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Immunology > Chapter 4: Antibody Structure and the Generation of B-cell Diversity > Flashcards

Chapter 4: Antibody Structure and the Generation of B-cell Diversity Flashcards

1
Q

Immunoglobulin (Ig)

A
  • antibodies are of a class of glycoproteins produced by plasma cells (stimulated B-cells)
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2
Q

IgM

A
  • first antibody produced in blood and lymph in a primary antibody response
  • 8% of Ig pool
  • is a pentameric antibody
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3
Q

IgG

A
  • makes up the vast majority of antibody in blood lymph
  • principle antibody in secondary antibody response agains an antigen
  • 80% of Ig pool
  • monomeric antibody
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4
Q

IgA

A
  • is found in the body cavities where is binds bacteria and viruses before they can infect tissue
  • 12% of Ig pool
  • dimeric antibody
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5
Q

IgE

A
  • important in allergic reactions
  • trace amounts in serum
  • monomeric antibodies
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6
Q

IgD

A
  • normally bound to B-cells as a cell receptor

- monomeric antibodies

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7
Q

The Structural Basis of Antibody Diversity

A
  • antibodies are composed of polypeptides with variable and constant regions
  • epitope recognition requires antibodies to have a special structure of
    2 identical heavy (H) chains
    2 identical light (L) chains
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8
Q

Each light and heavy chain has:

A
  • a constant region: which determines the location and functional class of the antibody
  • a variable region: which contains different amino acids for the many antibodies produced
  • an antigen-binding site is formed from the hypervariable regions of a heavy-chain V domain and a light V domain
  • the variability formation of the specific antigen binding site
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9
Q

Immunoglobulin chains are folded into compact and stable protein domains held together by….

A
  • disulfide bonds
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10
Q

Treatment of IgG with the enzyme papain results in…

A
  • proteolytic cleavage of the hinge of each heavy chain and reduction of the disulfide bonds that connect the two hinges
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11
Q

Flexible Hinge

A
  • on the IgG molecule allows it to bind with both arms to many different arrangements of antigens on the surfaces of pathogens
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12
Q

IgG antibody is made up of…

A
  • two identical heavy chains and two identical light chains
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13
Q

Epitopes can bind to…

A
  • pockets, grooves, extended surfaces, or knobs in antigen-binding sites
  • antigen binding sites vary in shape and physical properties
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14
Q

Linear Epitope

A
  • formed from contiguous amino acids
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15
Q

Discontinuous Epitope

A
  • formed from amino acids from different parts of the polypeptide that are brought together when the chain folds
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16
Q

Monoclonal Antibodies

A
  • produced from a clone of antibody-producing hybridoma cells
  • used to treat a variety of diseases
    Rituxan: anti-CD20 and cell killing by ab/compliment
    Adalimumab: blocker of anti-TNF-alpha
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17
Q

Production of a mouse monoclonal antibody

A
  • lymphocytes from a mouse are immunized with antigen are fused with myeloma cells by using polyethyleneglycol
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18
Q

Myelomas

A
  • tumors of plasma cells used to make hybridomas

- hybridomas only express the antibody made by the B-cell partner

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19
Q

Before you get infected…

A
  • generation of immunoglobulin diversity in B cells before encounter with antigen
20
Q

Gene Rearrangement

A
  • the DNA sequence encoding a V region is assembled from two or three gene segments
21
Q

Two type of gene segment that encode the light-chain V region are called…

A
  • variable (V)

- joining (J)

22
Q

Two light-chain loci versions

A
  • kappa or lambda, only one is used
23
Q

Heavy-chain locus includes…

A
  • an additional set of diversity (D) gene segments for a total of 3 segments
24
Q

Random Somatic Recombination of gene

A
  • diversity in the antigen-binding sites of immunoglobulins
  • enzymes responsible for recombining are V, D, and J
  • also called V(D)J recombinase
25
Q

RAG Complex

A
  • recombination activating gene

- gene segments encoding the VARIABLE region are joined by recombination at recombination sequences recognized by RAG

26
Q

Alternative mRNA Splicing

A
  • developing and naive B cells use this to make both IgM and IgD
  • these B cells have not been yet activated by the antigen
27
Q

The Isotype of an antibody is determined…

A
  • by its heavy chain
  • only heavy chains made by mature B cells before they encounter antigen are mu and delta corresponding to IgM and IgD, respectively, on B cell surfaces
28
Q

Differential Splicing (no gene arrangement)

A
  • simultaneous expression by both forms from the same heavy chain locus is accomplished by differential splicing of the same primary RNA transcript
29
Q

Each B cells produces…

A
  • immunoglobulin of a single antigen specificity
    Allelic Exclusion
    B cells are mono specific
30
Q

Allelic Exclusion

A
  • in developing B-cells ensures that only one heavy chain and one light chain are expressed, which results in B cells producing antibodies of a single antigen specificity
31
Q

B cells are Monospecific

A
  • an encounter with a given pathogen engages a subset of B cells that will make antibodies that bind only to that pathogen
  • this is clonal selection
  • focus of B-cell/antibody response to a specific antigen
32
Q

Immunoglobulin is first made…

A
  • in a membrane-bound form that is present on the B-cell surface
  • when B cells first make IgM and IgD, they are associated with the cell membrane
  • they need anchors to stick to the plasma membrane
33
Q

Two anchors of a receptor

A
  • IgB (beta) and Iga (alpha)
  • are invariant chains which are transmembrane proteins that anchor the antibody heavy chain, constant region, to the plasma membrane
34
Q

Diversification happens…

A
  • after you get sick

- antibodies are produces after B cells encounter antigen

35
Q

Secreted antibodies are produced…

A
  • by an alternative pattern of heavy-chain RNA processing
36
Q

Gene rearrangement in immune B cells leads to the expression of…

A
  • a functional heavy and light chain and to the production of membrane-bound IgM and IgD on the mature B cells
37
Q

After and encounter with antigen…

A
  • the secreted antibodies are produced by the B cell (now known as the plasma cell)
    Alternative RNA Splicing (no gene arrangement)
  • membrane bound has a hydrophobic anchor sequence at the end of the heavy chain, where the secreted on has a hydrophilic one
38
Q

Secreted IgM is in a ________ shape

A
  • pentamer
39
Q

Somatic Hypermutation

A
  • rearranged V-region sequences are further diversified
  • once a B cell has been activated by antigen, further diversification of the whole of the V-domain coding sequences occurs
40
Q

There is a random point mutation…

A
  • at a very high rate throughout the V-region of the heavy and the light chain genes
  • constant regions are not effected
41
Q

Activation-Induced Cytidine Deaminase (AID)

A
  • somatic hyermutation results in B cell bearing mutant antibodies at the variable region
  • dependent on the enzyme
  • some of these mutant antibodies will bind antigen better (higher affinity)
  • B cells containing these mutant receptors will compete for the antigen and are preferentially selected to mature in plasma cells
42
Q

Improved Antigen-Binding Sites

A
  • the almost random variation produced by somatic hypermutation allows selection of variant immunoglobulins with improved antigen-binding sites
43
Q

Isotype switching produces…

A
  • immunoglobulins with different C regions but identical antigen specificities
  • only occurs in B-cells that have been activated
44
Q

Activation-induced Cytidine Deaminase (AID)

A
  • like somatic hypermutation, isotype switching (or class switching) is dependent on this enzyme
45
Q

C regions

A
  • further DNA recombination allows V regions to be joined with different C regions
46
Q

Antibodies with different C regions have…

A
  • different effector functions

- produced by plasma cells (stimulated B-cells)

Immunology (13 decks)

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