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MCB 2020 > 4.12 Adaptive immunity B cells > Flashcards

4.12 Adaptive immunity B cells Flashcards

1
Q

Where to lymphocytes develop and circulate?

A
  • Lymphocytes develop in the primary lymphoid organs and enter the blood circulation.
  • They can leave the blood and circulate through the secondary lymphoid tissues (every 24 hrs for T cells), but not any other tissues
  • They are in a quiescent state - “naïve”
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2
Q
A
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3
Q

What is tolerance of B and T cells?

A

T and B cells with receptors that bind “self” antigens are removed during differentiation in the primary lymphoid tissues (there are exceptions!) - TOLERANCE

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4
Q
A
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5
Q

What are antigens?

A
  • Antigens are molecules which are recognised by receptors on lymphocytes, and elicit a specific immune response to that antigen
  • Antigens can be proteins, CHO’s, lipids , nucleic acids
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6
Q

At what stages does clonal selection and clonal expansion occur?

A
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7
Q

How and where are T and B cells activated?

A
  • Occurs in the secondary lymphoid organs.
  • B cells are activated when free antigens drain via the lymphatics to the lymph nodes
  • Antigen Presenting Cells (dendritic cells and macrophages) which have internalised antigen in the tissues migrate via the lymphatics to the lymph nodes and display degraded antigen peptides to T cells.
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8
Q

What are epitopes on antigens for B cells?

A
  • The site where the antibody binds is called the epitope or determinant
  • There can be more than one epitope recognised in any given antigen
  • Protein determinants can be linear or discontinuous
  • B cell receptors bind to conformational shapes
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9
Q

What are the two forms of Ig?

A
  • Surface Ig (IgM) - embedded in the B cell membrane which acts as the B cell antigen receptor
  • Secreted Ig - secreted by activated B cells (plasma cells)
  • Each B cell expresses multiple copies of Ig (around 105/ cell) which bind the same antigen
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10
Q

What are the two distinct regions of antibodies?

A
  • The constant region (Fc) can take one of 5 forms (isotypes)
  • The variable region (Fab) can take one of an almost infinite variety of forms
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11
Q

Which part of the antibody binds the antigen?

A
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12
Q

What is the difference between antigen binding and antibody affinity?

A
  • Antigen binding is the function of the F’ab region
  • Antibody affinity is a measure of the strength of the bond
  • between an antibodies binding site, and an antigen.
  • Usually, the higher the affinity, the better the outcome of antigen- antibody binding
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13
Q

What are the five different isotypes of antibodies produced by B cells?

A
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14
Q

What are the different calsses of antibodies?

A
  • IgM - on the membrane of naïve B cells, secreted into plasma as a pentamer
  • IgG - high concentrations in plasma and tissue fluids
  • IgA - high concentrations in mucosal secretions (often a dimer)
  • IgE - low levels in plasma, tissue fluids, (bound to mast cells)
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15
Q

Considering the F’ab region what can antibody binding to antigen on a pathogen results in?

A
  • Prevention of pathogen binding at mucosal surfaces (IgA)
  • Neutralisation of toxins (IgG, IgM)
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16
Q

What does antibody binding to antigen result in on the F’c region?

A
  • Triggering the classical pathway of the complement cascade (IgG, IgM)
  • Opsonisation : the Fc region binds directly to Fc receptors (FcR) on phagocytes (IgG;).
  • Transplacental immunity (IgG)
  • Triggering degranulation of mast cells, eosinophils (IgE)
  • Inducing the release of cytotoxic products from macrophages and NK cells (by binding FcR)
17
Q

Which antibody isotype is released after antigen encounter?

A
  • Remember, the antibody found on the surface of naïve B cells, and released after antigen encounter, is IgM
  • Membrane bound Ig Is B cell antigen receptor
    IgM
18
Q

How does isotype switching occur?

A
  • Occurs only after B cells have been stimulated by antigens to make IgM
  • Involves irreversible DNA recombination events
  • External signals (from T cells and the pathogen) determine the isotype produced
  • Is accompanied by an increase in the affinity of the newly produced isotypes
19
Q

How does affinity maturation occur?

A
  • Antibodies produced after antigen binding to surface IgM “mature”
20
Q

What are the genes for heavy chain to chose from in antibodies?

A
21
Q

What are the genes for light chain to chose from in antibodies?

A
22
Q

When does immunoglobulin gene rearrangements occur?

A
  • Immunoglobulin gene rearrangements occur during the development of B cells from pluripotent stem cells in the bone marrow
  • Heavy chain rearranges first, then light chain genes
  • Rearrangement accompanied by rapid division and many cells die
  • Many enzymes critical for this process
23
Q

Which genes and enzymes control differentiation in the heavy and light chain gene rearrangements in B cells?

A
  • Heavy and light chain gene rearrangements in B cells are the result of random somatic gene rearrangements (D-J, V-DJ, V-J)
  • Differentiation controlled by genes (eg btk)
  • Recombinations of V, D and J genes are facilitated by recombinase enzymes - recombinase activating genes (RAG’s), terminal deoxynucleotide transferases (TdT ), and exonucleases
  • Defects in above genes result in a block in recombination and an absence of circulating B cells
24
Q

What happens if immature B cells display auto-reactive antibodies?

A
  • Before leaving the bone marrow, those that bind self molecules in the bone marrow are deleted – note that this process is not perfect!
  • B cells that survive this process migrate to the circulation, where they now express IgM antibodies of a single specificity
25
Q

How does isotype switching occur?

A
  • Change the constant domains
  • Recombine VDJ elements that are fixed but change switch sequence
  • Does not switch of Fc recombination genes
26
Q

When exactly does isotype switching occur?

A
  • Occurs only after B cells have been stimulated by antigens
  • Involves irreversible recombination events
  • External signals (from T cells or the pathogen) determine the isotype produced

MCB 2020 (38 decks)

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