Humoral Immunity: B-Cell Activation, Affinity Maturation and Class Switching Flashcards

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1
Q

In summary, describe the phases of the humoral immune response

A
  • resting mature naive B cell, makes IgM on cell surface
  • activated B cell (antigen binds, helper T cells, cytokines)
  • clonal expansion + differentiation
  • form plasma cells -> IgM secreted (plasma cells make lots of Ig)
  • class/isotype switching occurs -> make IgG instead
  • B cells start to make high-affinity antibodies - affinity maturation
  • eventually generate memory B cells
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2
Q

Describe Ig expression during B cell maturation & how this activates the B cell

A
  • functional Ig expressed as membrane (cell surface) IgM (sIgM)
  • membrane IgM acts as a B cell receptor (together w IgD)
  • binding of antigen to IgM activates tyrosine kinase
  • this activates signal transduction pathways for cell division + differentiation
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3
Q

What 3 things does B-cell activation require?

A
  1. antigen binding to B-cell receptor (sIgM), resulting in stimulation of signal transduction pathways
  2. co-stimulation by T cells
  3. co-stimulation by cytokines
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4
Q

What are the 2 forms of IgM?

A
  • membrane bound on B cell surface -> antigen receptor
  • secreted (circulation, tisues, mucosa)
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5
Q

The activated B-cell begins to secrete soluble IgM. What is this mechanism called?

A

Differential splicing

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6
Q

Describe the process of differential splicing

A
  • mechanism required for soluble IgM to be secreted
  • Cμ is not coded for by single exon
  • there are 4 exons w/ 2 alternative versions of exon four
  • differential splicing gives 2 diff mRNAs coding for 2 proteins which differ at the C terminal end
  • note V region, coded by VDJ complex, is identical

so splicing can occur at 2 places on the pre-RNA, to give rise to either secreted μ chain OR membrane μ chain - protein.

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7
Q

What is the difference in structure between secreted IgG and membrane IgG?

A
  • secreted has tail piece
  • membrane has hydrophobic transmembrane region + cytoplasmic tail
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8
Q

Secreted antibodies circulation i the blood and access various sites to deal w/ pathogens. What are 3 effector functions of antibodies?

A
  • neutralisation of microbes + toxins (block entry)
  • opsonisation of microbes to enhance phagocytosis
  • activation of complement (pathogen killing) (lysis)
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9
Q

Different classes of antibodies work best at certain sites, examples?

A
  • IgM, IgG - blood
  • IgA - mucosa
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10
Q

Different classes of antibodies work best against certain pathogens. Give one example

A

IgE - parasites

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11
Q

What is class (isotype) switching?

A

During an immune response B cells become capable to produce antibodies of different classes but without changing specificity (respond to the same Ag)

  • ability to perform diff effector functions
  • can deal better w/ pathogens
  • isotype switch needs signal from helper T cells

IgM switch to -> IgG, IgA, IgE
IgG switch to -> IgA, IgE

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12
Q

Which 2 things are not altered in class switching?

A
  • specificity for antigen
  • the light chain
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13
Q

Different classes of antibody have different constant (Fc) regions to carry out different functions, but first Ig made is always IgM. What are the 2 main mechanisms of class switching called?

A
  • Minor - IgD only, by differential splicing, made at same time as IgM
  • Major - all other classes, by DNA rearrangement
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14
Q

Describe minor class switching

A
  • Cμ and Cδ are transcribed as part of single precursor RNA
  • differential splicing can remove Cμ exons
  • so the Cδ exons are now used
  • result is same VDJ is now joined to -> making IgD
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15
Q

Describe major class switching

A
  • endonuclease recognition site (switch region) before each CH segment
  • cut before Cμ + cut before alternative C segment
  • original VDJ now transcribed along with new C region
  • note: no change in light chain
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16
Q

Which heavy chains determine which antibody class is made?

A
  • IgM - mu
  • IgG - gamma
  • IgD - delta
  • IgA - alpha
17
Q

How do T cells and cytokines facilitate antibody class switching?

A
  • CD40 on T Cell interacts with CD40 on B cells
  • cytokines prod by T cell
    • IFN-γ -> switch to IgG1, IgG3
    • IL-4 -> switch to IgE
    • TGF-β (+ others) -> switch to IgA
18
Q

What is meant by ‘affinity maturation’?

A
  • antibodies prod early during immune response have lower affinity for antigen
  • later during immune response + in secondary immune responses -> prod of high-affinity antibodies
  • the process that leads to inc affinity of antibodies = affinity maturation
19
Q

What is the mechanism of affinity maturation?

A
  • somatic mutation of Ig V genes
  • followed by selection of B cells that produce Abs w/ highest affinity
  • affinity maturation needs signals from helper T cells
20
Q

What happens to B cells with low affinity in comparison to those with high affinity?

A
  • B cells w/ high affinity Ag receptors are selected to survive
  • B cells w/ low affinity Ag receptors may fail to survive
  • due to comp for Ag recognition on follicular dendritic cells in germinal centres
  • preferential selection of B cells w/ high affinity Ag receptors during immune responses
21
Q

Where are the germinal centres?

A
  • in lymphoid organs eg. lymph node
  • cells rapidly dividing in light + dark zone
22
Q

What does affinity maturation allow for?

A
  • higher affinity gives stronger cell signalling
  • faster cell replication
  • high affinity sub-clone outgrows the original clone