B-cells Flashcards

1
Q

What are B-cells?

A

B-cells are cells that arrise in the bone marrow thry recognise antigen via B-cell receptors and produce antivodies

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2
Q

What is the B-cell response?

A

A naive B-cell is activated once it binds an antigen- activated Bcells can become plasma cells or memory cells- these cells can reporduce via clonal expanssion

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3
Q

What are plasma cells?

A

Cells that produce antibodies (2000/second)

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4
Q

What are BCRs?

A

B cels receptors- theyre antibodies that are membrane bound

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5
Q

What is the structure of a BCR?

A

Antibodies made of two light and two heavy chains that have cosntant and variable regions theyre all held together by disulfide bonds (known as the hinge(

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6
Q

Where are antigen binding sites in antibodies?

A

Variable regions

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7
Q

Antobodies have two segments what are they?

A

Fc and FAB fragments

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8
Q

What is the Fc region of antibody?

A

The constant region with heavy chains

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9
Q

What is the FAB region?

A

Fragment of antogen binding found in the variable zone of the antibody

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10
Q

How is antobody diversity produced?

A

VDJ recombination

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11
Q

How does VDJ recombination create diversity?

A

Antobodies have loci that are spliced together but they can be spliced together in varying combinations leading to variety in antibodies

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12
Q

How is VDJ recombination of a light chain work?

A

Start with germ line DNA and splice V and J segements together RNA is then produced which is spliced to join the constant segment- then translated to a light chain

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13
Q

How does VDJ recombination occur for heavy chains?

A

V D and J regions spliced together into RNA then join constant region and are transcribed to antibodies.
Same as light chain but plus D regions

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14
Q

Where does VDJ recombination occurs?

A

At recombination signal sequences

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15
Q

Where are recombination signal sequences (RSS) found?

A

Between/ flanking VDJ segments

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16
Q

Where does VDJ recombination occur in the body?

A

Bone marrow

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17
Q

What happens when mature B-cells are activated by antigens?

A

They differentiate into plasma or memory cells

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18
Q

How can B- cells be activated?

A

Only by helper T-cells for the same antigen

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19
Q

Two types of B-cell activation?

A

Thymus dependent (T-cell) or thymus independent (no T-cell)

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20
Q

What is thymus independent activation?

A

Antigen binds directly to immune receptors on the B-cell

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21
Q

How does thymus dependent activation work?

A

TCR binds the epitope (antigen) then antigen is internalised MHC class 2 molecules present MHC through TCR and release cytokines. MHC activates B-cells

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22
Q

How do T-cells cause activation of B-cells?

A

T cells express CD40L which stimulates B-cells to proliferate and become plasma cells. Also release iL-4 droves proloferation and il-5/6 ther drive plasma cells

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23
Q

Where does B-cell proliferation occurs?

A

Germinal centres of the lymphnodes

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24
Q

How does B-cell proliferation occur in lymphnodes?

A

B-cells move into lymphnode brcoming trapped in T-cell zone so they come in contact. They then move to the germinal centre which is made up of proliferating B-cells

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25
Q

What happens in germinal centres?

A

B-cells undergo:
Somatoc hypermutation
Affinity maturation
Class switching

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26
Q

What is somatic hypermutation?

A

Introduces point mutation in the variable region of the light and heavy chain-further diversifies antibodies.

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27
Q

How does somatic hypermutation occur?

A

Its occurs using a cystine deaminase called AID- introduces nicks in DNA that are repaird leading to point mutations -requires single strand DNA

28
Q

What is affinity maturation?

A

Process of B-cell selection based on their abilities to bind to the antigen

29
Q

What happens to cells that arent specific enough for affinity maturation?

A

They lack signals need to survive so die

30
Q

What is antibody class switching?

A

Antibody classes switch from producong IgM antibodies to produces IgA to IgG to IgE. Become more specific with different C regions

31
Q

There are 3 types of antibody functions what are they?

A

Neutralisation,opsonisation and complement activation

32
Q

Whatare 3 examples of antibody neutralisation?

A
  • antobodies bind toxins
  • antibodies can block viral binding
  • can block adherence to host cells by bacteria
33
Q

What is opsonisation?

A

An example is phagocytosis which is done by macrophages neutrophils

34
Q

What is complement activation?

A

Ehancement of opsonisation leading to lysing bacteria

35
Q

What are Fc receptors?

A

They bind to the Fc portion of the antibody found on NK cells, mast cells and neutrophils- specific to each antobdot isotype

36
Q

What are the 4 antibody subclasses?

A

IgM
IgG
IgA
IgE

37
Q

What are IgM?

A

First low affinity antibodies expressed

38
Q

What are IgG?

A

Opsonises pathogens for phagocytosis

39
Q

What are IgE ?

A

Antobodies that localise with mast cells on the mucosa

40
Q

Why do we need vaccination?

A

As the humoral immune system progresses it cause higher affinity enzymes to ne produced faster

41
Q

What can B-cells differentiate into?

A

Plasma cells-release antibodies

Memory cells- for next time

42
Q

What is BCR?

A

B-cell receptor a membrane bound antibody

43
Q

Where are antigen binding sites found on BCRs?

A

Found within the variable regions

44
Q

What determines isotype of an antibody?

A

Carboxy terminus of the heavy chain

45
Q

What are Complimentary determining regions? (CDRs)

A

These are where the antigen binds

46
Q

How many CDR loops on an antigen?

A

3
CDR1/2 found on V segment of light chains
CDR3 is the most variable and found on the heavy chain

47
Q

How is antibody diversity generated?

A

VDJ recombination

48
Q

How does VDJ recombination occur?

A

It’s occurs at recombination signal sequences (RSS) RSS are brought together by the RAG complex which opens DNA allowing palindromic sequences to be added, then nucleotides are added by TdT unpair nucleotides are excised and DNA repaired.

49
Q

Where do you find RSSs?

A

At 23bp heptamer

-23bp nonamer

50
Q

How does VDJ recombination generate diversity?

A

Through combinational diversity and by junctions diversity.

51
Q

How do you generate combinational diversity in VDJ?

A

Through different combinations of gene segements

52
Q

How does junctional diversity work?

A

Generates diversity via the addition of nucleotides during recombination

53
Q

Where do B-cells develop?

A

In the bone marrow

54
Q

How can B-cells be activated?

A

Thymus dependently

Thymus independently

55
Q

How does thymus dependent activation work?

A

APC binds epitope and internalises. Presented on MHC2 molecule. T-helper recognises through TCR and release cytokines. B-cell then release specific antigens

56
Q

What does CD40L do on T-cells?

A

Stimulates B-cells to proliferate and become plasma cells

57
Q

What does interleukin-4 do?

A

Drives B-cell proliferation

58
Q

What do interleukin-5/6 do?

A

Drives plasma cell production.

59
Q

What happens in a germinal centre?

A

B-cell passed through T-cell zone and become trapped until contact a T-cell presented antigen. They then move into the germinal centre where they displace old B-cells into the mantle.

60
Q

What happen to B-cells in germinal centres?

A

They undergo
Somatic hypermutation
Affinity maturation
Class switching

61
Q

How does somatic hyper mutation occur?

A

Induces point mutations in the variable regions of antibodies. This is by AID (cystine deamination) introducing a nick in the DNA that is then repaired.

62
Q

What is affinity maturation?

A

Mutated B-cells are selected based on their ability to bind antigen. More survival signals sent to those who aren’t more specific.

63
Q

What is class switching?

A

DNA recombination that Changes the constant region of the heavy chain. IgG IgA and IgE

64
Q

What do IgG antibodies do?

A

Opsonise pathogens for phagocytosis

65
Q

What do IgA antibodies do?

A

Functions on epithelial surfaces -neutralisation of toxins and binding prevention

66
Q

What’s the role of IgE?

A

Localise mast cells

67
Q

What does BLIMP 1 do?

A

Switches off proliferation and affinity maturation