how does a cytotoxic T cell (or NK cell) avoid being killed by the perforin and granzymes that it secretes to kill a target cell?
and wound healing. The effector helper TH cells recognize the same complex of foreign peptide and class II MHC protein on the target‑cell surface as they initially recognized on the dendritic cell that activated them. They activate their target cells by producing a combination of membrane‑bound and secreted co‑stimulatory proteins. Treg cells suppress immune cells using cell‑surface and secreted inhibitory proteins.
Both T cells and B cells require multiple signals for activation. Antigen binding to the TCRs or BCRs provides one signal, while co‑stimulatory proteins binding to co‑receptors and cytokines binding to their complementary receptors provide the others. Effector TH cells provide the co‑stimulatory signals for B cells, whereas APCs provide them for T cells.
Which statements are true? explain why or why not.
24–1 T cells whose receptors strongly bind a self-peptide–MHC complex are killed off in peripheral lymphoid organs when they encounter the self peptide on an antigen-presenting dendritic cell.
24–2 To guarantee that the antigen-presenting cells in the thymus will display a complete repertoire of self peptides to allow elimination of self-reactive T cells, the thymus recruits dendritic cells from all over the body.
24–3 The antibody diversity created by the combinatorial joining of V, D, and J segments by V(D)J recombination pales in comparison to the enormous diversity created by the random gain and loss of nucleotides at V, D, and J joining sites.
Discuss the following problems.
24–4 Why do living trees not rot? Redwood trees, for example, can live for centuries, but once they die they decay fairly quickly. What might this suggest?
24–5 It would be disastrous if a complement attack were not confined to the surface of the pathogen that is the target of the attack. Yet, the proteolytic cascade involved in the attack liberates biologically active molecules at several steps: one that diffuses away and one that remains bound to the target surface. How does the complement reaction remain localized when active products leave the surface?
[Hint: imagine what would happen if the G:U mismatch created by AID was replicated several times; how would the sequences of the final mutations relate to the original G-C base pair?] 24–7 For many years it was a complete mystery how cytotoxic T cells could see a viral protein that seemed to be present only in the nucleus of the virus-infected cell. The answer was revealed in a classic paper that took advantage of a clone of T cells whose T cell receptor was directed against an antigen assoicated with the nuclear protein of the 1968 strain of influenza virus. The authors of the paper found that when they incubated high concentrations of certain peptides derived from the viral nuclear protein, the cells became sensitive to lysis by subsequent incubation with the cytotoxic T cells. Using various peptides from the 1968 strain and the 1934 strain (with which the cytotoxic T cells did not react), the authors defined the particular peptide responsible for the T cell response (Figure Q24–1).
A. Which part of the viral protein gives rise to the peptide that is recognized by the clone of cytotoxic T cells?
24–6 Based on its sequence similarity to Apobec1, which deaminates Cs to Us in RNA, activation-induced deaminase (AID) was originally proposed to work on RNA. But definitive experiments in E. coli demonstrated that AID deaminates Cs to Us in DNA. The authors of the paper expressed AID in bacteria and followed mutations in a selectable gene. They found that AID expression increased mutations about fivefold above the background level in the absence of AID expression. More importantly, they found that 80% of the induced mutations were G→A or C→T. Does this fit with your expectation if AID-induced mutations arose by deamination of C to U in the DNA?