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Antibodies. Heroes of the humoral response. Adaptive immunity. Lab #3. 1/25/11. Adaptive defenses. Humoral immunity. Antigen-antibody complex. Antigen. Antibody. Inactivates by. Fixes and activates. Neutralization (masks dangerous parts of bacterial exotoxins; viruses).
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Antibodies Heroes of the humoral response Adaptive immunity Lab #3 1/25/11
Adaptive defenses Humoral immunity Antigen-antibody complex Antigen Antibody Inactivates by Fixes and activates Neutralization (masks dangerous parts of bacterial exotoxins; viruses) Agglutination (cell-bound antigens) Precipitation (soluble antigens) Complement Enhances Enhances Leads to Inflammation Phagocytosis Cell lysis Chemotaxis Histamine release Figure 21.15
Antigens • Things that illicit an immune response • Usually proteins or glycoproteins • Can be small or large
Antibodies - general form Antigen-binding site Heavy chain variable region Hinge region Heavy chain constant region Stem region Light chain variable region Light chain constant region Disulfide bond (cysteine bridge) (a) Figure 21.14a
Antibodies • Immunoglobulins—gamma globulin portion of blood • Proteins secreted by plasma cells (activated B cells) • Capable of binding specifically with antigen detected by B cells. • Bind an antigen with arms of the Y.
Basic Antibody Structure • T-or Y-shaped monomer of four looping linked polypeptide chains • Two identical heavy (H) chains and two identical light (L) chains • Variable (V) regions of each arm combine to form two identical antigen-binding sites
Basic Antibody Structure • Constant (C) region of stem determines • The antibody class (IgM, IgA, IgD, IgG, or IgE) • The cells and chemicals that the antibody can bind to • How the antibody class functions in antigen elimination
Classes of Antibodies • IgM • A pentamer; first antibody released • Potent agglutinating agent • Readily fixes and activates complement • IgA (secretory IgA) • Monomer or dimer; in mucus and other secretions • Helps prevent entry of pathogens
Classes of Antibodies • IgD • Monomer attached to the surface of B cells • Functions as a B cell receptor • IgG • Monomer; 75–85% of antibodies in plasma • From secondary and late primary responses • Crosses the placental barrier
Classes of Antibodies • IgE • Monomer active in some allergies and parasitic infections • Causes mast cells and basophils to release histamine
Generating Antibody Diversity • Billions of antibodies result from somatic recombination of gene segments • Hypervariable regions of some genes increase antibody variation through somatic mutations • Each plasma cell can switch the type of H chain produced, making an antibody of a different class
Antibody Targets • Antibodies inactivate and tag antigens • Form antigen-antibody (immune) complexes • Defensive mechanisms used by antibodies • Neutralization and agglutination (the two most important) • Precipitation and complement fixation
Neutralization • Simplest mechanism • Antibodies block specific sites on viruses or bacterial exotoxins • Prevent these antigens from binding to receptors on tissue cells • Antigen-antibody complexes undergo phagocytosis
Agglutination • Antibodies bind the same determinant on more than one cell-bound antigen • Cross-linked antigen-antibody complexes agglutinate • Example: clumping of mismatched blood cells
Precipitation • Soluble molecules are cross-linked • Complexes precipitate and are subject to phagocytosis
Complement Fixation and Activation • Main antibody defense against cellular antigens • Several antibodies bind close together on a cellular antigen • Their complement-binding sites trigger complement fixation into the cell’s surface • Complement triggers cell lysis
Complement Fixation and Activation • Activated complement functions • Amplifies the inflammatory response • Opsonization • Enlists more and more defensive elements
Adaptive defenses Humoral immunity Antigen-antibody complex Antigen Antibody Inactivates by Fixes and activates Neutralization (masks dangerous parts of bacterial exotoxins; viruses) Agglutination (cell-bound antigens) Precipitation (soluble antigens) Complement Enhances Enhances Leads to Inflammation Phagocytosis Cell lysis Chemotaxis Histamine release Figure 21.15
Polyclonal antibodiesgenerally an immune response activates a number of different plasma cells which can produce only one type of antibody.Each individual antibody will have its own affinity for antigen and specificity for the antigen.The sum of these antibodies that recognize a particular antigen is called Polyclonal antibodies because they arise from many different B cells (plasma cells).
Monoclonal Antibodies • Commercially prepared pure antibody • Produced by hybridomas • Cell hybrids: fusion of a tumor cell and a B cell • Proliferate indefinitely and have the ability to produce a single type of antibody. With a homogenous affinity and specificity. • Used in research, clinical testing, and cancer treatment. mAb
Anti-antibodies An immune response can be directed Against a part of a particular animals Antibody common chain. As a consequence, we can detect when such A antibody is present. Example anti-human IgG antibody (made in rabbits or mice)