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Immunology > Lecture 8 (Exam 2) > Flashcards

Lecture 8 (Exam 2) Flashcards

1
Q

These are generally integral transmembrane proteins present on the plasma membrane.

A

Receptors

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2
Q

The extracellular domains recognize soluble _______ or membrane structures of neighboring cells.

A

Ligands

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3
Q

Ligand-binding involves a _________ alteration of the receptor.

A

Conformational

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4
Q

Signaling requires a ligand-induced clustering of receptors, called…

A

Cross-linking

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5
Q

Clustering and conformational alterations result in changes in the cytosolic portion of the receptor that promotes interactions with other ________ molecules.

A

Signaling

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6
Q

________ receptors are intracellular transcription factors that are activated by lipid-soluble ligands (for example, estrogen, progesterone, retinoic acid, etc.) that can cross the plasma membrane.

A

Nuclear

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7
Q

The enzymatic phosphorylation of ______, ______, or ______ in the cytosolic portion of the receptor initiates the signal transduction.

A

Tyrosine
Serine
Threonine

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8
Q

These enzymes are called _______ kinases:

  • Tyrosine kinases phosphorylate specific tyrosine residues
  • Serine/threonine kinases phosphorylate serine or threonine residues
  • Lipid kinases phosphorylate lipid substrates
A

Protein

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9
Q

There are also specific ________ for all types of protein kinases which remove the phosphate residue and thus modulate signaling.

A

Phosphatases

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10
Q

Phosphatases usually play (EXCITATORY/INHIBITORY) roles in signal transduction.

A

Inhibitory

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11
Q

Another protein modification that can facilitate a signaling event is the covalent addition of ________ molecules that either target proteins for degradation or drive signal transduction in many cells.

A

Ubiquitin

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12
Q

Protein signaling molecules can also me modified by the covalent addition of ______ that may promote plasma membrane localization of signaling molecules.

A

Lipids

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13
Q

Another protein modification that can facilitate signaling events are the ________ and ________ of the N-terminal tails of histones. This effects gene expression, DNA replication, and DNA recombination.

A

Acetylation

Methylation

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14
Q

The components of signaling pathways can either be ________ signaling proteins or ________ proteins.

A

Modular

Signaling

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15
Q

Many eukaryotic signal transduction proteins have component-based architectures. They are built from combinations of (1) _________ domains and (2) _________ domain(s).

A

Interaction

Catalytic

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16
Q

In the modular architecture of signaling proteins, intact these proteins display the sophisticated _________ regulation – the alteration of the activity of a protein through the binding of an effector molecule at a specific site.

A

Allosteric

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17
Q

In the modular architecture of signaling proteins, the protein’s output activity is tightly (REPRESSED/ACTIVATED) under basal conditions. However, it can be robustly (REPRESSED/ACTIVATED) by a specific set of input effector ligands.

A

Repressed

Activated

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18
Q

Tyrosine kinase families are key players in the regulation of the immune functions. These families include…

A

Src family
Syk family
Tec family

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19
Q

Signaling molecules are composed of distinct domains, each with a specific binding or _______ function.

A

Catalytic

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20
Q

Who are the members of the Src family?

A

c-Src
Lyn
Fyn
Lck

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21
Q

Who are the members of the Syk family?

A

Syk

ZAP-70

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22
Q

Who are the members of the Tec family?

A

Tec
Btk
Itk

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23
Q

_____ domains are composed of about 100 amino acids folded into a particular conformation that bind to phosphotyrosine-containing peptides in certain proteins.

A

SH2

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24
Q

SH2 domains (x2) are present in _____ and _____ tyrosine kinases, which bind phosphotyrosine motifs in the Ag receptor complex.

A

Syk

ZAP-70

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25
Q

_____ domains are composed of about 50 amino acids folded into a particular conformation that bind to proline-rich stretches in certain proteins.

A

SH3

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26
Q

_____ domains found in the Tec family kinases recognize specific phospholipids.

A

PH (Pleckstrin Homology)

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27
Q

_____ tyrosine kinase recognizes a lipid moiety on the inner leaflet of the plasma membrane termed phosphatidylinositol triphosphate (PIP3).

A

Btk (Tec family)

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28
Q

How many functional domains are there of the Src?

A

Five

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29
Q

This is the 1st domain of Src, it’s on the n-terminal and contains a myristic acid moiety, essential for its localization to the inner surface of the cell membrane.

A

SH4 domain

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30
Q

This is the 2nd domain of Src and provide functional specificity to each member of the Src family.

A

Unique domain

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31
Q

This is the 3rd domain of Src, and it binds proline-rich sequences to mediate intra- and intermolecular interactions.

A

SH3 domain

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32
Q

This is the 4th domain of Src, and it binds phosphorylated tyrosine residues on Src and other proteins.

A

SH2 domain

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33
Q

This is the 5th domain of Src, and it is a catalytic domain.

A

SH1 (kinase) domain

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34
Q

Src can be switched from an inactive to an active state by ___________ state.

A

Phosphorylation

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35
Q

There are two major phosphorylation sites on Src, at ______ (or ______) and at ______.

A

Tyr416 (Y416)

Tyr527

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36
Q

On Src, a more critical phosphorylation site is Tyr527. The phosphorylation of Tyr527 (ACTIVATES/INACTIVATES) Src through the interaction of P-Tyr527 with the SH2 domain, which effectively folds Src up into a closed, inaccessible bundle.

A

Inactivates

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37
Q

Dephosphorylation of Tyr527 opens up the molecule (Src) to an (INACTIVE/ACTIVE) state.

A

Active

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38
Q

A ______ can be auto-phosphorylated, which activates Src by displacing the P-______ from the binding pocket, allowing the substrate to gain access.

A

Tyr416

Try416

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39
Q

Many of the substrates that Src can phosphorylate with its ________ domain form part of signaling process.

A

Kinase (SH1)

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40
Q

Signaling systems often involve a ________ mechanism of sequential phosphorylation and dephosphorylation of proteins in the ________.

A

Cascade

Cascade

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41
Q

Adaptor proteins (DO/DO NOT) have a catalytic activity.

A

Do not

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42
Q

Adaptor proteins contain only _______-_______ interaction domains.

A

Protein-protein

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43
Q

Adaptor proteins are molecular hubs that physically link different enzymes and promote the assembly of complexes of signaling molecules. These proteins include…

A

LAT (Linker for the Activation of T cells)

BLNK (B cell linker)

44
Q

Adaptor proteins may contain several _____ and _____ domains.

A

SH2

SH3

45
Q

Adaptor proteins may contain a few _______ residues that may serve as docking sites for other signaling proteins with SH2 domains.

A

Tyrosine

46
Q

Adaptor proteins often contain _______-rich stretches that can bind other proteins that contain SH3 domains.

A

Proline

47
Q

The essential role of LAT (Linker for the Activation of T cells) has been first demonstrated in _______ T-cell line that express no LAT and are defective in TCR-mediated signaling.

A

Jurkat

48
Q

Jurkat cells transfected with the LAT gene (REDUCE/RESTORE) TCR signaling, indicating that LAT is indispensable for T-cell activation via the TCR.

A

Restore

49
Q

Targeted disruption of the LAT gene in mice revealed a requirement for LAT in ______ development.

A

T-cell

50
Q

Animals lacking LAT exhibited an early arrest of thymocyte development and no mature alpha/beta T-cells were found in their _______ _______ organs.

A

Peripheral lymphoid

51
Q

This is a type of adaptor protein that is an integral membrane protein.

A

LAT

52
Q

This is a cytosolic adaptor protein belonging to the Grb2 family.

A

GADS

53
Q

This is an adaptor protein that has proline-rich domain and SH2 binding domains.

A

SLP-76

54
Q

The ______ proteins are guanine nucleotide exchange factors (GEFs) for GTPases that activate actin cytoskeletal rearrangements and transcriptional alterations.

A

VAV

55
Q

When LAT is phosphorylated, it recruits ________ and the _______ adaptor protein.

A 
Phospholipase C (PLCy) 
GADS
56
Q

Once LAT is phosphorylated and has recruited PLCy and GADS, then _______ associates with GADS via SH3 domain and recruits ______ after being tyrosine-phosphorylated.

A

SLP-76

VAV

57
Q

The TCR complex consists of the ______ ______ non-covalently linked to the _____ and _____ proteins. The association of these proteins with one another is mediated by charged residues in their transmembrane regions.

A

Alpha/Beta TCR
CD3
Zeta

58
Q

Both Alpha and Beta TCR chains have _______-terminal cytoplasmic tails that are 5 to 12 aa long.

A

Carboxyl

59
Q

In Alpha and Beta TCR chains, their cytoplasmic regions are too small to transduce signals so _____ and _____ proteins serve as signal-transducing subunits of the TCR complex.

A

CD3

Zeta

60
Q

_____ and _____ interact with class I and class II MHC molecules (respectively).

A

CD8

CD4

61
Q

CD4 has –

  • _____ extracellular Ig-like domains
  • A ________ transmembrane region
  • A highly _______ cytoplasmic tail 38 amino acids long.
A

Four
Hydrophobic
Basic

62
Q

CD8 is composed to two related chains called _____ and _____.

A

CD8a (alpha)

CD8B (beta)

63
Q

CD8a and CD8B have –

  • ______ extracellular Ig domain(s)
  • A ________ transmembrane region
  • A highly _______ cytoplasmic tail that is about 25 amino acids long.
A

One
Hydrophobic
Basic

64
Q

CD8 binds to class I MHC molecules that also interact with ____ _________.

A

B2 microglobulin

65
Q

Activating immune receptors have separate polypeptide chains for recognition and associated signaling polypeptide chains that contain cytosolic ______.

A

ITAMs (immunoreceptor tyrosine-based activating motifs)

66
Q

Inhibitory immune receptors in the immune system typically have _______ on the cytosolic portion of the same chain that uses its extracellular domain for ligand recognition.

A

ITIMs (immunoreceptor tyrosine-based inhibitory motifs)

67
Q

The FcyRIIB is an (ACTIVATING/INHIBITORY) receptor found on B cells and myeloid cells. It contains the Fc receptor for IgG.

A

Inhibitory

68
Q

FcERI is an (ACTIVATING/INHIBITORY) receptor and contains the Fc receptor for IgE.

A

Activating

69
Q

The TCR complex has _____ signaling chains and _____ ITAMs.

A

6x

10x

70
Q

The number of ITAMs phosphorylated is a cytosolic interpretation of _____ affinity to the TCR. The stronger or prolonged binding of _____ to the TCR results in increasing numbers of phosphorylated ITAMs.

A

Ag

Ag

71
Q

Ag affinity of TCR can influence the nature of the cellular response at different stages of differentiation and activation. (WEAK/STRONG) TCR signals are required for positive selection of T cells in the thymus. (WEAK/STRONG) TCR signals in the thymus results in negative selection of T cells and their death by apoptosis.

A

Weak

Strong

72
Q

The immunologic synapse stabilizes T cell-APC interaction and promotes the migration of adhesion molecules within the T cell membrane. Cytoplasmic tails of some of these molecules contain _______ that initiate a signaling cascade when brought into close proximity.

A

ITAMs

73
Q

The cytoplasmic tails of _____ complex molecules bear ITAMs.

A

CD3

74
Q

The cytoplasmic tails of CD3 complex molecules bear ITAMs. These ITAMs contain four amino acids, indicated as two Xs flanked by ______ and ______. Multiple ITAMs are located at 10-12 amino acid intervals along the cytoplasmic tail. In contrast, the cytoplasmic tails of the TCR lack ITAMs (too short).

A

Tyrosine (Tyr)

Lysine (Lys)

75
Q

A series of stimuli activate NF-kB activation in T and B lymphocytes and other immune cells. Activated _____ phosphorylates _____ on 2 conserved serine residues and induces _____ polyubiquitinylation.

A

IKK
IkB
IkB

76
Q

Ubiquitin induces recognition of IkB-UUUUU by the ________ and causes successive proteolytic degradation.

A

Proteasome

77
Q

Following the IkB degradation, the cytoplasmic NF-kB dimers are released and translocated into the _______, where gene transcription is activated.

A

Nucleus

78
Q

Following the IkB degradation, the cytoplasmic NF-kB dimers are released and translocated into the _______, where gene transcription is activated.

A

Nucleus

79
Q

Put the following steps of the Ras-MAP kinase pathway in order –

A. ZAP-70 phosphorylates/activates membrane-associated adaptor protein LAT.

B. Upon Ag recognition, CD4/CD8-associated Lck is activated.

C. SOS converts Ras-GDP to Ras-GTP that activates MAP kinase and ERK.

D. Lck phosphorylates ITAMs of zeta chains.

E. The cascade activates AP-1.

F. Then, ZAP-70 binds to the phosphorylated zeta chains and become self-phosphorylated and activated.

G. Activated LAT binds GADS adaptor that docks an GTP/GDP exchange factor called SOS.

A
  1. B
  2. D
  3. F
  4. A
  5. G
  6. C
  7. E
80
Q

This is the term that describes T-cell unresponsiveness at the cellular level.

A

Clonal anergy

81
Q

Clonal anergy is a hyporesponsive state characterized by a reduced capacity to synthesize ______.

A

IL-2

82
Q

Anergia T-cells (DO/DO NOT) proliferate in response to appropriate Ag stimulation.

A

Do not

83
Q

Anergy can be broken by exogenous (outside) ______.

A

IL-2

84
Q

Anergy can be induced by substimulatory levels of Ags in the (ABSENCE/PRESENCE) of –

  • CD28:CD80/86 interactions between costimulatory receptors on T-cells and counter-receptors on APCs
  • A costimulatory signal provided by soluble cytokines
A

Absence

85
Q

TCR (signal 1) and CD28 (signal 2) induce different signaling pathways that result in the activation of several transcription factors. In the nucleus, ______ cooperates with AP1 and NF-kB to induce gene expression of a productive immune response.

A

NFAT

86
Q

When TCR engagement (signal 1) occurs in the absence of CD80/CD28 (signal 2) co-stimulation, calcium-mediated signals induce the activation of ______ only. This alone elicits the expression of a distinct set of anergy-inducing genes.

A

NFAT

87
Q

Products of anergy-inducing genes inhibit ______ function at different levels and induce a status of ______ unresponsiveness.

A

T-cell

T-cell

88
Q

The immunologic synapse is initiated by TCR recognition of ______.

A

pMHC

89
Q

TCRs of circulating CD4+ T cells that recognize peptide and MHC class II (pMHC class II) form a (STRONG/WEAK) bond that is stabilized by CD4 molecule, aka the non covalent interaction of CD4 with the non peptide-bonding portion of MHC class II.

A

Weak

90
Q

Adhesion molecules expressed by T-cells (leukocyte function antigen-1, LFA-1) interact with ______ on APC.

A

ICAM-1 (Intercellular Adhesion Molecule 1)

91
Q

The LFA-1 and ICAM-1 complexes move (TOWARD/AWAY) pMHC, TCR, and CD4 complex.

A

Away

92
Q

At the same time as LFA-1 and ICAM-1 complexes, _____ and _____ complexes and costimulatory _____ and _____ move toward the pMHC, TCR, and CD4 complex.

A

CD2
LFA-3
CD28
CD80/86

93
Q

Formation of the pMHC, TCR, and CD4 complex provides a first signal through the TCR-associated ______ complex to the T-cell. The first signal is necessary but NOT SUFFICIENT to stimulate a naive T-cell to proliferate and differentiate.

A

CD3

94
Q

T/F. A second signal (or more properly, a group of signals) provided by one or more co-stimulatory molecules is also required for T-cell activation.

A

True

95
Q

The _____ is composed of three polypeptide chains (y, d, and e) arranged in two pairs (ye and de).

A

CD3

96
Q

The ______ are the regions of signaling proteins that are phosphorylated and dock other signaling molecules.

A

ITAMs

97
Q

These T-cell accessory molecules function in signal transduction by the TCR complex. They are expressed on the T-cell and contain ITAMs.

A

CD3

zeta chains

98
Q

CD4 is a T-cell accessory molecule that functions in signal transduction. It is expressed on the (T-CELL/APC) and its ligand, class II MHC, is expressed on the (T-CELL/APC).

A

T-cell

APC

99
Q

CD8 is a T-cell accessory molecule that functions in signal transduction. It is expressed on the (T-CELL/APC) and its ligand, class I MHC, is expressed on the (T-CELL/APC).

A

T-cell

APC

100
Q

CD28 is a T-cell accessory molecule that functions in signal transduction (co-stimulation). It is expressed on the (T-CELL/APC) and its ligand, which can be B7-1, B7-2, CD80, or CD86, is expressed on the (T-CELL/APC).

A

T-cell

APC

101
Q

CTLA-4 (a homolog CD28) is a T-cell accessory molecule that functions in signal transduction (negative regulation) or T-cell inhibition. It is expressed on the (T-CELL/APC) and its ligand, which can be B7-1, B7-2, CD80, or CD86, is expressed on the (T-CELL/APC).

A

T-cell

APC

102
Q

PD-1 (Program death-1) is a T-cell accessory molecule that functions in signal transduction (negative regulation) or T-cell inhibition. It is expressed on the (T-CELL/APC) and its ligand, PD-L1/PD-L2, is expressed on the (T-CELL/APC).

A

T-cell

APC (also tissue cells and tumor cells)

103
Q

LFA-1 functions in adhesion for the T-cell. Its ligand is ICAM-1. Which one is on the T-cell and which one is on the APC?

A 
LFA-1 = T-cell
ICAM-1 = APC (and endothelium)
104
Q

This tyrosine kinase family has both and SH3 and SH2 domain.

A

Src (Lyn and Lck)

105
Q

This tyrosine kinase family has two SH2 domains.

A

Syk (Syk and ZAP-70)

106
Q

This tyrosine kinase family has and SH2 domain, an SH3 domain, and a PH domain.

A

Tec (Btk and Itk)

Immunology (10 decks)

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