Tuesday, February 9, 2016

Rare Diseases and the Molecular Biology of Adaptive Immunity

There are at least three generally recognized types of immune responses in animals: innate, intrinsic, and adaptive. In adaptive immunity, the response adapts to the specific chemical properties of foreign antigens. Adaptive immunity is a system wherein somatic T cells and B cells are produced, each with a unique and characteristic immunoglobulin (in the case of B cells) or T-cell receptor (in the case of T cells). Through a complex presentation and selection system, a foreign antigen elicits the replication of a B cell that produces an antibody whose unique immunoglobulin attachment site matches the antigen. Antigen-antibody complexes may deactivate and clear circulating antibodies, or may lead to the destruction of the organism that carries the antigen (e.g., virus or bacteria). The process of producing unique proteins requires that recombination and hypermutation take place within a specific gene region. Recombinations yield on the order of about a billion unique somatic genes, starting with one germinal genome. This process requires the participation of recombination activating genes (RAGs). The acquisition of an immunologically active recombination activating gene is presumed to be the key evolutionary event that led to the development of the adaptive immune system, present in all jawed vertebrates (gnathostomes). In addition,a specialized method of processing immunoglobulin heavy chain mRNA transcript accounts for the high levels of secretion of immunoglobulin proteins by plasma cells (1). As one might expect, inherited mutations in RAG genes cause some of the rare immune deficiency syndromes (2), (3).

- Jules Berman (copyrighted material)

key words: immune disease, rare disease, orphan drugs, orphan diseases, zebra diseases, rare disease day, jules j berman

Rare Disease Day is coming up February 29 (a rare day for rare diseases). In honor of the upcoming event, I'll be posting blogs all month, related to the rare diseases and to rare disease funding.


[1] Borghesi L, Milcarek C.From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion. Immunol Res 36:27-32, 2006.

[2] Zhang J, Quintal L, Atkinson A, Williams B, Grunebaum E, Roifman CM. Novel RAG1 mutation in a case of severe combined immunodeficiency. Pediatrics 116:445-449,2005.

[3] de Villartay JP, Lim A, Al-Mousa H, Dupont S, D chanet-Merville J, Coumau-Gatbois E, et al. A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection. J Clin Invest 115:3291-3299, 2005.