Immunogenicity
Antigens (Ag)- substances able to induce a specific active immune response
Immunogens- are agents that are capable of inducing an immune response
Antigens- agents capable of binding specifically to components of the immune system such as lymphocytes or antibodies.
All immunogens are antigens, but not all antigens are immunogens
Some substances require another substance to couple to it that makes it antigenic (hapten).
Requirements for immunogenicity
1. Foreignness
- not a definitive requirement for immunogenicity
- some self-components can be immunogenic
2. Molecular Weight
- <1000 Daltons- non-immunogenic
- 1000 to 6000 Daltons may or may not be immunogenic
- >6000 Daltons- generally immunogenic
3. Chemical Complexity
- Physiochemical complexity is usually necessary (more than one a.a. in peptide)
Haptens
- low molecular weight compounds that are non-immunogenic by themselves but become immunogenic after conjugation to high molecular weight carrier substances that are immunogenic.
Antigenicity
- an immune response induced by an immunogenic substance generates antibodies or lymphocytes specifically reactive with the antigen
Epitope (antigenic determinant site)- individual site on surface of antigen that binds specifically with the binding site of an Ab or the receptor on the lymphocyte surface; recognized by ab paratopes
Paratope- complementary Antibody binding site
Major Classes of Antigens
1. Carbohydrates or polysaccharides- ex. bacterial capsules, ABO blood groups
2. Lipids- routinely not antigenic; ex. sphingolipids
3. Nucleic Acids- poorly immunogenic themselves, good antigens as haptens
4. Proteins or glycoproteins- excellent Ags; the greater the complexity and mol. wt. the greater the antigen; largest general class
5. Metals- ex. Hg, Ni (haptens)
6. Organic Chemicals
Sequential and Conformational Epitopes
- two general classes of epitopes
Sequential Epitopes
- short stretches of a.a. which can be recognized by the elicited Ab even when the short peptie exists free in solution or is chemically coupled
- Only requirement- the right sequence of a.a. is produced
Conformational Epitopes
- require the native 3-D config. of the molecule to be intact for their expression.
- denaturation destroys the epitope and causes the Ab not to bind
Physiochemical Forces in Ag-Ab interaction
“Antibody binding DOES NOT involve covalent chemical bonds.” Weaker bonds are utilized, thus reactions are reversible.
1. Electrostatic interactions- + to - ; usu. amino acid interactions, i.e. lysine-aspartate
2. Hydrogen bonding
3. Hydrophobic bonding- driven by the need of hydrophobic side chains of leucine, isoleucine, etc. to repel H2O molecules and form non-hydrated domains
4. Van der Waal’s forces- the attraction between induced oscillating dipoles in the electron clouds of two closely adjacent molecules; force is proportional to the 7th power of the distance separating the two molecules
Immunologic Specificity
- Ab specific for one epitope or hapten can easily distinguish that epitope or hapten from other similar structures
- the ability of a polyclonal antiserum to resolve minor differences between the original antigen or hapten and similar but structurally different haptens or antigens
Cross-reactivity
- refers to the situation where the cell receptor or antibody an react with two molecules becaust they share one or more identical epitopes or the epitopes are similar enough in sequence and shape to bind to the receptor
Examples:
1. Toxoids
2. ABO Blood group antigens- Ab elicited by certain environmental carbohydrate antigens react with A or B antigens.
Affinity and Avidity
Affinity- how well it binds
Avidity- advantage conferred due to multivalency of Ab.
Antigenic Specificities/ Classifications
- epitopes can be classified on the basis of origin, species, molecular class and subclass, and individual molecular species
Adjuvants- substance when mixed with an immunogen that enhances the immune response.
Tags: Adjuvants, antigenicity, antigens, carbohydrates, Electrostatic interactions, epitope, epitopes, glycoproteins, haptens, Immunogenicity, Immunologic Specificity, lipids, nucleic acids, paratope, polysaccharides, proteins, toxoids
