Adaptive Immunity - B cells

Question 1

Where do B cells mature?

Answer 1

In the bone marrow

Question 2

Where are B cells found?

Answer 2

Circulate in the blood and the lymph and are found in large numbers in lymphoid organs

Question 3

How do B cells recognise antigens?

Answer 3

Through B cell receptors which are the actual antibodies against the antigen they respond to (IgM or IgD)

Question 4

What does ‘diversity’ in BCR mean?

Answer 4

They have the potential to respond to numerous antigens

Question 5

Once activated what do B cells change into?

Answer 5

Plasma cells which churn out lots of antibodies against that specific antigen

Question 6

What are the 3 main molecules that are involved in recognition of foreign antigen by adaptive immune system?

Answer 6

• T cell receptor
• B cell receptor (Immunoglobins)
• Major histocompatibility complex

Question 7

What allows the development of a repertoire of receptors with specificity for wide ranges of antigens?

Answer 7

Multiple genes encoding

Question 8

What 2 chains are immunoglobins made up of?

Answer 8

A heavy chain and a light chain

Question 9

What 2 regions are present in immunoglobins?

Answer 9

A constant region and a variable region

Question 10

What shape is an immunoglobin?

Answer 10

Y-shaped

Question 11

What region in immunoglobins is the region that changes between antibodies?

Answer 11

The variable region

Question 12

What does the springy section of immunoglobins allow them to do?

Answer 12

lets it bind with other molecules and cells

Question 13

How many different classes of immunoglobins are there?

Answer 13

5

Question 14

What are the main antibody functions?

Answer 14

• Neutralisation - antibody can bind to and stop from working
• Opsonisation - main function - Stick to surface of microbe
• Complement activation

Question 15

What are the main components of opsonization?

Answer 15

• Opsonized phagocytosis (IgG)
• ADCC (NK cell-mediated killing) (IgG)
• Mast cell degranulation (IgE)

Question 16

What is each development stage of B cell development defined by?

Answer 16

Rearrangements of the immunoglobin heavy and light chain genes

Question 17

How do B cell receptors generate diversity?

Answer 17

• Heavy chain involves rearrangement of Variable, Diversity and Joining genes
• Light chain rearrangement of Variable and Joining genes
• Binding site for antigen is in the variable region so cell can choose any combination of these genes to produce unique antibody binding sites

Question 18

During B cell development what are the B cell receptors?

Answer 18

• Immature B cell receptor is mainly IgM (mainly produce IgM not only on surface to act as receptor - they also release IgM)
• IgM can be classed as early receptor but main receptor is IgD
• Mature B cell express both IgM and IgD on surface

Question 19

What is negative selection in B cell development?

Answer 19

• Like the TCR there is great diversity in the B cell receptor repertoire
• Need to ensure that there is no reactivity against self antigens
• Therefore in bone marrow as B cells are developing they undergo negative selection

Question 20

What is meant by mature B cells being antigen naïve?

Answer 20

Have not yet been exposed to a foreign antigen

Question 21

How can B cell activation occur in regards to T cells?

Answer 21

In a T cell dependent or independent manner

Question 22

Whether B cells are activated by T cells or not depends on the type of antigen. What are these antigens called?

Answer 22

• Antigens which require T cell help are called thymus dependent antigens
• Antigens that don’t require T cell help are called thymus-independent

Question 23

Where does B cell activation mainly occur?

Answer 23

In lymphoid organs such as lymph nodes

Question 24

Apart from lymphoid organs where can B cell activation occur?

Answer 24

Can get naïve B cells in periphery so some peripheral activation (particularly thymus-independent)

Question 25

What does the activation of naïve B cells result in?

Answer 25

The rise of plasma cells | - Plasma cells are antibody factories

Question 26

What is the process of thymus dependent B cell activation?

Answer 26

- Interaction between T cell and BCR also requires co-receptor binding (CD40 and CD40L) to stabilise the interaction - Cytokine signals released from T helper cell induce proliferation - Generates a pool of plasma cells which produce antibody - Also generated memory B cells - Plasma cells initially produce IgM before undergoing 'class switching'

Question 27

What is meant by the term 'class switching' in thymus dependent B cell activation?

Answer 27

- Initially the plasma cells produce IgM which is quite effective, but not as effective as IgG - Eventually will stop producing IgM and will switch to IgG - IgM produce is specific for unique antigen and when switches to IgG is still specific for unique antigen - antigen binding site remains the same

Question 28

What does 'affinity' mean?

Answer 28

Strength of binding of single antibody to antigen

Question 29

What does 'avidity' mean?

Answer 29

Ability of antibodies to form complexes (antibody-antibody binding)

Question 30

How does antibody affinity and avidity increase towards antigen on secondary exposures?

Answer 30

- IgM response is weak. Cells therefore class switch to IgG (or IgA/IgE) - Occurs by gene rearrangement but antigen binding site remains the same - Repeated exposure to antigen causes affinity maturation. The antibody has increasing affinity for the antigen which produces a stronger response

Question 31

What is the process of thymus independent B cell activation?

Answer 31

- Certain antigens such as bacterial LPS can activate B cells directly - Cells differentiate into plasma cell and produce IgM however antibody response is weaker than TD B cell activation - TI B cell activation does not lead to the generation of memory B cells (no long term immunity)

Question 32

In lymphoid organs cross talk between B and T cells leads to generation of both arms of the adaptive immune response. What are the 'two arms' of the adaptive immune response?

Answer 32

- Humoral Immunity - Cellular immunity - Peak of activity of immune response is when the body has B and T cells both working optimally

Question 33

What is the primary and secondary immune response?

Answer 33

- Primary exposure to antigens leads to the development of memory - this is the primary immune response and takes time to develop - In the primary immune response IgM acts early but as B cells undergo class switching an IgG response follows - Due to the generation of memory T and B cells this means that upon a second exposure we have a pool of cells waiting to respond immediately so the response is immediate - In addition, we have cells that are primed to produce a more effective IgG (rather than IgM) response immediately - This is the basic principle of vaccination

Question 34

What is immunological tolerance?

Answer 34

- A state of immune unresponsiveness to a particular antigen or set of antigens - Immunological tolerance is an active response to a particular epitope and is just as specific as an immune response

Question 35

Which cells can be made tolerant?

Answer 35

Both B and T cells - more important to tolerise T cells as B cells cannot make antibodies to most antigens without the help of T cells

Question 36

What are the 2 main types of tolerance depending on anatomical location?

Answer 36

1. Central - occurs while developing immune cells are still present in the primary lymphoid organs (the thymus and the bone marrow), prior to export into the periphery 2. Peripheral - occurs out with thymus and bone marrow

Question 37

Where does central tolerance T cells occur?

Answer 37

Occurs in the thymus

Question 38

What is the process of central tolerance T cells?

Answer 38

- T cells have to bind to MHC molecules (but not too strongly). Those that bind with correct MHC binding survive (positive selection) - T cells must not bind to self-antigens. Those that do are eliminated (negative selection) - This process leads to elimination of over 90% of T cells - The rest emigrate to peripheral tissues and secondary lymphoid organs - However, not all self reactive T cells are eliminated

Question 39

Explain the process of peripheral tolerance T cells?

Answer 39

- Not all self reactive T cells are eliminated centrally - However, peripheral tolerance prevents their action - T cell activation is a 3 signal process - Signal 1 but no signal 2 results in anergy. APC upregulates CD80/86 in response to TLR stimulation - Signal 1 and 2 but no 3 (cytokine survival signal) results in deletion by apoptosis - Treg's can also directly block activity by binding to the antigen (both self and foreign)

Question 40

Where does central tolerance B cells occur?

Answer 40

In the bone marrow

Question 41

Explain the process of central tolerance B cells?

Answer 41

- B cell central tolerance involves negative selection only | - Therefore B cells which bind strongly to self antigen are eliminated

Question 42

Where does peripheral tolerance in B cells occur?

Answer 42

In secondary lymphoid organs

Question 43

Explain the process of peripheral tolerance in B cells?

Answer 43

- Self reactive B cells still require help from self reactive T cells - Since most self reactive T cells are eliminated, self reactive B cells do not receive T cell help and therefore become anergic - Having B and T cells that both respond to a specific self antigen is slim

Question 44

What des breach of tolerance to 'self-antigens' mean?

Answer 44

Autoimmune diseases occur where our body does attack self antigens - A breach of tolerance mans there has been a breakdown in the process somewhere