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 (AgIg)ternary complex of T-cell receptor, antigen and the major histocompatibility complex (AgTCRMHC
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

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