ANTIGENS:

IMMUNOGENICITY
AND ANTIGENICITY
ANTIGENS
ANTIGEN: DEFINITION AND ESSENTIAL
FEATURES
Antigen
• A substance that can induce an immune response.
• Essential features of antigens
• It is essential that molecules first be recognized as foreign if they are to stimulate the immune system.
• Processing that antigens must undergo places physical and chemical restrictions on the types of
foreign molecules that can stimulate the immune system.
• Most effective antigens are:
• Large
• Rigid.
• Chemically complex. “Molecules that are not totally chemically inert”.
FACTORS THAT INFLUENCE ANTIGENICITY

Antigenicity: The ability of a molecule to be recognized by antibodies or lymphocytes.

• Molecular size: Large molecules are better antigens then small molecules.
• Very small molecules may, however, bind to large proteins, and the resulting complexes may provoke
an immune response

• Complexity: The more complex an antigen, the better.

• Starch and other simple repetitive polysaccharides are poor antigens.
• Complex bacterial lipopolysaccharides (LPS) are good antigens.
• Complex proteins are better antigens than large repeating polymers such as lipids, carbohydrates and
nucleic acids.
FACTORS THAT INFLUENCE ANTIGENICITY

Structural stability:
• In order to recognize a molecule as a foreign the immune system must recognize its
shape.
• Highly flexible molecules that have no fixed shape are poor antigens, e.g. gelatine (protein
with structural instability). It is poor antigen unless it is stabilized by incorporation of tyrosine
or tryptophan molecules.
• Flagellin, major protein of bacterial flagella, is structurally unstable weak antigen
FACTORS THAT INFLUENCE ANTIGENICITY

• Degradability:
• Not all foreign molecules are capable of stimulating an immune response. Stainless steel pins
and plastic joints are implanted in the body without triggering an immune response.
• The lack of antigenicity of the large, inert organic polymers is due to their molecular
uniformity and their inertness.
• Foreign molecules that are unstable and destroyed very rapidly may not provide sufficient
antigen to stimulate an immune response.
FACTORS THAT INFLUENCE ANTIGENICITY

• Foreignness:
• The suppression of cells that react with normal body components (self antigens) occur because
these cells are exposed to self-antigen when immature (usually early in foetal life) and
consequently eliminated (selectively killed or otherwise suppressed).
• Trauma testes (or vasectomy) ---------------- Anti-sperm antibodies.
• Extensive cell destruction (heart attack) ------- anti-mitochondrial antibodies.
FACTORS THAT INFLUENCE ANTIGENICITY

Route of
Host
administratio
n Genetics

Complexity Dose
Antigenicity

Foreignnes
s Size
Chemical
Stability
AUTOANTIGENS:

• Antigens that induce autoimmunity are called autoantigens.

• Autoantigens Autoimmune responses Autoantibodies.
• Hormones (thyroglobulin).
• Structural components (basement membranes).
• Complex lipids (myelin).
• Intracellular components (mitochondrial proteins).
• Nucleic acids.
• Nucleoproteins.
• Cell surface proteins.
CHARACTERISTICS OF ANTIGENS

• Any molecule that is immunogenic must also be antigenic, but the reverse need to be true.
• Proteins are the best antigens because of:
• Molecular size.
• Structural complexity.

• Polysaccharides (starch and glycogen) are not good antigens:

• Readily degraded within cells.

• Lipids are poor antigens:

• Relative simplicity.
• Structural instability.
• Rapid metabolism
ANTIGENS TYPES

• Non microbial antigens :

• Snake venoms.
• Mosquito bite.
• Pollen grains.
• Serum proteins.
• Milk and food proteins (Macromolecules of diet).
• Antibody molecules.
• Histocompatibility antigens (Organ grafts).

• Bacterial antigens
• Capsule (K-antigen) capsular antigen.
• Cell wall (O-antigen) somatic antigen.
• Flagellum (H-antigen) flagellar antigen.
• Pili (F-antigen)

• Viral antigens
• The capsid proteins are good antigens, highly capable of provoking antibodies.
CELL SURFACE ANTIGENS

• Histocompatibility antigens: on WBCs graft rejection.

• Clusters of Differentiation (CD):
• Lymphocytes possess large number of different surface proteins each of which possesses many
distinct epitopes.
• CD: denotes a protein of specific function.
• CD4 is associated with cells that help immune response.
• CD8 is found on cells that suppress immune response
IMMUNOGENICITY

Immunogenicity: The difference in the ability of foreign

molecules to stimulate an immune response.
FACTORS INFLUENCING IMMUNOGENICITY:
CONTRIBUTION OF THE IMMUNOGEN
• Foreignness
• Size
• Chemical Composition
• Primary Structure
Sequence determinants
• Secondary Structure
• Tertiary Structure Conformational determinants
• Quaternary Structure

• Physical Form
• Particulate > Soluble
• Denatured > Native

• Degradability
• Ag processing by Ag Presenting Cells (APC)
FACTORS INFLUENCING IMMUNOGENICITY:
CONTRIBUTION OF THE BIOLOGICAL SYSTEM
• Genetics
• Species
• Individual
• Responders vs Non-responders

• Age
FACTORS INFLUENCING IMMUNOGENICITY:
METHOD OF ADMINISTRATION
• Dose
• Route
• Subcutaneous > Intravenous > Intragastric

• Adjuvant
• Substances that enhance an immune response to an Ag
CHEMICAL NATURE OF IMMUNOGENS

• Proteins
• Polysaccharides
• Nucleic Acids
• Lipids
• Some glycolipids and phospholipids can be immunogenic for T cells and elicit a cell mediated
immune response
TYPES OF ANTIGENS: T-INDEPENDENT

Polysaccharides
• Properties
• Polymeric structure
• Polyclonal B cell activation
• Yes -Type 1 (TI-1)
• No - Type 2 (TI-2)
• Resistance to degradation
• Examples
• Pneumococcal polysaccharide, lipopolysaccharide
• Flagella
TYPES OF ANTIGENS: T-DEPENDENT

• Proteins
• Structure
• Examples
• Microbial proteins
• Non-self or Altered-self proteins
HAPTEN-CARRIER CONJUGATES

• Definition
• Structure Haptenic determinants
• native déterminants
• haptenic déterminants

Native determinants
ANTIGENIC DETERMINANTS: RECOGNIZED BY B
CELLS AND AB
• Composition
• Proteins, polysaccharides, nucleic acids
• Sequence (linear) determinants
• Conformational determinants

• Size Fe

• 4-8 residues

• Number
• Limited (immunodominant epitopes)
• Located on the external surfaces of the Ag
ANTIGENIC DETERMINANTS: RECOGNIZED BY T
CELLS
• Composition
• Proteins (some lipids)
• Sequence determinants
• Processed
• MHC presentation (lipid presentation by MHC-like CD1)

• Size
• 8 -15 residues

• Number
• Limited to those that can bind to MHC
 SUPER ANTIGENS

• Definition
Conventional Antigen Super antigen

Examples
Staphylococcal enterotoxins
Staphylococcal toxic shock toxin
Staphylococcal exfoliating toxin
Streptococcal pyrogenic exotoxins

Monoclonal/Oligoclonal T cell response

Polyclonal T cell response
1:10 - 1:10
4 5
1:4 - 1:10
DETERMINANTS RECOGNIZED BY THE INNATE
IMMUNE SYSTEM
• Adaptive Immune System – Discrete Determinants
• Reacts with a specific pathogen

• Innate Immune System – Broad Molecular Patterns

• Reacts with a variety of pathogens

• PAMPs – Pathogen Associated Molecular Patterns

• PRRs – Pattern Recognition Receptors
 PAMP PRR Biological Consequence of Interaction

Double stranded RNA TLR-3 Production of interferon (antiviral)

LPS (lipopolysaccharide of Gram – bacteria TLR-4 Macrophage activation; Secretion of inflammatory cytokines
Flagellin (bacterial flagella) TLR-5 Macrophage activation; Secretion of inflammatory cytokines
U-rich single stranded viral RNA TLR-7 Production of interferon (antiviral)
CpG containing DNA TLR-9 Macrophage activation; Secretion of inflammatory cytokines
Microbial cell wall components Complement Opsonization; Complement activation
Mannose-containing carbohydrates Mannose-binding Opsonization; Complement activation
protein
Polyanions Scavenger receptors Phagocytosis
Lipoproteins of Gram + bacteria TLR-2 (Toll-like Macrophage activation; Secretion of inflammatory cytokines
Yeast cell wall components receptor 2)
Double stranded RNA TLR-3 Production of interferon (antiviral)
LPS (lipopolysaccharide of Gram – bacteria TLR-4 Macrophage activation; Secretion of inflammatory cytokines
Flagellin (bacterial flagella) TLR-5 Macrophage activation; Secretion of inflammatory cytokines