DNA Polymorphisms: RFLPS

 DNA POLYMORPHISMS: RFLPS

Several new genetic polymorphisms, detected directly at the DNA level, have been de-scribed in the Ig region. These are known as restriction fragment length polymorphisms (RFLPs) because they result from variation in DNA base sequences that modify cleavage sites for restriction enzymes. RFLPs have been described in both the V and C regions. Their significance is under active investigation.

As aforementioned, the most widely used method for determining immunoglobulin allotypes is hemagglutination-inhibition, using antisera derived from fortuitously immu-nized human donors. Because of the scarcity of such antisera, investigations to examine the role of allotypes in immune responsiveness and disease susceptibility have been hampered. Recently, molecular methods that allow the detection of allotypes at the genomic level have been developed, thus circumventing the problems arising from the paucity of antisera.

Comments

Post a Comment

Popular posts from this blog

Pathogenesis - IgE Mediated (Immediate) Hypersensitivity

Image
  PATHOGENESIS The pathogenesis of immediate hypersensitivity reactions involves a well-defined sequence of events: 1.             Synthesis of specific IgE antibodies.   2.             Binding of IgE antibodies to Fc ε  -I receptors on basophils and mast cells; once bound, IgE acts as an antigen receptor.   3.             Cross-linking of receptor-bound IgE by a multivalent antigen initiates the release of preformed vasoactive compounds and the synthesis and later release of medi-ators of inflammation.   4.             The preformed substances released by basophils and mast cells have significant effects on target tissues, such as smooth muscle, vascular endothelium, and mu-cous glands. They also act as chemoattractant cytokines and may elicit c...
Read more

T-Dependent and T-Independent Antigens

  T-DEPENDENT AND T-INDEPENDENT ANTIGENS The studies with hapten-carrier complexes were followed by many others in which inbred rodents were sublethally irradiated to render them immunoincompetent, and their immune systems were then reconstituted with T lymphocytes, B lymphocytes, or mixtures of T and B lymphocytes obtained from normal animals of the same strain. After reconstitution of the immune system, the animals were challenged with a variety of antigens, and their antibody responses were measured. For most antigens, including complex proteins, heterologous cells, and viruses, a measurable antibody response was only observed in animals reconstituted with mixtures of T and B lymphocytes. In other words, for most antigens, proper differentiation of antibody-producing cells required T cell “help.” The antigens that could not induce immune re- sponses in T-cell–deficient animals were designated as T-dependent antigens. Structurally, T-dependent antigens are usually complex protein...
Read more

Immunoglobulin Metabolism

Image
  IMMUNOGLOBULIN METABOLISM All proteins produced by an organism will eventually be degraded or lost through the excreta. However, the speed of the metabolic elimination and the fractional turnover rate (the fraction of the plasma pool catabolized and cleared into urine in a day) and the synthetic rate vary considerably from protein to protein. Within the immunoglobulin group, differ-ent immunoglobulin isotypes have different synthetic rates and different catabolic rates. One of the most commonly used parameters to asses the catabolic rate of im-munoglobulins is the half-life (t  1/2 ), which corresponds to the time elapsed for a reduction to half of the IgG concentration after equilibrium has been reached. This is usually deter-mined by injecting an immunoglobulin labeled with a radio-isotope ( 131 I is preferred for the labeling of proteins to be used for metabolic studies due to its fast decay rate) and follow-ing the plasma activity curve. Figure 6.4 shows an example of a ...
Read more