A. Ataxia telangiectasia i. RAG-1 or RAG-2 mutations resulting in decreased recombinase activity
B. Irradiation-sensitive ii.  ATM mutations SCID (IR-SCID)
C. Omenn syndrome iii. Artemis mutations 5.8 Matching: Match the immunoglobulin class to its main function:
A. IgA i. Most abundant in serum and strongly induced during an immune response
B. IgD ii. First one produced after B-cell activation
C. IgE iii. Defense at mucosal sites
D. IgG iv. Defense against parasites but also involved in allergic diseases
E. IgM v. Function not well known; may serve as auxiliary BCR 5.9 Fill-in-the-Blanks: Out of the five different antibody classes, two are secreted as multimers. _____ is secreted as a dimer and _______ is secreted as a pentamer, both of which have a(n) _______ as part of the multimeric complex. IgM and ______ are both expressed at the surface of mature B cells and are derived from the same pre-mRNA transcript. The balance of expression between these two is determined by alternative _______________ and is regulated by the snRNP __________. The process that regulates membrane-bound versus secreted forms of antibodies is determined by two factors: ___________ and ___________. Fcγ receptors on macrophages and neutrophils bind to the Fc portions of _____ and _____ isotype antibodies of the IgG class. Mast cells, basophils, and activated eosinophils, however, will bear Fcε receptors that bind to _______ class antibodies. IgA and IgG class antibodies are able to bind to ______, which actively transports them to different body tissues and recycles them at the kidney glomerulus to prevent their loss and prolong their half-lives.
5.10 Multiple Choice: Which of the following is not true concerning the evolutionary history of the adaptive immune system?
A. Adaptive immunity arose abruptly in evolution.
B. Fruitflies and mosquitoes exhibit diversity in the secreted Dscam protein by alternative splicing of a vast array of different exons, while freshwater snails exhibit diversity in FREP genes by differential accumulation of genomic mutations in these genes.
C. Jawless fish recombine VLR genes during DNA replication to engender diversity in these genes, which are expressed on lymphocytes and have GPI-anchored and secreted forms.
D. RAG-1 arose from transposases while the RSSs it recognizes arose from terminal repeats from DNA transposons.
E. MHC class I and class II genes arose before T cells and immunoglobulins in cartilaginous fish.
General references.
Fugmann, S.D., Lee, A.I., Shockett, P.E., Villey, I.J., and Schatz, D.G.: The RAG proteins and V(D)J recombination: complexes, ends, and transposition. Annu. Rev. Immunol. 2000, 18:495–527.
Jung, D., Giallourakis, C., Mostoslavsky, R., and Alt, F.W.: Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu. Rev. Immunol. 2006, 24:541–570.
Schatz, D.G.: V(D)J recombination. Immunol. Rev. 2004, 200:5–11.
Schatz, D.G., and Swanson, P.C.: V(D)J recombination: mechanisms of initiation. Annu. Rev. Genet. 2011, 45:167–202.
Section references.
5-1 Immunoglobulin genes are rearranged in the progenitors of antibody-producing cells.