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

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

Cyclosporine

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What protein binds to ITAMs (ζ chains)? 2

Docking site for a Syk kinase called Zap-70

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What is the inhibitory receptor for NK cells? 2

KIR (binds HLA Class I)

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What is the inhibitory receptor for B cells? 2

FcγRIIB (also for myeloid cells)

CD22

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What is the inhibitory receptor for T cells? 2

CTLA 4

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

Tyrosine Kinase Receptor:

PLCγ signaling leads to NF-κβ activation

Iκβ must be degraded for activation (regulator)

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What are the non-receptor tyrosine kinases? 3

Integrins

Src Kinases

Syk family (Syk & Zap-70)

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What does CD40 Ligand and CD40 deficiency result in? 4

T-cell isotype switching deficiencies

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What does CD3γ deficiency result in? 4

No T-cell development resulting in early-onset SCID

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What does CD8 deficiency result in? 4

Inability to eliminate EBV

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What does ZAP-70 deficiency result in? 4

Recurrent infections and poor survival past two years of age

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What is ZAP-70? 9

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

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What is the role of ITAMs? 10

Contain many phosphorylation sites that ZAP-70 can bind to

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

Ca2+

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What is activated through PLCγ1 activation? 10

NFAT (TF), NF-κβ (TF), AP-1 (TF)

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

Src - Sh2, Sh3

Syk - Sh2, Sh2

Tec - Sh2, Sh3

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What does ZAP-70 phosphorylate? 13

LAT (adaptor protein) within T cells

BLNK (adaptor protein) within B cells

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What are two regulators of gene expression? 14

AP-1

NF-κβ

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

Signal transduction molecule that uses ITAMs

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What is the role of complement in Signaling? 19

Utilizes the same pathways as do BCR and TCRs

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

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

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How does cytokine signaling get turned off? 20

SOCS - suppressors of cytokine signaling

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

IL-7

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

JAK-STAT - direct signaling

JAK phosphorylates STAT (trks)

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

Type II cytokine receptor

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

To transcriptionally change the role of the cell

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

Pneumonia Chronic diarrhea Widespread skin rashes

What is the problem in ADA deficiency? 28

Mutation in the gene for adenosine deaminase - autosomal recessive

What are possible treatments for ADA deficiency? 29

Bone marrow transplant Transfusion of RBCs Gene Therapy

What does the mutation of adenosine deaminase cause? 30

Accumulation of deoxyadenosine resulting in increased lung inflammation and damage

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

GPCR transporters

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

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

What chains make up CD3?

a γ and ε chain

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

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

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

PLCγ-calcium-NFAT pathway (NFAT Ras and Rac MAP K Pathways PKC-NFκβ Pathway End-goal --> production of IL-2

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

Igα and Igβ linked covalently via disulfide bonds

What are the Src Kinases in B cell Signaling?

Lyn, Fun, and Blk

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

T cell Signaling (Lak - Adaptor protein) - to produce IL-2 B cell Signaling (Blnk - adaptor protein) - Ig class switching - to produce Abs

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

contains ITIMs which recruit phosphatases

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

to make sure collateral damage to host tissue is limited

What are the two methods by which inhibitory receptors inhibit?

ITIMs (phosphatases) and E3 ubiquination

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

CR2 (CD21)

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

Inhibitory receptor - CTLA4 binds with a higher affinity to CD80/86 than CD28 does (out competes it)

How does TNF cause apoptosis in cells?

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

What is the defect in X-linked SCID?

Defective: IL-7 signaling IL-15 signaling

What do the deficiencies in X linked SCID lead to?

IL-7: T cell number greatly reduced B cells normal, but no CD4 help IL-15: Lack of maturation and proliferation of NK cells

What causes early onset SCID?

CD3γ - No T cell development

What is the most common form of primary immunodeficiency?

X-linked agammaglobulinemia (XLA)

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

B cell tyrosine kinase mutation (btk) Pre-b cell receptors unable to send signals and maturation ceases = no light chain produced

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

Recurrent bacterial infections Inability to eliminate EBV = tumors

What occurs with a CD40/CD40L deficiency?

T cell isotype switching

What occurs in CD8 deficiency?

Inability to eliminate EBV

What occurs in ZAP-70 deficiency?

Recurrent infections and poor survival 2+ years

What mutation causes Autosomal SCI?

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

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

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

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

IL-1 IL-18 TLRs

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

Lung adenosine levels accumulate in lung = inflammation Lowering the receptors could decrease pulmonary symptoms