Saturday, August 28, 2010

Antigens and Antibodies

Immunogenicity → the ability to induce humoral/cell-mediated immune response

B-cell + Antigen → Effector B-cell + memory B-cell
                                           ↓
                                  plasma cell → Antibody


T-cell + Antigen → Effector T-cell + memory T-cell
                                            ↓
                                 CTLs + THELPER, etc → cytokines, cytotoxic factors

Antigenicity → the ability to combine specifically with antibodies and surface receptors on T-cells

Haptens → are antigenic but incapable of inducing a specific immune response by themselves, i.e. non-immunogenic. The chemical coupling of multiple molecules of a hapten to an immunogenic molecule called a "carrier" gives a hapten-carrier conjugate which is accessible to the immune system
  • anti-hapten antibody
  • anti-carrier antibody
  • anti-conjugate antibody
Adjuvants → substances which when mixed with antigen enhance the immunogenicity of that antigen, for example, synthetic polyribonucleotides, bacterial lipopolysaccharides and give the following effects:
  • antigen presence in prolonged
  • co-stimulatory signals are enhanced
  • local inflammation increases
  • non-specific proliferation of lymphocytes is prolonged
Aluminum potassium sulfate (Alum) is the only adjuvant approved for general use. Adjuvants are found to be of two types:
  1. Freund's incomplete adjuvant → made of antigen solution + mineral oil + emulsifier (mannide monooleate)
  2. Freund's complete adjuvant → made of antigen solution + heat-killed myobacteria (muramyl dipeptide) and is more potent that its "incomplete" counterpart
Epitopes → discrete sites on the antigen molecules that the lymphocytes recognize and may involve elements of the primary, secondary, tertiary or quaternary sturucture of the protein.

For example, consider the B-cell epitopes:
  • they are composed of hydrophilic amino acids and are therefore more exposed in solution (hydrophobic amino acids hide). Thus sequential/non-sequential residues are brought together by folded conformation ("conformational determinants")
  • they are located in flexible regions and display site mobility →  maximizes complementarity with the antibody's binding site
  • complex proteins contain multiple overlapping B-cell epitopes
Comparison of antigen recognition by B and T-cells

CharacteristicB-cellsT-cells
Interaction with antigen (Ag)binary complex of antigen and membrane Immunoglobulin (Ag═Ig)ternary complex of T-cell receptor, antigen and the major histocompatibility complex (Ag═TCR═MHC) 
Binding of soluble antigen?YesNo
Major Histocompatibility Complex (MHC) involved?NoYes
Chemical nature of the antigenproteins, polysaccharides, lipidsmostly proteins, some lipids and glycolipids
Epitope propertiesaccessible, hydrophilic, mobile, sequential or non-sequential amino acidsinternal linear peptides produced by processing of Ag bound to the MHC

No comments: