1. ANTIBODIES Agents of Immunity - A Guide for Teachers - Prepared by Johanna Mancini for Immunology Montreal August 2008

2. The Organization What 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

3. The Organization What 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

4. The Making of an Agent How 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

5. The Making of an Agent How 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.

6. Anatomy of an Agent Antibody 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-)

7. Anatomy of an Agent Antibody 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

8. Anatomy of an Agent Antibody Structure Each heavy and light chain has a constant and variable region The variable region binds the antigen in a “lock-and- key” manner

9. The Assignment Antibody 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

10. The Assignment Antibody 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

11. The Assignment Antibody 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

12. The Assignment Antibody Isotype IgM – 1 st 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

13. The Mission Antibody Function Antibodies are the main component of the Humoral Immune System They bind antigen and flag them for elimination via 1 of 3 ways:

14. 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

15. 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

16. 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

17. 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 it’s 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

18. References 1) Janeway, Charles A. et al. Immunobiology, 6 th 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, 7 th edition. Pearson Education, Inc. 2002.

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