Specific Defenses of the Host: The Immune Response Immunogen: A substance that induces a specific immune response Antigen (Ag): A substance that reacts with the products of a specific immune response

Antigenic Determinants Antibodies recognize and react with antigenic determinants or epitopes. Figure 17.3

Haptens Figure 17.4

Hapten: A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule.

Chemical Nature of Immunogens Proteins Polysaccharides Nucleic Acids Lipids –Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response

Epitope or Antigenic Determinant: That portion of an antigen that combines with the products of a specific immune response Antibody (Ab) : A specific protein which is produced in response to an immunogen and which reacts with an antigen.

Antibody Structure Figure 17.5a-c

Human Immunoglobulin Classes IgG - Gamma ( γ ) heavy chains IgM - Mu ( µ ) heavy chains IgA - Alpha ( α ) heavy chains IgD - Delta ( δ ) heavy chains IgE - Epsilon ( ε ) heavy chains

Monomer 80% of serum antibodies Fix complement In blood, lymph, intestine Cross placenta Enhance phagocytosis; neutralize toxins & viruses; protects fetus & newborn Half-life = 23 days IgG antibodies

Immunoglobulin Structure Heavy & Light Chains Disulfide bonds –Inter-chain –Intra-chain C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond

Immunoglobulin Structure Variable & Constant Regions –V L & C L –V H & C H Hinge Region C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond

Immunoglobulin Structure Domains –V L & C L –V H & C H1 - C H3 (or C H4 ) Oligosaccharid es C H1 VLVL CLCL VHVH C H2 C H3 Hinge Region Carbohydrate Disulfide bond

TORTORA FUNKE CASE IgG molecule

Pentamer 5-10% of serum antibodies Fix complement In blood, lymph, on B cells Agglutinates microbes; first Ab produced in response to infection Half-life = 5 days IgM antibodies C 4 J Chain

Dimer 10-15% of serum antibodies In secretions Mucosal protection Half-life = 6 days IgA antibodies J Chain Secretory Piece

Monomer 0.2% of serum antibodies In blood, lymph, on B cells On B cells, initiate immune response Half-life = 3 days IgD antibodies

Monomer 0.002% of serum antibodies On mast cells and basophils, in blood Allergic reactions; lysis of parasitic worms Half-life = 2 days IgE antibodies

Nature of Ag/Ab Reactions Lock and Key Concept Non-covalent Bonds – Hydrogen bonds – Electrostatic forces – Van der Waal forces – Hydrophobic forces Reversible Multiple Bonds Source: Li, Y., Li, H., Smith-Gill, S. J., Mariuzza, R. A., Biochemistry 39, 6296,

Affinity = attractive and repulsive forces Ab Ag High Affinity Ab Ag Low Affinity Affinity Strength of the reaction between a single antigenic determinant and a single Ab combining site

Calculation of Affinity Ag + Ab Ag-Ab K eq = [Ag-Ab] [Ag] x [Ab] Applying the Law of Mass Action:

Avidity The overall strength of binding between an Ag with many determinants and multivalent Abs K eq = 10 4 Affinity 10 6 Avidity 10

Specificity The ability of an individual antibody combining site to react with only one antigenic determinant. The ability of a population of antibody molecules to react with only one antigen.

Cross Reactivity The ability of an individual Ab combining site to react with more than one antigenic determinant. The ability of a population of Ab molecules to react with more than one Ag Anti-A Ab Ag A Anti-A Ab Ag B Shared epitope Anti-A Ab Ag C Similar epitope Cross reactions

Factors Affecting Measurement of Ag/Ab Reactions Affinity Avidity Ag:Ab ratio Physical form of Ag Ab excess Ag excess Equivalence – Lattice formation

Antibody-Dependent Cell- Mediated Cytotoxicity

Antibody titer: Is the amount of Ab in serum

Another look 1 o Ag 2 o Ag Total Ab IgM Ab IgG Ab D a y s A f t e r I m m u n i z a t i o n A b T i t e r