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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
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Structure
• Variable & Constant Regions– VL & CL
– VH & CH
• Hinge Region
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond
Immunoglobulin Structure
• Domains– VL & CL
– VH & CH1 - CH3 (or CH4)
• Oligosaccharides
CH1
VL
CL
VH
CH2 CH3
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
C4
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, 2000
http://www.med.sc.edu:85/chime2/lyso-abfr.htm
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
Keq = [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
Keq = 104
Affinity106
Avidity1010
Avidity
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
1o Ag 2o 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