Exam #2 Flashcards

1
Q

Complement

A

Group of plasma and cell surface proteins that fight invading organisms through inflammation, phagocytosis, and lysis

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2
Q

Mannose Binding Protein (MBP)

A

Binds mannose on surface of bacteria, viruses, and parasites - tags organism for phagocytosis
Activates complement pathway

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3
Q

C-reactive Protein

A

Binds to bacterial surface, acts like opsonin (binds to an Ag to promote phagocytosis)
Activates complement

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4
Q

IL-10

A

Inhibits macrophage activity

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5
Q

IL 12, 18, 23

A

Stimulate NK cells to produce IFN-γ

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6
Q

IFN-α and β

A

Stimulate NK cells and promote class I MHC expression

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7
Q

IFN-γ

A

Produced by NK cells, activates macrophages

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8
Q

TGF-β

A

Stimulates macrophages

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9
Q

MHC

A

Major histocompatibility complex - display antigens

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10
Q

Class I MHC is associated with which responsive T cells?

A

CD8+ T Cells

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11
Q

Class II MHC is associated with which responsive T cells?

A

CD4+ T cells

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12
Q

Which cells express Class I MHC?

A

All nucleated cells

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13
Q

Which cells express Class II MHC?

A

Dendritic cells, phagocytes, B lymphocytes, endothelial cells, thymic epithelium

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14
Q

Src Tyrosine Kinases

A

c-Src, Lyn, Fyn, Lck

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15
Q

Syk Tyrosine Kinases

A

Syk, ZAP-70

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16
Q

Tec Family Kinases

A

Tec, Btk, Itk

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17
Q

SH2 domains

A

bind phosphotyrosine-containing polypeptides

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18
Q

SH3 domains

A

bind proline-rich stretches (hydrophobic areas)

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19
Q

PH domains

A

recognize PIP3 (or other phosphatidylinositol-derived lipids)

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20
Q

CD4 is associated with what type of T cells?

A

T helper

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21
Q

CD8 is associated with what type of T cells?

A

Cytotoxic T cells

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22
Q

Early Events in T Cell Activation

A
  1. Ag recognition - TCR complexes cluster with CD4 or CD8
  2. CD4-associated Lck becomes active, phosphorylates ITAMs of CD3 and zeta chains
  3. ZAP-70 binds phosphotyrosines of zeta chains that self-phosphorylate and are activated
  4. Active ZAP-70 activates (phosphorylates) adaptor proteins such as LAT
  5. Adaptors become docking sites for PLCγ11 and exchange factors that activate Ras and MAP kinases
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23
Q

PI3k

A

converts PIP2 to PIP3

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24
Q

Pro-B cells can eventually differentiate into:

A

follicular B cells, marginal zone B cells, and B-1 cells

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25
Q

Pro-T cells can commit to either:

A

αβ T cells or γδ T cells

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26
Q

Rag-1 and Rag-2

A

regulate BCR rearrangement - at the beginning of B cell life

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27
Q

Notch-1 and GATA-3

A

transcription factors that commit lymphocytes to T cell lineage

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28
Q

H-chain chromosome #

A

14

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29
Q

κ-chain chromosome #

A

2

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30
Q

λ-chain chromosome #

A

22

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31
Q

Order of BCR Diversity gene rearrangement

A
  1. D segment chosen (DJ)
  2. V segment chosen (VDJ)
  3. J chosen (VDJC)
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32
Q

Which segments in BCR and TCR do NOT have D segment?

A

BCR - light chain

TCR - α chain

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33
Q

What nucleotide sequence does RAG add?

A

p (palindromic)

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34
Q

What nucleotide sequence does TdT add?

A

n (nontemplated)

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35
Q

Which is the first polypeptide chain completed in B cells?

A

H

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36
Q

Which is the first polypeptide chain completed in T cells?

A

β

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37
Q

What are the three signals required for proliferation of T lymphocytes?

A
  1. Ag recognition
  2. Costimulation
  3. Cytokines
38
Q

What are the steps in T-Cell Receptor Signaling?

A
  1. LCK is activated, phosphorlyation of CD3 and activation of ZAP70
  2. Activated ZAP70 phosphorylates LAT and SLP76
  3. LAT recruits GRB2, GADS, and PLC1
  4. PLC1 results in production of IP3 and DAG
  5. IP3 increases cytosolic free Ca2+
  6. DAG activates PKC
  7. LAT activates Ras and MAPK
39
Q

CTLA-4

A

Mediates immune checkpoint induced in naive T cells at time of their initial response to Ag - inhibitor

40
Q

PD1

A

Checkpoint that regulates inflammatory responses in tissues

41
Q

IL-2

A

survival signal for T cells - increases expression of anti-apoptotic protein Bcl-2

42
Q

CD69

A

Reduces surface expression of S1PR1 (keeps T cells in lymph node)

43
Q

S1PR1

A

T cells will leave the lymph node

44
Q

When is CD40 (CD154) increased in activated T cells?

A

24-48 hours after Ag recognition

45
Q

When is CTLA-4 (CD152) increased in T cells?

A

24-48 hours after Ag recognition

46
Q

T-bet

A

differentiation of effector cells in CD4+ T cells

47
Q

Blimp-1

A

generation of memory cells

48
Q

What are the two pathways from which memory T cells may develop?

A
  1. linear - some effector T cells “stick around” and become memory cells
  2. divergent - some cells will become memory cells “right away”
49
Q

PLCγ - effect

A

catalyzes hydrolysis of PIP2 to IP3 and DAG

50
Q

IP3

A

stimulates increase in cytosolic Ca2+ (from ER)

51
Q

DAG

A

activates protein kinase C (PKC)

52
Q

Ras*GTP pathway

A

activates ERK –> phosphorylates ELK –> transcribes fos –> combines with Jun and activates AP-1

53
Q

Rac*GTP pathways

A

activate JNK –> phosphorylates Jun –> combines with fos and activates AP-1

54
Q

Five NF-KB proteins

A
p65/RelA 
Rel B 
c-Rel 
p50/NF-KB1 (no activation domain) 
p52/NF-KB2 (no activation domain)
55
Q

Canonical NF-KB pathway

A
  1. p65/cRel + p50 is bound to IKB (NF-KB inhibitor)
  2. activated IKK (IKB kinase) phosphorylates IKB protein and induces polyubiquiniation
  3. protease recognizes IKB-UUUUUUU signal and degrades
  4. NF-KB (the p65/cRel & p50) are released, translocated to nucleus, and activated
56
Q

Alternative NF-KB pathway

A
  1. IKKα activated
  2. Phosphorylates RelB/p100 - partial proteolysis of P100 –> p52 (NF-KB2)
  3. NF-KB2/p52 dimerizes with RelB and translocates to nucleus
57
Q

T-Cell costimulators

A

CD28 and CD80/60

58
Q

Coreceptors on T helper cells

A

CD4

59
Q

Coreceptors on cytotoxic T cells

A

CD8

60
Q

Coreceptors on B cells

A

CD21, CD32, CD 19

61
Q

Difference between coreceptors and costimulators

A

Coreceptors: can bind to same Ag ligand complex recognized by Ag receptor
Costimulators: “second signals” do NOT recognize ligands

62
Q

Inhibitory receptors in T cells

A

CTLA-4

63
Q

Inhibitor receptors in B cells

A

CD22 and FCγRIIB

64
Q

TCR complex structure

A

αβTCR noncovalently linked to CD3 and ζ proteins (signal transducing subunits)

65
Q

Positive co-receptors on B cells

A

CR2 (CD21) complex w/ CD19, CD81 - lower threshold for B cell activation and increase signaling response

66
Q

Negative co-receptors on B cells

A

CD32 - contains ITIM, negatively regulates BCR signaling

67
Q

What is the role of complement in B cell activation?

A

Complex of the CR2 complement receptor - CD19 and CD81 (TAPA-1)

Ag bound to complement fragment C3d can engage both CR2 and membrane Ig, leading to signaling cascades form both BCR and CR2 complexes

68
Q

How does CR2 complex enhance response of BCR?

A

Binding of C3d-CR2 brings CD19 closer to BCR-associated kinases

This phosphorylates CD19 cytoplasmic tail

  1. Enhances phosphorylation of ITAM in Igα and Igβ
  2. Activates PI3-kinase

PI3 kinase activates Btk and PLCγ

69
Q

FcγRIIB

A

inhibits activated B cells, DCs, and macrophages

70
Q

CD22

A

inhibits B cells only

71
Q

SHP

A

SH2-domain containing phosphatase (associates with ITIM of inhibitor receptors)

72
Q

SHIP

A

SH2-domain containing inositol phosphatase (associates with ITIM of inhibitor receptors)

73
Q

What are the two mechanisms of inhibitory signaling?

A
  1. Inhibitory receptors (recruit phosphatases)

2. E3 ubiquitin ligases

74
Q

C3b and C4b activity and effect

A

Activity: opsonization of Ag
Effect: Increase phagocytosis by macrophages and neutrophils

75
Q

C3a and C5a activity and effect

A

Activity: chemotaxis, degranulation
Effect: Attract neutrophils and monocytes to inflammatory sites, release of inflammatory mediators from mast cells and basophils

76
Q

C3b activity and effect

A

Activity: clear immune complexes
Effect: reduce buildup of harmful Ab-Ag complexes

77
Q

C3d activity and effect

A

Activity: B cell activation
Effect: Promote humoral immune response

78
Q

Stages of lymphocyte maturation

A

stem cell –> pro lymphocyte –> pre lymphocyte –> immature lymphocyte –> mature lymphocyte

79
Q

What cytokine stimulates development of T cell progenitors?

A

IL-7

80
Q

What cytokine stimulates development of NK cells?

A

IL-15

81
Q

Which transcription factors induce genes required for B cell development?

A

EBF, E2A, and PAX-5

82
Q

What is the pre-BCR Ag receptor chain?

A

Ig μ heavy chain

83
Q

What is the pre-TCR Ag receptor chain?

A

β chain

84
Q

positive selection

A

process in which cells that have low avidity to self are stimulated to survive
* have low recognition of self-Ags, but can still recognize MHC

85
Q

negative selection

A

T cells: if they have strong avidity to self-Ag, will be eliminated via apoptosis (clonal deletion)
B cells: get 2nd attempt in Ig rearrangement (receptor editing)
* κ to λ light chain
* if receptor editing fails, will have apoptosis

86
Q

Pro B Cell options for proliferation and specialization

A

B1 cells

B2 cells - follicular B2 cells or marginal zone B2 cells

87
Q

B1 cells

A
  • derived from fetal-liver HSCs
  • express limited BCR diversity b/c TdT is not expressed in fetal liver
  • secrete IgM
88
Q

B2 cells

A
  • develop from bone marrow HSCs

* follicular B2 cells or marginal zone B2 cells

89
Q

Follicular B2 cells

A
  • require constant replenishment from bone marrow
  • respond to Ag via T-cell dependent manner
  • undergo Ig isotype switching
  • after T-cell dependent activation, will develop to plasma cells and memory B cells
90
Q

Marginal zone B2 cells

A
  • localize to splenic marginal zone, respond to bloodborne Ag
  • self-renewing
  • respond independent of T cells
  • limited BCR diversity
  • respond to blood borne microbes and differentiate into short-lived IgM secreting plasma cells
91
Q

αβ vs γδ T cells

A

10% T cells = γδ - have limited diversity

90% T cells = αβ