Haptens, immune response

Haptens, a special class of antigen, are small molecules that induce specific antibody production when they are attached to a protein that acts as a carrier. Phosphorylcholine is one such hapten that has been widely used in the investigation of immune responses. The specific binding of this hapten... 

Raising the pi of macromolecules also can significantly alter the immune response toward them upon in vivo administration. Cationized proteins (those modified with diamines to increase their net charge or pi) are known to generate an increased immune response compared to their native forms (Muckerheide et al., 1987a, b Apple et al., 1988 Domen et al., 1987 Domen and Hermanson, 1992). The use of cationized BSA as a carrier protein for hapten conjugation can result in a dramatically higher antibody response toward a coupled hapten (Chapter 19). 

This chapter describes the design, preparation, and use of hapten-carrier conjugates used to elicit an immune response toward a coupled hapten. The chemical reactions discussed for these conjugations are useful for coupling peptides, proteins, carbohydrates, oligonucleotides, and other small organic molecules to various carrier macromolecules. The resultant conjugates are important in antibody production, immune response research, and in the creation of vaccines. 

In an immune response, antibodies are produced and secreted by the B-lymphocytes in conjunction with the T, cells. In the majority of hapten-carrier systems, the B cells end up producing antibodies that are specific for both the hapten and the carrier. In these cases, the T lymphocytes will have specific-binding domains on the carrier, but will not recognize the hapten alone. In a kind of synergism, the B- and T-cells cooperate to induce a hapten-specific antibody response. After such an immune response has taken place, if the host is subsequently challenged with only the hapten, usually it will respond by producing hapten-specific antibodies from memory cells formed after the initial immunization. For a review of immunobiology (see Janeway, 2004). 

Synthetic haptens mimicking some critical epitopic structures on larger macromolecules are often conjugated to carriers to create an immune response to the larger parent molecule. For instance, short peptide segments can be synthesized from the known sequence of a viral coat protein and coupled to a carrier to induce immunogenicity toward the native virus. This type of synthetic approach to immunogen production has become the basis of much of the current research into the creation of vaccines. 

Some synthetic carriers actually are designed to have low immunogenicity on their own to minimize the potential for antibody production against them. When a hapten is coupled to these molecules, the immune response is directed principally toward the modification, not at the carrier. This design approach guides most of the immune response toward the desired target and minimizes the production of carrier-specific antibodies. 

Details on the cellular immune responses occurring following the recognition of xenobiotic haptens as antigens by the immune system are described in chapters 33-35 of this volume. Ultimately, a certain combination of mediators is selectively activated and subsequently helps determine and differentiate the characteristic immune response (e.g., Thl vs. Th2). For example, dermal sensitizing chemicals (e.g., oxazolone and dinitrochlorobenzene) elicit a higher proportion of Thl cytokines such as IFNy and... 

Weltzien, H.U., et al., T cell immune responses to haptens. Structural models for allergic and autoimmune reactions. Toxicology, 107, 141, 1996. 

Antigen is a substance that stimulates an immune response, especially the production of antibodies. Antigens are usually proteins or polysaccharides, but can be any type of molecule, including small molecules (haptens) coupled to a carrier-protein. 

A hapten is too small to initiate an Immune response but nay do so when attached to a larger molecule. 

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