ANTIBODIES Agents of Immunity - A Guide for Teachers -

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ANTIBODIESAgents of Immunity- A Guide for
Teachers -

• Prepared by Johanna Mancini for Immunology
  Montreal
• August 2008

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The OrganizationWhat are they?

• Antibodies are
• Protective agents of the immune system
• Neutralize foreign agents called antigens
• Essential part of the Adaptive Immune System
  (AIS)
• AIS learns to respond to invading pathogens

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The OrganizationWhat are they?

• Antibodies are
• - Y-shaped Immunoglobulins (Ig)
• Comprised of 2 heavy and 2 light chains
• 5 different types IgA, IgD, IgE, IgG, IgM
• Each have a specific role
• Contain Variable Regions which recognize and bind
  antigen via lock and key method

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The Making of an AgentHow Antibodies are
Generated

• Antibodies occur in 2 forms
• Soluble secreted in blood and tissue
• Membrane-bound found on surface of B-cell, also
  known as a B-cell receptor (BCR)
• - BCR binds circulating antigen, activating the
  B-cell and forming plasma cells or memory B-cells

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The Making of an AgentHow Antibodies are
Generated

• Activation of a B cell and Clonal Expansion
• 1) Antigen binds the
• BCR on a B-cell,
• activating it
• 2) B-cell begins to
• divide (Clonal
• Expansion), forming
• either plasma cells
• (antigen factories)
• or memory B-cells.

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Anatomy of an AgentAntibody Structure

• Antibodies are globular proteins called
  Immunoglobulins (Ig)
• Y-shaped
• Made up of 4 polypeptide chains
• 2 identical heavy
• 2 identical light
• connected by disulfide bonds (-S-S-)

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Anatomy of an AgentAntibody Structure

• Antibodies can also be divided into two regions
  based on their function
• Fab (fragment, antigen binding) region.
• Tip of the antibody
• Binds the antigen
• Fc (fragment, crystallizable) region
• Base of the antibody
• Can bind cell receptors, complement proteins and
  other molecules

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Anatomy of an AgentAntibody Structure

• Each heavy and light chain has a constant and
  variable region
• The variable region binds the antigen in a
  lock-and-key manner

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The AssignmentAntibody Isotype

• Mammals express 5 different isotypes of
  antibodies (IgA, IgD, IgE, IgG and IgM) with
  different functions and locations
• Class of antibody is defined by the heavy chain

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The AssignmentAntibody Isotype

• Basic antibody is composed of 1 Ig unit, i.e. is
  a monomer
• Some are dimeric (IgA) or pentameric (IgM)
• Isotype changes during development of B-cell

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The AssignmentAntibody Isotype

• Immature B-cells only express surface IgM
• As it matures, it expressed both IgM and IgD
• After reaching maturity, the B-cell is ready to
  interact with antigen and produce antibody
• As antibodies are formed, some undergo isotype
  switching and produce IgE, IgA or IgG

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The AssignmentAntibody Isotype

• IgM 1st class of circulating antibody
• - found in pentameric form
• IgG - most abundant antibody
• IgA - located in the mucous membranes
• - found in dimeric form
• IgD - found on surface of B-cells
• - probably involved in memory cell formation
• IgE - involved in allergies, i.e. trigger
  release of
• histamine

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The MissionAntibody Function

• Antibodies are the main component of the Humoral
  Immune System
• They bind antigen and flag them for elimination
  via 1 of 3 ways

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• Neutralization
• Viruses and intracellular bacteria require a
• host cell in order to replicate
• Antibodies prevent their entry into the cell
• by binding the antigen, making it harder
• for it to pass through the cell membrane.
• Antibodies cannot attack pathogens hidden
• within cells

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• Opsonization
• Upon binding to an
• antigen, antibodies flag the
• foreign agent for destruction
• or elimination by other
• immune cells, such as natural
• killer cells or macrophages

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• Activation of Complement
• Similar to opsonisation, antibody will
• flag the antigen for elimination.
• However, elimination is initiated by a
• cascade of proteins which collect on
• the cell membrane and form a hole,
• leading to cell lysis

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Vocabulary

• adaptive immunity the response of
  antigen-specific lymphocytes to antigen,
  including the development of immunological memory
• antibody an antigen-binding immunoglobulin,
  produced by B-ells, that functions as the
  effector of an immune response
• antigen a foreign molecule that does not belong
  to the host organism and that elicits an immune
  response
• B-cell a type of lymphocyte that develops in the
  bone marrow and later produces antibodies, which
  mediate humoral immunity
• complement an immune response whereby a cascade
  of proteins attack extracellular forms of
  pathogens
• Fab (fragment, antigen binding) region the
  regions of the antibody that binds the antigen
• Fc (Fragment, crystallizable region) the region
  of the antibody that binds to cell receptors
• heavy chain heavy chains come in a variety of
  heavy chain classes or isotypes, each which
  confers a distinct function to the antibody
• humoral immunity the type of immunity that
  fights bacteria and viruses in the body fluids
  with antibodies that circulate in blood plasma
  and lymph
• immune system is the name used to describe the
  totality of the host defence mechanism
• immunoglobulin all antibody molecules belong to
  this family of plasma proteins
• isotype antibody class determined by the heavy
  chain
• light chains smaller of the two components
  making up an antibody
• memory B-cell a clone of long-lived lymphocytes,
  formed during the primary immune response, that
  remains in a lymph node until activated by
  exposure to the same antigen that triggered its
  formation. Activated memory cells mount the
  secondary immune response.
• naïve B-cell a B-cell that has never bound
  antigen before
• neutralization when antibodies inhibit the
  infectivity of a virus or the toxicity of a toxin
• opsonisation is the alteration of the surface of
  a pathogen or other particle so that it can be
  ingested by phagocytes
• plasma cell a derivative of B-cells that
  secretes antibodies, i.e. antibody factory
• variable region regions that contains the
  antigen binding site

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References

• 1) Janeway, Charles A. et al. Immunobiology,
  6th edition. Garland Science, 2005.
• 2) Wikipedia Antibodies. Accessed August 2007.
  http//en.wikipedia.org/wiki/Antibody
• 3) Campbell, Neil A., Jane B. Reece, Lawrence G.
  Mitchell. Biology, 7th edition. Pearson
  Education, Inc. 2002.

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