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Immunology > Lecture 9 (Exam 2) > Flashcards

Lecture 9 (Exam 2) Flashcards

1
Q

The _____ is a transmembrane form of an Ab molecule.

A

BCR

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2
Q

Naive mature B-cells express _____ and _____ on the surface.

A

IgM

IgD

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3
Q

Class-switched B-cells and memory B-cells may express _____, _____, or _____ classes of Ab.

A

IgG
IgA
IgE

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4
Q

The BCR is associated with the invariant signaling ____ and ____ molecules. These are disulfide linked to one another and are non-covalently associated with the BCR.

A

Ig-alpha

Ig-beta

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5
Q

Ig-alpha and Ig-beta contain ______ in their cytoplasmic tails which mediate signaling functions.

A

ITAMs

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6
Q

Co-receptors including _____, _____, and _____ associate with the BCR complex especially when both the BCR and one or more of the co-receptors area inked through an Ag-complement or Ag-Ab complex. Depending on which molecules are ligated, signaling by the BCR-Ig-alpha/Ig-beta complex is enhanced or inhibited.

A

CD19
CD21
CD32

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7
Q

_____ functions as the dominant signaling component of B-cells.

A

CD19

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8
Q

_____ is also known as a complement receptor 2 (CR2).

A

CD21

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9
Q

_____/_____ co-receptors positively regulate B-cell activation and serve to lower the Ag threshold for B-cell activation.

A

CD19

CD21

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10
Q

______ co-receptor contains and ITIM and negatively regulates BCR signaling (inhibitory).

A

CD32 (FcyRIIB)

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11
Q

This B-cell co-receptor is a stabilizer for CD19 and necessary for its normal expression.

A

CD81

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12
Q

This B-cell co-receptor is inhibitory and B-cell specific (lacking can cause autoimmunity).

A

CD22

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13
Q

Binding of the lymphocyte to an Ag via receptor provides signal 1, which (IS/IS NOT) sufficient for full B-cell activation (may lead to anergy).

A

Is not

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14
Q

T/F. Co-stimulatory molecules on the surface of B-cells are required for cell-cell interaction and the signal transduction events leading to generation of signal 2.

A

True

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15
Q

B-cell signaling is initiated through the BCR-Ig-alpha/Ig-beta complex and results in phosphorylation of _____ (dephosphorylation of ______). This is followed by an ordered activation of kinases and phosphatases. The cascade is modulated by signals from co-receptors. Second messengers lead to activation of transcription factors followed by activation of the effector function (Ab production).

A

ITAMs

ITIMs

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16
Q

T/F. Signal initiation by Ag occurs by cross-linking of the BCR and is facilitated by the co-receptor for the BCR.

A

True

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17
Q

Ag binding facilitates a conformational change in BCR-associated ______, making them accessible to Src kinases such as Lyn, Fyn, and Blk which are linked by lipid anchors to the inside of the plasma membrane.

A

ITAMs

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18
Q

Activated Src kinases phosphorylate the ITAMs of ____ and _____.

A

Ig-alpha

Ig-beta

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19
Q

Phosphorylated ITAMs of Ig-alpha and Ig-beta provide a docking site for the tandem ____ domains of the Syk tyrosine kinase.

A

SH2

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20
Q

The activated Syk phosphorylates critical tyrosine residues on _____, also known as _____, and other adaptor protein.

A

BLNK

SLP-65

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21
Q

Activated Syk recruits other enzymes that go on to activate PLCy2, Ras and Rac, and Btk. These go on to activate several transcription factors which turn on genes involved in cell growth, differentiation, and survival. These transcription factors are…

A

NFAT
NF-kB
AP-1

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22
Q

Activated Syk recruits other enzymes that go on to activate PLCy2, Ras and Rac, and Btk. These go on to activate several transcription factors which turn on genes involved in cell growth, differentiation, and survival. These transcription factors are…

A

NFAT
NF-kB
AP-1

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23
Q

T/F. The downstream pathways are different in the activation of T-cells and B-cells.

A

False. The downstream pathways are identical.

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24
Q

Cleavage of C3 by the C3 convertases results in the production of C3b that binds covalently to the microbe or Ag-Ab complex. C3b is further degraded into a fragment called _____, which remains bound to the microbial surface or on Ag-Ab complex.

A

C3d

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25
Q

B-cells express a receptor for C3d that is called the _____ or _____.

A

CR2

CD21

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26
Q

The complex of C3d and Ag binds to B-cells, with the BCR recognizing the ____ and CR2 recognizing the micro-bound C3d.

A

Ag

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27
Q

The CR2 is expressed in a complex with _____ with an ITAM, and _____.

A

CD19

CD81

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28
Q

The ______ is important for linking the membrane CD21-CD19-CD81 complex to the cytoskeleton.

A

CD81

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29
Q

Microbial Ags opsonized by C3d can simultaneously engage both the CR2 molecule and BCR. The signaling cascades from both the BCR complex and the CR2 complex greatly enhance B-cell activation as compared with the response to Ag alone. This dual binding lowers the _______ of B-cell activation.

A

Threshold

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30
Q

The enhancement of BCR signaling by CD21-CD19-CD81 complex is mediated by:

1) Phosphorylation of potential substrates in the BCR complex by CD19-bound _____.
2) _______ mobilization by a PI3 kinase dependent mechanism.

A

Lyn

Calcium

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31
Q

T/F. The CR2-CD19-CD81 complex is often called the B-cell co-receptor complex because CR2 binds to Ags at the same time BCR binds to Ag through attached C3d.

A

False. CR2 binds to Ag through attached C3d and BCR binds directly to Ag.

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32
Q

The C3d-CR2 binding brings ______ in proximity to BCR-associated kinases. Its cytoplasmic tail rapidly becomes tyrosine phosphorylated.

A

CD19

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33
Q

CD19 tyrosine phosphorylation follows the efficient recruitment of _____ kinase that amplifies BCR signaling by greatly enhancing the phosphorylation of ITAM tyrosine in Ig-alpha and Ig-beta.

A

Lyn

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34
Q

Phosphorylated CD19 also activates _____-kinase, which in turn further augment signaling initiated by Ag binding to BCR. It activated Btk and PLCy2 on the inner leaflet of the plasma membrane.

A

PI3

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35
Q

The net result of co-receptor activation is that the response of the Ag-stimulated B-cell is greatly (ENHANCED/REDUCED).

A

Enhanced

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36
Q

B-cells activation is tightly controlled to limit immune responses against microbes in order to avoid collateral damage to host tissues. Inhibition of signaling is essential to prevent uncontrolled lymphoproliferation and ________.

A

Inflammation

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37
Q

The inhibitory signals in lymphocytes is mediated primarily by inhibitory receptors and also by enzymes known as ______ ______ ligases.

A

E3 ubiquitin

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38
Q

Inhibitory receptors typically recruits and activate ________ that counter signaling events induced by Ag receptors.

A

Phosphatases

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39
Q

An inhibitory receptor has an extracellular ligand-binding domain and a cytosolic ______ motif.

A

ITIM

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40
Q

Ligand binding of an inhibitory receptor results in _______ of the ITIM tyrosine by a _____ family kinase.

A

Phosphorylation

Src

41
Q

The phosphorylated ITIMs recruit an _____ domain-containing tyrosine ________ that can attenuate immune receptor signaling.

A

SH2

Phosphatase

42
Q

The key inhibitory receptors in B-cells include…

A

FcyRIIB (CD32)

CD22

43
Q

_______ is an important attenuator (inhibitor) of signaling in activated B-cells, DCs, and macrophages.

A

FcyRIIB (CD32)

44
Q

_______ is a B-cell specific inhibitor (expressed only on B-cells).

A

CD22

45
Q

Phosphorylated ITIMs recruit SH2 domain-containing tyrosine phosphatases such as _____ and _____. These remove phosphates from PIP3 and thus inhibits PI3-kinase activity in lymphocytes, NK cells, and innate immune cells.

A

SHP

SHIP

46
Q

________ is a protein (76 aa) that is transferred to lysine residues on specific substrates that are recognized by specific E3 ubiquitin ligases.

A

Ubiquitin

47
Q

A _________ chain can be generated by attachment of other ubiquitin molecules.

A

Polyubiquitin

48
Q

The shape of the ubiquitin chain is important and depends on which ______ residue on the preceding ubiquitin molecule in the chain is used.

A

Lysine

49
Q

If lysine in position ____ of the first ubiquitin is used, a lysine-____ type ubiquitin chain will be generated and the protein will be targeted for proteasome degradation.

A

48

48

50
Q

If a lysine-____ ubiquitin chain is used, proteins are not targeted for degradation.

A

63

51
Q

T/F. The engagement of peptide-MHC (pMHC) class II complexes with the TCR:CD3:CD4 complex is a first signal to a CD4+ T-cell. The CD28:CD80/86 interaction provides co-stimulation to the CD4+ T-cell.

A

True

52
Q

The TCR activation and CD28-CD80/86 co-stimlation results in secretion of _____ by activated T-cells.

A

IL-4 (type of cytokine)

53
Q

The engagement of ______ (on APC/B-cell) and ______ (on T-cell) provides co-stimulation to the B-cell.

A

CD40

CD40L (CD154)

54
Q

The CD40:CD40L co-stimulation results in expression of _____ by B-cells.

A

IL-4R

55
Q

Superposition of the signals coming from _____, _____:_____, and _____ pathways lead to activations of B-cell.

A

BCR
CD40:CD40L
IL-4R

56
Q

_______ come from cell micro-environment and control the fate of naive CD4+ T-cell activation.

A

Cytokines

57
Q

All cytokine receptors consist of one or more __________ proteins.

A

Transmembrane

58
Q

The extracellular domains of cytokine receptors are for cytokine binding, whereas cytoplasmic tails are responsible for initiation of intracellular ________.

A

Signaling

59
Q

The signaling pathways of cytokine receptors are activated by ligand-induced receptor _________.

A

Clustering

60
Q

There are 5 main classes of cytokine receptors. Except ________ receptors, the four receptor families include single-pass transmembrane proteins.

A

Chemokine

61
Q

Receptors for different cytokines are classified into families on the basis of:

1) Conserved __________ domain structures
2) ________ mechanisms

A

Extracellular

Signaling

62
Q

Type ____ cytokine receptors typically consist of unique ligand-binding chains and one or more signal-transducing chains, which are often shared by several receptors for different cytokines.

A

One

63
Q

Type I cytokine receptors family can be divided into subgroups based on structural homologies or the use of shared signaling chains. The type I cytokine receptors are…

A 
IL-2
IL-4
IL-7
IL-9
IL-15
IL-21
64
Q

All of the type I cytokine receptors engage _______ signaling pathways.

A

JAK-STAT

65
Q

Many type I and type II cytokine receptors lack a protein tyrosine kinase domain and rely on ______ to initiate the cytoplasmic signal transduction cascade.

A

JAKs

66
Q

For type I or type II cytokine receptors, ligand binding induces oligomerization of the receptors, which then activates the cytoplasmic receptor-associated _____.

A

JAKs

67
Q

JAKs subsequently phosphorylate ________ residues along the receptor chains with which they are associated.

A

Tyrosine

68
Q

For type I or type II cytokine receptors, the phosphotyrosine residues are a target for a variety of ______ domain-containing STAT proteins.

A

SH2

69
Q

After binding to the receptor chains, (JAKS/STATS) are phosphorylated by the (JAKS/STATS) proteins.

A

STATs

JAKs

70
Q

Phosphorylation enables the STAT proteins _______ and translocate into the nucleus, where they alter the expression of cytokine-regulated genes.

A

Dimerize

71
Q

Type II cytokine receptors are also called the ________ receptor family.

A

Interferon

72
Q

Type ____ cytokine receptors consist of one ligand-binding polypeptide chain and one signal-transducing chain.

A

Two

73
Q

All of the type II cytokine receptors engage _______ or ______ and _______ signaling pathways.

A

JAK-STAT
JAK-STAT
Tyk-STAT

74
Q

Type II cytokine receptor family includes receptors for…

A

IFN-alpha/beta
IFN-y (gamma)
IL-10

75
Q

_____ is a protein encoded by the TYK gene that mediates immune signaling. Similar to JAKs, this protein activates STATs transcription factors.

A

TYK2

76
Q

This cytokine receptors are part of a large family of preformed trimers.

A

TNF receptor family

77
Q

This cytokine receptor family have conserved cysteine-rich extracellular domains and shared intracellular signaling mechanisms that typically stimulate gene expression.

A

TNF receptor family

78
Q

Signaling of some TNF receptors may lead to…

A

Apoptosis

79
Q

Most important of the TNF receptors are…

A

TNFRI
TNFRII
CD40
Fas (First Apoptosis Signal)

80
Q

The ligands for TNF receptors also form trimers. Some of these ligands are membrane bound (for ______) whereas others are soluble (for ______).

A

TNFRII

TNFRI

81
Q

Ligation of the TNFRI results in the recruitment of an adaptor protein called ______, which in turn can activate factor _____ that acts as E3 ubiquitin ligase. Downstream consequences include the activation of the NF-kB pathway and the JNK MAP kinase pathway or the induction of apoptotic death.

A

TRADD

TRAF

82
Q

The members of the IL-1 receptor family (TLRs) share a conserved cytosolic sequence, called the ______/______ (TIR) receptor domain.

A

Toll-like/IL-1

83
Q

The engagement of the IL-1R or TLRs results in receptor dimerization and the recruitment of _______ adaptor containing TIR (Toll/IL-1 Receptor) domain.

A

MyD88

84
Q

The TIR-containing adaptors (MyD88) link TLRs/IL-1R to different members of the _______ family.

A

IRAK

85
Q

IRAKs in turn link adaptors to ______, an E3 ubiquitin ligase required for NF-kB activation.

A

TRAF6

86
Q

IL-1R signaling also include ______ kinase activation and the phosphorylation of _____ and _____, inducers of type I interferon transcription.

A

MAP
IRF3
IRF7

87
Q

Binding of a _______ to its receptor induces many different cellular responses like:

  • Adhesion
  • Migration
  • Chemotaxis
  • Cellular shape changes
  • Reorganization of the actin cytoskeleton
  • Upregulation of integrin expression
  • Integrin activation
A

Chemokine

88
Q

The engagement of a ______ by a chemoattractant results in an activation of the associated G-protein.

A

GPCR (G-Protein Coupled Receptor)

89
Q

What kind of pathway do chemokine receptors use?

A

GPCR

90
Q

When a chemokine agonist binds to the extracellular side of its receptor, it stabilizes the receptor into a confirmation that activates ________ G-proteins inside the cell.

A

Heterotrimeric

91
Q

The G-proteins have three subunits: ____, ____, and ____.

A

Alpha (a)
Beta (B)
Gamma (y)

92
Q

In a G-protein, the _____ subunit interacts with the G-protein _____ subunit which forms a tight complex with the _____ subunit. In the inactive state, the _____ subunit binds GDP.

A

G-alpha
Beta
Gamma
G-alpha

93
Q

Upon ligand binding and activation of the GPCR, ______ dissociates from G-alpha.

A

GDP

94
Q

GDP is then replaced by _____, and _______ dissociates from the receptor and from G-Beta/Gamma, and both of these complexes subsequently activate a variety of downstream effectors that ultimately lead to the physiological response.

A

GTP

G-alpha-GTP

95
Q

The G-alpha subunit inhibits some ______ ______ leading to a decrease of intracellular _____-levels and _____-dependent protein kinase activity.

A

Adenylyl cyclase
cAMP
cAMP

96
Q

The G-Beta/Gamma-complex activates _____ that induces the activation of PI3Ky. This complex also activates _____.

A

Ras

PLC

97
Q

PLC hydrolyzes _____ to generate _____, which mobilizes calcium from non-mitochondrial stores.

A

IP2

IP3

98
Q

_____ activates PKC (along with calcium from IP3).

A

DAG

Immunology (10 decks)

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