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