42.4 What Is the Humoral Immune Response?

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42.4 What Is the Humoral Immune Response?

• B cells are the basis for the humoral immune
  response.
• B cells first make a receptor protein on the cell
  surface.
• If activated by antigen-binding the cell gives
  rise to clones of plasma and memory cells.
• The plasma cells secrete antibodies into the
  blood stream.

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42.4 What Is the Humoral Immune Response?

• For B cell to develop into a plasma cell, a
  T-helper cell (TH) with the same specificity must
  also bind to the antigen.
• Division and differentiation of the B cell is
  stimulated by signals from the TH cell.
• As plasma cell develops, ER and ribosomes
  increasefor synthesis of antibodies, up to 2000
  per second!

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42.4 What Is the Humoral Immune Response?

• Antibodies belong to a protein class called
  immunoglobulins.
• All are tetramers with two light chains and two
  heavy chains, held together by disulfide bonds.
• Each polypeptide chain has a constant region and
  a variable region.

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Figure 42.10 The Structure of an Immunoglobulin
(Part 1)
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Figure 42.10 The Structure of an Immunoglobulin
(Part 2)
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42.4 What Is the Humoral Immune Response?

• Constant region determines the class of
  antibodythe function and destination.
• Variable regions are specific for each
  immunoglobulin the 3D structure is responsible
  for antibody specificity.
• The two antigen-binding sites on an
  immunoglobulin are identical (bivalent).

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42.4 What Is the Humoral Immune Response?

• Ability to bind two antigen molecules at once,
  along with multiple epitopes on many antigens
  results in large complexes that are easy targets
  for ingestion and breakdown by phagocytes.

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In-Text Art, Ch. 42, p. 868 (1)
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42.4 What Is the Humoral Immune Response?

• Five classes of antibodies are determined by the
  constant regions of the heavy chains.
• IgG is most abundant soluble greatest amounts
  made during secondary immune response.

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42.4 What Is the Humoral Immune Response?

• Some IgG bind to antigens, then attaches to
  macrophages via the heavy chain.

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In-Text Art, Ch. 42, p. 868 (2)
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Table 42.2
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42.4 What Is the Humoral Immune Response?

• Immunoglobulin diversity results from DNA
  rearrangements and other mutations.
• Each mature B cell makes only one specific
  antibody to a specific epitope.
• It would be impossible to have a gene for every
  epitope.

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42.4 What Is the Humoral Immune Response?

• The B cell genome has alleles for several regions
  of an antibody combinations of these alleles
  generates diversity.
• Each gene encoding an immunoglobulin is a
  supergene made by recombination of clusters of
  smaller genes.

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Figure 42.11 Heavy-Chain Genes
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42.4 What Is the Humoral Immune Response?

• During B cell development the genes are cut out
  and rearranged. One gene from each cluster is
  chosen randomly for joining, others are deleted.
• A unique supergene is assembled.
• Resultenormous diversity of specific antibodies.

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42.4 What Is the Humoral Immune Response?

• Each B cell precursor assembles two
  supergenesone for the light chain, one for the
  heavy chain.
• Genes for the light chains are made in a similar
  way, with an equally large amount of diversity.
• Light and heavy chain diversity together yield
  about 324 million possibilities.

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42.4 What Is the Humoral Immune Response?

• Mutations that occur during recombination
  generates even more diversity.
• Immunoglobulin genes have high spontaneous
  mutation rates.
• Once the B cells specificity has been
  determined, it cannot change.

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42.4 What Is the Humoral Immune Response?

• Once pre-transcriptional processing is completed,
  a supergene is transcribed and translated to
  produce an immunoglobulin light or heavy chain.
• These combine to form an active immunoglobulin
  protein.

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Figure 42.12 Heavy-Chain Gene Recombination and
RNA Splicing
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42.4 What Is the Humoral Immune Response?

• Class switching
• B cells can make only one type of antibody at a
  time, but can change the class of antibody they
  make.
• Early B cells produce IgMreceptors that
  recognize specific antigens.

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42.4 What Is the Humoral Immune Response?

• If B cell becomes a plasma cell, a deletion
  occurs in the DNA, resulting in an antibody with
  a different constant region of the heavy chain.
• The antibody still has the same variable regions,
  and thus the same specificitybut a different
  function.
• TH cells induce class switching through cytokine
  signals.

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Figure 42.13 Class Switching Exchanging C
Regions
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42.4 What Is the Humoral Immune Response?

• Specificity of antibodies make them useful for
  detecting substances.
• Immune responses result in polyclonal antibodies
  a mixture of antibodies to respond to multiple
  antigens, made by several different B cell
  clones.
• Monoclonal antibodies are produced by one B cell
  clone and have specificity for only one epitope.

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42.4 What Is the Humoral Immune Response?

• Monoclonal antibodies are used for
• Immunoassaysdetecting small amounts of molecules
  in tissue or fluids
• Immunotherapyusing monoclonal antibodies
  specific for antigens on cancer cells. Can be
  coupled with radioactive or toxic ligands