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A/I Board Review > Cell Signaling > Flashcards

Cell Signaling Flashcards

1
Q

Which is on the cell surface of all developing B cells, disappearing only when terminally differentiating into plasma cells?

A. CD19
B. CD20
C. CD21
D. IgD
E. IgM
A

CD19

CD20 is also absent from plasma cells but is not present on early pro-B cells

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2
Q

What process can rescue immature B cells that express highly self-reactive antibodies ?

A

RECEPTOR EDITING (elimination of self-reactive Ig): Replacement of an autoreactive receptor recognizing a multivalent self-antigen with a new receptor that is not self-reactive–requires ongoing RAG expression so that light-chain gene rearrangement can continue replacing self-reactive light-chain gene until no additional light-chain V and J gene segments are available for recombination

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3
Q

Which immunoglobulin isotype can be expressed without further gene rearrangement?

IgA
IgD
IgG
IgE

A

IgD

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4
Q

Which stage of antibody construction marks the pre-B cell?

A. Expression of IgM on surface
B. Rearrangement of D to J
C. Expression of cytoplasmic mu heavy chain
D. Rearrangement of V to DJ

A

C. Expression of cytoplasmic mu heavy chain

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5
Q

Which protein is directly responsible for the introduction of random nucleotide sequence during early B cell development?

A

TdT - terminal deoxynucleotidyl transferase

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6
Q

Which immunoglobulin type activates complement the best?

A

IgM

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7
Q

What molecular process allows the same set of antibody genes to produce both a soluble protein and a membrane bound receptor?

A

Alternative Splicing

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8
Q

Which innate immune pathway is most likely defective in a patient with severe rhinoviral infection leading to death?

TLR signaling
RLR signaling
CLR signaling
NLR signaling

A

RLR (RNA-sensing RIG-I-like receptors)

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9
Q

Which proteins are recruited when an ITIM is phosphorylated?

A

SHP-1, SHP-2, SHIP (inhibitory phosphatases)
SHP’s are protein tyrosine phosphatases
SHIP is an inositol phosphatase that removes 5’ phosphate from PIP3

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10
Q
  1. Name the tyrosine kinase that is critical for initiating the TCR signaling cascade.
  2. Where is it located?
  3. How is this kinase regulated?
A
  1. Lck
  2. cytoplasmic domain of CD4 or CD8 coreceptor
  3. CD45 dephosphorylates Lck, which activates Lck. Csk phosphorylates Lck, which deactivates Lck.
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11
Q

What does Lck do?

A

CD4/CD8 coreceptor activates, Lck then phosphorylates ITAMs on CD3 complex, which allows ZAP-70 to bind to CD3-zeta

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12
Q

What does ZAP-70 do?

A

Binds to phosphorylated-CD3-zeta (CD3zeta previously phosphorylated by Lck), which activates ZAP-70 and allows ZAP-70 to phosphorylate adapter proteins (LAT, SLP-76) leading to assembly of enzyme scaffolds, including enzymes: PLCgamma1, PI3-Kinase, Grb2/SOS

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13
Q

What does PLCgamma do and how is it activated?

A

generates IP3 and DAG. Activated by first being recruited to LAT (when LAT is phosphorylated by ZAP-70), then ITK or BTK will phosphorylate PLCgamma, leading to activation of PLCgamma.

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14
Q

What do DAG and IP3 do?

A

DAG -> activates PKC-theta -> activates CARD11 (CARMA1) complex -> IKK -> IkBalpha -> activates NFkB

IP3 -> Ca++ intracellular increase -> activates calcineurin -> calcineurin dephosphorylates NFAT -> NFAT goes into nucleus

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15
Q

What do Ras-GRB and SOS do?

A

Guanine exchange factors that are recruited to activated-LAT scaffold -> GTP/GDP exchange on Ras and Rac -> MAP kinases -> AP-1 transcription factor

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16
Q

What does PI3-Kinase do? How is it activated?

A

generates PIP3, which leads to Akt, mTOR pathway activation, and PLC-gamma activation
PI3K is activated by either recruitment to phosphorylated scaffold (LAT), or by costimulatory receptor CD28 interacting with CD80 or CD86

17
Q

Which Fc receptor provides feedback inhibition of cellular responses? What is it’s CD marker?

A

FcγRIIB = CD32

*FcγRIIA and FcγRIIC thought to activate cells and help with phagocytosis

18
Q

Which Fc receptor has the highest affinity for IgG? What is it’s CD marker?

A

FcγRI = CD64, a high-affinity phagocyte receptor that strongly binds IgG1 and IgG3.

*FcγRII is CD32, and FcγRIII is CD16 (multiples of 2?)

19
Q

What is the T cell survival signal and what does it bind?

A

IL-2, binds to IL2r = CD25

20
Q

What do the following costimulatory proteins, found on T-cells, bind to, and what are their functions?

  1. CD28
  2. CTLA4
  3. ICOS
  4. CD40L
  5. PD-1
A
  1. CD80/86 (B7-1/B7-2); activation of naive cells
  2. CD80/86 (B7-1/B7-2); inhibitory through ITIM
  3. ICOSL; Ab class switching (activation)
  4. CD40; Ab class switching (activation) by stimulating AID
  5. PD-L1/PD-L2; inhibitory through ITIM, cell death
21
Q

What molecules do NKT cells recognize? What receptors are such molecules presented on?

A

Lipids; presented on CD1d receptors.

22
Q

What does CD58 do?

A

CD58 (LFA-3 or lymphocyte function-associated antigen) on APCs binds to CD2 (LFA-2) on T cells to strengthen adhesion

23
Q

What does CD21 (CR2) do?

A

provides signals that enhance BCR if the antigen is opsonized by C3b. On the surface, C3b is bound to the antigen and degraded to C3d, which is the ligand for CD21. CD21 forms a complex with CD19 and CD81 to help activate B cells.

24
Q

Which Fc receptor is expressed on NK cells and binds to antibody-coated cells, allowing cytotoxic killing of the infected cell by ADCC?

A

FcγRIII (CD16)

25
Q
  1. Which toll-like receptors (TLRs) are endosomal and mainly detect nucleic acids?
  2. Which TLRs are expressed on the surface and detect PAMPs in the extracellular environment?
A
  1. TLRs 3, 7, 8, 9
    - TLR 3 = dsRNA [MyD88 independent]
    - TLR 7/8 = ssRNA, short dsRNA, imidazoquinolones
    - TLR 9 = Unmethylated CpG motifs (bacteria and DNA viruses)
  2. TLRs 1, 2, 4, 5, 6
    - TLR 1:TLR 2 heterodimer = lipoarabinomannan, lipopeptides (mycobacteria, bacteria)
    - TLR 2:TLR 6 heterodimer = Zymosan (fungi), peptidoglycan, HSP70
    - TLR 4 = LPS, lipotechoic acids, HSP70 [MyD88 or MyD88 independent]
    - TLR 5 = Flagellin
26
Q

What are the major transcription factors associated with the following CD4 T cell subsets? What cytokines induce their development?

  1. Th1
  2. Th2
  3. Th17
  4. Treg
A
  1. Tbet, STAT4. Induced by IL-12, IL-18, IFN-γ
  2. GATA3, STAT6. Induced by IL-4, IL-25, IL-33, TSLP
  3. RORγT, STAT3. Induced by IL-6, IL-1, IL-23
  4. FOXP3, STAT5. Induced by TGFβ
27
Q

What receptors are class I MHC-like molecules that present nonpeptide (lipid and glycolipid) antigens?

A

CD1 (isoforms CD1a-CD1e)

28
Q
  1. Which subtype of mast cells expresses C5aR (CD88)?

2. This mast cell subtype also responds to opiates/vancomycin through what receptor?

A
  1. MCtc

2. MRGPRX2 (Mas-related G-protein coupled receptor member X2)

A/I Board Review (8 decks)

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