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Immunology Exam 2 > Lecture 8 > Flashcards

Lecture 8 Flashcards

1
Q

What are the 2 types of plasma membrane receptors? Give 2 examples of each

A

GPCRs
Ex. Chemokines and prostaglandins

RTKs (or Src kinases)
Ex. Insulin (RTK)
Ex. Integrin (Src)

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2
Q

Describe nuclear receptors and give an example.

A 
Inside cell (usually in the nucleus)
Can only bind lipid soluble ligands

Ex. Glucocorticoids/Vitamin D

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3
Q

During signal transduction, describe Tyrosine, Serine, Threonine receptors.

A

They are phosphorylated by Tyrosine, Serine, and Threonine kinases.

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4
Q

What are 3 other modifications for signal transduction?

A

Ubiquitination
Addition of lipids
Acetylation/methylation

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5
Q

Describe Tyrosine Kinase family receptors. What are the 3 domains they contain?

A

All are made of SH3, SH2, and PH domains or some combo of them

  • SH2 phosphorylation
  • SH3: Proline rich peptides
  • PH:PI3 or phosphatidylinositol (aka lipids)
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6
Q

What are the 3 types of Tyrosine Kinase receptors?

A

Src
Syk
Tec

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7
Q

Describe Src tyrosine receptor in terms of their domains. Give 2 examples.

A

Src (ex. Lyn and Lck)
SH3 domain
SH2 domain

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8
Q

Describe Syk tyrosine receptor in terms of their 2 domains. Give 2 examples.

A

Syk (Syk and ZAP-70)

SH2 x 2 domains

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9
Q

Describe Tec tyrosine receptor in terms of their 3 domains. Give 2 examples.

A

Tec (Btk and Itk)
SH2 domain
SH3 domain
PH domain

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10
Q

What activates the Src family and specifically where on the Tyrosine residue?

(There is one spot that can inactivated)

A

Activated by both phosphorylation and dephosphorylation

Phosphorylated at Tyr416= active
Phosphorylated at Tyr527=inactive
Dephosphorylation at Tyr527

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11
Q

Do adaptor proteins have any catalytic activity?

A

NO!

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12
Q

What is the main function of adaptor proteins and give an example?

A

Main Job: Link enzymes and promote assembly of LAT and BLNK

LAT and BLNK needed for proper activation and signaling of B and T cells

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13
Q

What 4 structures do adaptor proteins contain?

A

Can contain:
SH2 and SH3
Tyrosine residues (will bind SH2 on other cells)
Proline-rich peptides (will bind SH3 on other cells)

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14
Q

What are the 3 adaptor proteins in T-cell activation?

A

LAT
SLP-76
VAV (recruited by Tyrosine phosphorylation)

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15
Q

Describe the adaptor protein LAT. Where is it and what does it recruit?

A

Only one in membrane

Recruits PLC gamma and GADS (Similar to GRB2)

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16
Q

Describe the adaptor protein SLP-76. What is it rich in and what does it bind? What does this binding lead to?

A

Proline rich

Binds with SH3 domain on GADS –> phosphorylation of Tyrosine residue

17
Q

Describe the adaptor protein VAV. What is it an example of?

A

Is an example of GEF

GEF will replace GDP with GTP activation of enzymes/TF.

  • Actin/cytoskeletal rearrangement
  • Transcription changes
18
Q

What are the 4 components of the TCR?

A

Alpha Beta TCR
CD3 (x2)- Signal Transducer
Zeta chain- Signal Transducer
CD8 or CD4 coreceptor

19
Q

Describe CD4 and CD8 coreceptors in TCR complex. What are each composed of and what does CD8 bind to?

A

CD8 has alpha and beta chains

  • Each with 1 Ig domain
  • Binds with MHC class I an interacts with Beta 2 microglobulin

CD4 has 4 Ig like domain (variant and heavy chains)

20
Q

Describe ITAMS. Where is it found. Describe positive and negative selection in terms of ITAMs and TCR signals.

A

Activating

Found on CD3 and Zeta chains

Number of ITAMs is indicative the affinity of the Ag to the TCR

 - Weak TCR signal for self Ag= positive selection
 - Strong TCR signal for self Ag= negative selection

The longer an Ag is bound to TCR= increased number of active ITAMs

21
Q

Describe ITIMS. Where are they commonly found?

A

Inhibit

Commonly found on FcyRIIB (on B cells and myeloid cells)

22
Q

Describe the process of T-cell activation.

A

Ag binds TCR and coreceptor (Activates Lck)

Lck phosphorylates ITAMs –> activates ZAP70

Zap70 (type of syk) autophosphorylates after interaction with active zeta chain

Zap70 –> activate adaptor proteins (ex. LAT)
-Activates PLCy 1 or RAS/MAPK

23
Q

What are the 3 results of PLC pathway activation?

A

PIP2 binds to PLC and splits it into PI3 and DAG

PKC

  • Phosphorylates ikB, which causes dissociation from NFkB
  • NFkB –> nucleus
  • TF for IL-2 gene production

Increased Ca2+

24
Q

What does PI3 do after PIP2 binds to PLC and splits it into PI3 and DAG?

A

PI3 is phosphorylated to cause an increase in Ca2+

25
Q

What does DAG do after PIP2 binds to PLC and splits it into PI3 and DAG?

A

DAG is phosphorylated to PKC

26
Q

What does an increase in calcium cause?

A

Binds calmodulin

+NFAT–> nucleus (TF for IL-2 gene production)

27
Q

What 3 ways can you activate the NFKB pathway?

A

TCR/BCR
TLRs
CD40

28
Q

What happens after activation of TCR/ BCR, TLRs, or CD40 in terms of NFkB?

A

Activates IKK, which phosphorylates IKB

Phosphorylation of IkB causes Ubiquitination

IkB normally binds NFkB, but if it is ubiquitinated NFkB is now free

Free NFkB to nucleus –> GENE TRANSCRIPTION

29
Q

Describe the RAS-MAPK pathway.

A

Lck –> ZAP70 –> LAT –> GRB2 –> SOS –> Ras-GDP and Ras-GTP

Ras-GTP from the previous step –> MAPK –> AP-1

30
Q

How do you regulate TCR/BCR signaling? What does this cause and give 3 examples?

A

Coreceptors

This causes ITAM phosphorylation

CD4 (T cell)
CD8 (T cell)
CR2/CD21 (B cell)

31
Q

Describe 2 forms of Costimulation that leads to activation of T cells.

A

CD28 (on T cells)- CD80/86 (aka B7 on APCs)

CD40L (on T cells)- CD40 (on APCs)

32
Q

Describe 2 forms of costimulation that leads to T-cell inhibition.

A

CTLA-4- CD80/86

PD-1- PDL1

33
Q

Describe costimulation that leads to B-cell inhibition.

A

FcyRIIB (on B cells): CD22

34
Q

What 2 signals are required for costimulation? And what happens if only one of those signals is found? What does this cause?

A 
TCR= signal 1
CD28= signal 2

Signal 1 only= only NFAT –> decreased ability for IL-2 gene transcription

  • NFAT alone stimulation anergy- inducing genes
  • These genes inhibit T cell function and induce T-cell unresponsiveness
35
Q

What is the immunologic synapse?

A

Space where MHC and TCR contact each other with all other accessory molecules

36
Q

What are the 4 accessory molecules of the immunologic synapse and what is their function?

A

Accessory molecules stabilize the interaction:

CD4+ binds TCR-MHC –> CD4:TCR:MHC

LFA1: ICAM1 move away from TCR:MHC complex

CD2:LFA-3 and costimulation CD28:CD80/86 moves towards TCR:MHC complex (Allows for close interaction leading to signal #2)

Immunology Exam 2 (10 decks)

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