Lecture 19 - B cells - Generation of Adaptive Immunity Flashcards Preview

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

Flashcards in Lecture 19 - B cells - Generation of Adaptive Immunity Deck (40):
1

What are B-1 B cells?

Describe:
• Location
• Function
• BCR

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)

2

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

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

3

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

1. Follicular B cells
2. Marginal zone B cells

4

Describe Marginal zone B cells
• Location
• Function

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

5

Compare the activation threshold for MZ and Follicular B cells

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

6

What are the majority of mature B cells formed from?

Follicular B cells

7

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

IgM & IgD

8

Compare circulation of MZ and Follicular B cells

MZ: non-recirculating
Follicular: recirculate through lymphoid tissues

9

Compare residence of MZ and Follicular B cells

MZ: marginal zone of spleen
Follicular: follicle of spleen

10

Describe the antigens to which B cells can respond

Native molecules:
• Proteins
• Glycoproteins
• Polysaccharides
• Viral particles
• Bacteria

11

What are the effector functions of B cells?

Ab production:
• C' activation
• Neutralisation
• Opsonisation

12

Describe differentiation of B cells after clonal selection & proliferation.

Into which cell types do the clones differentiate?

On what does this differentiation depend?

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

13

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

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

14

Describe linked recognition

Why is this important?

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)

15

How does native antigen get to naïve B cells?

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

16

What is a mature B cell?

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)

17

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

MZ B cells

18

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

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

T-dependent:
• Protein

19

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

It affects signal transduction in the cell

It improves the response

20

What type of cell are FDCs?

What is their major function?

• 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

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

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

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

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

Which chemokines are present in the T cell zone?

CCL19
CCL21

24

Which chemokines are present in the B cell zone?

CXCL13

25

What is the receptor for CXCL13?

CXCR5

26

What is the receptor for CCL19?

CCR7

Also for the receptor CCL21

27

What is a plasmablast?
When does this occur?

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

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

Either:

1. Differentiation into plasmablast

or

2. Migration back into a follicle to form a GC
Exposed to AID:
→ CSR
→ SHM

29

Describe the processes that occur within the germinal centre

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

What is the difference between SHM and affinity maturation?

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

What is 'Secondary diversification'?

SHM in mature B cells during the adaptive immune response

32

Is CSR reversible or irreversible?

Irreversible

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

33

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

IgG and IgA

(i.e. have undergone CSR)

34

Describe germinal centres

• 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

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

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

What is the function of S1P1?

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

37

Differentiate between primary and secondary lymphoid follicles

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

What is the effect of CSR?

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

39

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

Upregulation of CCR7

40

Where do T cells reside in the spleen?

PALS: peri-arteriolar lymphoid sheath