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Immunology - Unit 1 - Zach H. > Lecture 7: Immune Receptors and Signal Transduction Part I > Flashcards

Lecture 7: Immune Receptors and Signal Transduction Part I Flashcards

1
Q

True or False:

Ligand-binding involves a conformational alteration of the receptor.

A

True

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2
Q

What does signaling require?

A

ligand-induced clustering of receptors, called cross-linking

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3
Q

What does clustering and conformational alterations result in?

A

changes in the cytosolic portion of the receptor that promotes interactions with other signaling molecules

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4
Q

What are nuclear receptors?

A

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

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5
Q

What do the extracellular domains of receptors recognize?

A

soluble ligands or membrane structures of neighboring cells

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6
Q

What does the phosphorylation of tyrosine, serine, or threonine in the cytosolic portion of the receptor do?

A

initiates the signal transduction

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7
Q

What do lipid kinases do?

A

phosphorylate lipid substrates

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8
Q

What do serine/threonine kinases do?

A

phsphorylate serine or threonine residues

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9
Q

What do tyrosine kinases do?

A

phosphorylate specific tyrosine residues

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10
Q

What do phosphatases do?

A

remove the phosphate residue and thus modulate signaling

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11
Q

What enzyme usually plays inhibitory roles in signal transduction?

A

phosphatases

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12
Q

What does the SH2 domain bind to?

A

binds phosphotyrosine

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13
Q

What does SH3 domain bind to?

A

binds proline-rich peptides

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14
Q

What does PH domain bind to?

A

binds inositol phospholipids (e.g., PIP3)

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15
Q

What are the 3 tyrosine kinase families?

A

> Src family (c-Src, Lyn, Ryn, and Lck)

> Syk family (Syk and ZAP-70)

> Tec family (Tec, Btk, and Itk)

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16
Q

What do SH2 domains (Src Homology 2) present?

A

Syk and ZAP-70 tyrosine kinases bind phosphotyrosine motifs in the Ag receptor complex.

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17
Q

How many amino acids are SH2 domains composed of?

A

100 amino acids

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18
Q

How many amino acids are SH3 domains composed of?

A

50 amino acids

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19
Q

What recognizes PIP3?

A

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

20
Q

What do adaptor proteins lack?

A

catalytic activity

21
Q

What are the only domains that adaptor proteins contain?

A

protein-protein interaction domains

22
Q

What are adaptor proteins?

A

Molecular hubs that physically link different enzymes and promote the assembly of complexes of signaling molecules:

  • LAT (Linker for the Activation of T cells)
  • BLNK (B cell linker)
23
Q

Can adaptor proteins contain a few SH2 and SH3 domains?

A

Yes

24
Q

True or False:

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

A

True

25
Q

What can adaptor proteins contain that may serve as docking sites for other signaling proteins with SH2 domains?

A

tyrosine residues

26
Q

What is the mechanism of adaptor proteins in T cell activation?

A

1) LAT is phosphorylated and recurits PLCgamma and the GADS adaptor
2) SLP-76 (proline-rich stretch) associates with GADS via SH3 domain and recruits VAV after being tyrosine-phosphorylated.
3) the VAV proteins are guanine nucleotide exchange factors (GEFs) for GTPases that activate actin cytoskeletal rearrangemtns and transcriptional alterations.

27
Q

What do activating immune receptors have?

A

separate polypeptide chains for recognition and associated signaling polypeptide chains that contain cytosolic ITAMs

28
Q

What do inhibitory immune receptors have?

A

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

29
Q

What type of inhibitory receptor is found on B cells and myeloid cells?

A

Fc-gamma-RIIB

30
Q

In TCR and BCR signaling, what causes activation of an associated Src family kinase?

A

Ag binding and clustering

31
Q

What esposes the tyrosine residues of a ITAM motif in TCR and BCR signaling?

A

conformational change unfolds the cytoplasmic tail of receptor to expose the tyrosine residues of a ITAM motif

32
Q

After activation of an associated Src family kinase due to Ag binding and clustering, what does the Src tyrosine kinase phosphrylate?

A

available tryosines in the ITAMs that was exposed do to the conformational change of the cytoplasmic tail of the receptor

33
Q

How many SH2 domains does Syk tyrosine kinase have that bind to a ITAM phosphotyrosine?

A

has tandem SH2 domains

34
Q

What do activated Syk kinases do?

A

phosphorylate adaptor proteins and enzymes that activate downstream signaling pathways of the immune receptor

35
Q

What is the number of ITAMs phosphorylated a measure of?

A

cytosolic interpretation of Ag affinity to the TCR

36
Q

What results in increasing numbers of phosphorylated ITAMs?

A

stronger or prolonged binding of Ag to the TCR

37
Q

True or False:

Ag affinity of TCR can influence the nature of the cellular response at different stages of differentiation and activation.

A

True

38
Q

What is required for positive selection of T cells in the thymus?

A

weak TCR signals

39
Q

What kind of signal results in negative selection of T cells and their death by apoptosis in the thymus?

A

strong TCR signals

40
Q

What is a coreceptor?

A

transmembrane signaling protein on a lymphocyte that can facilitate Ag receptor activation

41
Q

What can the coreceptor with its signaling enzymes do?

A

increase ITAM phosphorylation and activation of the Ag receptor

42
Q

What are CD4 and CD8 on T helper and cytotoxic T cells, respectively?

A

coreceptors

43
Q

What is the coreceptor on B cells?

A

CR2/CD21

44
Q

What is an example of costimulation in the activation of T cells?

A

CD28-CD80/86

45
Q

In the modulation of signaling by inhibitory receptors, give an example of T cell receptor inhibition.

A

CTLA-4 (analog CD28)

46
Q

What are inhibitory receptors in B cells?

A

CD22 and Fc-gamma-RIIB

Immunology - Unit 1 - Zach H. (12 decks)

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