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HDM - Final > Immune Receptors And Signaling - Thieson (Completed and Verified) > Flashcards

Immune Receptors And Signaling - Thieson (Completed and Verified) Flashcards

1
Q

What is an immunosuppressant of the PLCγ-NFAT pathway? 2

A

Cyclosporine

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2
Q

What protein binds to ITAMs (ζ chains)? 2

A

Docking site for a Syk kinase called Zap-70

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3
Q

What is the inhibitory receptor for NK cells? 2

A

KIR (binds HLA Class I)

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4
Q

What is the inhibitory receptor for B cells? 2

A

FcγRIIB (also for myeloid cells)

CD22

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5
Q

What is the inhibitory receptor for T cells? 2

A

CTLA 4

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6
Q

What signaling pathway results in NF-κβ activation? What must be degraded for its activation? 2

A

Tyrosine Kinase Receptor:

PLCγ signaling leads to NF-κβ activation

Iκβ must be degraded for activation (regulator)

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7
Q

What are the non-receptor tyrosine kinases? 3

A

Integrins

Src Kinases

Syk family (Syk & Zap-70)

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8
Q

What does CD40 Ligand and CD40 deficiency result in? 4

A

T-cell isotype switching deficiencies

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9
Q

What does CD3γ deficiency result in? 4

A

No T-cell development resulting in early-onset SCID

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10
Q

What does CD8 deficiency result in? 4

A

Inability to eliminate EBV

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11
Q

What does ZAP-70 deficiency result in? 4

A

Recurrent infections and poor survival past two years of age

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12
Q

What is ZAP-70? 9

A

The main Syk kinase that recognizes activated receptors, localization to the proper location, and phosphorylation

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13
Q

What is the role of ITAMs? 10

A

Contain many phosphorylation sites that ZAP-70 can bind to

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14
Q

What is the main ion involved in the Phospholipase C pathway?

A

Ca2+

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15
Q

What is activated through PLCγ1 activation? 10

A

NFAT (TF), NF-κβ (TF), AP-1 (TF)

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16
Q

11 What domains do Src, Syk, and Tec family Kinases have?

A

Src - Sh2, Sh3

Syk - Sh2, Sh2

Tec - Sh2, Sh3

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17
Q

What does ZAP-70 phosphorylate? 13

A

LAT (adaptor protein) within T cells

BLNK (adaptor protein) within B cells

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18
Q

What are two regulators of gene expression? 14

A

AP-1

NF-κβ

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19
Q

What is the main role of Igα and Igβ in B cells? 17

A

Signal transduction molecule that uses ITAMs

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20
Q

What is the role of complement in Signaling? 19

A

Utilizes the same pathways as do BCR and TCRs

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21
Q

How do Toll-like receptors on lymphocytes inhibit cell signaling? 20

A

By stimulating production of proteins called suppressors of cytokine signaling (SOCS) –> IL-1

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22
Q

How does cytokine signaling get turned off? 20

A

SOCS - suppressors of cytokine signaling

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23
Q

What cytokine is the ligand (and binds) Type 1 cytokine receptors? 24

A

IL-7

24
Q

What kind of signaling do Type 1 and 2 cytokine receptors use? What type of signaling is this? 24

A

JAK-STAT - direct signaling

JAK phosphorylates STAT (trks)

25
Q

What type of cytokine receptor does IFN (α and β) and IFN-γ use? 24

A

Type II cytokine receptor

26
Q

What is the main idea of TLR effect on a cell? 27

A

To transcriptionally change the role of the cell

27
Q

What are the clinical manifestations of Adenosine deaminase deficiency (ADA)? 29

A

Pneumonia

Chronic diarrhea

Widespread skin rashes

28
Q

What is the problem in ADA deficiency? 28

A

Mutation in the gene for adenosine deaminase - autosomal recessive

29
Q

What are possible treatments for ADA deficiency? 29

A

Bone marrow transplant

Transfusion of RBCs

Gene Therapy

30
Q

What does the mutation of adenosine deaminase cause? 30

A

Accumulation of deoxyadenosine resulting in increased lung inflammation and damage

31
Q

What is the main cell receptor used by chemokines to effect a cell?

A

GPCR transporters

32
Q

How are CD3 and ζ chains associated with the TCR complex? Why are they needed?

A

They’re non covalently linked to the TCR complex

Required for T cell signaling because the TCR has such a short cytoplasmic tail with no ITAMs

33
Q

What chains make up CD3?

A

a γ and ε chain

34
Q

What role does CD4 and CD8 play in the intracellular T cell signaling?

A

They bring the Src kinases closer and help associate with the ζ chains

35
Q

What three pathways do Zap-70 ITAMs activate and what is the overall end-goal?

A

PLCγ-calcium-NFAT pathway (NFAT

Ras and Rac MAP K Pathways

PKC-NFκβ Pathway

End-goal –> production of IL-2

36
Q

What are the two chains of a B cell receptor and how are they linked to one another?

A

Igα and Igβ

linked covalently via disulfide bonds

37
Q

What are the Src Kinases in B cell Signaling?

A

Lyn, Fun, and Blk

38
Q

What is the end-goal of T cell signaling vs B cell Signaling?

A

T cell Signaling (Lak - Adaptor protein)
- to produce IL-2

B cell Signaling (Blnk - adaptor protein)

  • Ig class switching
  • to produce Abs
39
Q

How does CD22 (FcγRIIB) regulate in B cells and Myeloid cells?

A

contains ITIMs which recruit phosphatases

40
Q

Why are inhibitory receptors necessary for NK, B, and T cells?

A

to make sure collateral damage to host tissue is limited

41
Q

What are the two methods by which inhibitory receptors inhibit?

A

ITIMs (phosphatases)

and

E3 ubiquination

42
Q

What are the coreceptors on B cells that allow for phosphorylation and activation of ITAMs?

A

CR2 (CD21)

43
Q

What is the inhibitory receptor on T cells? How does it inhibit the CD28 activating receptor on T cells?

A

Inhibitory receptor - CTLA4

binds with a higher affinity to CD80/86 than CD28 does (out competes it)

44
Q

How does TNF cause apoptosis in cells?

A

TNF binds TNF-R –> formation of death domain

TRADD binds the death domain

TRAF binds TRADD-Death domain-TNF-R

TRAF will either cause activation of AP-1 or Apoptosis

45
Q

What is the defect in X-linked SCID?

A

Defective:

IL-7 signaling

IL-15 signaling

46
Q

What do the deficiencies in X linked SCID lead to?

A

IL-7:
T cell number greatly reduced
B cells normal, but no CD4 help

IL-15:
Lack of maturation and proliferation of NK cells

47
Q

What causes early onset SCID?

A

CD3γ - No T cell development

48
Q

What is the most common form of primary immunodeficiency?

A

X-linked agammaglobulinemia (XLA)

49
Q

What deficiency is present in X-linked agammaglobulinemia (XLA)? What does it not allow

A

B cell tyrosine kinase mutation (btk)

Pre-b cell receptors unable to send signals and maturation ceases = no light chain produced

50
Q

What are symptoms associated with X-linked agammaglobulinemia (XLA)?

A

Recurrent bacterial infections

Inability to eliminate EBV = tumors

51
Q

What occurs with a CD40/CD40L deficiency?

A

T cell isotype switching

52
Q

What occurs in CD8 deficiency?

A

Inability to eliminate EBV

53
Q

What occurs in ZAP-70 deficiency?

A

Recurrent infections and poor survival 2+ years

54
Q

What mutation causes Autosomal SCI?

A

Mutation in the common γ chain of type II cytokine receptors - X linked

55
Q

What is IL-1 receptor pathway? What is its ultimate goal? 27

A

Both TLR and IL-1R once ligated and activated sends signals using adapter proteins to cause colonization of IRAK

IRAK activates NFκβ and AP-1

End-goal –> induces Type 1 IFN transcription

55
Q

What are the ligands for IL-1R and TLR receptor families?

A

IL-1

IL-18

TLRs

55
Q

Why does ADA Deficiency result in lung inflammation? What’s a possible treatment that could reverse this?

A

Lung adenosine levels accumulate in lung = inflammation

Lowering the receptors could decrease pulmonary symptoms

HDM - Final (15 decks)

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