i) The human genome is an elegant but cryptic store of information.
The roughly three billion bases encode, either directly or indirectly, the instructions for synthesizing nearly all the molecules that form each human cell, tissue and organ. And although the human genome has only about 23,000 protein-coding genes, Homo sapiens can produce millions of different antibodies, capable of reacting with virtually any known invading pathogen. The immune system generates this diversity of antibodies by shuffling a few hundred genes to create countless permutations, in a process called V(D)J recombination (also known as somatic recombination). In this process, RAG enzymes work as a multi-subunit complex to induce cleavage of a double-stranded DNA molecule between the antigen receptor coding segment and a flanking recombination signal sequence (RSS). They do this in two steps. They initially introduce a ‘nick’ in the 5' (upstream) end of the RSS heptamer (a conserved region of 7 nucleotides) that is adjacent to the coding sequence, leaving behind a 3'-hydroxyl group at the coding end and a 5'-phosphate group at the RSS end. The next step couples these chemical groups, binding the OH-group (on the coding end) to the PO4group (that is sitting between the RSS and the gene segment on the opposite strand). [Assess each subsequent statement (1-9) as either factually correct (= “true”) or incorrect (= “false”)]: 1. This produces a 5'-phosphorylated double-stranded break at the RSS and a non-covalently closed hairpin at the coding end. 2. This activates the enzyme NADPH oxidase. 3. This is an important enzymatic step in a process known as V(D)J recombination, which is strictly limited to B cells. 4. This generates a hairpin, leaving a blunt double-stranded break at the end of the RSS. 5. This is an important enzymatic step in a process known as somatic recombination, which is limited to macrophages. 6. This is an event of the mechanism of genetic recombination in the early stages of immunoglobulin (Ig) and T-cell receptors (TCRs) production. 7. This is an event of the mechanism of genetic recombination in the late stages of Ig and TCRs production. 8. Only Statement #1 is true. 9. Statement #2 is false. ii) Disparities between innate and adaptive immunity [complete the sentence and assess the resulting statements (10-19) as either factually correct (= “true”) or incorrect (= “false”)]: 10. are not in the area of immunological memory. 11. are in the area of ‘speed of initiation/implementation’ of responses. 12. are not in the area of ‘speed of initiation/implementation’ responses. 13. are encoded in the human genome. 14. are in the area of usage of invariant mechanisms to recognize pathogens. 15. include requirements of gene rearrangement. 16. do not include requirements of gene rearrangement. 17. do not include clonal distribution of receptors.
do not include differences in the number of specificities recognized in the given type of immune response. but does not opsonize it. C3b binds both to C4b2a and C3bBb. 22.18. 19. superoxide dismutase and protein kinase. 40. Bb is active enzyme of the C3 convertase C3bBb and C5 convertase C3b2Bb. C2a binds to surface C4b forming the classical C3 convertase. 37. 31. repairing the coding joint and ligation carried out by exonuclease. the Artemis:DNK-PK complex. 30. cytidine deaminase and terminal deoxynucleotidyl transferase. variable truncation of the coding segment and. 23. the introduction of a small number of two types of non-germ line residues [termed palindromic (P) and nontemplated (N) nucleotides] occur at the recombinant junctions. the Artemis:DNK-PK complex and terminal deoxynucleotidyl transferase. respectively) include those of [complete the sentence and assess the resulting statements (34-42) as either factually correct (= “true”) or incorrect (= “false”)]: 34. 38. C3bBb complex is a C3 convertase. 27. 21. 33. cleaving many C3 molecules to C3a and C3b. C4a is a peptide mediator of inflammation (weak activity). C1r cleaves C1s to active protease. reverse transcriptase. C3b binds C6 for cleavage by C2a.and Nnucleotides (before the trimming of unpaired nucleotides. 29. These sequence alterations fall within the binding domain of the encoded antigen receptor and constitute an important source of diversity in the immune system. C1s cleaves C4 and C2. 25. C3a is a peptide mediator of inflammation (intermediate activity). iii) Assess each subsequent statement (20-33) about the complement system as either factually correct (= “true”) or incorrect (= “false”): 20. often. C4b2a.
. GPTase. forming the active C5 convertase C4b2a3b and C3b2Bb. 26. 24. 32. 39. terminal deoxynucleotidyl transferase and catalase. 36. myeloperoxidase and NADPH oxidase. Properdin is a plasma protein that stabilizes the C3bBb convertase on a pathogen surface. 35. DNA polymerase and DNA ligase. DAF and MCP (CD46) disrupt the C3bBb convertase on a pathogen cell surface. phosphatase and acetyltransferase. C4b covalently binds to pathogen. The enzymatic activities directly involved in the generation of P. telomerase and lysozyme. are not in the area of recognition of pathogen-associated molecular patterns. iv) When Ig and TCR genes are assembled from their germ line components. C3b binds factor B. 28. 41. C3b binds noncovalently to the microbial surface. the nuclease Artemis and activation-induced cytidine deaminase.
61. D. Some TLRs signal through their ectodomains. TLRs signal through their cytoplasmic TIR domains. 65. 51. TLR specificity is likely determined by the variable regions present in the inner surface.42. and J genes translocated near the Cα DNA exon 45. 62. mRNA specific for J chains 48. The origin of the word “toll” is Ernest Hemingway’s novel “For Whom the Bell Tolls. All TLRs signal through domains that interact with the MyD88 protein encoded by the MyD88 gene [Myeloid differentiation primary response gene (88)]. 55. mRNA specific for either a γδ or a αβ TCR 47. resulting in the induction of the proinflammatory cytokine expression.
. a DNA sequence for V. mRNA specific for either κ or λ light chains 46. 63. A typical extracelullar TLR region is composed of 18-25 copies of a lysinerich repeat. TLR signaling may involve the serine-threonine kinases IRAK1 and IRAK4 in association with the ubiquitin E3 ligase TRAF-6. v) If you could molecularly analyze a normal (= non-tumor and non-transfected) plasma B cell making IgA antibody. 58.” 52. 57. a DNA sequence coding for both the γδ and αβ TCR vi) Assess each subsequent statement (50-70) concerning Toll-like receptors (TLRs) as either factually correct (= “true”) or incorrect (= “false”): 50. 54. The origin of the word “toll” is the German phrase “Das ist ja toll!” 53. 56. TLR signaling can activate the transcription factor NF-κB. All mammalian TLR proteins have a TIR (‘Toll-IL-1 receptor’) domain in their cytoplasmic tail. Some TLRs sense microbes or their components delivered through macropinocytosis. mRNA specific for µ chains 49. Ligand binding can bring together two TLR intracellular domains. 59. histone diacetylase and histone methyl transferase. which are brought into proximity by the dimerization of their ectodomains. The origin of the word “toll” is the song “For Whom the Bell Tolls” by the American band Metallica. you would find [assess the following options (43-49) as either factually correct (= “true”) or incorrect (= “false”)]: 43. 60. 64. An accessory protein MD-2 associates with the central section of the curved ectodomain of TLR-4 and is necessary both for the correct trafficking of TLR-4 to the cell surface and for the recognition of LPS. mRNA specific for the RAG-1 and RAG-2 proteins 44. MD-2 is required for all TLRs to recognize their ligands. TLRs are encoded by genes that undergo gene rearrangement during cell differentiation.
are related to the gene coding for the enzyme activation-induced cytidine deaminase (AID) that plays an important role in somatic hypermutation. are coding for enzymes generating junctional diversity by adding nucleotides nontemplated in germline DNA. DNA repair protein XRCC4. are critical for diversification of the V-domain coding sequences by somatic hypermutation. DNA polymerase µ and DNA polymerase λ. 76. 70. gene conversion and isotype switching. are the specifying genetic elements of the V(D)J recombinase. 69. viii) Suppose that the human TCR repertoire contains a very small number of TCRs (let’s call them the TCR2012). During random testing. 8% of CD3-positive peripheral blood lymphocytes from a human volunteer were found to be TCR2012-positive. The given MHC-peptide 2012 complex stimulates lymphocytes expressing the TCR2012 via processes known as [complete the sentence and assess the resulting statements (80-87) as either factually correct (= “true”) or incorrect (= “false”)]: 80. 68. vii) The RAG-1 and RAG-2 genes [complete the sentence and assess the resulting statements (71-79) as either factually correct (= “true”) or incorrect (= “false”)]: 71. antigen hypermutation. 75. A typical extracelullar TLR region is composed of 18-25 copies of a leucinerich repeat. Endosomal TLR-7 binds ssRNA and signals via MyD88 to induce IFN gene expression. strongly suggesting recent infection with a pathogen expressing the 2012-associated epitope. DNA-PKcs. code for proteins that associate with ubiquitous DNA-modifying proteins involved in the repair of DNA double-strand breaks and the modification of the ends of broken DNA strands such as Ku. Artemis. 67. 79. 74. Some TLRs recognize microbial components taken into cells by phagocytosis. DNA ligase IV. code for proteins important during the immunoglobulin isotype switching processes.
. 73.66. 81. Some TLRs detect microbes or their components delivered through receptormediated endocytosis. antigen stimulation. have no introns. Typical TLRs are single-pass transmembrane proteins. whose pathogen recognition domain consist of a repeated motif of 20-29 amino acid residues rich in the hydrophobic acid isoleucine. are not important in the process of generating the coding joint in chromosomal DNA. recognizing specifically a complex of an MHC molecule and a rare pathogen-derived ‘peptide 2012’. 72. 77. are important in the process of generating the signal joint in a circular piece of extrachromosomal DNA. 78.
Chemokine production 98. clonal selection. Clonal deletion 101. TLR signaling 102. 86. C3b of the complement pathway 92. Circulating T cells 94. Skin-infiltrating macrophages 89. 83. clonal expansion. tears. Defensins in sweat.82. ix) Which of the following can be considered as one of the innate immune mechanism entities and characteristics? [Assess the following expressions and statements (88-103) concerning the innate immune mechanism entities and characteristics as either factually correct (= “true”) or incorrect (= “false”): 88. Mucosa-infiltrating B cells 91. Digestive enzymes and antimicrobial peptides 93. Slow response 103. somatic hypermutation. Mucosa-infiltrating NK cells 90. Complement activation
. Cytokine production 97. germline recombination. Inflammation 100. Antigen processing 99. class switching. Phagolysosomes 96. 85. 84. somatic recombination. 87. and gut lumen 95.