B and T Cell Cooperation Flashcards
Why do primary adaptive responses develop slowly?
Because naive T and B cells that recognise a new foreign antigen are few in number.
Which component of an antibody determines its effector function?
The type of heavy chain used.
Which phase precedes the response to a new foreign antigen in a primary response?
The lag phase.
*This is absent in a secondary response.
List 4 differences between a primary response and a secondary response.
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.
Define somatic hypermutation.
A cellular mechanism by which a B cell adapts its antibody production to foreign antigens.
What is a T independent antigen?
An antigen that causes antibody production by B cells without T cell involvement.
How does antibody production in the primary and secondary response differ in response to T independent antigens when compared to T dependent antigens?
- 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.
List the two most common locations where lymphocytes are found.
1 - In lymph nodes.
2 - In the spleen.
How long will an individual lymphocyte remain in a lymph node before migrating?
12-24 hours.
Via which structures do lymphocytes enter lymph nodes?
1 - High endothelial venules.
2 - Afferent lymph vessels.
Via which structures do lymphocytes exit lymph nodes?
Efferent lymphatic vessels.
List the two lymph ducts.
1 - Thoracic duct.
2 - Right lymphatic duct.
Where does lymph empty into from the lymph ducts?
The venous circulation.
What is the difference between primary and secondary lymphoid organs?
- Primary lymphoid organs generate lymphocytes from immature progenitor cells.
- Secondary lymphoid organs are the locations where lymphocytes are activated.
List the 2 primary lymphoid organs.
List 5 secondary lymphoid organs.
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).
List 8 locations where mucosa associated lymphoid tissue (MALT) is found.
1 - GI tract.
2 - Nasopharyngeal tract.
3 - Thyroid gland.
4 - Breast.
5 - Lungs.
6 - Salivary glands.
7 - Eyes.
8 - Skin.
Why is it advantageous for lymph to circulate around the body?
To increase the chances of encountering an antigen.
How many lymph nodes are there in the body?
700.
What enters lymph nodes via afferent lymph vessels?
Dendritic cells.
List the layers of a lymph node.
1 - Cortex.
2 - Paracortex (T zone).
3 - Medulla.
What is contained within the cortex of a lymph node?
Follicles.
What are germinal centres?
Where are they located?
- 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.
In which area of a lymph node do high endothelial vessels empty?
The paracortex (T zone).
What is meant by an extrafollicular antibody response?
Where does extrafollicular growth occur?
Where does follicular growth occur?
- 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.
List 2 cells that can be found within the medulla of a lymph node.
1 - Plasma cells.
2 - Macrophages.
Describe the histological organisation of the spleen.
- 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.
List 3 cells that can be found within the red pulp of the spleen.
1 - Macrophages
2 - RBCs.
3 - Platelets
List 3 cells that can be found within the white pulp of the spleen.
1 - Dendritic cells.
2 - T cells.
3 - B cells.
List 4 characteristics of T-dependent antibody responses.
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.
What type of antibody responses occur in extrafollicular foci?
Both T-dependent and T-independent responses.
What type of antibody responses occur in germinal centres in the spleen?
T-dependent responses only.
List the processes that occur at the beginning of antibody responses to protein antigens.
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.
List 4 molecules involved in the presentation of specific antigen fragments upon endocytosis of an antigen.
1 - MHC class 2.
2 - CD80.
3 - CD86.
4 - CD40.
What is the difference between B cell and dendritic cell uptake of antigens?
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.
What is B cell activation necessary for?
How are B cells activated?
- B cells must be activated in order to differentiate into plasma cells.
- B cells are activated by receiving signals from CD4+ T cells.
Define cognate interaction.
The interaction between dendritic cells, CD4+ T cells and activation-induced B cells during T-dependent responses.
List 4 molecules that are involved in cognate interaction.
On which cells are these molecules found?
1 - CD40 (B cells).
2 - CD40L (T cells).
3 - ICOSL (B cells).
4 - ICOS (T cells).
List 4 cytokines that reinforce the signals provided by cognate interaction.
1 - IL-4.
2 - IL-6.
3 - IL-21.
4 - IFN gamma.
Describe the process of cognate interaction between a B and T cell.
Where does this interaction take place?
- 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.
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?
- 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.
How does the initiation of T-independent antibody responses differ from that of T-dependent responses?
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.
List 4 cells that can be found in a germinal centre.
1 - Centroblasts.
2 - Centrocytes.
3 - Follicular dendritic cells.
4 - Follicular T helper cells.
Describe the organisation of a germinal centre.
- A dark zone and a light zone form two halves of the inner circle.
- The mantle zone surrounds the inner circle.
What are centroblasts?
Where are they found?
- Proliferating B cells that undergo somatic hypermutation for affinity maturation.
- They are found in the dark zones of germinal centres.
What are centrocytes?
Where are they found?
- 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.
What is the function of follicular dendritic cells?
Where are they found?
- 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.
What are follicular T helper cells?
Where are they found?
- T cells that give survival signals to centrocytes.
- They are found in the light zone.
What is activation-induced cytidine deaminase (AID)?
What is its function?
- A protein expressed in B cells.
- It is required for class switch recombination and Ig V gene hypermutation.
What is B cell lymphoma-6?
The master transcription factor for commitment of germinal centre B cells, and is required for the generation of follicular CD4+ T cells.
Which interleukin is important for the generation of follicular CD4+ T cells?
IL-21.
What is blimp-1?
A transcription factor required for the plasma cell programme.
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?
- 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.
Where does Ig V gene hypermutation occur?
In centroblasts in the dark zone.
Summarise the germinal centre reaction.
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.
