Immune Receptors And Signaling - Thieson (Completed and Verified) Flashcards
What is an immunosuppressant of the PLCγ-NFAT pathway? 2
Cyclosporine
What protein binds to ITAMs (ζ chains)? 2
Docking site for a Syk kinase called Zap-70
What is the inhibitory receptor for NK cells? 2
KIR (binds HLA Class I)
What is the inhibitory receptor for B cells? 2
FcγRIIB (also for myeloid cells)
CD22
What is the inhibitory receptor for T cells? 2
CTLA 4
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)
What are the non-receptor tyrosine kinases? 3
Integrins
Src Kinases
Syk family (Syk & Zap-70)
What does CD40 Ligand and CD40 deficiency result in? 4
T-cell isotype switching deficiencies
What does CD3γ deficiency result in? 4
No T-cell development resulting in early-onset SCID
What does CD8 deficiency result in? 4
Inability to eliminate EBV
What does ZAP-70 deficiency result in? 4
Recurrent infections and poor survival past two years of age
What is ZAP-70? 9
The main Syk kinase that recognizes activated receptors, localization to the proper location, and phosphorylation
What is the role of ITAMs? 10
Contain many phosphorylation sites that ZAP-70 can bind to
What is the main ion involved in the Phospholipase C pathway?
Ca2+
What is activated through PLCγ1 activation? 10
NFAT (TF), NF-κβ (TF), AP-1 (TF)
11 What domains do Src, Syk, and Tec family Kinases have?
Src - Sh2, Sh3
Syk - Sh2, Sh2
Tec - Sh2, Sh3
What does ZAP-70 phosphorylate? 13
LAT (adaptor protein) within T cells
BLNK (adaptor protein) within B cells
What are two regulators of gene expression? 14
AP-1
NF-κβ
What is the main role of Igα and Igβ in B cells? 17
Signal transduction molecule that uses ITAMs
What is the role of complement in Signaling? 19
Utilizes the same pathways as do BCR and TCRs
How do Toll-like receptors on lymphocytes inhibit cell signaling? 20
By stimulating production of proteins called suppressors of cytokine signaling (SOCS) –> IL-1
How does cytokine signaling get turned off? 20
SOCS - suppressors of cytokine signaling
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
