Humoural Immunity - Part 3

Question 1

When does the antigen-dependent stage occur?

Answer 1

It occurs after a pathogen invades the body.

Question 2

Describe the antigen-dependent stage process

Answer 2

1. As the stem cell develops, it goes through the lymphoid progenitor stem cells giving rise to the B-cells but also the T-cells that migrate to the thymus.
2. T-cells have their own T-cell receptor that is generated through a VDJ recombination process. T-helper cells are a subset of T-cells which are involved in the activation of the B-cells through an infection.
3. The activated B-cell migrates to the germinal centre (GC) where it will undergo affinity maturation (AM). This process improves the affinity for attacking antigen.
4. The AM process involves clonal expansion and somatic hypermutation in the dark zone of the GC and then migrates to the light zone to undergo selection. This process occurs multiple times.
5. Then, the Ab will receive signals to tell them which antibody they are fighting then they will undergo class switching to ensure they have the appropriate effector functions.
6. After the B cell will differentiate to plasma cells and release secretory Ab whilst maintaining receptors on their surface. A few will become memory B cells. Both will circulate in the bloodstream.

Question 3

How are some B-cells activated?

Answer 3

When the body encounters a pathogen, a subset of naive B cells will be activated. However, only a few will be activated whilst the rest will continue patrolling.

Question 4

What are the two stages of B-cell activation?

Answer 4

T-cell independent B cell activation
T-cell dependent B-cell activation
Not the same as antigen-independent and dependent stage of the life cycle

Question 5

Summarise the process of T-cell independent B-cell activation

Answer 5

1. When the pathogen invades, the B cells are partially activated ready to bind and process the antigens. Then, the B-cells will make clones through clonal expansion.
2. Some clones will become the first defence and secrete IgM; the others will migrate to the lymph node to wait for T-cell activation.

Question 6

Summarise the T-cell dependent B-cell activation

Answer 6

It requires a triple verification process to ensure they are not activated by mistake. 
1. First, the B-cell encounters the pathogen and internalises the antigens. Then it is presented in bits and pieces on the surface of the B-cell via the MHC class II receptor. 

2. Second, activated by the T-cell which in turn is activated by the same pathogen. The pathogen is engulfed by dendritic cells and presented on the surface. The T-helper cell will detect it an be activated. Then, the B-cell is activated. The CD40L and CD40 is a handshake to confirm the cell is a T-helper cell and not anything else.
3. Third, signals such as cytokines are produced by the T-helper cell. The fully activated B-cells will undergo affinity maturation, class switching and different-states into plasma cells which secrete antibodies.

Question 7

Summarise what B-cell activation involves

Answer 7

• differentiation and clonal expansion of activated B-cells
• 3 signals: antigen binding to BCRs; co-stimulation by activated Th cell specific to the same antigen and Th cell-derived cytokines
• Signal transduction pathway

Question 8

What are signal transduction pathways?

Answer 8

Complex pathways for example the binding of antigen to the BCR activating tyroskine kinases such as SYK. Then phosphorylating downstream proteins for cell proliferation, differentiation and survivial.

Question 9

Why is affinity maturation important?

Answer 9

It is needed to fine tune antibody affinity to antigen.

Question 10

Describe the process of clonal expansion

Answer 10

1. After VDJ and VJ recombination, the body will produce more than a billion naive/resting B-cells. This is because they are not exposed to the antigen yet.
2. Each B-cell has a unique BCR on its surface. When the pathogen attakcs, the B-cells will bind and be activated.
3. This will make a clone of itself- clonal expansion and then lead on to affinity maturation.

Question 11

How does the antigen bind without affinity maturation?

Answer 11

It can bind to the antigen but at a low affinity. This means the antibody takes longer, binds loosely or quickly falls away after binding.

Question 12

Where does affinity maturation occur?

Answer 12

In the germinal centre of the lymph node

Question 13

What is the germinal centre?

Answer 13

Circular cell clusters at the periphery of the lymph node.

Question 14

What are the two cells that help with the affinity maturation process?

Answer 14

T follicular helper cells (Tfh)

Follicular Dendritic Cells (FDC)

Question 15

What are T-follicular helper cells?

Answer 15

A subset of T cells that are able to enter the GC. Other T cells only stay in the T cell zone of the lymph node.

Question 16

What are follicular dendritic cells?

Answer 16

Not the normal dendritic cells. They are cells that present antigens in the GC.

Question 17

What are the two zones of the GC?

Answer 17

the dark and light zone

Question 18

Which two process occur in the GC?

Answer 18

Affinity maturation and class switching

Question 19

Describe the process of B-cells when they enter the GC

Answer 19

1. When B-cells are activated by T helper cells, they migrate into the GC and undergo clonal expansion.
2. Then, they will undergo affinity maturation which involves somatic hypermutation and selection.
3. Then, the B-cell with the highest affinity will undergo class switching before differentiating into plasma cells or memory cells.

Question 20

Describe in detail the affinity maturation process

Answer 20

1. After the activated B-cells enter the GC, they go to the dark zone for clonal expansion.
2. Then activation-induced cytidine deaminase (AID) will generate point mutations in the variable region gene of the B cells at random points. All the B cells which were clones are now slightly different - this is somatic hypermutation.
3. These cells go to the light zone for selection.
4. In this zone, FDC will present the antigen on its surface, then the B cells will compete for the limited amount of antigens on the FDC.
5. B-cells that are able to bind to the antigens will take as much antigen as they can and present it to the Tfh cells to get a survival signal. These are different from the T helper cells that activated them initially.
6. The cells that have reduced affinity will be bumped off the FDC. WIthout the cell survival signals from Tfh, they will apoptose.
7. The B-cells that survive will migrate back to the dark zone and repeat the process until antibody affinity is high enough.

Question 21

How is Ab affinity improved?

Answer 21

Through multiple cycles of affinity maturation. It is survival of the fittest - the better affinity Ab are selected for. The body does not have control, it is random. During the rounds, the antibodies will improve, stay the same or decrease affinity for the antigen.
These rounds will fine tune the affinity of the Ab to the antigen until it is maximised.