Antigens
Antigens
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
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:
• 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.
• 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
• 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