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MIIM30002 - Principles of Immunology > Lecture 19 - B cells - Generation of Adaptive Immunity > Flashcards

Lecture 19 - B cells - Generation of Adaptive Immunity Flashcards

1
Q

What are B-1 B cells?

Describe:
• Location
• Function
• BCR

A

Not part of the Adaptive immune response, because they cannot form memory cells

However, can still:
• Make Ab against Ag
• Present antigen

Reside mainly in the pleural and peritoneal cavities

Function:
• ‘Natural Abs’ against carbohydrate Ag
• Thus, part of early ‘innate’ response against infection
(NB natural because they are present in circulation in unimmunised mice)

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2
Q

Compare the origin of B-1 and B-2 B cells

A

B-1 B cells:
• First produced in the liver of the foetus
• Undergo self-renewal in the periphery
• Persist in adult, making up 5% of B cells
• FL-HSC

B-2 B cells:
• Produced & continually replaced in the bone marrow
• Produced after birth
• BM-HSC

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3
Q

What are the two lineages of B-2 B cells?

A
  1. Follicular B cells

2. Marginal zone B cells

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4
Q

Describe Marginal zone B cells
• Location
• Function

A

Location:
• Reside in the marginal zone of the spleen, as opposed to the follicle
• Largely non-recirculating

Function:
• Early participation in adaptive response
• Limited diversity
• Lower threshold (for activation, proliferation, differentiation)
• Ab responses against common bacterial Ag

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5
Q

Compare the activation threshold for MZ and Follicular B cells

A

Follicular B cells have a higher activation threshold than MZ B cells

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6
Q

What are the majority of mature B cells formed from?

A

Follicular B cells

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7
Q

What Ig do Follicular B cells express (in the naïve state)?

A

IgM & IgD

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8
Q

Compare circulation of MZ and Follicular B cells

A

MZ: non-recirculating
Follicular: recirculate through lymphoid tissues

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9
Q

Compare residence of MZ and Follicular B cells

A

MZ: marginal zone of spleen
Follicular: follicle of spleen

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10
Q

Describe the antigens to which B cells can respond

A 
Native molecules:
 • Proteins
 • Glycoproteins
 • Polysaccharides
 • Viral particles
 • Bacteria
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11
Q

What are the effector functions of B cells?

A

Ab production:
• C’ activation
• Neutralisation
• Opsonisation

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12
Q

Describe differentiation of B cells after clonal selection & proliferation.

Into which cell types do the clones differentiate?

On what does this differentiation depend?

A
  1. Pool of clones
  2. Differentiate into:
    • Memory cells
    • Plasma cells

Differentiation depends on the signals the GC B cells receive, which induce either BLIMP-1 or other transcription factors

If the B cells expresses BLIMP-1 it will differentiate into a plasma cell

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13
Q

Which signals does a naïve B cell require to differentiate into an effector cell?

A
  1. Cognate antigen
  2. Activation signal (Tfh cell):
    • CD40L-CD40
    • ICOS-ICOSL
    • IL-21
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14
Q

Describe linked recognition

Why is this important?

A

Requires both B and T cell to respond to a foreign cognate antigen for the generation of an immune response against it.

This process is very important for self-tolerance, as it is very unlikely that both a CD4+ T cell and a B cell will be autoreactive

  1. B cell encounters Ag (viral coat protein) w/ surface bound Ab
  2. RME of Ab+Ag; Ag processing
  3. Presentation of an epitope of this Ag on MHC class II
  4. Tfh cell recognises cognate antigen on MHC II w/ its TCR
  5. T cell help for B cell:
    • CD40-CD40L interaction
    • ICOSL-ICOS
    • Cytokines (IL-21)
  6. B cell forms a germinal centre and make high affinity Ab against Ag (viral coat protein)
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15
Q

How does native antigen get to naïve B cells?

A

FDCs: Follicular dendritic cells

  1. Opsonised and C’ covered antigen enters LN via afferent lymphatics
  2. Macrophages in Sub-capsular sinus bind Ag w/ their C’ receptors
  3. Ag not endocytosed; maintained on surface of macrophage
  4. Ag transported into follicle & bound by Follicular DCs with CR1/2
  5. B cells encounter the antigen on the FDC and become activated
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16
Q

What is a mature B cell?

A

Developed in the bone marrow and has gone out into the periphery

Is yet to encounter antigen

(For T cells, they are called naïve T cells)

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17
Q

Which type of B cells have direct contact w/ the blood in the spleen?

A

MZ B cells

18
Q

Compare antigen composition in T-dependent and -independent Ab responses

A 
T-independent
 • Polysaccharide
 • Lipid
 • Cross linking of Ag to Ab on the cells surface
 • Production of Ab

T-dependent:
• Protein

19
Q

What does cross-linking of Ab and Ag on the cell surface affect?

A

It affects signal transduction in the cell

It improves the response

20
Q

What type of cell are FDCs?

What is their major function?

A
  • Non immune cells - don’t come from the lineage in the BM
  • Takes the shape of an immune cell
  • Nothing to do with DCs

They are a “depot for antigen”

They bind C’ bound foreign, native antigen on their surface with CR-1 and CR-2 for recognition by naïve B cells in the follicle

21
Q

How do B cells and T cells know where to reside?

A

Chemokine gradients

Cells have receptors on their surface that allow them to follow chemokine gradients into their respective locations

T-cell zone (paracortex):
• CCR7 receptor on T cells recognise:
• CCL19 & CCL21 bind to CCR7

B cell zone :
• CXCL13 expressed here
• CXCR5 expressed on B cells

22
Q

Describe how naïve T cells and mature B cells encounter each other in the lymph node

A
  1. B cell begins to express CCR7 (as well as CXCR5)
  2. T cell begins to express CXCR5 (as well as CCR7)
  3. The cells are attracted to the boundary of the follicle and the T cell zone
23
Q

Which chemokines are present in the T cell zone?

A

CCL19

CCL21

24
Q

Which chemokines are present in the B cell zone?

A

CXCL13

25
Q

What is the receptor for CXCL13?

A

CXCR5

26
Q

What is the receptor for CCL19?

A

CCR7

Also for the receptor CCL21

27
Q

What is a plasmablast?

When does this occur?

A

Some B cells that were stimulated by Tfh migrate to form a primary focus

Here, plasmablasts develop

Plasmablasts produce low affinity IgM which serves as initial humoral immunity

28
Q

Describe the events directly after B cell interaction with Tfh at the boundary of the follicle and the T cell area

A

Either:

  1. Differentiation into plasmablast

or

  1. Migration back into a follicle to form a GC
    Exposed to AID:
    → CSR
    → SHM
29
Q

Describe the processes that occur within the germinal centre

A
  1. Exposed to new enzyme: AID
  2. SHM: introduction of mutations into the variable region
  3. CSR: rearrangement of the heavy chain

Differentiation:

4a. Memory cells
4b. Plasma cells

30
Q

What is the difference between SHM and affinity maturation?

A

SHM: AID introduces mutations into the DNA coding for the variable region of the Ab

Affinity maturation: selection of the mutated Ab that now has increased affinity for the Ag

31
Q

What is ‘Secondary diversification’?

A

SHM in mature B cells during the adaptive immune response

32
Q

Is CSR reversible or irreversible?

A

Irreversible

Once switched from IgM to IgG, it is impossible to go back to IgM

33
Q

Which classes of Ab are likely to be present if someone is vaccinated against a specific Ag?

A

IgG and IgA

i.e. have undergone CSR

34
Q

Describe germinal centres

A

• Activated, clonal B cells that have been stimulated by Tfh undergo rapid proliferation and maturation events

“Island of rapid proliferation amongst non-proliferating, resting B cells”

  • Exposure to AID
  • Location of secondary diversification (CSR and SHM)
35
Q

Suggest a reason why naïve lymphocytes are difficult to activate on their own

A

To prevent activation against the wrong thing (auto-antigen)
e.g. Linked recognition required for B cell activation

This helps to ensure self-tolerance, because an autoimmune response will only occur if both a self-reactive T cell and a self-reactive B cell are present at the same time

36
Q

What is the function of S1P1?

A

Receptor on lymphocytes that retains them in lymphoid organs in the early stages after activation

37
Q

Differentiate between primary and secondary lymphoid follicles

A

Follicles are the region in secondary lymphoid organs where B cells are localised

Secondary lymphoid follicles have germinal centres, while primary ones don’t

38
Q

What is the effect of CSR?

A

Generation of Ab with the same specificity, but with different effector function

39
Q

What happens to B cells once they encounter their cognate antigen (on FDCs)?

A

Upregulation of CCR7

40
Q

Where do T cells reside in the spleen?

A

PALS: peri-arteriolar lymphoid sheath

MIIM30002 - Principles of Immunology (30 decks)

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