ACAAI Board Review: Basic Science Questions and Correct Answers| Graded A+

What is the hapten- carrier effect? Small-molecule antigen requires covalent linkage to a larger carrier to stimulate adaptive immune response. The process is achieved in collaboration between hapten-specific B cells and carrier-specific T cells. This is the basis of developing conjugated vaccines. What are the common superantigens and related diseases? SEB and SEC cause food poisoning; TSST and SPE-C cause toxic shock syndrome. Superantigens bind the Vβ region of TCRs (CDR4) and outside of the peptide-binding groove on the MHC molecule. Conjugated vaccines are T-independent antigens linked to a carrier protein, which can trigger a T- dependent response and memory. Examples of conjugated vaccines include 13-valent pneumococcal vaccine (Prevnar 13), Hib vaccines, and meningococcal vaccines (MCV4-Menactra and Menveo). Which type of T cells recognizes lipid antigens and what is the molecule involved? Natural killer T (NKT) cells and CD1 molecule. What are the binding sites for TCR on MHC class I and class II molecules, respectively? α3 and β2. Viruses develop strategies to evade MHC class I presentation. Herpes simplex virus (HSV) can block TAP transportation, and cytomegalovirus (CMV) can remove MHC class I molecule from ER. MHC class I molecule presents which type of antigens and where does the antigen-MHC class I loading happen? Intracellular antigens (e.g., viral antigen in cytoplasm) and the loading site is endoplasmic reticulum (ER). HLA-DM is an intracellular protein involved in MHC class II antigen processing and does not present antigenic peptides nor is it a component of MHC class II. MHC class II molecule presents which type of antigens and where does the antigen-MHC class II loading happen? Extracellular antigens (e.g., antigens from phagocytosed bacteria) and loading site is phagolysosome. Mutation in the AIRE gene produces disorders such as autoimmune polyglandular syndrome (APS). Lymphocytes are not deleted or tolerized to endocrine-related self- antigens. The endocrine organs are attacked by autoreactive T lymphocytes and autoantibodies. κ light chains are rearranged first. If receptor editing is needed, a λ light chain will be used. Lack of costimulation, or lack of an innate immune system response to the antigen, blunts the required upregulation to achieve costimulation (i.e., a second signal). T lymphocytes recognize the antigen, but receive no support to activate. After repeated recognition without costimulation, the lymphocyte becomes unresponsive to that antigen (i.e., anergic). Once a cell is anergic, costimulation will not restore activation. Which B-cell-exclusive process is involved in developing central tolerance and which two enzymes are important in this process? Receptor editing. RAG1, RAG2. Treg cells play a critical role in maintaining normal immune function. Classically Treg cells express CD4, CD25 and FoxP3. FoxP3 mutation in human causes immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, which is a fatal autoimmune disorder characterized by a triad of watery diarrhea, eczema, and endocrinopathy. Mutations in Fas or caspase 10 manifest as autoimmune lymphoproliferative syndrome (ALPS). The lymphocytes do not know when to die. They accumulate in the lymph organs. There is a lack of tolerance, producing autoimmune problems SNPs, which manifest human genome variations across different geographic and ethnic groups, are widely used in GWAS as gene-mapping tools to study the association between genes and diseases. Histone acetylation opens the chromatin to allow transcription. Histone deacetylation represses gene expression and is reduced in chronic obstructive pulmonary disease (COPD). Omalizumab binds to Cε3. The ratio of κ-bearing lymphocytes to λ- bearing lymphocytes can be used as an indication of clonality and is, therefore, useful in diagnosing and typing B-lymphocyte lymphomas. The most variable part of Ig molecule is CDR3. What molecules belong to Ig superfamily? TCR, MHC molecules, CD4, CD8, CD19, B7-1, B7-2, Fc receptors, KIR, and VCAM-1. The shortest half-life of all IgG subclasses is IgG3. IgM fixes complement most efficiently of any Ig isotype. Rheumatoid factor (RF) is an antibody against the Fc portion of IgG. RF is most commonly IgM, but can also be any other isotype. The only Ig to cross the placenta is IgG. The Ig class with highest plasma concentration is IgG. The Ig class with highest total body concentration and daily production is IgA. The poly-Ig receptor is synthesized by mucosal epithelial cells and expressed on their basolateral surfaces. Once inside the epithelial cell, IgA bound to the poly-Ig receptor is actively transported in vesicles to the luminal surface. Ig isotypes table Somatic hypermutation leads to changes in the V but not the C regions. Class switch recombination changes the C but not the V regions. Alternative splicing changes Ig from transmembrane to secretory form. Functional features of Ig Which somatic recombination process introduces the greatest diversity in immune receptors and which enzyme is important in this process? Junctional diversity and TdT. Fc receptors table CD3 deficiency produces severe combined immunodeficiency (SCID). Costimulator Expression and Function