1.06 - B-Cells & Antibodies Flashcards

1
Q

What are antibodies?

A

Proteins secreted by activated B cell
The same protein is located on the B-cell surface but is then known at the B-Cell receptor
Each B-Cell secretes a unique protein

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2
Q

What can antibodies bind to?

A

A variety of substances
Proteins
Lipids
Polysaccharides

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3
Q

What is the affinity of antibodies?

A

It is the binding strength between the antibody and antigen at a single binding site

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4
Q

What are the roles of antibodies in the immune system?

A

Neutralisation: antibodies prevent bacterial adherence and also block toxins from working
Opsonisation: surrounding a cell or microorganism and marking it for phagocytosis
Complement activation: Antibodies bound to target will activate complement cascade

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5
Q

Describe the structure of antibodies

A

Consist of four chains: 2 heavy (joined by sulphide bonds) and 2 light chains.
Each chain contains a variable and constant region
The constant region determines the antibody isotope
The variable region determines antibody specificity
The variable region contains three areas of increased variability known as complementarity determining regions (CDRs)

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6
Q

What are the five antibody isotypes?

A
IgG
IgM
IgA
IgE
IgD
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7
Q

What are the effector functions of IgG?

A

Opsonisation of antigens for phagocytosis by macrophages and neutrophils
Activation of classical pathway of complement
Antibody-dependent cell-mediated cytotoxicity mediated by natural killer cells
Neonatal immunity: transfer of maternal antibody across the placenta and gut
Feedback inhibition of B cell activation

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8
Q

What are the effector functions of IgM?

A

Activation of the classical pathway of complement

Antigen receptor of naive B lymphocytes

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9
Q

What are the effector functions of IgA?

A

Mucosal Immunity: secretion of IgA into the lumen of the GIT and respiratory tracts
Activation of complement by the lectin or alternative pathway

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10
Q

What are the effector functions of IgE?

A

Mast cell degranulation (immediate hypersensitivity reactions

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11
Q

What are the effector functions of IgD?

A

Antigen receptor of naive B lymphocytes

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12
Q

What are the structures of the 5 antibody isotypes?

I.e. Monomer, Dimer etc.

A
IgG: Monomer
IgM: Pentamer
IgA: Dimer
IgE: Monomer
IgD: Monomer
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13
Q

Which antibody type is not secreted?

A

IgD

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14
Q

What are the two separate steps in the generation of antibody diversity?

A

VDJ recombination: different genes are randomly selected during B cell maturation
B cell receptor is mutated in germinal centre during an immune response to increase its affinity for the antigen

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15
Q

Describe the process of B-cell receptor light chain rearrangement and production

A

Germline DNA contains 4 segments: L-V—J–C
Somatic recombination joins the V & J segment in the rearranged DNA: L-VJ–C
Transcription then occurs to produce primary transcript RNA: L-VJ–C
Splicing of the RNA removes the introns and brings the L and VJ segments together as well as the VJ next to the C: LVJC
Translation of the mRNA produces the functional polypeptide chain that is sent to the cell surface

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16
Q

Describe the process of B-cell receptor heavy chain rearrangement and production

A

Germline DNA contains 5 segments: L-V—D—J–C
The C region contains 4 exons (3 for constant region. 1 for hinge region)
Somatic recombination brings D-J segments together in rearranged DNA: L-V—DJ-C
Another stage of somatic recombination brings the V to the DJ segment: L-VDJ—C
Transcription forms primary transcript RNA: L-VDJ–C
Splicing of the introns forms mRNA: LVDJC
Translation forms the functional polypeptide chain that is sent to the cell surface

17
Q

What are the names given to the cell in each stage of B-Cell development?

A
Stem Cell
Early Pro-B cell
Late Pro-B-cell
Large pre-B-cell
Small pre-B-cell
Immature B cell
Mature B cell
18
Q

Describe the Stem Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: Germline
L-Chain Genes: Germline
Surface Ig: Absent

19
Q

Describe the Early Pro-B-Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: D-J Rearranging
L-Chain Genes: Germline
Surface Ig: Absent

20
Q

Describe the Late Pro-B-Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: V-DJ Rearranging
L-Chain Genes: Germline
Surface Ig: Absent

21
Q

Describe the Large Pre-B-Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: VDJ Rearranged
L-Chain Genes: Germline
Surface Ig: u Chain transiently at surface as part of pre-B-cell receptor. Mainly intracellularly

22
Q

Describe the Small Pre-B-Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: VDJ Rearranged
L-Chain Genes: V-J Rearranging
Surface Ig: Intracellular u chain

23
Q

Describe the Immature B-Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: VDJ Rearranged
L-Chain Genes: V-J Rearranged
Surface Ig: IgM expressed on cell surface

24
Q

Describe the Mature B-Cell in B cell development, with relation to H-Chain genes, L-chain genes and any surface Ig present

A

H-Chain Genes: VDJ Rearranged
L-Chain Genes: V-J Rearranged
Surface Ig: IgD and IgM made from alternatively spliced H-chain transcripts expressed on cell surface

25
Q

Where are the two main phases of B-Cell development located?

A

Bone marrow and Periphery

26
Q

Where are B-cells located?

A

Developing B-cell and long-lived plasma cells are found in the bone marrow
Mature B-cells are found in the spleen and lymph nodes and circulate in the blood

27
Q

Describe T-Dependent Antibody Synthesis

A

Antibody synthesis in response to protein antigens
Leads to formation of germinal centre
Leads to formation of memory B cells and long-lived plasma cells
Gives rise to secondary humoral response

28
Q

What are the stages of T-Dependent antibody synthesis?

A
Activation and migration of T and B lymphocytes
T:B cell interaction
B-cell differentiation: Ig secretion, isotype class switching
Germinal centre reaction: affinity maturation, long lived plasma cells, isotype switching, memory B cells
29
Q

What are the two things B cells can do after activation at the T:B cell border?

A

Move to the extra follicular area and become plasma blasts and plasma cells and secrete antibody
Move to the follicle and proliferate becoming a germinal centre to make a higher quality antibody

30
Q

What interaction is important for class switching of antibodies?

A

CD40 on B-cells and CD40L on helper T cells

31
Q

Describe the germinal centre

A

B-cells in the follicle rapidly proliferate generating the germinal centre
Centroblasts are rapidly proliferating germinal centre B cells in which the B cell receptor is being mutated
Centrocytes are germinal centre B cells that reexpress their new B cell receptor to check whether it is of higher affinity
Centrocytes with Bcell receptors of higher affinity get survival signals from follicular dendritic cells and T cells

32
Q

Describe somatic hypermutation

A

Process by which germinal centre B cells mutate their B cell receptor to increase its affinity
Random mutations (some advantageous, some deleterious) are made by special enzymes expressed in these cells
Accumulation of advantageous mutations is known as affinity maturation
B cells with B cell receptors with higher affinity for the antigen survive and become memory B cells and long- lived plasma cells

33
Q

What are AID and UNG and what is their function?

A
They are enzymes important for somatic hypermutation and class switching recombination
Mutate and remove certain residues to cause mutation
34
Q

Describe class switch recombination

A
Also known as isotype switching
Make an antibody type that is appropriate for a particular function
Class switch to IgA, IgG or IgE
While germinal centre formation is not absolutely required for class switch recombination, most affinity matured B cells will make IgG antibody
35
Q

What are the two phases of B cell maturation?

A

Antigen independent B cell maturation

Antigen dependent B cell maturation

36
Q

Describe Antigen independent B cell maturation

A

Occurs in bone marrow and involves production of naïve B cell from stem cell progenitor
Genes rearranged to make functional B cell receptor
Receptor editing occurs if B cell receptor is not functional
B cells that bind strongly to antigen are removed

37
Q

Describe Antigen dependent B cell maturation

A

Occurs after naïve B cell encounters an antigen that binds its receptor
Rearranged VDJ segments mutated to make higher affinity antibodies
B cells that bind strongly to antigen are given survival signals

38
Q

Describe Plasma Cells

A

Antibody producing cells
No longer have cell surface B-Cell receptor
Increased cytoplasm and rough ER

39
Q

Describe T independent B cell responses

A

B cells can be activated by cross-linking of multiple B cell receptors, in the absence of T cells
This requires multivalent antigen - usually bacterial polysaccharides, lipopolysaccharides or multimeric proteins
T independent reactions do not result in germinal centre reactions, somatic hypermutation, memory B cells or long-lived plasma cells