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Life protection > I&I humoral immune system > Flashcards

I&I humoral immune system Flashcards

1
Q

What antibodies to mature B cells express?

A

Mature naïve B cells express a membrane-bound IgM and IgD

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2
Q

What do membrane IgM act as?

A

Membrane IgM acts as B cell Ag receptor (B cell receptor/BCR)

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3
Q

What are the steps in B cell activation with IgM?

A

Ag recognition by membrane IgM => activation of signalling
pathways => B cell activation

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4
Q

What is IgD co-expressed with?

A

IgD is co-expressed with IgM on mature naïve B cells

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5
Q

What is the 1st immunoglobulin to be produced?

A

IgM is the 1st immunoglobulin to be produced; Ag receptor

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6
Q

What is IgD produced at the same time as?

A

IgD is produced at the same time with IgM

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7
Q

What is the mechanism by which allows co-expression of IgM and IgD?

A

-Differential splicing
–Exons for Cμ and Cδ are transcribed as part of a single
precursor RNA
–Differential splicing can remove Cμ exons => now Cδ exons are
used => IgD (same VDJ as IgM joined to Cδ)

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8
Q

Where are follicular B cells found?

A

Spleen, lymph nodes

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9
Q

What do follicular B cells recognise?

A

recognise protein antigens => antibodies (anti-protein Ag)

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10
Q

What do follicular B cells produce?

A

produce mainly high-affinity IgG class/switched antibodies

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11
Q

Where are marginal zone B cells?

A

Spleen and lymph node

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12
Q

What do marginal zone B cells recognise?

A

recognise polysaccharide; glycolipid; nucleic acid antigens

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13
Q

What antibodies to marginal zone B cells produce?

A

produce mainly IgM class antibodies

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14
Q

Where are B-1 B cells found?

A

Peritoneal cavity
Mucosal tissue

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15
Q

What do B-1 B cells recognise?

A

recognise polysaccharide; glycolipid; nucleic acid antigens

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16
Q

What do B-1 B cells produce?

A

produce mainly natural low-affinity IgM class antibodies

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17
Q

What signals do B cells need in order to produce antibodies?

A

-helper T cell dependent B cell responses
-helper T cell dependent antibodies

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18
Q

What do B cells produce mainly?

A

produce mainly high-affinity IgG class/switched antibodies

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19
Q

How are B cell zone/follicles and T cell zone connected?

A

-Linked recognition
-Sustained contact by SLAM family
-Receptors and cytokines for B cell activation

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20
Q

What must B cells and Helper T cells recognise in order to interact?

A

B cells and Helper T cells must recognise epitopes of the same molecular complex in order to interact

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21
Q

What are the steps involved in B cell proligeration and differentiation?

A
  1. Naive B cells travel to the lymph node via the bloodstream and leave via the efferent lymph
  2. B cells that encounter antigen in the follicle form a primary focus. Some proliferating B cells migrate into the follicle to form a germinal center
  3. Plasma cells that migrate to the medullary cords or leave via the efferent lymphatics
  4. Plasma cells migrate to the bone marrow
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22
Q

What happens to B cells in the germinal centre?

A

Sustained B cell proliferation and differentiation.

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23
Q

What happens in size to the germinal centre with an immune response and once the infection clears?

A

Grows in size with immune response,
disappears when infection cleared

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24
Q

What B cell survives in the germinal centre?

A

Survival of B cell that has a high affinity for the
antigen

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25
Q

What is the goal of affinity maturation?

A

Production of high affinity antibodies = more
efficient

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26
Q

What is the affinity like for antibodies produced early during primary immune response?

A

Abs produced early during primary (1st) immune response
have lower affinity (weak binding) for antigen

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27
Q

What happens to affinity as you move later in the first immune response/2nd immune response?

A

Later 1st immune response/ 2nd immune responses =>
production of high affinity antibodies

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28
Q

What process increases affinity of antibodies over the immune response?

A

Achieved through process of Somatic Hypermutation

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29
Q

What signals are needed for affinity maturation?

A

Affinity maturation needs signals from helper T cells

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30
Q

What is somatic hypermutation?

A

Process of introducing mutations in the variable region of
Immunoglobulins (rearranged VDJ/VJ)

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31
Q

What is somatic hypermutation initiated by?

A

Initiated by enzyme AID expressed in Germinal centre B cells only.

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32
Q

What do higher affinity antibodies do to proliferation of B cells?

A

Higher affinity antibodies => stronger cell signalling; faster
proliferation of B cells => advantage over low affinity B cells

33
Q

What is the effect on Ag recognition by somatic hypermutation?

A

-Somatic mutations in Ig V genes lead to selection of high-affinity B cells

34
Q

Where is somatic hypermutation localised in?

A

Somatic hypermutation is localised in rearranged VDJ or
VJ (corresponding to variable region)

35
Q

What are B cells with high affinity selected for?

A

B cells with high affinity Ag receptors are selected
to survive

36
Q

What do B cells with low affinity fail to do?

A

B cells with low affinity Ag receptors may fail to
survive

37
Q

Where is competition for Ag recognition and what zone is this?

A

Competition for Ag recognition on follicular
dendritic cells in the germinal centres ( light zone)

38
Q

What is there preferential selection of in affinity maturation?

A

Preferential selection of B cells with high affinity Ag
receptors during immune responses- those that
have successfully presented to TfH cells, and
received survival signals.

39
Q

What are the steps invovlved in B cell selection in germinal centers?

A
  1. B cell activation by protein antigen and helper T cells
  2. B cells with somatically mutated Ig V genes and Igs with varying affinities for antigen
  3. B cells encounter antigen on follicular dendritic cells(FDC) and present antigen to TFH cells
  4. B cells with high affinity antigen receptors preferentially recognise antigen on FDCs, interact with TFH cells and are selected to survive
40
Q

What type of proteins are antibodies?

A

Tetrameric proteins

41
Q

What is the structure of antibodies?

A

2 identical heavy chains
2 identical light chains

42
Q

What are the chains in antibodies held together by?

A

held together by disulphide bonds

43
Q

What is the structure of heavy chain in antibodies?

A
  • 3-4 constant domains
  • 1 Variable domain
44
Q

What is the structure of light chain in antibodies?

A

-1 Constant domain
-1 Variable domain

45
Q

What is the difference in variable domains between different immunoglobulins?

A

amino acid sequence varies highly
between different immunoglobulins

46
Q

What domains make up the antigen binding site?

A

Variable domain of heavy and light chain

47
Q

What is the function of antibodies?

A

Binding to extracellular microbes and toxins
-Neutralisation
-Elimination via
–Opsonisation which increases phagocytosis
-Complement activation
–Opsonisation
–Lysis

48
Q

What is isotype switching?

A

Its where B cells become capable to produce Abs of different classes but without changing specificity(respond to the same Ag)

49
Q

In isotype switching, what does IgM switch to?

A

IgG, IgA, IgE

50
Q

In isotype switching what does IgG switch to?

A

IgA, IgE

51
Q

What does isotype switching in antibodies give the ability to perform?

A

ability to perform different effector functions

52
Q

What can isotype switching in antibodies deal better with?

A

Can deal better with pathogens

53
Q

What does isotype switch need signals from?

A
  • isotype switch needs signals from helper T cells
54
Q

What does isotype switching not alter?

A

-Isotype switching does not alter specificity for Ag
-Isotype switching does not alter the light chain

55
Q

How do T cells help with Ab isotype switch?

A
  1. CD40L on T cell interacts with CD40 on activated B
    cells
  2. Cytokines produced by T cell
56
Q

What does the cytokine IFN-gamma isotype switch to?

A

=> switch to IgG1, IgG3

57
Q

What does the cytokine IL-4 isotype switch to?

A

IL-4 => switch to IgE

58
Q

What does the cytokine TGF-beta, IL-5 isotype switch to?

A

TGF-beta, IL-5 => switch to IgA

59
Q

What are the steps in DNA rearrangement in isotype switching?

A
  • Initiated by AID at switch regions
  • Removal of entire intervening DNA
    sequences between switch regions
  • Ligation of the original switch region and
    new switch region
60
Q

What are the steps involved in B cell selection in germinal centers?

A
  1. Activation of B cells and migration into germinal center
  2. B cell proliferation
  3. Somatic mutation and affinity maturation; isotype switching
  4. Exit of high affinity antibody-secretinig memory and B cells
61
Q

What is the effector function of the Fab region of antibodies?

A

Fab - bind and neutralise/block entry of Ags

62
Q

What is the effector function of Fc portion of antibodies?

A

Fc portion- complement activation, interaction with other cells with Fc receptors e.g. macrophages

63
Q

What are the steps involved in hypervariable regions and antigen binding?

A
  • Amino acid (aa) residues in hypervariable
    regions make contact with aa residues in the the
    antigen
  • Binding of diverse antigens by antibodies is
    mainly due to hypervariable regions of VH and VL
  • The rest of the variable region forms a
    framework => keeps hypervariable regions in
    position to interact with the antigen
64
Q

What are the steps involved in clonal selection?

A
  • Lymphocyte clones specific for ~10^7-10^9 antigens
  • Present before exposure to antigen
  • In the presence of Infection, Antigens are
    recognised by lymphocyte clone with the specific
    antigen receptor for that antigen
    => expansion of antigen-specific clone
    => generation of Abs specific for that Ag only
65
Q

How many gene segments is the variable region in heavy chain encoded by?

A

VH encoded in 3 gene segments (V, D, J)

66
Q

How many gene segments is the variable region in light chain encoded by?

A

VL encoded in 2 gene segments (V, J)

67
Q

What does gene segment recombination lead to?

A

Gene segment recombination => Ab diversity

68
Q

What is gene segment recombination?

A

Gene segment recombination = random arrangement
of gene segments in different combinations

69
Q

When does gene segment rearrangement take place?

A

Gene segments rearrangements (VDJ/VJ) take place
during B cell development in bone marrow

70
Q

What is produced after the first successful VDJ rearrangement?

A

Heavy chain produced

71
Q

What is produced after the second successful VDJ rearrangement?

A

Light chain produced

72
Q

What do mature naive B cells express?

A

Mature naïve B cells express full IgM/antigen
receptor

73
Q

In somatic DNA rearrangement what is each segment that needs to be joined flanked by?

A

Each segment to be joined is flanked by
Recombination signal sequence (RSS)

74
Q

Where does RAG-1 recombinase cut DNA at?

A

RAG-1 recombinase cuts DNA at precise
location- endonuclease

75
Q

What are pseudogenes?

A

Genes that aren’t functional

76
Q

What does junctional diversity increase?

A

increases the number of Ab
generated

77
Q

How does junctional diversity work?

A

Introduction and deletion of nucleotides at the
junction between different segments ( ie V, J, D)

78
Q
A

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