ANTIGENS

Things for todayUnderstand difference between antigen and

immunogenChemical nature of an immunogenFactors affecting immunogenicityHaptensB-cell and T-cell epitopes

a) Antigen (Ag) - a substance that reacts with the products of a specific immune response. A substance that can be recognised by the immunoglobulin receptor of

B cells, or by the T cell receptor when complexed with MHC, is called antigen.

b) Immunogen - a substance that induces a specific immune response.

c) Hapten - Haptens are small molecules which are nonimmunogenic, thus could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Free haptens can react with the products of a specific immune

response. Haptens have the property of antigenicity but not immunogenicity.

d) Epitope or Antigenic Determinant - the discrete sites of an antigen that combines with the products of a specific immune response.

e) Antibody (Ab) - a specific protein which is produced in response to an immunogen and which reacts with an antigen.

Vocabulary

Immunogenicity and AntigenicityImmunogenicity is the ability to induce a

humoral and/or cell mediated immune response:

Antigenicity is the ability to combine specifically with the final products of the above responses (i.e., antibodies and/or cell-surface receptors)

Chemical nature of immunogenProteins (most potent immunogens)PolysaccharidesNucleic acidsLipids (some glycolipids and phospholipids)

Humoral Branch- Proteins and polysaccharides

Cell med. Branch- Proteins and lipids

Factors influencing immunogenicity

Factors

Contribution of

immunogen

Contribution of

biological system

Method of administrati

on

Immunogenicity: contribution of immunogenForeignness- is essential to immunogenicity because self-

responsive cells are eliminated during lymphocyte development, leaving only cells that respond to non-self, so-called "foreign" epitopes.

Size Bigger>Smaller

Chemical composition Heteropolymers>homopolymers Protein Antigens

Primary structure --- sequence determinants Secondary structure Tertiary structure Quarternary structure

Physical form Particulate> Soluble Degradability Ag processing by Ag-presenting cells (APC)

L-amino acids and D amino acids

Conformationaldeterminants

Immunogenicity: contribution of biological system

GeneticsSpeciesIndividual

Responders vs Non-responders The species or individuals may lack or have altered genes

that code for the receptors for antigen on B cells and T cells or they may not have the appropriate genes needed for the APC to present antigen to the helper T cells.

AgeUsually the very young and the very old have a

diminished ability to mount an immune response in response to an immunogen.

Immunogenicity: method of administrationDose

There is a dose of antigen above or below which the immune response will not be optimal.

Boosters repeated administrations>single dose

RouteSubcutaneous >Intraperitoneal> Intravenous >

IntragastricAdjuvant

Adjuvants (from Latin adjuvare, to help) are substances that, when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen.

Mechanisms of adjuvantsProlonged persistence of immunogen

molecules at the site of injection. Enhancement of co-stimulatory signals. Local inflammation is increased. Stimulation of lymphocyte proliferation in a

non-specific manner.

Classification of Adjuvant

Muramul dipeptide of mycobacterium

HaptensMany biologically important substances,

including drugs, peptide hormones, and steroid hormones, can function as haptens. Conjugates of these haptens with large protein carriers can be used to produce hapten-specific antibodies.

These antibodies are useful for measuring the presence of various substances in the body.

human chorionic gonadotropin (HCG) (Pregnancy test)

HaptensKarl

Landsteiner

Work demonstrated specificity and also enormous diversity of epitopes immune system can recognize)

EpitopesB-cell Epitopes

T-cell Epitopes

B-cell Epitopes The ability to function as a B-cell epitope is

determined bynature of the antigen-binding site on the

antibody molecules displayed by B cells.Presence of hydrophilic amino acids on the

protein surface that are topographically accessible to membrane-bound or free antibody.

May contain sequential (continous) or nonsequential (discontinous) amino acids.

located in flexible regions of an immunogen and display site mobility.

1. Linear epitopes ♣ continuous and found in native (nondenatured) and denatured proteins.

♣ specificity depends upon primary sequence. ♣ typical size is 5-6 subunits in length.

2. Conformational epitopes ♣ Discontinuous (involve multiple subunits, often located far apart in the primary sequence of the antigen molecule) and are thus found only in native (globular) proteins. ♣ Specificity depends upon conformation, or three-dimensional shape, which is a combination of tertiary and quaternary structure ... supported by primary and secondary structure, of course. ♣ Typical size is hard to pinpoint, but sequences of up to 16 amino acids in certain protein antigens have been shown to interact with their complementary paratope.

Types of Epitopes

T-cell EpitopesAntigenic peptides recognized by T cells form

trimolecular complexes with a T-cell receptor and an MHC molecule

Antigen processing is required to generate peptides that interact specifically with MHC molecules.

Epitopes recognized by T cells are often internal.