B and T Cell Cooperation

Question 1

Why do primary adaptive responses develop slowly?

Answer 1

Because naive T and B cells that recognise a new foreign antigen are few in number.

Question 2

Which component of an antibody determines its effector function?

Answer 2

The type of heavy chain used.

Question 3

Which phase precedes the response to a new foreign antigen in a primary response?

Answer 3

The lag phase.

*This is absent in a secondary response.

Question 4

List 4 differences between a primary response and a secondary response.

Answer 4

1 - The frequency of antigen-specific B cells is greater in the secondary response.

2 - The isotype of antibody produced changes from IgM and IgG (where IgM is more frequent) in the primary response to IgA and IgG in the secondary response.

3 - The affinity of the antibody produced is higher in the secondary response.

4 - More antibodies show somatic hypermutation in the secondary response.

Question 5

Define somatic hypermutation.

Answer 5

A cellular mechanism by which a B cell adapts its antibody production to foreign antigens.

Question 6

What is a T independent antigen?

Answer 6

An antigen that causes antibody production by B cells without T cell involvement.

Question 7

How does antibody production in the primary and secondary response differ in response to T independent antigens when compared to T dependent antigens?

Answer 7

• In both the primary and secondary response to T independent antigens, there is high antibody production which comes about quickly.
• In the primary response to T dependent antigens, there is a lag phase, followed by a moderate antibody production which comes about slowly.
• In the secondary response to T dependent antigens, there is a very high antibody production that comes about very quickly.

Question 8

List the two most common locations where lymphocytes are found.

Answer 8

1 - In lymph nodes.

2 - In the spleen.

Question 9

How long will an individual lymphocyte remain in a lymph node before migrating?

Answer 9

12-24 hours.

Question 10

Via which structures do lymphocytes enter lymph nodes?

Answer 10

1 - High endothelial venules.

2 - Afferent lymph vessels.

Question 11

Via which structures do lymphocytes exit lymph nodes?

Answer 11

Efferent lymphatic vessels.

Question 12

List the two lymph ducts.

Answer 12

1 - Thoracic duct.

2 - Right lymphatic duct.

Question 13

Where does lymph empty into from the lymph ducts?

Answer 13

The venous circulation.

Question 14

What is the difference between primary and secondary lymphoid organs?

Answer 14

• Primary lymphoid organs generate lymphocytes from immature progenitor cells.
• Secondary lymphoid organs are the locations where lymphocytes are activated.

Question 15

List the 2 primary lymphoid organs.

List 5 secondary lymphoid organs.

Answer 15

Primary lymphoid organs:

1 - Bone marrow.

2 - Thymus.

Secondary lymphoid organs:

1 - Lymph nodes.

2 - Tonsils.

3 - Spleen.

4 - Peyer’s patches.

5 - Mucosa associated lymphoid tissue (MALT).

Question 16

List 8 locations where mucosa associated lymphoid tissue (MALT) is found.

Answer 16

1 - GI tract.

2 - Nasopharyngeal tract.

3 - Thyroid gland.

4 - Breast.

5 - Lungs.

6 - Salivary glands.

7 - Eyes.

8 - Skin.

Question 17

Why is it advantageous for lymph to circulate around the body?

Answer 17

To increase the chances of encountering an antigen.

Question 18

How many lymph nodes are there in the body?

Answer 18

700.

Question 19

What enters lymph nodes via afferent lymph vessels?

Answer 19

Dendritic cells.

Question 20

List the layers of a lymph node.

Answer 20

1 - Cortex.

2 - Paracortex (T zone).

3 - Medulla.

Question 21

What is contained within the cortex of a lymph node?

Answer 21

Follicles.

Question 22

What are germinal centres?

Where are they located?

Answer 22

• The sites where mature B cells proliferate, differentiate, and mutate their antibody genes through somatic hypermutation.
• They are located in B cell areas in the follicles of the cortex.

Question 23

In which area of a lymph node do high endothelial vessels empty?

Answer 23

The paracortex (T zone).

Question 24

What is meant by an extrafollicular antibody response?

Where does extrafollicular growth occur?

Where does follicular growth occur?

Answer 24

• In adaptive antibody responses, B cells are induced to grow either in follicles or in extrafollicular areas as plasma cells.
• Extrafollicular growth occurs in the medullary cords of lymph nodes and in the spleen.
• Follicular growth occurs in the spleen and in germinal centres of lymph node follicles.

Question 25

List 2 cells that can be found within the medulla of a lymph node.

Answer 25

1 - Plasma cells. 2 - Macrophages.

Question 26

Describe the histological organisation of the spleen.

Answer 26

- The spleen is formed of red pulp and white pulp: - The white pulp is organised into follicles. - T zones traverse the follicles. - Marginal zones line the follicles. - The remainder of the spleen is red pulp.

Question 27

List 3 cells that can be found within the red pulp of the spleen.

Answer 27

1 - Macrophages 2 - RBCs. 3 - Platelets

Question 28

List 3 cells that can be found within the white pulp of the spleen.

Answer 28

1 - Dendritic cells. 2 - T cells. 3 - B cells.

Question 29

List 4 characteristics of T-dependent antibody responses.

Answer 29

1 - T-dependent responses are required for switching to IgG, A and E. 2 - T-dependent responses are required for high-affinity antibody production. 3 - T-dependent responses are required for the longest-lived antibody responses. 4 - T-dependent responses are required for B cell memory.

Question 30

What type of antibody responses occur in extrafollicular foci?

Answer 30

Both T-dependent and T-independent responses.

Question 31

What type of antibody responses occur in germinal centres in the spleen?

Answer 31

T-dependent responses only.

Question 32

List the processes that occur at the beginning of antibody responses to protein antigens.

Answer 32

1 - An antigen-specific B cell binds to an antigen via the B cell receptor. 2 - The antigen is internalised by receptor-mediated endocytosis. 3 - A high density of specific antigen fragments is presented.

Question 33

List 4 molecules involved in the presentation of specific antigen fragments upon endocytosis of an antigen.

Answer 33

1 - MHC class 2. 2 - CD80. 3 - CD86. 4 - CD40.

Question 34

What is the difference between B cell and dendritic cell uptake of antigens?

Answer 34

Specificity - B cells are highly specific due to the specificity of the B cell receptor, whereas dendritic cells are not specific in what they take up.

Question 35

What is B cell activation necessary for? How are B cells activated?

Answer 35

- B cells must be activated in order to differentiate into plasma cells. - B cells are activated by receiving signals from CD4+ T cells.

Question 36

Define cognate interaction.

Answer 36

The interaction between dendritic cells, CD4+ T cells and activation-induced B cells during T-dependent responses.

Question 37

List 4 molecules that are involved in cognate interaction. On which cells are these molecules found?

Answer 37

1 - CD40 (B cells). 2 - CD40L (T cells). 3 - ICOSL (B cells). 4 - ICOS (T cells).

Question 38

List 4 cytokines that reinforce the signals provided by cognate interaction.

Answer 38

1 - IL-4. 2 - IL-6. 3 - IL-21. 4 - IFN gamma.

Question 39

Describe the process of cognate interaction between a B and T cell. Where does this interaction take place?

Answer 39

- A physical cell-cell interaction must occur between B and CD4+ T cells, which requires B cell binding an antigen via the BCR, then processing and presenting the antigen to the T cell. - The interaction is either MHCII-TCR or CD40-CD40L. - This interaction occurs in the T zone of lymph nodes or the spleen.

Question 40

Where in secondary lymphoid organs are B cells activated by T cells in response to T-dependent antigens? List 2 possible locations where antigen-activated B cells migrate after being activated by a T cell. What happens to the B cells once they migrate to these areas?

Answer 40

- B cells can be activated in the T zone. They then migrate to: 1 - To the medullary cords, where they differentiate into extrafollicular plasmablasts. 2 - To the follicles, where they form germinal centres.

Question 41

How does the initiation of T-independent antibody responses differ from that of T-dependent responses?

Answer 41

With T-independent responses, there is no cognate interaction between dendritic cells, T cells and B cells, so B cells travel through the T zone as antigen-activated B cells and migrate to the medullary cords where they differentiate.

Question 42

List 4 cells that can be found in a germinal centre.

Answer 42

1 - Centroblasts. 2 - Centrocytes. 3 - Follicular dendritic cells. 4 - Follicular T helper cells.

Question 43

Describe the organisation of a germinal centre.

Answer 43

- A dark zone and a light zone form two halves of the inner circle. - The mantle zone surrounds the inner circle.

Question 44

What are centroblasts? Where are they found?

Answer 44

- Proliferating B cells that undergo somatic hypermutation for affinity maturation. - They are found in the dark zones of germinal centres.

Question 45

What are centrocytes? Where are they found?

Answer 45

- B cells that have undergone affinity maturation (as centroblasts) and are out of the cell cycle. - They are found in the light zones of germinal centres.

Question 46

What is the function of follicular dendritic cells? Where are they found?

Answer 46

- They are involved in the selection of memory B cells by presenting antigens to potential memory cells, of which only centrocytes with high affinity B cell receptors can bind (centrocytes compete for this antigen). - They are found in the light zone of the germinal centre.

Question 47

What are follicular T helper cells? Where are they found?

Answer 47

- T cells that give survival signals to centrocytes. | - They are found in the light zone.

Question 48

What is activation-induced cytidine deaminase (AID)? What is its function?

Answer 48

- A protein expressed in B cells. | - It is required for class switch recombination and Ig V gene hypermutation.

Question 49

What is B cell lymphoma-6?

Answer 49

The master transcription factor for commitment of germinal centre B cells, and is required for the generation of follicular CD4+ T cells.

Question 50

Which interleukin is important for the generation of follicular CD4+ T cells?

Answer 50

IL-21.

Question 51

What is blimp-1?

Answer 51

A transcription factor required for the plasma cell programme.

Question 52

After priming by a T cell, what is the functional difference between B cells that migrate to extrafollicular areas in the medullary cords and B cells that undergo a follicular response?

Answer 52

- In extrafollicular responses, B cells differentiate to become IgM and IgG plasma cells, producing antibody of modest affinity (similar to T-independent responses). - In follicular responses, B cells form germinal centres that give rise to class-switched plasma cells, producing antibody of high affinity and to memory B cells.

Question 53

Where does Ig V gene hypermutation occur?

Answer 53

In centroblasts in the dark zone.

Question 54

Summarise the germinal centre reaction.

Answer 54

1 - A centrocyte that has emerged from the dark zone as a centroblast having undergone somatic hypermutation and exited the cell cycle competes for a specific antigen bound to follicular dendritic cells. 2 - In the light zone, a centrocyte that has bound an antigen on a dendritic cell seeks cognate interaction with a follicular T cell. 3 - The selected centrocytes are activated and differentiate into plasma cells or memory B cells, and those that are not selected die by apoptosis.