Question II. During the recent Ebola epidemic, researchers in Sierra Leone found

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Question II. During the recent Ebola epidemic, researchers in Sierra Leone found that an antibody to a particular epitope of Ebola had potent virus-neutralizing activity against numerous Ebola isolates. This epitope was determined to be an heptapeptide with the following structure: AAIGLAW. Twenty individual macaques were immunized with AAIGLAW, but no protection against Ebola in vivo was observed in the immunized animals. What could be the best explanation(s) for this peptide vaccine failure? Assess the following hypothetical explanations (56-69) as either factually correct (true) or incorrect (false):

56. The peptide did not bind to any Toll-like receptor (TLR).
57. The peptide did not bind to any NOD-like receptor (NLR).
58. The peptide could not be processed or presented by non-professional antigen-presenting cells.
59. The peptide could not be processed by dendritic cells.
60. The peptide could not be processed by B cells.
61. The peptide could not be processed by activated macrophages.
62. The peptide-induced cytokine response was too weak.

63. The vaccine did not work, because the used heptapeptide was too long.
64. The vaccine did not work, because the used heptapeptide was too short.
65. The vaccine did not work, because T-cell epitopes were absent.
66. The vaccine did not work, because the used AAIGLAW heptapeptide contained too many alanine residues.

67. The vaccine did not work, because the used AAIGLAW heptapeptide contained only one tryptophan residue.
68. The vaccine did not work, because the heptapeptide failed to activate NK cells.
69. The vaccine did not work, because it did not induce adequate amounts of interferon-g to activate professional antigen-presenting cells

Explanation / Answer

56. True. Toll like receptors are a class of pattern recognition receptors present on macrophages, neutrophils, and dentritic cells. Binding to toll like receptors initiate signalling for innate immune responses, like phagocytosis.

57. False. NOD like receptors specifically recognize molecules like peptidoglycan.

58. True. APC can process antigens and large peptides. The given peptide is a small peptide which either fails to be processed or presented. The MHC - I antigens present peptides of length 13 -18 amino acids whereas MHC - II present peptides of length 9-11 amino acids. Shorter peptides cannot be presented by the MHC.

59. True. The peptide may be digested by the proteosome complex, but cannot generate fragments of desired length to be presented by the dendritic cells.

60. True. B-cells follow the same endosomal pathway of antigen processing and presentation. The antigen may be internalized and digested, but fails to be presented since the fragment is too short to be presented by professional APC.

61. False. Macrophages can process the antigen since it generally involves digestion mediated by lysosomal pathway (not proteasome). However, the fragments generated are not of sufficient length to bind to the MHC.

63. False. The used hexapeptide is too short to elicit an immune response.

64. True. Generally, antigenic fragments that are presented by HC-I are of 14 - 18 amino acid length, and those presented by mHC-II are 9 -11 amino acid long. Fragments shorter than these lengths cannot be accommodated in the peptide binding groove of MHC molecules.

65. False. T-cells recognize structural epitopes whereas B cells recognize conformational epitopes. That means, T cells recognize epitopes that are derived from the primary structure of the protein. B cells recognize antigenic epitopes which are in their 3-D conformantion.

66. True. The more is the complexeity of the peptide, the more is its immunogenecity. Simple peptides made of such amino acids cannot elicit a strong immune response.

67. False. The more is the number of bulky amino acids, the more is its immunogenecity. However, there is no exact specification about the number of bulky amino acids a peptide should contain.

68. False

69. False. IFN-g is involved in inducing anti-viral state, but does not confer immunity.

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