B cells and how they get activated Flashcards

1
Q

where do B cells develop?

A

in the bone marrow

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2
Q

how do B cells get activated?

A

Mature B cells get activated in the spleen or lymph nodes by naked antigen through the B cell receptor

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3
Q

what is naked antigen?

A

antigen that is not presented by MHC

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4
Q

where are mature B cell found?

A

circulating through the body

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5
Q

what can B cells do?

A
  • secrete antibody
  • can present antigen on MHCII to CD4 T cells
  • Can “class switch”
  • Can undergo “somatic hypermutation”
  • Undergo clonal expansion
  • Can differentiate into antobody producing plasma cells
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6
Q

what is the initiat step in B cell activation?

A

By signalling through the B cell receptor

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7
Q

what is the B cell receptor?

A

Antibody bound to the plasma membrane

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8
Q

why is it important to know how and why B cells are activated?

A
  • develop new cures for cancer: B cell malignancies (lymphoma and leukemia)
  • Develop new treatments for autoimmune diseases
  • Make new vaccines
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9
Q

how are B cell activated through the BCR?

A

Activation of a cell surface receptor through ligand binding doesn’t always directly link to the cell’s response

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10
Q

how does the activated BCR act?

A

The activated receptors can interact with a chain of other proteins within the cell that transmit the activation signal (signal transduction pathway)

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11
Q

what are kinases?

A

enzymes that phosphorylate themselves and other proteins- phosphorylation can generate binding sites for other proteins to allow the signal to transmit along the chain

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12
Q

what is the cellular messengering of BCR?

A

First messenger- antigen

Transmembrane B cell receptor (surface-bound immunoglobulin + Igalpha and Igbeta)

second messengers

Cascade

Functions

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13
Q

what is the structure of a BCR?

A

Cell surface immunoglobulin + one each of invariant signalling proteins Igalpha and Igbeta

  • disulfide-link to form a heterodimer between Igalpha and Igbeta
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14
Q

what are the co-receptors of B cells?

A

CD21 and CD19

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15
Q

what is the role of B cell co-receptors?

A

Decreases BCR signaling threshold by amplifying BCR signals

Allows B cells to respond to low levels of antigen

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16
Q

what is CD21?

A

complement receptor 2- binds to the complement-coupled antigen
- antigen coupled to complement fragment

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17
Q

what is CD19?

A

augments signalling through BCR + recruites PI3-Kinase (growth signal)

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18
Q

what is the role of CD81?

A

trafficks CD19 to the cell surface

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19
Q

how are BCR presented on the cell surface?

A

there are many BCRs on the surface of one cell and they can move around the membrane on lipid rafts

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20
Q

what is BCR receptor clustering?

A

the BCR are on lipid rafts. This allows them to move around the cell membrane and means the signal can agrigate to one region of the BCR to get a much stronger response.

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21
Q

what can cause aggregation of BCR?

A

highly repetitive structures can cause aggregration of BCR on the cells surface

22
Q

what is the role of T cells in B cell activation?

A

Needs T cells to help (cytokines and CD40L) to activate B cells

23
Q

what is the BCR triggered?

A

Monovalent soluble antigen can cause the Src family kinase Lyn to ‘disturb’ and open the BCR allowing signal transduction

24
Q

how does compliement act in BCR activation?

A

antigen bound to complimemt enhances the activation ability

25
Q

how does antigen bind to a BCR?

A

Antigen bound complement fragments C3d or C3b can bond to CD21, the antigen binds to the antibody resulting in cross-linking

26
Q

what is the intracellular signaling pathway in T cell activation?

A

-Tyrosine phosphorylation is an important mechanism by which transmembrane receptors transduce signals

  • Phosphotyrosine residues are recognised by proteins containing the phospho-dependent binding domain, SH2
  • SH2 domain proteins can act to recruit other molecules, as enzymes or as trancription factors
27
Q

what are ITIMs and ITAMs?

A

Phosphorylation sites in immune receptors

28
Q

what are ITIMs?

A

Immunoreceptor tyrosine-based inhibitory motifs

29
Q

what are ITAMs?

A

Immunoreceptor tyrosine-based activation motif

30
Q

what are Src family kinases?

A

Protein tyrosine kinases Fyn, Blk and Lyn associate with resting receptors

After ligand binding and receptor clustering the kinases phosphorylate tyrosines in ITAMs on Igalpha and Igbeta

31
Q

what are the features of Syk kinase?

A

Syk has 2 SH2 domains and binds to pITAMs on Igbeta

Syk becomes activated by binding ti the phosphorylated site

32
Q

what does syk activation induce?

A

formation of a membrane-associeated signalling complex

33
Q

what is BLNK?

A

a scaffold protein

34
Q

what is the structure of BLNK?

A

has multiple sites for tyrosine phosphorylation

35
Q

what phosphorylates BLNK?

A

Syk

36
Q

what is the role of BLNK once it is phosphorylated?

A

pBLNK recruits other Sh-2 domain proteins to form the multiprotein signalling complex

37
Q

what is Bruton’s tyrosine kinase?

A

a protein that comes into the complex once BLNK is phosphorylated by Syk

38
Q

what activates the PLCg2 pathway?

A

Bruton’s tyrosine kinase

39
Q

what is the end result of the PLCg2 pathway?

A

upregulation of transcription factors

40
Q

what does activation of transcription factors lead to?

A
  • increased B cell maturation
  • increased activation
41
Q

what does activation of the PI3K pathway require?

A

Phosphorylation of CD19 (B cell co-receptor) by LYN

42
Q

what does PI3K pathway activation lead to?

A

Leads to PIP3 production
This recruits BCR signalling components to the plasma membrane and activates them

43
Q

what is the main mediator of the PI3K pathway?

A

Serine/ threonine kinase AKT is the main mediator of the PI3K pathway

44
Q

what does the PI3K pathway regulate?

A

Cell cylce
Apoptosis

45
Q

what is the role of AKT in the PI3K pathway?

A

AKT induces pro-survival genes through IKK and mTOR

46
Q

what is mTOR?

A

kinase that controls cell growth and proliferation

47
Q

what is the role of the PI3K pathway?

A

-promotes growth
-promotes survival

48
Q

what activates the ERK pathway?

A

RAS activation

49
Q

what is ERK?

A

a MAPkinase

50
Q

how is ERK activated?

A

it is phosphorylated due to activated of RAS and this causes it to form a dimer
Dimerization allows translocation to the nucleus

51
Q

what is the role of ERK in the nucleus?

A

-proliferation
-Survival
-Differentiation

52
Q

how is ERK activated?

A

it is phosphorylated due to activated of RAS and this causes it to form a dimer
Dimerization allows translocation to the nucleus