Adaptive responses: T and B cells
Introduzido| English | Significado |
|---|---|
| helper T cells | helper T cells |
| cytotoxic T cells | cytotoxic T cells |
| plasma cell/ˈplæzmə sel/ | An activated B-cell descendant specialised for secreting antibodies. |
| co-stimulation | co-stimulation |
| anergy | anergy |
| adjuvants | adjuvants |
| clonal expansion | clonal expansion |
| regulatory T cells | regulatory T cells |
From a handful to a million in five days
- When a new virus arrives, only a handful of your T cells can recognise it. Five days later there are about a million of them.
- How the body decides to start that expansion, and who does which job afterwards, is the core of the adaptive response.
Helpers and killers
- Helper T cells 辅助性T细胞 (CD4) direct the response with cytokines: they switch macrophages to kill what they have eaten and help B cells change antibody class.
- Cytotoxic T cells 细胞毒性T细胞 (CD8) kill infected cells, by injecting perforin and granzymes or by Fas–FasL.
B cells and plasma cells
- An activated B cell becomes a plasma cell 浆细胞, an antibody factory that releases about 2000 antibody molecules a second.
- Others become memory B cells, which wait for the next encounter.
Match each cell to its job.
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The adaptive response is a division of labour.
The two-signal rule
- A naive T cell needs signal 1 (its receptor binding peptide on MHC) AND signal 2, co-stimulation 共刺激 such as B7 on a dendritic cell binding CD28.
- Signal 1 alone does not activate: it switches the T cell off, a state called anergy 免疫无能.
A naive T cell binds its peptide on MHC, but the presenting cell shows no B7. What happens?
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Signal 1 without co-stimulation tells the T cell to stand down.
Why the gate exists
- A library this large must bind some self proteins. Dendritic cells show B7 only after sensing microbes, so the gate opens for danger, not for self.
- Adjuvants 佐剂 in vaccines supply that danger signal. Tissue damage can open the gate for self, one route into autoimmunity.
Vaccine adjuvants work by supplying the danger signal that leads to co-stimulation.
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Adjuvants make dendritic cells express B7, so signal 2 accompanies the vaccine antigen.
Clonal expansion
- Only about 1 naive T cell in 10⁵–10⁶ recognises a given viral peptide. Once activated it divides about every 6 hours: clonal expansion 克隆扩增.
- 3 days is 12 divisions, $2^{12} \approx 4000$ cells; 5 days is 20 divisions, $2^{20} \approx 10^{6}$. That is why the adaptive response is days late but overwhelming.
Put the steps of a T-cell response in order.
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Antigen comes to the T cells first; the expanded clone then goes back to the infection.
Regulatory T cells
- Regulatory T cells 调节性T细胞 (Tregs, marked by FOXP3) hold other T cells back with suppressive cytokines.
- They stop responses from overshooting and keep self-reactive cells quiet.
Worked example: counting the clone
- One activated T cell divides every 6 hours for 4 days: 96 ÷ 6 = 16 divisions, so $2^{16} = 65\,536$ cells.
- Reaching about 1000 cells takes 10 divisions ($2^{10} = 1024$), or 60 hours. Each extra day multiplies the clone by 16.
One activated T cell divides every 6 hours for 4 days. How many cells are there?
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96 ÷ 6 = 16 divisions, and 2¹⁶ = 65 536.
Dividing every 6 hours, how many hours does one T cell take to become 1024 cells?
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1024 = 2¹⁰, so 10 divisions × 6 hours = 60 hours.
Worked example: the broken bridge
- (Fictional) A boy has X-linked hyper-IgM syndrome: CD40 ligand is missing on his helper T cells, so they cannot give B cells the CD40 signal.
- His B cells cannot switch from IgM to IgG, and his macrophages are poorly activated, so he gets both bacterial and opportunistic infections. One missing molecule cuts both halves of T-cell help.
Which antibody pattern is expected when CD40 ligand is missing?
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Without the CD40 signal B cells cannot switch class, so they keep making IgM.
Three common slips
- "Helper means gentle." Helper T cells drive macrophages to kill.
- "Seeing antigen is enough." Without signal 2 the T cell is switched off.
- Expecting antibody on day 1. A first response peaks at about 7–14 days.
Recap
- CD4 cells help, CD8 cells kill, plasma cells secrete antibody, memory cells wait.
- Signal 1 + co-stimulation activates; signal 1 alone causes anergy. Adjuvants supply signal 2.
- Dividing every 6 hours, one cell becomes about a million in 5 days. Tregs hold responses back.