds monomeric IgE)
29
Ag-Ab complexes can simultaneously bind to the ______ and ______ receptor through the Fc portion of the antibody. As a consequence of this simultaneous ligation of receptors, _________ associated with the cytoplasmic tail of the _______ inhibit signaling by the BCR complex and block B cell activation.
BCR
FcyRIIB
Phosphatases
FcyRIIB
30
FcR-mediated Ab feedback is a physiologic control mechanism in humoral immune responses. It is triggered by secreted Ab and blocks further Ab production as apposing the activation via ______.
CR2
31
IgE and _______ are used in the killing of helminths. Worms are too large to be engulfed by phagocytes and they are relatively resistant to the microbicidal products of neutrophils and macrophages.
FceRI
***This binds IgE
32
IgE, eosinophils, and mast cells function together to mediate the killing and expulsion of some helminthic parasites. Worms can be kill by a toxic cationic protein, known as the _______ _______ _______ present in the granules of eosinophils.
Major basic protein (MBP)
33
T/F. In Ab-dependent cellular cytotoxicity (ADCC), antibody binds antigens on the surface of target cell. Then, Fc receptors on NK cell recognize bound antibody. Cross-linking of Fc receptors signals the NK cell to kill the target cell. Target cell dies by apoptosis.
True
***See Slide 22
34
The ________ system consists of serum and cell surface proteins that interact with one another and with other molecules of the immune system in a highly regulated manner to generate products that function to eliminate microbes.
Complement
35
The complement system is one of the major effector mechanisms of humoral immunity and is also an important effector mechanism of innate immunity. It is activated by microbes and by _____ that are attached to microbes and other antigens.
Abs
36
Activation of complement involves the sequential ________ of proteins to generate enzyme complexes with proteolytic activity.
Proteolysis
37
The products of complement activation become ________ attached to microbes, to Abs bound to microbes and to other Ags, and apoptotic bodies.
Covalently
38
T/F. Complement activation is inhibited by regulatory proteins that are present on microbe and absent in normal host cells.
False. Complement activation is inhibited by regulatory proteins that are present on normal host cells and absent in microbes.
39
There are three pathways of complement activation, which are...
Classical
Alternative
Lectin
40
Complement activation depends on the generation of two proteolytic complexes, ______ and ______.
C3 convertase
| C5 convertase
41
This proteolytic complex cleaves C3 into two proteolytic fragments called C3a and C3b.
C3 convertase
42
This proteolytic complex cleaves C5 into C5a and C5b.
C5 convertase
43
The alternative pathway is activated by _____ binding to various activating surfaces.
C3b
44
The classical pathway is activated by _____ binding to Ag-Ab complexes.
C1
45
The lectin pathway is activated by binding of a ______ ______ to microbes.
Plasma lectin
46
The late steps of all three complement pathways are (DIFFERENT/THE SAME).
The same
47
T/F. Complement activated by all three pathways serves the same functions.
True
48
Complement is initiated by three major pathways. The ________ pathway is spontaneously and continuously activated. The ________ pathway is induced when antibodies bind to their corresponding antigen. The _______ pathway is triggered by the binding of mannan binding lectin (MBL or MBP-C) to mannose residues on the surface of microorganisms.
Alternative
Classical
Lectin
49
The lectin pathway is triggered by the binding of mannan binding lectin (MBL) to mannose residues on the surface of microorganisms. This activates the _______ and ______, which then cleave ______ and ______.
MASP1 (MBL-associated serine protease 1)
MASP2
C4
C2
50
Complement activation occurs in a sequential manner. The three pathways initiate the formation of enzymes known as _________.
C3 convertases
51
The C3 convertase for the alternative pathway is _______, and for the classical and lectin pathways is _______.
C3bBb
| C4bC2a
52
The C3 convertase enzymes cleave the central complement component _____ and generate the anaphylactic and antimicrobial peptide _____ and the opsonin _____, which can be deposited onto any nearby surface.
C3
C3a
C3b
53
If activation progresses, a new enzyme, the ________, is generated.
C5 convertase
54
The C5 convertase for the alternative pathway is ________, and for the classical and lectin pathways it is ________.
C3bBbC3b
| C4bC2aC3b
55
C5 convertase cleaves _____, releases the potent anaphylactic peptide ______ and generates _____.
C5
C5a
C5b
56
______ can initiate the terminal pathway, which recruits the components _____, _____, _____, and _____ to the surface of the target and inserts the _____ complex as a pore (termed the terminal complement complex) into the membrane, MAC.
```
C5b
C6
C7
C8
C9
C9
```
57
In the alternative pathway, spontaneous ______ of plasma C3 leads to the formation of a fluid-phase C3 convertase and the generation of C3b.
Hydrolysis
58
In the alternative pathway, if the C3b is deposited n the surfaces of microbes, it binds _______ and forms the alternative pathway C3 convertase.
Factor B
59
In the alternative pathway, the C3 convertase cleaves C3 to produce more ______, which binds to the microbial surface and participates in the formation of ________.
C3b
| C5 convertase
60
In the alternative pathway, the C5 convertase cleaves _____ to generate _____ and imitates event in the late steps of complement activation.
C5
| C5b
61
This alternative pathway protein C3 has two components. The first, ______, binds to the surface and functions as an opsonin component of C3 and C5 convertases. The second, _______, stimulates inflammation (anaphylatoxin).
C3b
| C3a
62
This alternative pathway protein creates Bb, which is a serine protease and the active enzyme of the C3 and C5 convertases.
Factor B
63
This alternative pathway protein is a plasma serine protease that cleaves factor B when it is bound to C3b.
Factor D
64
This alternative pathway protein stabilizes C3 convertases (C3bBb) on microbial surfaces.
Properdin (Factor P)
65
The classical pathway is initiated by binding of the ______ to IgG or IgM molecules that bound Ag. Among various IgG subclasses, _____ and _____ are most efficient activators of complement.
C1
IgG3
IgG1
66
C1 is composed of _____, _____, and _____ subunits.
C1q
C1r
C1s
67
In C1 subunits, the ______ binds to Ab, whereas _____ and ______ are proteases.
C1q
C1r
C1s
68
The C1q consists of 6 identical subunits arranged as radial arms. The globular H heads at the end of each arm are the contact regions for ________.
Ig
69
The C1r and C1s form a tetramer composed of two C1r and two C1s molecules. The ends of C1r and C1s contain the ________ domains of these proteins.
Catalytic
70
In the classical pathway, the C1 must bind to two or more _____ portions to initiate the complement cascade.
Fc
71
In the classical pathway, the Fc portions of soluble pentameric ______ are not accessible to C1. After it binds to surface-bound Ags, it undergoes a shape change that permits C1 binding and activation.
IgM
72
In the classical pathway, soluble _____ molecules will also not activate C1 because each one has only one Fc region, but after binding to cell surface Ags, adjacent _____ Fc portions can bind and activate C1.
IgG
| IgG
73
In the classical pathway, activated C1s cleaves the next protein in the cascade, _____, to generate _____.
C4
| C4b
74
In the classical pathway, C4b contains an internal ________ bond that forms covalent bonding with microbe to which the Ab is bound. It ensures that classical pathway activation proceeds on a microbial surface.
Thioester
75
In the classical pathway, activated C1s then cleaves C2 to generate a soluble _____ fragment of unknown importance and a larger _____ fragment that remains physically associated with ______. The resulting ______ complex is the classical pathway C3 convertase.
C2b
C2a
C4b
C4b2a
76
In the classical pathway, cleavage of C3 results in the removal of the small _____ fragment, and _____ can form covalent bonds with cell surfaces. Once it is deposited, it can bind Factor B and generate more C3 convertase by the alternative pathway (C3bBb).
C3a
| C3b
77
In the classical pathway, some of the C3b molecules generated by the classical pathway C3 convertase (C4b2a) bind to the C3 convertase. This forms the ________ complex, which functions as the classic pathway C5 convertase. It cleaves C5 and initiates the late steps of complement activation.
C4b2a3b
78
This classical pathway protein initiates the classical pathway.
C1
79
This classical pathway protein binds to the Fc portion of antibody that has bound antigen, to apoptotic cells, and to cationic surfaces.
C1q
80
This classical pathway protein is a serine protease that cleaves C1s to make it an active protease.
C1r
81
This classical pathway protein is a serine protease that cleaves C4 and C2.
C1s
82
C4 is a classic pathway protein that has two components. _____ stimulates inflammation (anaphylatoxin), and _____ covalently binds to a microbe and complement is activated. _____ also binds C2 for cleavage by C1s.
C4a
C4b
C4b
83
This classical pathway protein is a serine protease and functions as the active enzyme of C3 and C5 convertases to cleave C3 and C5.
C2a
84
This pathway is triggered by the binding of microbial polysaccharides to circulating lectins, such as plasma mannose-binding lectin (MBL).
Lectin pathway
85
MBL binds to _______ residues on bacterial polysaccharides.
Mannose
86
MBL (Mannose-binding lectin) associates with ______, ______, and ______.
MASP1
MASP2
MASP3
(MBL-associated serine proteases)
87
The MASP proteins are structurally homologous to the C1r and C1s proteases and cleavage of _____ and _____ to activate the complement pathway. The subsequent events in the lectin pathway are identical to those that occur in the classical pathway.
C4
| C2
88
This lectin pathway protein is an agglutinin, opsonin, and complement fixing.
MBL
89
This lectin pathway protein forms complex with MASP2 and collectins or ficolins and activates MASP3.
MASP1
90
This lectin pathway protein forms complex with lectins, especially ficolin-3.
MASP2
91
This lectin pathway protein associates with collectins or ficolins and MASP1 and cleaves C4.
MASP3
92
In the late steps of complement activation, the C5 convertases cleave C5 into a small C5a that is released and a C5b fragment that remains bound to the complement proteins deposited on the cell surface. C5b binds _____ and _____.
C6
| C7
93
The C7 complement of the resulting C5b,6,7 complex is hydrophobic, and it inserts into the lipid bilayer of cell membranes, where it becomes a high-affinity receptor for the _____ and the ________ complex is formed.
C8
| C5b,6,7,8
94
The formation of a fully active MAC is accomplished by the binding of _____ that polymerizes at the site of the bound C5b,6,7,8 to form pores in plasma membranes.
C9
95
MAC protein C5 has two components. _____ initiates assembly of the MAC, and _____ stimulates inflammation.
C5b
| C5a
96
This MAC protein is a component of the MAC and binds to C5b and accepts C7.
C6
97
This MAC protein is a component of the MAC and binds to C5b,6 and inserts into lipid membranes.
C7
98
This MAC protein is a component of the MAC and binds to C5b,6,7 and initiates the polymerization of C9.
C8
99
This MAC protein is a component of the MAC and polymerizes to form membrane pores.
C9
100
The ______ is a high-affinity (works early in responses) receptor for C3b and C4b. It promotes phagocytosis of C3b- and C4b-coated particles and clearance of immune complexes from the circulation.
CR1 (CD35)
101
Phagocytes use this receptor to bind and internalize microbes and debris. It also transducer signals that activate the killing mechanisms of the phagocytes. (Binds C3b and C4b)
CR1 (CD35)
102
The _____ (high affinity) binds the cleavage products of C3b (C3d, C3dg, and iC3b). On B cells, _____ enhance the responses of B cells to Ag.
CR2 (CD21)
| CR2 (CD21)
103
On follicular DC, _____ traps iC3-coated Ag-Ab complexes in the germinal centers.
CR2 (CD21)
104
______-______ virus enters B cells via CR2, infects these cells, and can remain latent in infected cells for life.
Epstein-Barr (EBV)
105
The ______, also called Mac-1, is an integrin that functions as a receptor for the iC3b fragment generated by proteolysis of C3b.
CR3
106
CR3 is also involved in the recruitment of leukocytes to sites of infection and tissue injury by binding to ______ on endothelial cells.
ICAM-1
107
The _____ binds iC3b, and the function of this receptor is probably similar to that of CR3.
CR4
108
These soluble complement regulators inhibit MAC formation in all pathways.
Clusterin
| Vitronectin (S protein)
109
This soluble complement regulator causes C3 convertase decay and binds to C3b and causes dissociation of Bb from alternative pathway C3 convertase. Co-factor for Factor I (FI).
Factor H (FH)
110
This soluble complement regulator degrades C3b in all three pathways, and degrades C4b in classical and lectin pathways.
Factor I (FI)
111
This soluble complement regulator activates FB by proteolysis into Bb in the alternative pathway.
Factor D (FD)
112
This soluble complement regulator stabilizes C3bBb and C3bBbC3b convertases in the alternative pathway.
Properdin (FP)
113
This soluble complement regulator prevents activation of classical and lectin pathways.
C1-INH
114
This membrane-associated complement regulator functions in C3 convertase decay in all three pathways.
MCP (Membrane cofactor protein)
115
This membrane-associated complement regulator functions in C3 convertase decay in the classical and lectin pathways.
DAF (Decay-accelerating factor)
116
This membrane-associated complement regulator inhibits MAC in all three pathways.
CD59
117
______ displaces C1r2s2 from C1q and terminates classical activation.
C1-INH
118
The classical C4b2a or alternative C3 convertase can be dissociated by ______. MCP and CR1 function similarly.
DAF
119
In the presence of cell membrane-bound MCP or CR1 cofactors, plasma Factor I proteolytically cleaves _____ attached to cell surfaces. It generates _____, an inactive form of _____.
C3b
iC3b
C3b
120
The Factor ____ can also serve as cofactors for Factor I -- mediated cleavage of C3b.
H
121
Microbes on which complement is activated by the alternative or classical pathway (most sensitive) become coated with ____, ____, or ____ and are phagocytized by the binding of these proteins to specific receptors on macrophages and neutrophils.
C3b
iC3b
C4b
122
The proteolytic complement fragments ____, ____, and ____ induce acute inflammation by activating mast cells, neutrophils, and endothelial cells.
C5a
C4a
C3a
123
The ____ protein generated from C3 binds to CR2 on B cells and facilities B cell activation and the initiation of humoral immune responses.
C3d
124
_____ deficiency is the most common human complement deficiency.
C2
125
_____, _____, and _____ deficiencies are associated with Systemic Lupus Erythematosus. Defects in complement activation lead to failure to clear circulating immune complexes. Complexes may be deposited in blood vessel walls and tissues, where they produce local inflammation.
C1q
C2
C4
126
____ and ____ deficiencies are not usually associated with increased susceptibility to infections because the alternative pathway may compensate the deficiency. ____ deficiency is associated with frequent serious pyogenic bacterial infections that may be fatal.
C2
C4
C3
127
Deficiencies in ______ and ______ result in increased susceptibility to infection with pyogenic bacteria.
Properdin
| Factor D
128
Deficiencies in what complements may result in disseminated infections by Neisseria bacteria?
C5, C6, C7, C8, and C9
129
Complement activation is associated with intravascular ________ and can lead to ischemic injury to tissues.
Thrombosis
130
In an autoantibody-mediated kidney disorder, membranous nephropathy, damage to glomerular epithelial cells can be mediated by the ______ that is generated after Ab binds to a glomerular auto-Ag.
MAC
131
Many pathogens express ______ ______, which can inhibit the alternative pathway of complement by recruiting Factor H, which displaces C3b from Bb.
Sialic acids
132
Other microbes, such as HIV, incorporate multiple host regulatory proteins into their envelopes. For instance, HIV incorporates the GPI-anchored complement regulatory proteins _____ and _____ when it buds from an infected cell.
DAF
| CD59
133
Neonates lack the ability to mount effective immune responses against microbes, and for several months after birth, their major defense against infection is passive immunity provided by maternal ________.
Antibodies
134
Newborns are protected from infection by maternal Abs transported across the _______ into the fetal circulation.
Placenta
135
Transport of maternal _____ across the placenta and across the neonatal intestinal epithelium is mediated by an _____-specific Fc receptor called the neonatal Fc receptor (FcRn).
IgG
| IgG
136
Maternal _____ in breast milk are ingested by the nursing infant.
IgA
137
Ingested _____ and _____ can neutralize pathogenic organisms that attempt to colonize the infant's gut.
IgA
| IgG
138
Abs in ingested milk transported across the gut epithelium of newborns by a specialized process known as...
Transcytosis
