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Immunology (aimen n) - use these > Humoral Immunity: B Cell Activation, Affinity... > Flashcards

Humoral Immunity: B Cell Activation, Affinity... Flashcards

1
Q

What are the 2 phases of the B cell life cycle?

A
  1. Antigen-independent Phase

2. Antigen-dependent phase

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2
Q

How does a B cell life cycle start?

A

B cell starts life as a stem cell and differentiates into a pro-B cell

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3
Q

Describe the first recombination that occurs in the B cell life cycle

A

Undergoes D→ J recombination to join D and J segments (selected randomly) from the gene segment repertoire

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4
Q

What is the second recombination a B cell undergoes?

A

V segment is recombined with DJ segment

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5
Q

What is the role of V(D)J recombination?

A

The Recombined V->DJ segment Hard codes in the heavy chain variable region

Expressed with the μ constant region to form a heavy chain

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6
Q

What makes a B cell a Pre-B cell?

A

Pro-B cell becomes a Pre-B cell when it expresses a heavy chain + a light chain placeholder

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7
Q

How is the light chain of a B cell encoded?

A

Pre-B cell undergoes another round of recombination to join V and J segments of either kappa/lambda chain

This hard codes in the variable and constant light chain regions

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8
Q

What is an immature B cell?

A

B cell becomes immature B cell once it expresses both heavy and light chain IgM

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9
Q

What mechanisms do B cells undergo to produce variability?

A

Other mechanisms present to introduce variability during V(D)J recombination e.g:
Junctional diversity:
- Junctional flexibility
- P and N nucleotide addition

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10
Q

What is the purpose of the variability mechanisms B cells undergo?

A

Generates more diversity even between B cells with the same combination of gene segments

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11
Q

Describe how a mature B cell is formed

A

Mature B cell is formed when the B cell is capable of expressing both IgM and IgD through alternative splicing

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12
Q

Where do mature B cells reside?

A

Mature B cells recirculate between the bloodstream, spleen and lymph nodes

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13
Q

When does the antigen-dependent phase (2nd phase) of B cell life cycle occur?

A

Occurs after pathogen (virus / bacteria) invades the body

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14
Q

Describe how stem cells differentiate into lymphoid cells

A

As stem cell develops, it undergoes lymphoid progenitor stem cell differentiation to give rise to B-cells and T cells (which migrate to thymus)

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15
Q

How are T cell receptors formed?

A

T-cells have their own TCR generated through a similar VDJ recombination process

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16
Q

What are T helper cells?

A

T helper cells are a subset of T-cells involved in B cell activation during infection

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17
Q

Where do activated B cells migrate during antigen-dependent phase?

A

Activated B cells migrate to the GC (germinal centre) where it undergoes affinity maturation

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18
Q

What is the role of affinity maturation process?

A

Affinity maturation improves the affinity of B-cells for the attacking pathogen antigens

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19
Q

What 3 steps are involved in affinity maturation?

A
  1. Clonal expansion
  2. Somatic hypermutation (in the dark zone)
  3. Selection (in the light zone)
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20
Q

How often does affinity maturation occur?

A

Affinity maturation process is repeated several times until highest possible affinity available

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21
Q

How does class switching occur?

A

Antibody receives signals that indicate which pathogens they’re fighting

Ab then undergoes class switching to gain the appropriate effector function

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22
Q

What is the purpose of class switching?

A

Class switching enables the presence of appropriate effector functions

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23
Q

What different types do B cells differentiate into after affinity maturation and class switching?

A

B-cells Differentiate into plasma cells, secreting antibodies whilst maintaining some BCRs on their surface.

A few become memory B cells.

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24
Q

Where do the differentiated B cells of the antigen-dependent phase reside?

A

Both memory and plasma B cells circulate in the bloodstream

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25
Q

How are B cells activated?

A

When the body encounters a pathogen, a subset of naive B cells that recognise the pathogen are activated.

(1 billion+ unique naive B-cells patrol the bloodstream. A small portion are activated by the pathogen, the rest keep patrolling)

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26
Q

How many B cells are in the body?

A

~1 billion+ naive B cells patrol the bloodstream.

A small portion are activated by the pathogen, the rest keep patrolling

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27
Q

How many B cells are activated when encountered with a pathogen?

A

Only a small portion of the naive cells are activated by the pathogen, while the rest remain patrolling

28
Q

What are the 2 stages of B cell activation?

A
  • T-cell independent B cell activation

- T-cell dependent B cell activation

29
Q

When the pathogen invades, the B-cells are partially activated when they bind to and process the antigens. Then, B-cells make clones of itself through clonal expansion.
Some clones become the first defence army, secreting IgM to hold off the invading pathogen.
The other clones migrate to the lymph node to wait for T-cell activation.
T-cell-dependent B-cell activation requires a triple verification process to ensure B-cells not activated by mistake.

A
30
Q

What is the first action of B cells once activated?

A

(T-cell independent)

Once activated B cells form clones of themselves (clonal expansion)

31
Q

What are the roles of the B cell clones formed from clonal expansion?

A

Some clones will become first defence, secreting IgM against the pathogen.
Other clones migrate to the lymph node for T cell activation

32
Q

How is B cell activation regulated?

A

T-cell-dependent B-cell activation Requires triple verification process to ensure the B cells aren’t activated by mistake

33
Q

Outline T-cell-dependent B cell activation

A
  1. B-cell encounter (BCR) + internalise pathogen’s antigen.
  2. Antigen is presented on B cell surface via MHC II
  3. Must be activated by T cell(which has also been activated by same pathogen)
  4. Pathogen is engulfed by DCs and presented on DC surface
  5. Thelper cells detect antigen on DC surface and are activated
  6. B cell is activated
  7. CD40-CD40L interaction confirms T helper cell => produces cytokines
  8. The Fully activated B cells undergo affinity maturation, class switching and differentiate into plasma cells(which secrete antibodies)
34
Q

What are the 3 signals required for B cell activation?

A
  • Antigen binding to BCRs
  • Co-stimulation by activated Th cell specific to the same antigen
  • Th cell-derived cytokines (signalling)
35
Q

Summarise B cell activation

A
  1. Differentiation and clonal expansion of activated B cells
  2. 3-signal verification
  3. Signal transduction pathway
36
Q

What are signal transduction pathways?

A

These are complex signal pathways for cell proliferation, differentiation and survival

37
Q

What activates the B cell signal transduction pathways?

A

Antigen-BCR binding > Activation of tyrosine kinase

38
Q

Outline the signal transduction pathway of B cells

A
  1. Antigen binds to BCR
  2. Activates protein tyrosine kinases (e.g. SYK)
  3. SYK phosphorylates downstream proteins (for cell proliferation, differentiation, survival)
39
Q

After VDJ/VJ recombination, the body produces ~1bn ……………………

A

resting circulating B-cells (naive B-cells).

40
Q

What is a naive B cell?

A

Naive B cell: Not exposed to antigen yet

41
Q

Which B cells are selected for during affinity maturation?

A

Each B-cell has a unique BCR on its surface - BCR that binds the pathogen best is activated

42
Q

How is the best affinity BCR chosen for?

A

The chosen B cell(that best binds the pathogen) clones itself (clonal expansion) and those clones undergo affinity maturation

43
Q

Describe the initial Ab-antigen affinity

A

When the B-cell antibody initially generated (by VDJ recombination) binds to the antigen, it binds at a low-affinity

44
Q

Describe the low affinity antibody-antigen complex

A
  • Antigen takes longer to bind antibody
  • Antigen binds loosely to antibody
  • Antigen quickly detaches after binding
45
Q

How does affinity maturation process mould shape of antibody to better fit the antigen?

A

When B cells activated, affinity maturation process generates mutations in variable region genes to select for genes with highest affinity.

Slowly moulds shape of variable region to fit better with the antigen.

46
Q

Where does affinity maturation occur?

A

Affinity maturation occurs in the germinal centre of the lymph node

47
Q

What are germinal centres?

A

GCs = circular cell clusters on the periphery of the lymph node

48
Q

Which 2 types of cell aid with affinity maturation process?

A

Tfh - T Follicular Helper Cells: The Only T-cell that can enter GC

FDCs - Follicular Dendritic Cells: not normal DCs, presents antigens in the GC

49
Q

Where do other T and Th cells reside in lymph node?

A

Other T cells remain in the T cell zone of the lymph node

50
Q

What are the components of the Germinal centre?

A

The germinal centre (GC) is composed of:

  • Light zone
  • Dark zone
51
Q

Which 2 processes occur in the Germinal Centre?

A

2 processes occur in the GC:

  1. Affinity maturation
  2. Class switching
52
Q

When do B cells enter germinal centre?

A

When the B-cell is activated by Thelper cells, it migrates into the GC dark zone for clonal expansion

53
Q

What are the stages of affinity maturation?

A

Once cloned, B cells undergo affinity maturation(consisting of):

  • Somatic hypermutation (dark zone)
  • Selection (light zone)
54
Q

Which B cells undergo class switching?

A

The B cell with the highest affinity for the antigen will undergo class switching

55
Q

What do Mature B cells differentiate into?

A
  • plasma cells OR

- memory B cells

56
Q

What is AID?

+ Its role?

A

AID = activation-induced deaminase

Generates point mutations within variable region gene of B cells at random points = somatic hypermutation

57
Q

Describe the outcome of somatic hypermutation

A

All B cells that were previously clones now differ from one another

58
Q

When do B cells enter light zone of the germinal centre?

A

Hypermutated B cells enter GC light zone for selection

59
Q

What is the role of FDCs in affinity maturation?

A

FDC (follicular dendritic cells) present the antigen on its surface during selection

60
Q

How do hypermutated B cells interact with FDCs and Tfh cells?

A

B cells compete for the limited amount of antigens on the FDC surface and present the antigen to Tfh cells

61
Q

What is the role of Tfh cells in affinity maturation?

A

Tfh cells provide ‘survival’ signal to the B-cell during selection

62
Q

What happens to low affinity B cells during affinity maturation?

A

B cells with low affinity (unable to bind to FDC) undergo apoptosis due to lack of survival signal from Tfh cells

63
Q

What is the result of affinity maturation on high affinity B cells?

A

B cells that survive the process migrate back to dark zone to repeat process until affinity is high enough.

64
Q

How does affinity change with each affinity maturation cycle?

A

Ab affinity improves with each cycle of affinity maturation

The process is random

65
Q
A

Without the survival signals from the T follicular helper cells, B-cells would die off.
Those that survive migrate back to the dark zone.
The process begins again until Ab affinity is high enough.

Immunology (aimen n) - use these (14 decks)

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