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IIH > B Cell Development and the Function of Antibodies > Flashcards

B Cell Development and the Function of Antibodies Flashcards

1
Q

Describe the generic structure of an antibody.

A
  • 2 light chains (a combination of kappa or lambda) and 4 heavy chains (a combination of IgG,A,M,E or D).
  • Disulfide bonds connect to heavy chains and light chains.
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2
Q

List 3 diseases that affect antibody production.

A

1 - X-linked agammaglobulinaemia (XLA).

2 - Common variable immune deficiency (CVID).

3 - Hyper IgM syndrome.

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3
Q

From which cells are antibodies derived?

A

B cells.

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4
Q

List the cells that generic B cells may develop into.

A

1 - Plasma cells (primary antibody producing cells).

2 - Memory B cells.

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5
Q

Describe the processes involved in B cell development.

A

1 - B cell precursor rearranges its immunoglobulin genes.

2 - Immature B cells that are bound to self cell-surface antigens are removed from the repertoire of B cells.

3 - B cells that are bound to foreign antigens are activated.

4 - Activated B cells give rise to plasma cells and memory cells.

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6
Q

During transcription and translation of immunoglobulin genes, which chains of an antibody are expressed first?

In which order are the genes of this chain rearranged?

Once this chain has undergone all rearrangements, is it found intracellularly or on the cell surface?

What is the name of an immature B cell that is in this stage of development?

A
  • The heavy chains.
  • Diversity (D) and joining (J) genes are rearranged first.
  • D and J genes are then rearranged with variable (V) genes.
  • After rearrangement of the heavy chain, it is still mostly intracellular.
  • B cells undergoing this stage of development are known as pro B cells.
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7
Q

During transcription and translation of immunoglobulin genes, which chains of an antibody are expressed last?

In which order are the genes of this chain rearranged?

Once this chain has undergone all rearrangements, is it found intracellularly or on the cell surface?

What is the name of an immature B cell that is in this stage of development?

A
  • The light chains.
  • All variable (V), diversity (D) and joining (J) genes are rearranged simultaneously.
  • After rearrangement of the light chain, the immunoglobulin is expressed on the cell surface.
  • B cells undergoing this stage of development are known as pre B cells.
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8
Q

Give an example of an immunoglobulin that is expressed:

1 - In both mature and immature B cells.

2 - In mature B cells only.

A
  • IgM is expressed in both immature and mature B cells (however in mature B cells it is sIGM as it is secreted).
  • IgD is only expressed in mature B cells.
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9
Q

What is the difference between IgM and IgD with regards to their production?

A

They are made from alternative splicing of the heavy chain transcripts.

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10
Q

Which genes are needed for recombination?

A

RAG genes.

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11
Q

If an antibody chain is produced from the paternal chromosome, can recombination occur with the maternal chromosome?

What about the other way around?

A

Rearrangements can occur from either inherited chromosome, but only one chromosome is used at a time.

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12
Q

What proportion of gene rearrangement joins are successful?

A

30%.

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13
Q

Describe the process of allelic exclusion in developing B cells.

What is the purpose of allelic exclusion?

A
  • Successful rearrangement of the kappa gene results in the shutting down of rearrangement of genetic material from the lambda gene.
  • If no successful rearrangement occurs with the kappa gene, rearrangement of the lambda gene takes place. If this fails, the cell dies.
  • This ensures that a B cell produces antibody of one specificity, as rearrangement must take place.
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14
Q

What is the kappa:lambda ratio of light chains in humans?

A

2:1 - 3:1.

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15
Q

How is further recombination stopped once the immunoglobulin is finished?

A

By preventing the expression or function of RAG.

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16
Q

List the fates of an immature B cell that expresses immunoglobulins that respond to self antigens.

What is this process called?

A

1 - Apoptosis occurs.

2 - The B cell undergoes receptor editing to change their surface immunoglobulins so that they no longer respond to self antigens.

3 - They migrate to the periphery and become anergic (unresponsive) B cells.

  • This process is known as negative selection.
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17
Q

Describe the environment of the bone marrow in which B cells differentiate and proliferate.

A
  • Stromal cells form a network in the spaces of the bone cavity that extends from the endosteum to the endothelial cell basement membrane of the sinusoidal vessels that supply the bone.
  • Hematopoietic cells differentiate and proliferate in this environment.
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18
Q

List the binding sites of a generic antibody.

A

1 - 2x antigen binding sites (where there are two heads, each containing one light chain and one heavy chain).

2 - 1x fc receptor binding site (where there is one head containing two heavy chains).

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19
Q

Which binding site of an antibody confers specificity?

A

The antigen binding site.

20
Q

Which antibody binding site confers function?

A

The fc receptor binding site.

21
Q

What determines the properties of an antibody fc receptor binding site?

A

The type of Ig heavy chain used.

22
Q

List the types of immunoglobulin heavy chains.

For each, state the function an antibody will have if this immunoglobulin is used.

A

1 - IgD, bound to naive B cells.

2 - IgM, bound to naive B cells (in the serum).

3 - IgG, used for memory B cells (in the serum).

4 - IgE, binds to mast cells.

5 - IgA, used in mucosa (and also in the serum).

23
Q

List the immunoglobulins in order of levels in the serum.

A

1 - IgG.

2 - IgA.

3 - IgM.

4 - IgD.

5 - IgE.

24
Q

List the antibodies that are involved in the classical pathway of complement activation.

A

1 - IgG.

2 - IgM.

25
Q

Which antibody is involved in the alternative pathway of complement activation?

A

IgA.

26
Q

Which antibody is involved in placental transfer?

A

IgG

27
Q

List the antibodies that bind to macrophage and phagocyte fc receptors.

A

1 - IgG.

2 - IgM.

3 - IgA.

4 - IgE.

*All apart from IgD.

28
Q

Which antibody has a high affinity to the receptors on mast cells and basophils?

A

IgE.

29
Q

Which antibodies react to staphylococcal protein A?

A

IgG.

30
Q

Which antibodies often exist as pentamers or dimers?

What links the antibodies?

A
  • IgM and IgA.

- J chains link the antibodies.

31
Q

What is the difference between affinity and avidity?

A
  • Affinity is the strength of an interaction between two molecules.
  • Avidity is the total strength of all non-covalent interactions between an antigen and an antibody / a complex of antibodies.
32
Q

What is the advantage of antibodies forming complexes consisting of multiple antibodies?

A

It increases avidity as an antibody complex consisting of multiple individual antibodies will only lose binding to an antigen if all constituent antibodies fail to bind.

33
Q

What is required of IgA in order for secretion to be possible?

A

IgA must form a dimer.

34
Q

List 3 functions of dimerised IgA in the gut.

A

1 - Secreted IgA on the gut surface can bind and neutralise pathogens and toxins.

2 - IgA is able to bind and neutralise antigens internalised in endosomes.

3 - IgA can export toxins and pathogens from the lamina propria while being secreted.

35
Q

What is the result of IgE binding to mast cells?

A

Initiation of the acute inflammatory reaction.

36
Q

Define epitope.

A

The part of an antigen to which an antibody binds.

37
Q

List 4 non-covalent forces that determine the shape of an antibody-antigen complex.

A

1 - Electrostatic forces.

2 - Hydrophobic forces

3 - Van der Waals forces.

4 - Hydrogen bonds.

38
Q

What is the advantage of antibodies having two arms for binding sites?

A

It allows them to crosslink antigens to form immune complexes for easier removal.

39
Q

List 3 functions of antibodies.

A

1 - Neutralisation.

2 - Opsonisation.

3 - Complement activation.

40
Q

Via which receptors do immune cells recognise antibody-coated antigens?

What action do antibodies have upon binding these receptors?

What does stimulation of these receptors do?

A
  • Fc gamma receptors.
  • Antibody binding to these receptors can either cause stimulation or inhibition.
  • Stimulation may lead to phagocytosis of the antibody-coated antigen and the cell to which the antigen is bound.
41
Q

How are immune cells able to recognise infected host cells?

A

Pathogen derived antigens are sometimes localised to the host cell membrane, where antibodies can bind to them.

42
Q

Give an example of a strategy that pathogens have evolved to avoid the actions of antibodies.

Which pathogen uses this strategy?

A
  • By developing a protective capsule that prevents the activation of complement proteins.
  • Used by Staphylococci.
43
Q

What is the difference between T-dependent and T-independent antibody responses?

A
  • T-dependent antigens can stimulate B cells to become activated but require cytokine assistance delivered by helper T cells.
  • T-independent antigens can stimulate B cells to become activated and secrete antibodies without assistance from helper T cells.
44
Q

What is the dominant antibody involved in T-dependent responses?

What other antibodies might be involved?

A
  • IgG.

- Also sometimes IgA and IgE.

45
Q

What is the dominant antibody involved in T-independent responses?

What other antibodies might be involved?

A
  • IgM.

- Also sometimes IgG.

IIH (26 decks)

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